N G C LIN

o~Ai
gpQ
IMNt NH XUI BN I HC QC GIA H Ni
 GS. TS. NGC LIN

MIN DCH HC
C S
(In ln th ba, c sa cha v b sung)

NH XUT BN I HC QUC GIA H NI

 Ill

Mc lc

Chng I. Khi nim c bn v min dch hc 3

1.1. nh ngha v min dch hc 3
1.2. Lch s nghin cu min dch hc 3
1.3. Nhng khi nim tng qut v min dch hc 6
1.3.1. Min dch tip thu hoc thch ng v min dch t nhin 6
1.3.2. Cc khng nguyn (antigens) 10
1.3.3. Cc khng th v b th 10
1.3.4. Cc xitokin (cytokine) 12
1.3.5. Hin tng phn v (anaphylaxis) 13
1.3.6. Ci bn thn v khng phi bn thn (self, nonself) 14
1.3.7. Cc phn ng khng nguyn - khng th in vitro 14
1.3.8. Cc loi p ng min dch v l thuyt la chn dng 14
1.3.9. S tim chng (vaccination) 15
1.3.10. S iu ha min dch 15
1.3.11. Cytokine trong iu ho min dch bm sinh v thch ng 16
Chng n . Khng nguyn 19
2 . 1. nh ngha v khi nim chung v khng nguyn 19
2.2. Phn ng cho 20
2.3. Hapten v protein mang 21
2.4. Tnh khng nguyn ca cc cht sinh trng hp (biopolymer) 21
2.5. S thch ng ca cc vi sinh vt bng cch ci bin cc 23
khng nguyn ca chng
2.6. Immunogen v kh nng p ng min dch 24
Tm tt chng II 25

Chng HL Cc khng th v th th ca khng nguyn 27

3.1. Cu trc chung ca cc immunoglobulin (Ig) 27
3 .2 . Ci trc phn t ca cc immunoglobulin ring bit 31
3.3. M quan h gia cu trc v chc nng ca cc khng th 37
3.4. C s di truyn v tnh a dng ca khng th 37
3.5. Cc khng th dn dng (monoclonal antibodies) 43
3.6. Khng th ti t hp (recombinant antibody - rAb) 44
IV

3.7. Cc th th ca lympho B (BCR ) 45

3.8. Cu trc ca cc th th lympho T (TCR) 46
3.9. Cc du hiu protein bit ho t bo 47
Tm tt chng III 50
Chng IV. Cc phc h ph hp t chc ch yu 51
4.1. M u 51
4 .2 . Cu trc chung ca h thng HLA 52
4.3. Cu trc cc phn t v h gen ca HLA 53
4.4. S phn b, iu ho biu hin v chc nng ca cc 55
phn t HLA
4.5. H thng HLA lin quan n qun th chng tc v cc 58
bnh l
4.6. Cc phng php nghin cu h thng HLA 58
Tm tt chng IV 60

Chng V. B th 61
5 . 1. Khi nim 61
5 .2 . Cc protein ca b th 62
5.3. Cc tin trnh hot ho b th 63
5.3.1. Con ng hot ho c in 63
5.3.2. Con ng hot ho b th nh lectin MBL 64
5.3.3. Con ng hot ho bn cnh v cc yu t hot ho b th 65
5.3.4. Phc h tn cng mng (MAC) 68
5.4. Hiu qu sinh hc ca s hot ho b th 69
5.5. B th v cc c ch trn thot ca vi sinh vt 69
5.6. Cc h thng khc ca huyt tng tham gia vo cc c 72
ch bo v v c ch vim
5.7. Cc bnh l pht sinh do thiu ht b th bm sinh 72
Tm tt chng V 74

Chng VI. Phn ng khng nguyn - khng th 75

v cc k thut ha sinh min dch
6 . 1. Phn ng khng nguyn - khng th 75
6 . 1. 1. Cc c tnh chung ca 8 lin kt khng nguyn - 75
khng th
6 . 1.2 . Cc c im v cht lng v s lng ca phn 77
ng khng nguyn - khng th
6.1.3. Phn loi cc phn ng khng nguyn - khng th 78
6 .2 . Cc k thut min dch 79
6 .2 . 1. K thut kt ta trong mi trng lng 79
 V

6.2.2. Xt nghim khuch tn min dch theo Ouchterlony 80

6.2.3. in di min dch khuch tn (Immunodiffusion 80
electrophoresis)
6.2.4. Cc phng php ngng kt min dch (Immuno - 81
agglutination)
6.2.5. Cc phng php min dch s dng b th 81
6.2.6. Cc k thut min dch s dng thuc th nh du 83
6.2.7. K thut min dch phng x 84
6.2.8. K thut min dch lin kt enzim (ELISA) 85
Tm tt chng VI 86

Chng VII. Cc c quan v t bo ca h 87

m in dch, bit ha v chc nng
7.1. C quan ngun 87
7.2. Cc c quan s cp 87
7.2.1. Tuyn c (Thymus) 88
7.2.2. Ti Fabricius v ty xng 88
7.3. Cc c quan lympho th cp 89
7.4. Ngun gc cc t bo ca h min dch 89
7.5. Cc t bo thuc dng lympho, bit ha v chc nng. 91
7.5.1. c im chung ca s bit ha cc t bo lympho 91
7.5.2. S bit ha ca lympho T v du hiu khng 92
nguyn bit ha
7.5.3. S bit ha lympho B 95
7.5.4. S bit ha cc dng t bo khc theo chc nng 96
min dch
Tm tt chng VII 101

Chng VTII. S tng tc gia cc t bo min dch 103

v diu ho p ng min dch
8.1. S tng tc gia cc t bo c thm quyn min dch 103
8.1.1. Hp tc i thc bo - lympho T v trnh din 104
khng nguyn
8 . 1.2 . Hp tc lympho Th - lympho B 109
8 .2 . S iu ho p ng min dch 111
8 .2 . 1. iu ho p ng min dch bng cc khng th v 112
mng li idiotip
8.2.2. iu ho p ng min dch nh cc t bo lympho T 114
8.2.3. iu ho p ng min dch bng kim tra di truyn 115
VI

8.2.4. iu ho p ng min dch nh s tng tc min 116

dch - thn kinh ni tit
Tm tt chng VIII 119

Chng DC Min dch bnh l qu m n 121

9.1. Khi nim chung v min dch bnh l 121
9.2. Cc hin tng qu mn 122
9 2 . 1. Qu mn phn v do IgE 122
9.2.2. Qu mn c hiu kiu II v III do IgM v IgG 123
9.2.3. Qu mn trung gian t bo hay qu mn mun 127
9.2.4. Qu mn do kch thch (Kiu V) 129
Tm tt chng IX 130

Chng X. Min dch chng vi sinh 133

v m in dch ung th
10.1. Min dch chng vi sinh vt 133
10. 1. 1. Cc c ch t nhin v thch ng loi tr vi sinh 134
vt nh lp da v tuyn nhy
10.1.2. Phn ng vim ti ch v h thng chng li nhim trng 134
10.1.3. p ng min dch c hiu chng nhim khun 134
10.2. Min dch ung th 136
10.2.1. Khi nim ung th, cc gen ung th v km hm 136
ung th
10.2 .2 . p ng min dch c hiu chng ung th 137
10.2.3. Min dch t nhin chng ung th 138
1C.2.4. Liu php min dch v min dch phng tr ung th 139
10.3. Hi chng tng sinh min dch v cc bnh ung th 140
10.3.1. Khi nim 140
10.3.2. Tnh n dng ca bnh tng sinh min dch lympho 140
10.4. Mt s c im lm sng ca ung th 147
10.4.1. Ch th ung th (Tumour marker) 147
10.4.2. Phn loi ch th ung th theo kh nng c hiu bnh 148
10.4.3. Mt s ch th ung th lin quan vi bnh 148
Tm tt chng X 152

Chng XI. Min dch bnh l: 153

thiu ht m in dch v hi chng suy
gim m in dch mc phi (AIDS)
11. 1. Khi nim 153
 VII

11.2. Thiu ht min dch nguyn thy ca cc t bo B 153

11.2.1. Bnh khng c Y- globulin trong mu 153
11.2.2. Thiu ht IgA, cc phn lp IgG v tng IgM 154
11.3. Thiu ht min dch nguyn thy ca cc t bo T 154
11.3.1. S pht trin bt thng ca t bo ngun lympho 154
giai on sm ca s bit ha
11.3.2. Biu hin thiu ht cc phn t phn lp II ca MHC 155
11.3.3. Hin tng mt iu ha gin mao mch do di truyn 155
11.3.4. Thiu ht cc protein kt dnh bch cu 155
11.4. Thiu ht min dch cc thc bo v b th 155
11.5. S thiu ht min dch th cp v AIDS 156
11.5.1. Cc bnh v mu v ung th 156
11.5.2. Thiu ht min dch do ri lon trao i cht 156
11.5.3. Bnh AIDS v con ng ly truyn 156
Tm tt chng XI 163

Chng XII. Dung np min dch v bnh t min 165

12.1. Dung np min dch 165
12.1.1. Khi nim 165
12.1.2. Cc c ch to ra dung np min dch 166
12.2 .2 . Cc t khng nguyn tham gia 167
12.2.3. Cc nguyn nhn ca bnh t min 168
12.2.4. Cc c ch hiu qu ca bnh t min 169
Tm tt chng XII 171

Chng XIII. S tin ha m in dch ca 173

cc loi ng vt
13.1. M u 173
13.2. Kh nng min dch ng vt khng xng sng 174
13.2.1. Cc biu hin t bo ca h min dch 174
13.2.2. Cc cht ha gii ha hc 174
13.2.3. Cc phn ng min dch ng vt khng xng sng 175
13.3. Kh nng min dch ca ng vt dy sng v c 176
xng sng
13.3.1. Cc ng vt hi tiu 176
13.3.2. Cc ng vt c xng sng bc thp 177
13.3.3. c im min dch ca cc lp c xng 177
13.3.4. c im min dch ca ng vt bin nhit 179
13.3.5. c im min dch ca cc loi chim 180
13.3.6. c im h min dch ca b linh trng 184
VIII

Tm tt chng XIII 192

Chng XIV. Phng v cha bnh 195

bng liu php m in dch
14.1. Vi nt lch s 195
14.2. Tim chng, vacxin phng v cha bnh 196
14.2.1. Nguyn tc chung ca vacxin 196
14.2.2. Cc dng vacxin ang c nghin cu v s dng 197
14.3. Liu php min dch khng th 200
14.4. S dng cc thuc km hm min dch 204
14.5. S dng cc xitokin v antixitokin 205
14.6. Liu php min dch t bo 208
14.7. Liu php gen chng ung th 209

Chng XV. Min dch trong cy ghp 211

15.1. Khi nim v phn loi cy ghp 211
15.2. Cc c ch thi b mnh ghp 212
15.3. Phn loi cc phn ng thi b mnh ghp 214
15.4. Mt s c im lm sng trong cy ghp 215
15.4.1. C th cho mnh ghp hoc cquan 215
15.4.2. C th nhn mnh ghp 216
15.5. Liu php km hm min dch trong cy ghp 216
15.6. Mang thai l trng thi t nhin ca cy ghp d gen 218

Cu hi n tp min dch c s 221

Mt s dng cu hi min dch 226

Ph lc 231
Ph lc I. c im cu trc v chc nng ca cc khng 233
nguyn CD
Ph lc II. Gii ngha danh t min dch 275

Ti liu tham kho 339

Li gii thiu

Sch Min dch hc c s" c bin son nhm p ng yu

cu dy v hc mn min dh hc cc trng i hc Khoa hc
t nhin, i hc S phm, i hc Nng nghip, i hc Y, i
hc Dc. Sch l ti liu tham kho i vi cn b ging dy v
l ti liu hc tp cn c i vi sinh vin.
Sch cung cp nhng kin thc rt c bn, kinh in v cp
nht v min dch hc, mt mn hc c lch s pht trin mi hn
so vi nhiu mn hc khc.
Sch gm 15 chng c kin trc mt cch h thng, ph
hp vi logic nhn thc. Tc gi - GS.TS Ngc Lin rt
thnh cng trong la chn lng thng tin min dch hc cn v
cng-nh t"ong cch thc biu t chnh xc, d hiu cun
sch xng ng l sch gio khoa ca cc trng i hc c tm c
thuc i hc Quc gia.
Ti c vinh hnh gii thiu sch "Min dch hc c s" cng cc
bn c.

H Ni, ngy 5 thng 8 nm 1999

Nguyn nh Bng
Gio s Tin s Y khoa
Gim c Trung tm Quc gia
Kim nh Sinh vt phm
 3

Chng I. Khi nim c bn v min dch hc

1.1. n h n gh a v m in dch hc

Danh t Immunus theo ngha nguyn gc l: c min

gim. Tnh trng u tin min gim mt s bnh truyn nhim
nh bnh u ma (variole) bnh si (rougeole) v mt s bnh
khc v.v... c bit t lu nhng ngi b mc bnh mt
ln. Tt c c th sng cn c c tnh quan trng l nhn bit v
dung np nhng ci ca bn thn (Self), ng thi nhn bit v
thi b nhng ci khng phi ca bn thn (Nonself), xa l
vi c th. Min dch hc l mt mn khoa hc sinh hc v y hc
chuyn nghin cu cc qu trnh nhn bit cc cht l, gi l
khng nguyn (antigen) v hu qu ca s nhn bit , l s
p ng min dch (immune response). S nhn bit ny c c
l do kh nng tdng tc ca mt phc h cc t bo trong h
min dch ca c th ngi v ng vt.

1.2. L ch s n g h in cu m in dch hc

Min dch hc (Immunology) ngy nay tr thnh mt mn

khoa hc. Tuy ch mi tn ti khong trn 100 nm nhng s
ng gp ca n cho cc ngnh sinh hc ni chung v y dc hc
ni ring ngy cng thy r. Nhng pht minh ch yu trong
lnh vc nghin cu min dch hc theo thi gian c trnh by tm
tt nh sau:
Nm 1881: Nhng tng v tnh min dch (Immunity) ln
u tin c Luis Pasteur v Koch xng. Tip theo ,
hin tng thc bo (Phagocytosis) c Metchnikoff quan st
thy. K thut vacxin phng bnh di chnh thc c Luis
Pasteur p dng. Nm 1890, cc nh bc hc Von Behring v Eh-
4

lieh pht hin ra khng th (antibody) v tm ra v tr cc th

th (receptor) mng t bo. Vo thi k ny k thut iu tr
bnh bng huyt thanh, hin tung ngng kt t bo, hin tng
kt ta, kh nng chn on bnh theo huyt thanh c
nghin cu v ng dng trong y hc (Roux, Charriu, Widal v
Kraus).
Nm 1900: Richet v Potier pht hin ra hin tng phn v
(Anaphylaxis), Bordet v Arthus tm ra cc b th v hin tng
Arthus, Landsteiner tm ra cc khng nguyn nhm mu ABO
ca ngi, Wright tm ra hin tng Opsonin ha (Opsonization).
Nm 1910: nh du s pht minh ra cc hapten ca Land-
steiner.
Nm 1920: L thuyt v mng li do Heidelberger v Mar-
rack xng. K thut ng dng cht gii c (anatoxine) v
tim chng (vaccination) ca Ramon v Gleny c thc hin.
Nm 1930: nh du vic pht minh ra cc gama globulin ca
Tiselius v BCG ca Calmette v Gurin.
Nm 1940: Snell tm ra qui lut cy ghp m t bo, Medawar
tm ra hin tng dung np (tolerance) gip cho vic iu tr
cc bnh min dch sau ny. Bn cnh , cc k thut min dch
hunh quang (Immunofluorescence) ca Coombs v Coons,
khuch tn min dch (Immonodiffusion) ca Oudin c p
dng.
Nm 1950: L thuyt la chn dng ca Burnet ra i m
ra kh nng tm hiu tnh a dng ca khng th trong p ng
min dch. Vo nhng nm , cc nghin cu su sc v cu
trc v chc nng ca cc globulin min dch (Immunoglobulin)
c Porter v Edelman tin hnh.
Nm 1960: M u vic pht minh ra vai tr ca tuyn c
(Thymus) do Miller thc hin. Tip theo , Ishizaka tm ra cc
gen ca hin tng p ng min dch, Jean Dausset tm ra
phc h ph hp t chc ch yu (Major Histocompatibility
Complex) c mt bch cu ca ngi nh mt khng nguyn
ph hp t chc v c gi l HLA (Human Leucocyte Antigen).
Nm 1970: Jeme ra l thuyt mng li Idiotype v s hp
tc t bo trong p ng min dch. Trong nm 1975, Milstein v
Kohler da vo l thuyt la chn dng tm ra k thut lai t
bo cho php sn xut cc khng th n dng (Monoclonal anti
bodies).
 Nm 1980: Tonegavva m u cc pht minh v c tnh di
truyn ca cc immunoglubulin v cc th th T. Nhng nm
1981 tip theo, nhm nghin cu ca Montagmer vin Pasteur
Paris pht hin ra virus HIV gy bnh suy gim min dch
mc phi (AIDS) cho con ngi.
Nhng nm gn y, cc pht minh ca min dch hc phn t
(Molecular Immunology) mane li nhiu li ch to ln cho cc
ngnh sinh hc v y dc hc c v l lun v ng dng thc
tin. Bn cnh , nhng tin b trong nghin cu v sinh hc
phn t c ng dng cho lnh vc y hc v min dch hc.
Chang hn, ngi ta pht hin ra s dung hp gen bcr/ abl
trong bnh ung th bch cu (leukemia) ngun gc ty xng
trng thi mn tnh, phn tch trnh t genom ca HIV, v
pht minh ra phng php nhn dng tuyn chn ADN in vitro
(gi l phn ng dy chuyn polymeraz - PCR). Phng php
PCR kt hp vi phng php phn tch tnh a hnh v chiu
di ca mnh ct gii hn trong phn t ADN (RFLP) cho php
pht hin c bnh thiu ht min dch hoc t bin gen di
truyn cc bnh nhn. Trong nhng nm gn y, ngi ta
tm ra gen p. 53 l gen chng ung th (1989).
Nm 1990: Chng minh trc tip (ex vivo) kh nng chng ung
th ca gen RB. Trong nhng nm sp ti chc chn s c nhng
pht minh quan trng v min dch phn t mang li nhiu li
ch cho khoa hc sinh hc v y dc hc. c bit mi y ngi
ta tm ra kh nng gy bnh truyn nhim ca mt dng
phn t protein gi l cc PRION. Vi thnh cng ny nh khoa
hc M, tin s Stanley Prusiner nhn gii thng Nobel v y
hc (1997). Thnh cng ny d m ra mt quan nim mi:
Khng ch cc vi sinh vt, virus gy bnh truyn nhim cho
ngi v ng vt m c mt s phn t protein cng c kh
nng ny.
6

1.3. N hng khi nim t n g qut v m in dch hc

1.3.1. Min dch thch ng v min dch t nhin

Tnh min dch (Immunity) c hiu l kh nng bo v ca

c th chng li nhng tc nhn gy bnh xm nhp t bn
ngoi. Cc tc nhn gy bnh c th l yu t truyn nhim bnh
nh vi sinh vt (vi khun, vi nm, virus v cc c t ca chng),
cc cn trng, k sinh trng v cc protein l gy c cho c th.
Hng ngn nm trc cng nguyn, ngi Trung Hoa bit
bo v cho con ngi bng cch s dng mn vy ca ngi
khi bnh u ma ch st ln vt xc da ca ngi cha mc
bnh gy min dch cho ngi chng li cn bnh ny. Nm
1798, Jenner Anh thc hin li phng php ny nhm bo
v cc con b, trnh b bnh u ma tru b. Nh cc nghin
cu ca Louis Pasteur v trng phi ca ng (1880 * 1890),
phng php tim chng (Vaccination) gy min dch kiu trn
c nghin cu v p dng cho con ngi.
Tt c cc p ng min dch ca c th trc tin bao gm 8
nhn bit tc nhn gy bnh hoc nhng cht l, tip theo l
nhng phn ng nhm oi b chng ra khi c th. Nhng p
ng min dch ni chung c th phn chia thnh hai p n
p ng min dch t nhin (hoc khng thch ng) v p ng
min dch thch ng (hoc p ng min dch tip thu). p ng
min dch thch ng (hoc tip thu) c tnh c hiu cao vi
mt tc nhn gy bnh ring bit. S p ng ny ngy cng
c hon thin sau mi ln tip xc vi c&ng mt o vi ginh
vt. H thng min dch c hiu c th ghi nhd li tc nhn gy
bnh v ngn cn tc ng gy bnh ca chng ln tip xc lp
li tip theo. Ghi nh min dch l mt c tnh quan trng ca
nhng loi ng vt bc cao trong nc thang tin ho. c tnh
ny l c s khoa hc cho liu php min dch tim chng.
 Min dch th' dch Min dch trung gian t bo

Cc t chc ngoi t bo Cc t chc trong t bo

Hnh 1.1 S vng tun hon t bo kt hp gia min dch

t nhin v min dch tip thu VI s tham gia ca c c thnh
phn trong min dch dch th v min dch trung gian t bo.

Cc p ng min dch ch yu c thc hin l do hot ng

ca nhng bch cu (leucocyte). Cc bch cu ny bao gm cc t
bo lympho (lymphocyte) dng B, T, lympho cha ht to trong t
bo cht, cc thc bo (monocyte, macrophage), cc t bo bch
cu trung tnh (neutrophil leucocyte), bch cu a axit (eosino
phil leucocyte), cc t bo ph tr (accessory cell) gm bch cu
a kim (basophil leucocyte), cc t bo mast (mastocyte), cc t
bo dng tm cn gi l tiu cu (platelet cell, thrombocyte) v
mt s t bo ca m nh t bo Langerhan, Kupffer.
Cc t bo thc bo n nhn (MNP: mononuclear phagocytes)
l thnh phn quan trng nht ca thc bo c i sng lu di
v bt ngun t t bo ngun ca ty xng. Chc nng ca
chng l bt gi cc vt th l trong bao gm c cc tc nhn
gy bnh, nut v ph hy chng. Cc t bo ny thng khu tr
nhng ni c th d dng n bt cc vt th l. Chng hn
cc t bo Kupffer ca gan, cc t bo ca mng hot dch nh
khu bao quanh khoang khp. Trong mu c cc t bo mono
(monocvte) c th di chuyn v pha cc m v tr thnh i thc
bo ca m. Cc t bo ny c th trnh din cc khng nguyn
cho cc t bo lympho - T rt c hiu qa. Dng th hai ca lp
8

t bo thc bo l cc t bo a nhn trung tnh (PNN: Polynu-

clear Neutrophil) chim t l cao trong cc bch cu ca mu.

T B Dgun tu
xng l i mi

Yu t hoi ho T B ngun

t
T B khi thu dng tu T B kbi thu dong lym pio

T B Dgun

/
Erythropoietin I L 3, G M -C S F. I L 1, IL 6

Throm bpoietn,
IL

Nguyn bo
bng cu C FU
Tln thn Tin thn Tln thn bch cu
T bo nhn bychcu bchcu ht T mno
J _ khng l M fai IL3, GM*CSF, IL3, GM-CSF,
1LS G-CSF.. ^ -C S F
T <>
V
Hng cu Tiu cu ch cu
Bch a Bch cu Bch cu T B mono
k ir n M il (rng tinh

Hnh 1.2 Ngun gc ca cc t bo h min dch

v cc yu t tham gia bit ho t bo.
 9

(hng c th di chuyn v pha m p ng vi mt s kch

thch. Tuy nhin cc t bo ny c i sng ngn, d cht sau khi
bt gi v nut cc vt th l.
Cc t bo lympho hoc lympho (lymphocytes) c chc nng
nhn l)it c hiu cc vi sinh vt d p ng min ch thch
ng. Tt c cc lympho u bt ngun t cc t bo ngun ca
ty xng v dc chia thnh hai dng qun th (population) l
lympho-T v lympho-B. Cc lympho-T c pht trin v chn
mi tuyn c (Thymus) nn c k hiu l T. Cc lympho-B
dc pht trin trong tu xng (Bone marrow) cc ng vt c
v trng thnh, nhng cc loi chim lympho-B pht trin v
chn mi ti Fabricius (Fabricius Bursa). V th cc t bo
lympho ny c k hiu l B. Mi t bo B nhn bit mt khng
nguyn ring bit nh mt th the (Receptor) c hiu nm trn
b mt t bo ca n. Tip theo giai on nhn bit, t bo B s
phn chia v bit ho thnh cc t bo plasma (plasmocytes) c
kh nng tit ra phn t th th dng ho tan c gi l
khng th (antibody).
Cc t bo T tip tc c bit ha ph hp vi chc nng ca
chng thnh hai dng t bo l T b tr (T-helper: TH) c du
hiu bit ho khng nguyn trn b mt t bo l CD4 (t ch
m hay cm bit ho - Cluster of Differentiation) hoc gi tt l
T, v mt dng T gy c cho t bo (cvtotoxic lympho-T), vit tt
l Tc c du hiu bit ho khng nguyn b mt t bo l CD8
cn gi l T8. Qun th ph (subpopulation) TH li bit ho
thnh hai dng, mt dng tng tc vi t bo B gip cho s bit
ha v tng hp khng th ca t bo B, mt dng khc gi tt l
TD tham gia vo hin tng qu mn mun (delayed hypersen-
sivity) ca qu trnh min dch qua trung gian t bo tng tc
vi thc bo n nhn hoc i thc bo gip cho vic ph hy
cc tc nhn gy bnh.
Mt nhm t bo khc gi l cc lympho c ht ln trong t bo
cht, vit tt l LGL (Large Granular Lymphocyte) cng c kh
nng nhn bit cc t bo ung th v cc t bo b nhim virus
v ph hy cc t bo ny. Tuy nhin cc t bo LGL khc vi
lympho-Tc l chng s dng h thng nhn bit khng c hiu.
V th cc t bo LGL cn c gi l cc t bo git t nhin
TNK (Natural killer-T). Cc i thc bo ny chng hn nh
LGL cng c kh nng nhn bit v ph hy cc t bo ung th
10

v nhim khun hoc cc tc nhn gy bnh b bao ph bng cc

khng th c hiu (Xem hnh 1.2, 1.3, 1.4).
Mi loi t bo lympho (T v B) u c cc du hiu bit ho
khng nguyn ring bit, c bn cht l cc glycoprotein, to ra
cc th th b mt t bo tham gia vo qu trnh tng tc min
dch. Chi tit v cu trc phn t ca cc du hiu bit ho
khng nguyn s c trnh by cc chng tip theo.

1.3.2. Cc khng nguyn (antigens)

Ngy nay ngi ta c th nh ngha khng nguyn l bao gm

tt c nhng cht c nhn dng bi cu trc nhn bit tng
ng nm trn khng th hoc nm trn cc th th ca cc lym-
pho. V tr cu trc trn mt phn t khng nguyn c th phn
ng vi mt kiu cu trc ho hc ca phn t khng th hoc
phn t th th c gi l quyt nh khng nguyn (antigenic
determinant) hay l epitop. Phn phn t tng ng ca khng
th lin kt vi khng nguyn c gi l paratop. Mt khng
nguyn c th c mt vng khm (mosaic) ca cc epitop khc
nhau hoc gi l cc epitop lp li. Mt khng th ch c hiu
vi mt epitop ch khng phi vi ton b phn t khng
nguyn. Cn cc lympho-T thng nhn bit cc khng nguyn
c trnh din trn b mt ca cc t bo vt ch khc di
dng nhng mnh peptit nh. Chng hn, mt t bo b nhim
bi mt virus s bc l cc mnh peptit ca protein virus trn b
mt ca n. iu ny lp tc s c nhn bit bi cc t bo T
gy c, lm cho cc t bo vt ch nhim virus s b tiu dit
Cc mnh khng nguyn c trnh din lin kt vi cc phn t
protein chuyn ha nm trn cc t bo bch cu c bit l cc
t bo APC, cc t bo B v T. Cc phn t protein ny l sn
phm ca mt tng th cc gen m ho cho phc h ph hp t
chc ch yu (MHC: Major Histocompatibility Complex). Cc
phn t ny c vai tr c nh cc mnh peptit khng nguyn
c gi l cc phn t ca MHC.

1.3.3. Cc khng th v b th

Von Behring (1890) chng minh rng huyt thanh ca mt

ng vt gy min dch chng li c t ca bnh bch hu c
 11

cha mt cht trung ha c c t . Cht ny c ng gi l

khng the (antibody) ngha l mt loi protein c c tnh chng
li cc th vi khun gy bnh. Tt c cc phn t khng th ngy
nay c chng minh l cc globulin c chc nng min dch
(vit tt l Ig: Immunoglobulin) v c bn cht glycoprotein. Cc
khng th c chia lm 5 lp ty theo cu trc v chc nng
min dch l IgG, IgA, IgM, IgD, IgE. Cc phn t Ig c c tnh
hot ng sinh hc theo hai chc nng:
a C kh nng lin kt vi khng nguyn t nht hai v tr tip
nhn i vi khng nguyn. Kh nng lin kt vi khng
nguyn c c l do s bin i k diu ca phn tn cng
NH2 trn phn t khng th.
b. Mt khc, phn tn cng COOH ca phn t khng th c
kh nng thc hin mt s ln cc hot ng sinh hc di nh
hng ca s lin kt vi khng nguyn. Tt c cc khng th
u c cng mt cu trc phn t nhng khc nhau mc
ca vng lin kt vi khng nguyn.
Trong a s trng hp, mi khng th lin kt c hiu VI
ch mt khng nguyn. Cc phn t khng th c coi l nhng
cht rt d thch ng v tng tc rt linh ng vi cc yu t
ca h thng min dch nhn bit c hiu cc vi sinh vt
cing nh cc sn phm ca chng. Nhn chung, phn t khng
th c chia lm hai phn: Fab l phn lin kt VI khng
nguyn (Fragment antigen binding), Fc (Fragment cristallisable)
l phn d kt tinh phn ng vi cc t bo ca h thng min
dch qua cc th th ca cc t bo. Do , nu khng th c c
nh trn vi khun bng phn Fab th n s lin kt vi cc t
bo thc bo bng phn Fc. Hin tng bt gi vi khun v vt
th l bi cc thc bo cn c m bo bng mt b th C3b
hoc bng khng th. Hin tng ny c gi l s opsomn ha
(opsonization).
Tri vi khng th, tt c nhng cht l xm nhp t bn
ngoi vo c th c nhn bit bi khng th th gi l cc
khng nguyn. Tip theo vic pht hin ra phn ng khng
nguyn - khng th, Buchner (1889) v Bordet (1901) pht
hin v s dng mt yu t khng bn nhit c gi l b th
(complement, vit tt l C) gip cho vic trung ha tc nhn
truyn bnh v lm phn hy t bo vi khun. V chc nng, cc
khng th tng tc c hiu vi tc nhn truyn nhim bnh,
cn h thng b th c c nh ln tt c cc khng th thc
12

hin chc nng min dch. H thng b th bao gm khoang 40

protein bo tng c chc nng kim tra phn ng vim. Cc
thnh phn ca b th tng tc gia chng vi nhau v vi cc
yu t khc ca h thng min dch. Chng hn, nhiu loi vi
khun hot ha tc thi h thng b th theo c ch hot ho b
th hoc theo con ng lun phin ca s p ng min dch t
nhin khng c hiu. Theo ngha ny th vi sinh vt b bao ph
bi cc protein ca b th v b bt gi bi cc thc bo. H thng
b th cng c hot ha bi cc khng th c c nh trn
b mt vi khun. y l cd ch hot ho c in (classical path
way). Theo cch hot ha ny, s p ng min dch c b th v
khng th cng tham gia thuc loi min dch c hiu. S hot
ha b th l mt phn ng k tip nhau t thnh phn b th
ny n thnh phn b th khc. S hot ha theo con ng c
hiu v khng c hiu c nhng hiu qa sau y:
1. Hin tng opsonin ha hay bao bc cc vi sinh vt cc thc
bo bt gi.
2. Thc bo tn cng vo cc v tr b nhim trng (hin tng
ha hng ng: chimiotactism).
3. Lm tng dng mu ti v tr hot ha v tng tnh thm ca
cc mao mch i vi cc phn t ca huyt tng (plasma).
4. Gy tn thng cc mng t bo cht ca t bo, ca cc vi
khun gram m, ca cc virus c v bc v cc vi khun khc
gy nn hin tng cm ng hot ha. iu ny dn ti s
phn hy t bo. Cc chc nng chi tit ca b th s c
trnh by cc phn sau.

1.3.4. Cc xitokin (cytokine)

Thut ng xitokin dng ch ton b cc phn t c tit ra

bi cc t bo ca h thng min dch tham gia vo hot ng tn
hiu gia cc t bo trong p ng min dch. Tt c cc xitokin
u c bn cht l glycoprotein hoc protein v c phn loi
nh sau:
1. Cc inteferon (IFN) c chc nng ngn nga s lan truyn ca
mt s virus gy bnh. Dng u tin gm IFNa v IFNp dc
sn xut t cc t bo b nhim virus. Dng th hai ca inte-
feron (IFNy) c tit ra t cc t bo T hot ho. Cc IFN
to ra s i khng chng li qu trnh nhim virus i vi t
 13

bo khng b nhim. Ngoi ra, cc IFN cn kim tra s tng

tc gia cc lympho v cc t bo gy c i vi cc t bo b
nhim.
2 Cc intelkin l mt nhm ln ca xitokin (c nh s' t ILl
n IL27) c sn xu't ch yu t cc t bo T, mc d mt
s trong chng c th c sn xut t cc thc bo n nhn
hoc t cc t bo khc. Intelkin c sn xut t cc lympho
th gi l lymphokin. Chng c nhiu chc nng, ch yu l
kim tra s bit ha v s sinh sn t bo. Mi mt intelkin
phn ng c hiu VI cc t bo bc l th th ring cho n.
3.Cc yu t kch thch qun lc (CSF: Clony Stimulating Fac
tor) kim tra s phn chia v sinh sn ca cc t bo ngun v
cc t bo mu s khai (haematopoietic precursor). Chnh s
cn bng gia cc CSF khc nhau s xc nh mt phn cc t
l tng i ca cc kiu t bo khc nhau c sn xut t
ty xng. Mt s CSF cng kch thch s bit ho ca cc
bch cu bn ngoi ty xng. Mt s" cc xitokin khc c th
l cc yu t hoi t ung th (TNFa v TNFP) v cc yu t"
bin dng sinh trng p (TGFP) u c cc chc nng khc
nhau nhng chng c bit quan trng trong cc phn ng
vim v gy c t bo.
4. Cc cht truyn dn sinh hc (mediator) : Mt s ln phn t
tham gia vo s pht trin ca cc p ng min dch ngoi
khng th, cn c mt s phn t khc c mt trong hyt
thanh. l cc protein ca giai on p ng min dch cp
tnh. Chng hn protein phn ng- c (CRP) c i lc cao i
vi protein- c ca cu khun bnh phi (Pneumococcus). Khi
CRP lin kt vi cu khun ny s to iu kin cho b th c
8nh vo cu khun v kch thch thc bo bt gi vi khun
gy bnh.

1.3.5. H in tng phn v (anaphylaxis)

Vo nm 1902, Richet v Portier gy min dch cho ch

bng mt cht c pha long tch chit t con sa. Khi tim lp
li cht c ny cho ch, cc ng nhn thy phn ng khng
dung np lm ch cht vi liu lng khng gy c. Phn ng
ny c gi l hin tng phn v. Cc hin tng qu mn cm
khc nhau (hypersensitivity) c m t nh sau: qu mn
14

cm tc th c gi l phn v, qu mn cm gy c do cc
phc h min dch, qu mn cm mun v qu mn cm kch
thch. Hin tng phn v c vai tr tham gia ca khng th lp
IgE v cu trc ca chng c lm sng t (Ishizaka).

1.3.6. Ci bn thn v khng phi bn thn (self, nonself)

H thng min dch cn phi nhn bit v phn bit c ci

bn thn v ci khng phi bn thn ngha l phn bit c
nhng cht l so vi c th v nhng cht do chnh c th sinh
ra. Tuy nhin trong nhng trng hp bnh l, c th c th sn
xut ra cc khng th chng li cc cht ca bn thn gy nn
bnh l. l cc trng hp ca bnh t min (autoimmune'
disease) c Ehrlich v Morgenoth (1902) pht hin ra.

1.3.7. Cc phn ng khng nguyn - khng th in vitro

Nh tnh c hiu phn ng min dch khng nguyn - khng

th v nhy ca n, cc k thut xt nghim min dch
c hnh thnh cho php nh lng cc cht nng
nanogam/ lt. l cc k thut kt ta min dch, ngng kt
min dch, phn ng c nh b th, khuch tn min dch,
phng php nh du min dch hunh quang v in di min
dch.

1.3.8. Cc loi p ng min dch v l thuyt la chn dng

Tt c cc p ng min dch din bin theo hai giai on ch

yu l nhn bit khng nguyn v phn ng loi b khng
nguyn. Trong p ng min dch c hiu, cc lympho m bo
cho giai on nhn bit, cn giai on nhn bit s to iu kin
cho mt qu trnh la chn dng (clonal selection). Mi mt t
bo T hoc B ch nhn bit mt khng nguyn ring bit, v ton
b, h thng min dch c th nhn bit c hiu hng nghn
khng nguyn v mi mt lympho ch nhn bit mt khng
nguyn. Do Burnet (1958) a ra l thuyt chn dng, theo
th mt dng t bo min dch ch c th sn xut ra mt kiu
khng th p ng li vi mt quyt nh khng nguyn nht
nh. L thuyt ny c lm sng t bng k thut lai t bo
 15

ca Milstein v Kohler (1975) khi h nhn mt dng khng th

n dng (monoclonal antibody) c sn xut t ch mt dng t
bo lympho.

1.3.9. S tim chng (vaccination)

Nguyn tc ca s tim chng l da vo hai c tnh c bn

ca p ng min dch thch ng. l tnh c hiu v s ghi
nh min dch. Cc t bo ghi nh cho php h thng min dch
pht trin s p ng mnh hn khi c ln tip xc th hai vi
khng nguyn. S p ng th cp ny ng thi nhanh hn v
c hiu qu hn s p ng ban u. Nguyn tc tim chng l
da vo vic ci bin cc vi sinh vt hoc c t ca chng lm
cho chng tr nn mt tc nhn khng gy bnh nhng khng
lm mt tnh khng nguyn ca chng. V d vi khun bch hu
tit ra c t exotoxin lm ph hu cc t bo c. c t ny c
th c ci bin bng cch x l vi focmon s mt c tnh
nhng vn gi c cc epitop. Cht ny c s dng nh mt
vacxin. Mt nguyn tc khc ca tim chng l s dng ton b
cc tc nhn gy bnh truyn nhim nh virus gy bnh vim
ty xm lm bi lit tr em (poliomyelite) c lm suy yu
mt c tnh nhng vn gi c tnh khng nguyn ca n.

1.3 . 10 . S iu ha m in dch

- Yu t th nht l cc lympho -T km hm (suppressor T-

lymphocyte). Chng c th lm ngng li s lan truyn ca
mi giai on p ng min dch. Tht vy, thng xuyn vn
c s cn bng gia p ng min dch hiu qu v p ng
min dch c ch. Trong trng hp p ng km hm khng
thy c bt k mt hin tng min dch no c th pht hin
c khi c s tip xc lp li vi mt khng nguyn. Trng
hp ny ngi ta gi l s dung np min dch (immune toler
ance).
- Yu t th hai l s iu ha idiotip. Thut ng idiotip (idios)
c ngha l c bit hoc cu trc ny ca khng th dnh
ring cho vt ch v cho mt loi khng nguyn. Mt khng
th hon ton mi xut hin trong c th biu th mt khng
nguyn mi c nhng epitop mi tng ng vi v tr tip nhn
16

khng nguyn ca n. Hnh thc iu ha ny lun sinh ra

mt p ng min dch kiu anti- idiotip iu chnh s p
ng trc . Do , kiu p ng anti - idiotip bn thn n li
l ngun gc cho mt p ng anti- idiotip tip theo.v.v... T
, p ng min dch sinh ra mt chui cc hin tng
phc h: khng ch c s tng sinh ca nhiu dng t bo B v
T mang cc v tr tip nhn tng ng vi cc epitop khc
nhau ca mt khng nguyn cm ng m cn xut hin cc
dng t bo c ch v cc dng t bo kch thch bi cc mng
li idiotip. S iu ho min dch thc hin qua trung gian t
bo cn lin quan n l thuyt la chn dng c trnh by
tng qut hnh hnh 1.5 v 1.6 .
H thng min dch cn ng vai tr rt quan trng cho c th
trn quan im sinh l bnh. Min dch hc c th c ng dng
trong cc lnh vc nghin cu min dch v bnh truyn nhim,
min dch v ung th, min dch v cy ghp, min dch v cc
bnh suy gim min dch mc phi AIDS, cc bnh t min
(autoimune disease).

1.3.11. Cytokine trong iu ho min dch bm sinh v

thch ng
Cytokine c sn xut t nhng t bo ca h min dch t
nhin (bm sinh) hoc min dch tip thu c chc nng p ng
chng vi sinh vt, khng nguyn, tham gia vo phn ng vim,
hot ho t bo, iu ho tng sinh v bit ho t bo lympho,
kch thch s pht trin v hnh thnh cc t bo mu. Trong
iu tr lm sng, cytokine l nhng tc nhn iu tr cho nhiu
bnh nhim trng v chng ung th. Trong min dch bm sinh,
cc cytokine nh TNF, IL-1, IL-12, IFN-y c tit ra t i thc
bo, t bo NK khi c th nhim c t LPS, peptidoglycan vi
khun hoc c kch thch bi IFN- ca t bo T, c chc nng
iu ho qu trnh vim ti ch v h thng.
Trong p ng min dch tip thu, cc cytokine nh IL-2 , IL-4,
IL-5 v IFN-y cng c dng t bo T tit ra c chc nng iu
ho s sinh trng v bit ho ca chnh cc dng t bo hiu
qu nh i thc bo, t bo a acid, t bo mast.
 S sinh sn v chn ca
t bo B c la chn

Cc khng th 2 c sn xut

Hnh 1.5 Theo l thuyt la chn dng, mi t bo sn xut khng th

(t bo B) c t chng trnh tng hp ch mt loi khng th
c mt di dng mt th th nm trn b mt t bo ca n tng tc
c hiu vi mt khng nguyn. Sau khi tip xc vi khng nguyn, t
bo B c kch thch, sinh sn v s bit ha thnh cc t bo plasma
tng hp ra cc khng th. Mt s t bo B khc c hiu vi khng
nguyn cho, khng bit ho v s tr thnh cc t bo ghi nh min
dch, c i sng lu di. (Theo I. Roitt et al, 1993)
18

Khng nguyn I
> A <J
<1 ^

i' Oi ' &

T - c c h
T - hot ho T - gy c T - b tr '
di thc bo

_ o
t bo B

U
r K h n g th 1
V

i thc bo T b o K
c hot ho T- gy c 1 (ADCC)
C c t bo h u q u
1 --------

Hnh 1.6 Con ng min dch qua trung gian t bo. Cc p ng

min dch qua trung gian t bo xy ra tip theo s trnh din khng
nguyn v s hot ho cc t bo T, c kim tra bng cc lympho T
c ch (suppressor T cell) v lympho T b tr (Helper T cell). Mt s t
bo T (cc t bo hot ho i thc bo) tit ra cc lymphokin hot ho
cc chc nng thc bo ca i thc bo v dit vi khun. Cc t bo T
gy c c hot ho bng khng nguyn cng VI s gip ca cc
t bo b tr v hp tc tip theo vi cc t bo B sn xut khng
th. Cc t bo K (Killer Cell) c th th mng c i lc cao lin kt VI
mnh Fc ca cc Ig, hip ng tc dng vi khng th phn hu t
bo ch b nhim khun, cn gi l ADCC (T bo gy c ph thuc
khng the: Antibody- dependent cell mediated Cytotoxicity). Cc t
bo NK phn ng khng cn tnh c hiu. (Theo I. Roitt et al, 1993).
 Hinh 1.3. ( Vu* t bao
bach cu ca h mien
dich bm sinh va mien
dich tiep thu.
Tir trn xung dirai:
1. Oai thirc bao.
2. Bach cu trung tinh
3. Bach cu ira axit.
4. Bach cu ua kim.
5. T bao mast.
6. Tbaodit tir nhin(NK).
( T h o . J e n e w a v it al 20())

Bac h cu i/a axit

Bach cu i/a kim

T bao mast
 ai thue bcio

r
c

Hnh 1.4. Cc t ho APC chuyn nghip.

T trai qua phi:
T bao x thy (dendritic cell), i thc bao (macrophage) va lympho B.
T trn xung di:
nh hin vi quang hc (a, b, c); nh hin vi in t xuyn qua (d, e. f) va nh
hin vi in tquet (g. h. j).
(Theo Jeneway et al., 2005)
 19

Chng II. Khng nguyn

2.1. n h n g h a v k h i n im c h u n g v k h n g n g u y n

Thut ng khng nguyn (antigen, vit tt Ag) dng chi

mt cht c kh nng gy ra p ng min dch khi c a vo
c th ca mt ng vt thch hp hoc mt cht c kh nng
phn ng vi mt khng th hoc mt t bo ca h thng min
dch. Nh vy, tt c nhng cht t nhin hoc tng hp c h
thng min ch nhn bit u c gi l cc khng nguyn.
Khi mt khng nguyn xm nhp vo c th, cc lympho c th
nhn bit c hiu bng cch kt hp vi khng nguyn nh th
th c hiu. S nhn bit ny gy cm ng sinh sn lympho-B
v bit ha qun th t bo ny thnh cc t bo plasma c kh
nng sn xut khng th chng li khng nguyn xm nhp.
l p ng min dch th dch. p ng min dch cng c th
gy ra s xut hin qun th lympho-T min dch mang cc th
th c hiu vi khng nguyn. l s p ng min dch qua
trung gian t bo.
Tnh phn ng ca khng nguyn hoc kh nng nhn bit,
kh nng lin kt c hiu ca khng nguyn vi khng th hoc
vi th th ca t bo ph thuc vo mt phn cu trc gii hn
ca khng nguyn. Phn cu trc gii hn ny c gi l quyt
nh khng nguyn (antigenic determinant) hay epitop. cn phi
phn bit hai c tnh khc nhau ca cc epitop l tnh khng
nguyn (antigenecity) v tnh sinh min dch (immunogenecity).
Tnh khng nguyn l c tnh ca mt epitop c cu trc ba
chiu lin kt b sung vi phn cu trc ba chiu ca phn t
khng th. Phn cu trc ny ca phn t khng th hoc ca
th th c gi l paratop. Tnh min dch ca mt epitop l c
tnh gy ra mt p ng min dch trong mt c th. Trong
trng hp khng nguyn l cc protein, ngi ta c th nhn
20

bit c kch thc ca mt epitop khng nguyn vo khong 5

n 10 gc axit amin bng phng php phn hy ha hc hoc
phn hy enzim i vi khng nguyn ny. Ngi ta cng phn
bit mt dng epitop th hai, gi l epitop gin on. Loi epitop
ny c xy dng t cc axit amin cch xa nhau theo trnh t
sp xp nhng li gn nhau v khng gian ca protein do s gp
li ca chui polipeptit.
S nhn bit gia khng nguyn v khng th ca n hoc
gia khng nguyn v cc th th ca t bo c thm quyn
min dch mang tnh c hiu rt cao. iu c ngha l mt
khng nguyn A ch c th c nhn bit bi mt khng th
anti-A hoc ch c th c nhn bit bi mt loi t bo lym pho
c th th lin kt c hiu vi khng nguyn A.

2 .2 . P h n n g c h o

Ngi ta ni phn ng cho khi mt khng th c kh nng

kt hp vi mt khng nguyn khc vi loi khng nguyn kch
thch s sn xut khng th ng vt gy min dch. Phn
ng ny c th do hai khng nguyn c mt hoc nhiu epitop
ging nhau hoc mt s epitop ca chng c th gn ging nhau
lin kt vi cng mt loi khng th. Chng hn mt epi-
top ca mt khng nguyn protein c mt chc gc axit amin
trong ch c mt hoc hai gc axit amin khc nhau th cu
trc ca cc epitop ni trn vn cn kh ging nhau cho mt
khng th nhn bit. Do , phn ng cho vn c th xy ra. C
th nu ra v d i vi cc khng nguyn c cha gc ng po-
liozit. Nhm mu A ca ngi c khng nguyn N-
axetilgalactozamin, cn nhm mu B l galactoz. Trong nhng
hon cnh b nhim vi khun, khng nguyn N-
axetilgalactozamin c th b phn hy, mt gc N-axetil chuyn
thnh galactozamin. Cht ny cng c nhn bit bi khng
th anti-B. Nh vy, khng th anti-B khng th phn bit c
s khc nhau gia galactoz v galactozamin.
 21

2.3 H a p ten v p r o te in m an g

C rt nhiu cht ha l c c phn t lng nh, phn cc

mnh c kh nng gy ra s tng hp mt khng th dc hiu
sau khi c kt hp vi phn t mang c kch thc ln hn.
Cc cht ha hc ny c gi l hapten v c COI l tng
dng vi nhng quyt nh khng nguyn tch ri. Cc hapten
c kha nng phn ng vi cc khng th c hiu ca chng. Mt
quyt nh khng nguyn thuc v mt i phn t t nhin
trong khi mt hapten cn phi lin kt VI mt phn t bng mt
phn ng ha hc c th gy cm ng sn xut mt khng
th. gy ra mt phn ng min dch in vivo, mt hapten cn
phi kt hp vi mt protein mang. V vy, ngi ta c th tng
hp nhng polipeptit nhn to c cu trc bit c th mang
mt hoc hai quyt nh khng nguyn. S kt hp ca hapten
v protein mang s to ra mt cu trc sinh min dch c t nht
hai quyt nh khng nguyn khc nhau.

2.4. T n h k h n g n g u y n c a c c c h t sin h tr n g hp
(b io p o ly m e r )

c tnh khng nguyn ca mt cht c xc nh bng s c

mt hay vng mt ca tnh sinh min dch. Ngi ta phn bit ra
cc loi khng nguyn sau y:
- Autoantigen c mt chnh bn thn mt c th.
- Alloantigen c trng cho cc nhm c th trong cng mt
loi.
- Isoantigen c mt tt c cc c th ca cng mt loi.
- Xenoantigen (heteroantigen) c mt cc c th ca nhng
loi khc nhau.
Cc cu trc cng khc nhau s cng biu hin tnh khng
nguyn r rt.
Protein: Hu nh tt c protein dng hnh si hoc hnh cu
u l nhng cht sinh min dch. Mc d protein l mt nhm
cht khng nguyn rt ln trong thin nhin, nhng do cu trc
v thnh phn ho hc ca chng rt phc tp nn vic hiu bit
cu trc khng nguyn ca cc protein cha c nhiu. Ch
trong mt s trng hp nh myoglobin, lyzozim v mt s virus
22

(virus cm, virus vim ty xm polio) ngi ta mi bit r c s

cu trc khng nguyn ca chng mc phn t.
Cc polixacarit: y l nhm khng nguyn quan trng th
hai trong thin nhin v c trng lng phn t t mt n vi
triu dalton. Cc dextran, levan v mannan l nhng khng
nguyn c mt r t nhiu vi khun. c tnh khng nguyn ca
nhiu loi glycoprotein trc ht c biu hin bi phn cc gc
ng ca chng. Chng hn cc khng nguyn nhm mu ABO
ca ngi c trnh by di y:

1. Gal NAc (p 1,3) - Gal(P 1,3) - Glu NAc(p 1,3) - Gal(a 1,2)- Fue.
= Khng ngun H(O)
2. Khng nguyn H + (a 1,3) Gal NAc. = Khng nguyn A
3. Khng nguyn H + (a 1,3)- Gal. = Khng nguyn B
S cu to cc khng nguyn nhm mu A, B, o

Cc lipit: Him khi ngi ta nhn thy s biu hin tnh

khng nguyn ca lipit nu n khng kt hp vi polixacarit v
protein. Cc diolipit cha photpholipit c mt thnh t bo vi
khun hoc mng trong ca ti th t bo tim b cng c tnh
khng nguyn.
Cc axit nucleic: Kh c th nhn c s p ng min d;ch
chng li cc axit nucleic. Tuy nhin, trong huyt thanh ca
bnh nhn mc bnh t min, ngi ta thng tm thy cc
khng th c kh nng lin kt vi ADN hai chui hoc mt
chui tch ri, hoc ADN c gn vi histon.
Cc loi cht polipeptit v gluxit c tng hp nhn to
c s dng c kt qu nghin cu p ng min dch. Mt
s thuc chit xut t thc vt hoc c tng hp cng gy ra
hin tng qu mn vi ngi.
Cc siu khng nguyn (superantigens): Siu khng nguyn l
mt thut ng dng ch cc phn t nhy cm c kh nng
lin kt vi cc phn t lp II ca MHC, ng thi lin kt vi
cc trnh t peptit c trng cho mt s h ca cc th th lym-
pho-T (chng hn TCR-VP). Cc siu khng nguyn ny hot ha
mt s ln cc dng t bo T (clon-T). Quan nim v siu khng
nguyn c th c m rng cho cc phn t c ngun gc t cc
vi khun c kh nng lin kt vi cc Ig mng t bo (mlg) v
 23

hot ha cc lympho-B (v d cc protein A v protein G ca mt

s chng Staphylococcus).
Cc t cht (Adjuvants): T cht l mt cht hoc mt hn hp
cc cht c kh nng lm tng tnh min dch ca cc khng
nguyn, v ni chung thng gy ra cc phn ng vim. T cht
thng lm chm qu trnh loi b khng nguyn v to iu
kin cho vic bt gi v trnh din khng nguyn. T cht c
s dng thng xuyn l hydroxit nhm hoc cc cht c ngun
gc vi khun. T cht khng y ca Freund l mt nh
tng dc hnh thnh trong nc cng vi du khong v mt
tc nhn gy nh tng (Tween). T cht y ca Freund l
t cht khng y cng VI cc vi khun lao b git (Myco
bacterium tuberculosis).

2.5. S th c h n g c a c c vi sin h v t b n g c c h c i
b i n c c k h n g n g u y n c a c h n g

Ngi ta cho rng ton b kho d tr cc peptit c nhn bit

bi cc lympho - T ca mt c th, ph thuc vo cu trc ca cc
phn t ca MHC v ph thuc vo c ch dung np i vi cc
peptit ca bn thn khi c s bit ha ca cc lympho - T. Nu
mt lympho - T ca h thng min dch c phn ng chng li cc
thnh phn ca bn thn th s a n tnh trng bnh t
min. Trong qu trnh pht trin ca h thYig min dch, khi cc
t bo T nhn bit thnh phn ca bn thn c th gy ra phn
ng i khng th lp tc qun th t bo T b loi b bi
chnh h thng min dch.
Cc vi sinh vt c th s dng nhng chin lc khc nhau
tu thot khi s nhn bit ca vt ch bng cch ci bin cc
peptit khng nguyn ca mnh. Chng c th bt chc cc cu
trc peptit ca c th vt ch. Nhng s ci bin ny ch c
xut hin nu vi sinh vt sng lu di trong vt ch. l
trng hp ca bnh nhim trng mn tnh. Cng tng t nh
vy, cc t bo ung th c th b ph hy bi h thng min dch
v chng hon ton khc l vi cc t bo bnh thng ca c th.
Tuy nhin trong mt s trng hp cc t bo ung th c th t
ci bin khng nguyn ca chng trn thot khi s ph hy
24

ca h thYig min dch. l trng hp ung th tin trin hoc

di cn.

2.6. Im m u n o g e n v k h n n g p n g m i n d c h

Immunogen l mt khng nguyn c c hai tnh cht: tnh

khng nguyn v tnh sinh min dch. Tnh khng nguvn c
biu hin bng cc epitop c nhn dng v lin kt vi khng
th hoc vi th th ca khng nguyn. Tnh sinh min dch biu
hin kh nng p ng min dch to ra khng th hoc to
ra s p ng min dch qua trung gian t bo. Mt s' cht c
tnh khng nguyn nhng kch thc li qu nh khng th c
kh nng to ra p ng min dch. V d, 2,4D l mt cht kch
thch sinh trng cng c mt trong thuc tr su c khi lng
phn t rt nh khng th to ra c khng th khi gy min
dch. Mt vi peptit c phn t lng nh hn 3.000Da cng hu
nh khng to ra kh njig sinh khng th khi gy min dch.
Tuy nhin nhng cht trn khi kt hp vi cc prot.ein mang
(Carrier protein) s c kh nng tr thnh immunogen v p
ng min dch to khng th.
 25

Tm tt chng II

1. Mt phn t c coi l khng nguyn nu c kh nng lin

kt vi cc th th ca lympho T, lympho B hoc vi khng
th. c tnh ny c xc nh bng nhng s khc nhau v
cu trc b sung gia khng nguyn v th th ca t bo T,
t bo B (TCR. BCR) hoc paratop ca khng th c th c
gy min dch.
2. Phn t protein c cc quyt nh khng nguyn (epitop)
dng khm khc nhau nhng c khi dng cc epitop lp li.
Cc epitop thng c trnh t cc axit amin lin tc, cng c
th gin on nhng gn nhau v khng gian.
3. Hapten l nhng cht ho hc c phn t nh, c kh nng gy
ra s tng hp khng th c hiu vi n khi c kt hp vi
mt phn t cht mang c kch thc ln hn. Hapten khng
phi l khng nguyn hon chnh nhng c th c coi tng
ng vi nhng epitop tch ri.
4. Cc hp cht sinh trng hp (biopolymers) nh protein, polix-
acarit, lipit, axit nucleic v.v... c c tnh khng nguyn khc
nhau v c tnh sinh min dch khc nhau. Trong s cc hp
cht k trn, protein v polixacarit l 2 nhm khng nguyn
ln v quan trng nht.
5. Cc vi sinh vt v cc t bo ung th c th s dng nhng
cch khc nhau trn thot khi s nhn bit ca h cc t
bo min dch vt ch bng cch t ci bin cc khng nguyn
ca mnh.
 27

Chng III. Cc khng th v th th ca khng nguyn

Cc phn t tham gia p ng min dch c hiu bao gm cc

khng th cn gi l globulin min dch (Immunoglobulins, vit
tt Ig) c ha tan trong cc dch sinh vt hoc hnh thnh nn
cc th th trn mng t bo lympho-B (B cell receptor: BCR) v
cc th th ca lympho-T (T cell receptor: TCR). Cc phn t
khng th c bn cht l glycoprotein, m bo cho vic nhn
bit cc epitop ca khng nguyn bng v tr b sung khng gian
c mt trong phn t ca chng. V tr lin kt b sung ca phn
t khng th i vi khng nguyn dc gi l paratop c cu
trc rt a dng. Ngi ta tnh c rng mt c th trng
thnh c khong 1020 phn t Ig trong c trn 109 loi phn t
khc nhau v trn 10' cc dng lvmpho-T khc nhau.
Cc Ig l nhng phn t hai chc nng. Phn N tn cng ca
phn t c mang v tr paratop m bo cho vic nhn bit c
hiu khng nguyn. Phn c tn cng khi ng cc tn hiu sinh
hc c c l do s lin kt gia paratop v epitop.
Cc chui polipeptit ca cc Ig, TCR, BCR u c hnh
thnh t cc tiu n v dng hnh cu (subunits) c cu trc bn
chc to ra cc khu vc (domain) gm khong 100 axit amin v
mt cu disunphua. Cc tiu n v nh trn c gi l cc khu
vc chc nng (domain). Cu trc c s nh vy c tm thy
tt c cc protein thuc v siu h (superfamily) ca cc immu
noglobulin. Siu h ny bao gm mt tng th cc phn t pro
tein mng tham gia vo s tng tc gia cc t bo, c bit l
cc phn t ca MHC (hoc HLA ca ngi).

3.1. Cu tr c c h u n g c a c c im m u n o g lo b u lin (Ig )

Cc phn t Ig c hnh thnh t hai loi chui polipeptit l

chui nng (k hiu l H: heavy chain) v chui nh (k hiu l L:
light chain). Cc chui nng thuc v cc dng |i, s, yl, y2, 3, 4,
28

a l , a2, e. Cc chui nh bao gm hai dng K, X. Kiu chui nng

xc nh n v phn loi lp v di lp (class, subclass) ca cc
Ig. T khng th bao gm 5 lp l IgM, IgD, IgG, IgA v IgE
v cc di lp IgGl, IgG2, Ig3, IgG4, IgAl, IgA2. Cc phn t
Ig c cu trc i xng c th k hiu (H2, k2) hoc (H2, X2).
Con s n c th l 1 (i vi IgM mng, IgD, IgE, IgA dng
mono), l 2, 3 hoc 4 (i vi IgA dime, trime, tetrame), hoc 5
(i vi IgM pentame). Cc Ig polime (IgM, IgA) cn cha chui J
ni cc u c tn cng ca cc chui H. Cc chui L (Kappa: K v
lambda: X) u c hnh thnh t hai vng khu vc l: khu vc
d bin i (Vk hoc VA.) v khu vc khng i (Ck hoc CX). Cc
chui H gm mt khu vc N tn cng d bin i (V||) v 3 khu
vc khng bin i (i vi IgD, IgG v IgA) hoc 4 khu vc
khng bin i (i vi IgM v IgE). Khu vc khng bin i ca
chui nng c k hiu l CH. Mi mt khu vc d bin i u
bao gm 3 vng siu bin (hypervariable), cn gi l cc vng xc
nh tnh b sung (CDR). Cc paratop c hnh thnh t nhng
v tr t k nhau trong khong khng ca cc vng siu bin
c tch bit nhau bng hai vng bo th hn (hoc cc vng
khun). Vng nm gia hai khu vc C|l v CH2 ca chui H
c gi l vng khp hay vng bn l m bo cho tnh mm
do ca cc phn t khng th, ng thi hai cnh tay (V|., Cl,,
VH) CH1) ca phn t c th di ng trong khng gian. Cc vng
nm gia cc khu vc c th c phn gii bng cc proteaza
nh papain, pepxin (hnh 3.7). Papain phn gii IgG to nn hai
mnh Fab (L+VH+CH1) v mt mnh Fc (dime ca cc khu vc
Ch2 + Ch3). Thut ng Fab dng ch mnh lin kt vi khng
nguyn (antigen binding) v mnh Fc l mnh d kt tinh
(cristallisable). Pepxin phn hy IgG to thnh hai mnh F(ab)
v cc peptit pFc. Cc mnh Fab v Fv (V^+Vii) cha ng cc
paratop, trong khi cc phn Fc m bo cho nhng c tnh
gy hiu qu ch yu ca phn t khng th v khc nhau ty
theo cc lp v cc di lp ca cc Ig. S khc nhau th hin
t l bin i trong trao i cht, s vn chuyn qua nhau thai,
s vn chuyn qua cc t bo biu m bng cch lin kt vi mt
th th poli-Ig, kh nng hot ha b th v lin kt vi mng
t bo.
S lin kt gia khng nguyn v khng th c th gy ra hai
hiu qu:
1. Hot ha h thng b th.
 29

2. Hot ha cc t bo khc nhau c cc th th - Fc nm trong

mng t bo ca chng.
S hot ha b th theo con ng c in (con ng ca b
th Clq) b gii hn mt s lp v di lp nh IgM, IgG, IgG3
v mt phn nh cc IgG2. S biu hin ca cc th th-Fc khc
bit nhau tu theo cc kiu t bo nh t bo mast, lympho, i
thc bo, t bo a nhn trung tnh, t bo tiu cu V .V .. T
gy ra vic sn xut cc lp v cc di lp Ig sau khi gy min
dch vi mt khng nguyn, ko theo nhng hiu qu sinh hc
khc nhau ty thuc vo cc m t bo. S lin kt ca cc Ig vo
cc th th - Fc c th gy ra nhng tn hiu hot ha cc t bo
nh: hiu qu gy c ca cc lympho-T, kh nng thc bo ca
cc i thc bo v ca cc t bo a nhn trung tnh, gy hiu
qu loi b cc ht ca cc t bo mast v t bo tiu cu.
Cc chui nng ca Ig lun lun c kt hp vi cc gc
ng cc v tr khc nhau. Nhn chung, cc gc ng kt hp
vi Ig l cc oligoxacarit c cha mt hoc nhiu gc axit sialic,
cng mt chui nng c th c s khc nhau v kiu kt hp vi
cc gc ng, t s to ra mc b sung cho tnh cht khc
bit phn t ca cc Ig. Chng hn, cu trc ng ca IgG khc
vi IgA v IgD, hn na cu trc ng ca di lp IgA, khc
vi IgA2. Thm vo , s thay i bt thng ca cc gc ng
kt hp vo Ig s gy ra mt s bnh t min (autoimmune
diease).
Ni chung, cc phn t Ig tng i bn nhit ( 56c trong 30
pht), ngoi tr IgE km bn nhit v b ph hy trong nhng
iu kin ny.
Cc lp v di lp Ig c phn b khc nhau cc dch sinh
vt. Cc IgM ch yu c tm thy khu vc trong cc mao
mch. Cc lp IgG phn b ng u cc phn mao mch v
ngoi mao mch. Cc IgA ca huyt tng ch yu c sn xut
t cc t bo plasma dng IgA ca ty xng, trong IgAj
monome chim ti 90%. Cc Ig c tit ra t rut ch yu bao
gm cc IgA tit dime hoc polime v c t l tng ng gia
IgA, v IgA2. Ngoi ra, ngi ta cn tm thy mt lng nh IgM
tit. Cc Ig tit c sn xut t cc t bo plasma ca m lin
kt nm tip xc vi biu m nhy c cha cc th th poli-Ig c
nh cc Ig polime. Phc h Ig-th th poli-Ig di chuyn v pha
mng ca t bo biu m. , th th poli-Ig s b phn tch ra
thnh cc Ig tit (IgM hoc IgA polime) v chng s c kt hp
30

cng ho tr vi mt thnh phn tit. Cc IgA ch yu c tit

t nc mt, nc bt, cc dch mi hng trong mt, trong sa,
trong dch tit ca rut, ng sinh dc v mt s' tuyn nhy
(nim mc: mucosal).
S vn chuyn qua nhau thai ca cc khng th c bit lin
quan n 4 loi di lp IgG. S vn chuyn ny t ti cc i
cui thi k c mang v nng Ig ca mu thai nhi lc bng
vi nng Ig trong mu ngi m. S chuyn ha cc IgG trong
c th ca tr s sinh s c thc hin bng cch gim dn dn
nng Ig ca huyt thanh v chuyn sang mt thi k h thp
gamaglobulin sinh l gia thng th t v thng th su ca tr.
C th thai nhi cng tng hp dn dn cc loi Ig ring bit,
trc tin l IgM, sau n IgG v cui cng l IgA. S c mt
ca cc khng th c hiu ca lp IgM v IgA trong mu ca
cung nhau thai cho thy cc khng th ny c tng hp bi
h thng min dch ca bo thai. Du hiu c th c s
dng chn on s nhim trng ca bo thai bi cc virus.

Chui ng Domain

Vng
lin kt
khng
nguyn
Ch2 C||3

IgG IgG2v IgG4

H nh 3.1 Cu trc chung ca phn t IgG. Cc vng N tn cng ca

chui nng (H) v chui nh (L) c trng cho cc trnh t d bin i
(V) c gi l cc vng VHv VL. Phn cn li ca phn t c cu trc
tng i n nh. Phn khng i ca chui nh v chui nng tunk
ng c gi l CLv CH, tuy nhin phn khng bin i ca chui nng
bao gm 3 khu vc khc nhau l C||l, CH2 v CH3. Cc khu vc ny (do-
main) c dng hnh cu v c n nh bng cc cu disunua. Hai v
tr lin kt vi khng nguyn nm cc khu vc d bin i. Vng khp
hoc vng bn l ca chui nng nm v tr gia C||l v C|2 c (lc
tnh kh mm do cho php thay i khong cch gia hai v tr iin
kt gia khng th v khng nguyn, ng thi cng m bo cho s
tng tc c lp ca cc khng th i vi khng nguyn. Cc chui
polixacarit c gn vi khu vc CH2.
 31

Hnh 3.2 Cu trc pentame ca phn t IgM ca ngi. Cc chui

nng ca IgM c 4 khu vc vng khng bin i ca chui nng. Cc
n v khc nhau c lin kt vi nhau bng nhng cu disunfua gia
cc khu vc Cfi3 v C4 k cn. Cc chui ohgoxacarit cng nm cc
v tr ca chui nng cng nh nm mt v tr gi thit ca mt chui
J. (Theo I. Roitt et al., 1994)

3.2. Cu trc ph n t c a cc im m u n oglob u lin rin g b it

IgG: IgG l mt globulin min dch c s lng ln nht trong

huyt thanh ca ngi. Nng trung bnh trong huyt thanh
ca ngi kho trng thnh l t 10 n 14g/lt. Phn t IgG c
3 khu vc vng khng i ca chui nng l CH1, CH2, CH3. IgG
dng monome v bao gm 4 di lp (lp ph) l IgG,, IgG2,
IgGt, IgG,. Ngi ta bit, IgG2 c sn xut c u th p
ng li i vi cc polixacarit ca vi khun. Cc IgG l mt trong
nhng cht hot ho ch yu ca con ng hot ho b th theo
kiu c in. Cc th th Fcy c vai tr quan trng i vi s vn
chuyn IgG qua mng nhau thai t ngi m n thai nhi. iu
ny c vai tr quan trng i vi tr s sinh khi h thng min
dch khi h thng min dch ca tr cha chn mi.
32

lgM: IgM c cu trc l dng pentame trn c s c hnh

thnh t mt n v bao gm 2 chui nng n v 2 chui nh. Cc
chui |i khc vi chui y trnh t cc axit amin v s lng cc
khu vc khng bin i. C 4 domain vng khng bin i ca
chui nng nm di n v ca IgM c lin kt vi nhau bng
cc cu disunfua gia cc khu vc Cji3. IgM thng c gi l cc
macroglobulin min dch v c khi lng phn t rt ln. S
polyme ho cc monome ca IgM ph thuc vo s c mt ca
chui n J (Joint). Chc nng ca chui J l lm n nh cc
nhm SH (sunfohydril) ca cc vng FC hnh thnh cc cu
disunfua (S-S) cn thit cho cu trc pentame (hnh 3 .2 ). Nng
trung bnh ca IgM trong huyt thanh ngi t 0,5g n 2,5g/lt.
IgA : Cc IgA xut hin c chn lc trong qu trnh tit ca cc
tuyn nhy nh tuyn nc bt, tuyn l, tuyn m hi, tuyn mi
hng, tuyn sa, dch nhy c quan sinh dc, tit niu v cc
tuyn tiu ho d dy v rut. iu chng t IgA c vai tr
ngn chn s xm nhp ca cc vi sinh vt vo cc c quan ni
trn. IgA tun hon thng dng dime ngn nga s phn
hu ca cc proteinaz nh phn t ca n c mt mnh tit (mnh
S) lin kt 2 monome vi nhau. Mnh tit c phn t lng 60
kDa, v c tng hp ti ch cc t bo biu m. Cc IgA dime
khi c tng hp ti ch t cc t bo plasma c thm mt peptit
ni (peptit J) rt giu xistein v c khi ng 15 kDa. Chc nng
ca IgA l km hm s hot ng ca cc vi sinh vt b kt
dnh trn b mt ca cc t bo tuyn nhy v ng thi ngn cn
s xm nhp ca chng vo cc m. Cc IgA kt t s c c nh
ln cc t bo a nhn v hot ho b th theo con ng lun
phin nhau. c tnh ny ph hp vi cc dn liu chng minh
cho 8 hip ng tc dng gia IgA, b th v lyzozim trong qu
trnh ph hu mt s' dng vi sinh vt. Huyt tng ca ngi
bnh thng c cha mt lng IgA monome nng khong
2,5-3 mg/ml (hnh 3.3 v 3.4).
IgD: IgD ch c mt mt lng rt t (khong 1%) so vi cc Ig
khc ca huyt thanh. Khng th ny rt nhy cm i vi tc
ng ca proteaz, v c khuynh hng t phn hu nhanh. Trong
phn t IgD c mt cu disunfua lin kt gia 2 chui nng v
lin kt vi nhiu chui oligoxacarit, trong c mt chui giu
loi ng N-axetilgalactozamin. y l mt loi ng cng c
mt trong phn t IgA, nhng khng c bt k loi Ig no khc
 33

(hnh 3.5). Nng IgD trong huyt thanh ngi khe rt thp
khong t 0,04mg * 0,05mg/ml

Hnh 3.3 Cu trc IgAi ca ngi. S ny cho bit cc

cu disunfua gia cc chui nng v chui nh, gia cc
chui nng vi nhau v trong cc chui nng hoc trong cc
chui nh. Mt cu disunfua b sung lm n nh khu vc
Ca2 v mt cu disunfua lin kt chui J trong IgA polime.

H nh 3.4 Cu trc IgA tit (slgA) ca ngi. l mt

IgA dime c to bi 2 di n v IgA ni vi nhau bng
chui J v mnh tit s.
34

Domain Mu ui

H nh 3.5 Cu trc IgD ca ngi. S ny ch r cc cu

disunfua gia cc chui polipeptit v trong cc chui,
ng thi ch r v tr gi thit ca cc chui oligoxacarit.

H nh 3.6 Cu trc IgE ca ngi. S ch r 4 khu vc

khng bin i, cc cu disunfua gia cc chui v trong
cc chui, v tr cc chui polixacarit.
 35

F (a b ),

C c p e p t it n h pFc

IT :cr . I
CLUJ II-
r
PKPXIN

4L.
X
't
-& V tr i c t t h c a p c a
PA PAIN p apain

*****
\ Fc

H nh 3.7 S thu phn bng cc proteinaz i vi IgGj ca ngi.

Pepxin ct IgGj thnh cc mnh F(ab% v mnh F(c) v cc mnh
peptit c phn t nh. Trong khi papain phn gii IgC! v tr
gc 224 ca vng khp v gii phng 2 mnh Fab v mt mnh Fc.
im ct sau v tr 341 ca m nh Fc s to ra cc mnh Fc\

IgE: Nng IgE trong huyt thanh rt thp nh hn 0,3mg/l

nhng trnh t axt amin c sng t nh cc IgE n dng
ca u tu c tinh ch. Chui nng c khi lng kh cao l
72,5 kDa gm 550 axt amin v phn chia thnh 4 khu vc
khng bin i l Cel, Cs2, Cc3 v Ce4. Mnh Fc ca IgE cha
ng mt phn ln cc epitop c hiu ca phn t v lin kt
vi b mt t bo mast (mastocyte). Mnh Fc cng c cc quyt
nh khng nguyn. IgE thng tham gia vo cc phn ng
vim, phn ng d ng v hin tng qu mn (hnh 3.6). C th
tng kt mt sc> tnh cht ca cc lp Ig ngi theo bng 3.1
36

Bng 3.1. Mt s c tnh c bn ca cc Immunoglobulin ca

Cc Cc Allotyp Khi Nng Chc nng sinh hc

Ig lp ca lng trong
ph chui phn t huyt
nng thanh,
mg/100 ml
IgG gG C 150-170 800-1700 Nhn bit virus, vi
IgG2, khun, c t'
IgGj, Hot ho b th
IgG,
Lin kt vi th th Fcy
Qua mng nhau thai
IgM Khng 970, dng : 50-250 Xut hin u tin sau
pentame 9 : 60-270 khi kch thch Ag.
Dng Ngng kt hng cu vi
monome khun, virus.
trong Lin kt vi Ag, hot ho
bnh u b th.
tu
IgA IgA, Khng 160 0*100-400 Chng li vi khun, virus,
IgA2 c 320, dng 9 : 85-450 nguyn sinh ng vt
nh c mt tuyn nhy.
dime
trong IgA Hot ho b th theo con
tit v c ng xen k.
dng
Tham gia vo opsonin ho
tetrame
khi phn ng vi th th
Fca
IgD khng 175 < 10 Ch yu tm thy t boj
B, c th khi tip xc vi
Ag, truyn tn hiu hot
ho t bo B
gT khng 190 <0,03 Tham gia phn ng vim
d ng, qu mn khi lin
1 kt vi t bo mast
L__
 37

3.3. M i q u a n h gi a cu tr c v ch c n n g c a c c
k h n g th

Chc nng u tin ca cc khng th l lin kt vi khng

nguyn c hiu vi chng, tham gia vo cc p ng min dch
dch th (trung ho cc c t vi khun v virus), p ng min
dch trung gian t bo (tham gia hin tng opsonin ho, to
iu kin bt gi v tiu ho khng nguyn, vi khun v.v...). S
hot ho b th l c ch c hiu qu quan trng nht ca cc
IgG v IgG:t. H thng b th l mt nhm cc phc h protein
huyt thanh tham gia vo phn ng vim. Sau khi lin kt vi
khng nguyn, cc IgM, IgG, IgG) c th hot ho mt dy cc
enzim ca b th. Trong khi cc IgG^ t c hiu qu ny. Cc
IgG,, IgA, IgD v IgE khng c kh nng hot ho b th.
ngi tt c cc IgG u vt qua hng ro nhau thai n
vi tr s sinh v thc hin chc nng min dch th ng. Cc
ng vt khc khng c kh nng ny tuy nhin sau khi sinh IgG
ca sa m s c truyn cho c th ng vt con mi sinh qua
ng tiu ho. Cc nghin cu v cu trc ca cc khu vc chc
nng v cc di n v chc nng ca cc Ig cho thy mi mt
n v cu trc l kt qu ca s tin ho ring bit theo chc
nng c hiu. Chng hn cc vng d bin i V|, V| l vng
lin kt vi khng nguyn, cn cc khu vc khc tr th cho cc
chc nng sinh hc ca khng the. Ngi ta cng bit rng cc
di n v C lq ca b th tng tc vi khu vc Cy2 (IgG) v
mt v tr kim tra s trao i cht ca cc phn t Ig nm cng
mt khu vc. Nhng tng tc i vi cc i thc bo v t bo
mono c c l nh v tr khu vc Cy3. Cc v tr gi ln nhau
ca 2 khu vc mnh Fc c th l Cy2 v Cy3 c hiu qu hip
ng tham gia tng tc vi cc th th ca cc t bo.

3.4. C s d i tr u y n v tn h a d n g c a k h n g th

Theo l thuyt la chn dng ca Jerne v Burnet, Dreyer v

Bennett t c s khoa hc gii thch tnh a dng cu trc
ca cc khng th. C 3 c ch cho php h thng min dch sn
xut ra cc vng d bin i V ca chui nng v chui nh cc
mc khc nhau:
38

1. C nhiu gen nh (minigen) tn ti cc vng khc nhau ca

nhn t bo vi s lng rt ln m ho cho mi mt khu vc
ca chui nng v chui nh. Tnh a dng ca cc Ig cho php
biu hin trn 106 cc idiotyp khc nhau, do d ti t hp ca
cc minigen.
2 . S t bin soma: Mt gen V nguyn gc c th b t bin trong
qu trnh pht trin c th (ontogenesis) ca mt t bo B.
3. S ti t hp soma: Mt s lng no cc mnh gen (t Jj
n J n) c t hp li v nm bn cnh mnh gen m ho cho
phn ch yu ca vng V. iu c hnh thnh trong qu
trnh pht trin c th ca t bo B v t ti tng hp mt
protein c cha cc trnh t c m ho bi cc mnh gen
khc nhau.
C 3 c ch trn u c hiu qu hip ng gii thch tnh a
dng ca cc khng th. Trong nhng nm gn y nh cc tin
b trong nghin cu sinh hc phn t ngi ta bit cc loi
protein ca sinh vt bc cao (Eucariota) c m ho bng nhiu
exon ring bit cch ri nhau bng nhng on intron km hm
qu trnh tng hp. Cc on intron ny s b loi b bng s
chuyn on (translocation) ca ADN hoc bng cch ct b cc
mnh tng ng trn phn t mARN. Mt gen c phn chia
thnh cc phn: trnh t dn L cn cho s vn chuyn gen qua
li ni cht, mt mnh VA. m ho cho cc axit amin (c th t 1
n 98 i vi mnh v \ ca chut), mt mnh gen ni J m ho
cho 11 axit amin sau cng ca vng d bin i, v mt mnh
gen CA. m ho cho vng khng bin i. Khi lympho B chn v
bit ho thnh t bo plasma tng hp chui \ th phn t
ADN s t sp xp sao cho cc mnh L, VA. v J gn nhau (Hnh
3.8). Tuy nhin mnh gen cx. vn cn cch bit vi mnh J bng
mt on intron khong 1250 nucleotit. S lp rp li cc mnh
gen L, vx, J v CA. trong phn t mARN s cho php to ra kh
nng tng hp chui nh X lin tc.
Nguyn tc nh trn cng c p dng cho s tng hp chui
nng H v chui nh K, mc d cc mnh gen trng hp ny
ln hn rt nhiu so vi chui X. Ngi ta tm ra trn 200 gen
Vk v chia thnh 5 h khc nhau, mi chng cha cc gen c
quan h thn thuc vi nhau. Mc d cc gen ca cng mt h c
mt s khc bit vng khng bin i v vng siu bin nhng
nhn chung kh ging nhau. C 5 gen J khc nhau trong ch
 39

c 1 gen m ho cho vng khng bin di ca chui K (hnh 3.8,

3.9,3 10)
Mt dy cc gen m ho cho cc chui nng c c tnh l tt
c chng u m ho cho vng khng bin i ca mi di lp
v c tp hp li thnh mt nhm gen. Mt nhm ny bao gm
12 mnh gen D c c tnh d bin i v c ci xen gia cc
vng gen V v J. S t hp cc mnh gen D v J s m ho cho
vng siu bin th ba (ton b vng siu bin bao gm ba phn),
cn h a i v n g siu bin th n h t v th h ai s c m ho b n g
trnh t ca mnh gen V.
Ngi ta phn bit ba kiu khc bit cn c vo cu trc phn
t ca cc khng th. chnh l nhng mc khc nhau ca
cc epitop nh khu trn phn t Ig. T tnh a dng ca Ig
c biu hin ba mc sau y:
)Khc bit izotip (Isotype variation): Cc gen ca khc bit izo-
tip c mt tt c cc c th cng mt loi ng vt sn
x u t ra cc ch u i n n g ( m , Y, e, a ) v cc ch u i nh ( K, ),
l trnh t c bn ca cc vng V ca cc di lp.
2) Khc bit allotip (allotype variation): Khc bit ny bao gm s
khc nhau v gen trong cng mt loi ng vt v s
dng nhng alen khc ca cng mt locus. Mt allotip
khng c tm thy tt c cc thnh vin ca mt loi.
Chang hn allotip G3m (bo) ca IgG3 c trng cho mt gc
phenylalanin v tr 436 ca chui nng khng phi c tt
c cc c th ca cng mt loi. Cc khc bit allotip thng
xuyn nm cc vng khng bin i ca chui nng. n nay
ngi ta pht hin c 25 nhm quyt nh allotyp trn
chui nng gamma ca IgG, c gi l ch th Gm (Gamma
marker) v 2 quyt nh allotyp trn chui a l IgAiml) v
IgA2(m2). Ngoi ra vng khng bin i ca chui nh Kappa
cng biu hin allotyp Km(l), Km(l,2) v Km(3).
3) Khc bit Idiotip (Idiotype variation): nhng khc bit nm
khu vc d bin i c bit cc vng siu bin. Ni chung
mt idiotip c hiu cho ch mt clon t bo sn xut ra khng
th, to ra mt idiotip c th. Tuy nhin ngi ta cng tm
thy cc clon khc nhau c th biu hin cng mt idiotip. Cc
idiotip ny c gi l idiotip cng cng hay idiotip hi quy.
Mi s kin ti t hp cc vng gen bin i xy ra u do s
ct gt v ti t hp i km to thnh trnh t gen gm cc
vng gen L (gen dn), gen V (gen bin i) v gen J (gen ni) xch
40

li gn nhau, c chc nng. Tham gia vo qu trnh ny c cc

enzym thuc phc h Recombinase V(D)J trong c cha cc
protein RAG 1 v RAG 2 (sn phm ca cc gen hot ng ti t
hp - Recombination activating genes), ligase IV, Proteinkinase
ph thuc ADN (DNA-PK), protein Ku (l heterodime Ku 70, Ku
80) kt hp vi DNA PK. Mt s protein trn c hot ng ex-
onuclease v endonuclease.

Locus ch u n h X
V
1 V *1 _ LVv-a - Jii
4*1 C *1 J2 C* J *4

: * = = 4 i * = = m = = = = = m t= = = m t
L ocuschui nh K
t Vfl 12 V? 13 v*3 L V* -40 J-S c,

L ocus ch u i n n g * *
V M1 L 2 v *2 L3 Vm3 f lH s 51 1 r 0*1-27 J h 1-

H nh 3.8: S s t chc cc locus gen ca ca chui nh X, Kv

chui nng ca khng th ngi
Locus gen chui nh X nhim sc th 22 c khong 30 mnh gen v x
c chc nng, 4 cp gen <\ v cc gen cx
Locus gen chui nh K nhim sc th 2 c t chc tng t, c 40
gen Vk i km vi 5 J k nhng ch c 1 gen Ck
Locus gen chi nng nhim sc th 14 c khong 65 gen VH, 27
gen D v 6 gen J Hv cha hng lot cc gen c khc nhau. L l gen m
ho cc trnh t dn u ca cc gen (Theo Janeway C.A. et ,al, 2001)
 Chui nh Chui nng

AND mm

: T~ I
Tlthp soma

~ r
ADN ni D-J

~ . r ....
Ti t hp soma
L V J c
= .; r ~ : N
ADN ni VDJ
Sp xp li
- r - I- v ,---- --- --------,
Phin m -M h - m ww AAA

Bn phin m
L V DJ.
u tin ARN

Ct ni

m ARN

Phin dch

Cc chui
polypeptit ca Ig

Hnh 3.9: c'c gen vng bin i c to ra t cc mnh

gen hnh thnh tnh a dng ca khng th
1

\/ \/
L V- J

m t

H nh 3.10: C ch ti t hp cc mnh gen vng hin i ca Ig

1. AND mm.
2. C ch to vng cho ct ni cc manh gen.
3. C ch loi h cc mnh intron v exon khc*.
4. Lp gip cc minh gen ph hp c hot tnh cho vng bin i
 41

m nh* i l l l o j a r t B H I

IV J c L V D J r V
ADN mm = = M M
1
Tl t hp soma IV D- . ..... i .. .
m - <
ADN ni D-J
c
Ti t hp soma L VJ c L V 0; , ..... , ........ .
B
Bll 13 5 11 B
AON ni VDJ sip xp

~ -------- L VM ---- -------------

Phin m 1 -
_____
Bn phin m u
tin ARN l V J c
n . - f n 5 ii5 6 M
Ct ni
________ 1
mARN r ~ r ~ cp 0 \
7' *------------ w v
Phin dch

Cc chui polypptii
calg
T

Hnh 3.9: Cc gen vng bin i c to ra t cc

mnh gen hnh thnh tnh a dng ca khng th
42

L, V, l* V* Vr lr
1.
= o * = = o e h = :* = =

2.

3.

. -
1 ------------------------ |
Lt V, J u V, J
4. m ^ B f t f l -
----------------------- L H K J --------------------------

Hnh 3.10: C ch ti t hp cc mnh gen vng bin i ca g

1. ADN mm.
2. C ch to vng cho ct ni cc mnh gen.
3. C ch loi b cc mnh intron v exon khc.
4. Lp gip cc mnh gen ph hp c hoat tnh cho vng bin
i
 43

3.5. Cc k h n g th n dng (m onoclonal antibodies)

S p ng min dch tng hp khng th xy ra rt tinh vi:

mi ep ito p s c h m in dch s n x u t r a m t loi k h n g th
c hiu. Sau khi gy min dch vi mt khng nguyn ngi ta
s n h n c cc k h n g th c h i u , c cu trc rt k h c n h a u
bi v mi mt t bo B ch sn xut ra mt loi phn t th th
BCR v t ch c th tit ra mt loi khng th. Trong khi
mt phn t khng nguyn c th cha nhiu epitop khc nhau.
Ngi ta c th lm bt t mt dng t bo B bng cch lai soma
vi mt t bo ung th (dng u tu khng tit khng th). Bng
cch to drg (cloning) lai soma, c th nhn c th lai (hybri-
doma) sn xut ra ch mt loi phn t khng th. Cc khng
th ny c gi l khng th n dng, c cu trc phn t hon
ton ging nhau v c s dng rt a dng trong phn tch
sinh hc v cha bnh. S phng php sn xut khng th
n dng c trnh by hnh 3.11.
Trong mt s dng bnh l ca ngi nh cc bnh u tu (mye
loma), unf' th bch cu c tnh dng (leukemia) tin B, bnh
Waldenstrom, qu trnh tng sinh n dng ca mt dng t bo
B thng xy ra s to ra cc khng th n dng. Cc khng th
n dng ny c th c pht hin trong huyt thanh hoc nc
tiu ngi bnh bng phng php in di min dch hoc k
thut ELISA.
44

KHNG NGUYN lym pho B TB u tu

k h n g th k h n g th
d a dng n d n g

Hnh 3.11: S sn xut khng th n dng (tng kt phng php

ca Kohler v Milstein, Nature 1975, 256: 495-497). Mt chut nht
c gy min dch vi mt khng nguyn mang cc epitop khc nhau.
Huyt thanh min dch cha cc khng th a dng (polyclonal anti-
bodies), khc nhau v nhn bit cc epitop khc nhau ca khng
nguyn. Mi t bo B ch sn xut ra mt loi khng th s c dung
hp bng cch lai soma vi cc t bo u tu (khng tit khng th
nhng bt t trong nui cy). Sau khi chn dng (cloning) cc th lai,
mi dng qun th t bo bt ngun t ch mt th lai (clone, hybri-
doma) s sn xut ra ch mt loi phn t khng th hon ton ging
nhau. l khng th n dong (MAb).

3.6. Khng th ti t hp (recom binant antibody - rAb)

* Khng th ti t hp l khng th th h th 3 c sn xut

in vitro. c im ca khng th ny l:
- c to ra bng k thut di truyn, khng l thuc vo ng
vt th nghim.
- C c tnh n dng v c ngun t mt t hp gen c la
chn, to ra mt loi khng th c hiu vi mt epitop nht
nh, sau c biu hin trn mt dng t bo vi sinh vt
hoc mt c th nht nh (c th l thc vt hoc ng vt)
 45

- Vic sn xut khng th ti t hp bng k thut di truyn cho

php nhn dng, dung hp v ti t hp gen to ra nhiu dng
khng th c hiu kp (bispecific) hoc ch l cc mnh khng
th c chc nng nh F(ab), mnh bin i mt chui (scFv)
dng cho vic lp ghp vi c t min dch (immunotoxin)
to khng th iu tr bnh.
* 3 nguyn tc sn xut khng th ti t hp l:
- C s lng gen sn c m ha cho khng th.
- Chn lc c hiu qu cc gen thch hp trong vn gen.
- Chn lc khng th c tnh i lc v c hiu cao.
* Tm tt cc bc sn xut rAb:
- La chn cc gen t ngun gen.
- Xy dng cc on gen ti t hp ca rAb v nhn dng.
- Thit k cc vector chuyn gen v biu hin gen.
- La chn vi sinh vt (thng l E.coli) biu hin gen, c th
s dng phage.
- Tinh ch rAb t sinh vt biu hin.

3.7. Cc th th c a ly m p h o B (BCR )

Cc th th ca lympho B c to thnh t cc Ig c cu
trc ging nh mt phn t khng th ho tan nhng u
tn cng c ca cc chui nng c xuyn su vo mng t
bo lympho B. Vng xuyn qua mng t bo ca phn t Ig
c chiu di khong 20 gc axit amin v mt on ngn ca
trnh t tn cng c nm trong phn t bo cht. Cc BCR
ca lympho B chn bao gm mt IgM v mt IgD (mlgM,
mlgD) ca mng t bo, c mt chui nh ging nhau v cng
mt khu vc V||. Cc chui n v s l s ghp ni ca cng mt
bn sao |A-5. Cc Ig mng l nhng monome (i2L2 ) BCR ca
lympho B ghi nh khng cha ng mlgD ngha l ch gm
mt lp Ig (c th l mlgM, mIgG3 hoc mlgGl V..V..) ngoi
ra cc mlg ca lympho B cn kt hp vi mt heterodime
c hnh thnh t cc phn t Iga (CD79a) v IgP (CD79b).
Cc phn t Iga v IgP lin kt vi nhau bng mt cu dis-
unfua nm ngoi t bo. Chc nng ca cc phn t Iga v
IgP l truyn dn tn hiu nh s kt hp ca BCR vi khng
nguyn c hiu. S nhn bit khng nguyn ny c thc
46

hin vng d bin i ca phn t mlg. Vng ngp su

trong t bo cht ca cc Iga v IgP biu hin nh mt c
cht c th tng tc vi mt loi enzim gn bn trong mng
t bo pha t bo cht, l tirozinkinaz. Cng vi cc Iga
v Igp, tirozinkinaz tham ra vo truyn dn tn hiu trong
p ng min dch.

3.8. Cu trc ca cc th th lym pho T (TCR)

Cc th th ca lympho T hoc TCR (T - Cell receptor) dng

heterodime do hai chui polipeptit xuyn qua mng t bo l a
v p hoc y v 5 kt hp vi nhau. Mi chui polipeptit u bao
gm mt khu vc d bin i (V) tn cng N v mt khu vc
khng bin i (C) xuyn qua mng v bc l mt on rt ngn
pha tr o n g t bo cht u tn cng c. C r t nhiu loi th
th dng y5 tu thuc vo cu trc ca chui . Chng hn cc
chui s li n k t vi chui b n g cu d isu n fu a tro n g k h i ch u i
y2 c vng d bin i kh di v ch lin kt khng cng ho tr
vi s.
Khong 70% lympho ca mu tun hon cha cc th th TCR
v ch yu dng ap (95% l ap v khong vi phn trm l a)
Trong khi , m t bo t l phn trm y cao hn v ch yu
l cc tuyn nhy. Cc t bo T biu b c dng rng ca. ca
ngi khng c th th dng nhng li c mt chut. Cc
th th a(3 c th lin kt vi cc khng nguyn c trnh din
vi cc phn t ca HLA ca lp I v lp II ngi. (HLA: Hu
man Lymphocyte Antigen l khng nguyn ca cc t bo lym-
pho ca ngi tng ng vi MHC ca cc loi ng vt).
Cc th th ap v lin kt vi nhau trn mng t bo lym-
pho T thnh mt phc h cng vi phn t CD3. Phc h ny cn
thit bc l trn b mt ca cc th th TCR v m bo cho
s truyn dn cc tn hiu do s tng tc gia cc TCR vi
khng nguyn. Phc h ny bao gm 5 chui polipeptit: Cc
chui (y v e)x2 bao gm mt khu vc kiu Ig ngoi bo v mt
vng xuyn qua mng, mt vng t bo cht.
Cc chui polipeptit v r| c phn ngoi bo rt ngn ch gm
9 gc axit amin, mt mnh peptit xuyn qua mng v hai vng
rt di nm trong t bo cht. Hai chui polipeptit c th dng
 47

homodime (C,Q hoc (r|r|) hoc dng heterodime ((^r). Cc vng

t bo cht ca cc chui polipeptit ny c mt kiu moun yee
hoc ba kiu mun ng vai tr truyn dn tn hiu khi
chng tng tc vi cc tirozinkinaz (hnh 3.12).
Dng phc h TCR/CD3 trn c mt cc lympho T ap
thng lin kt vi cc phn t CD4 v CDg ca cc lympho T b
tr, tham gia tng tc min dch vi cc phn t phc h MHC
lp II v lp I.
S tng hp cc chui polipeptit ca cc th th lympho T
cng c thc hin nh cc gen tng ng v c th so snh vi
cc gen tng hp Ig.
Cng ging nh cc Ig, s tng hdp mt chui polipeptit ca
TCR c chc nng lun lun cn s ti t hp ca cc mnh gen
c mt cc t bo T chn mi bn trong tuyn c. S sp xp
cc mnh gen x y ra theo th t thi gian, trc tin l Y v ,
sau l ap, p v cui cng l a. C th l m ho cho cc
chui a v c s sp xp cc mnh gen Va Ja Ca v V Jy Cy,
cn i vi cc chui p v 5 l cc mnh gen vp Dp jp cp v V5
D J5 C (hnh 3.13).

3.9. Cc du h iu protein b it ho t bo

Cc phn t protein bit ho ca mng t bo bch cu

c pht hin nh s dng cc khng th n dng nhn bit
tnh c hiu chng. Chng c t tn l du hiu protein
bit ho hoc cm bit ho (CD: Cluster of Differentiation) v
c nh s th t. Hin nay ngi ta pht hin c 314
CD (xem ph lc 1). Chc nng min dch, cu trc phn t, 8
biu hin trn b mt t bo v mi quan h h hng gia chng
rt a dng v phc tp. Mt s ln cc CD v ang c
nghin cu v ngun gc gen biu hin v chc nng min dch
cng nh bnh l nh: CD3, CD4, CD7, CDg, CD10 v.v...
Chng hn, CD3 biu hin cc t bo tuyn c (Thymocytes)
v cc t bo T, v cho php s biu hin ca TCR, ng vai tr
trong vic truyn tn hiu khi TCR tip xc vi mnh peptid
khng nguyn. CD3 l mt glycoprotein xuyn mng c 4 domain
ngoi bo, kiu dng Ig. CD4 c mt tt c cc lympho THcha
chn v biu hin 2/3 cc lympho T ngoi vi. Hai domain u
tn cng N ca CD< l v tr lin kt vi mt vng ca cc phn
48

t HLA-II (Phc h ph hp t chc lp II) trong trnh din

khng nguyn. Vng ni bo ca CD4 c kt hp vi mt phn
t tyrosine kinase p56 lck truyn tn hiu cn thit cho s hot
ho lympho T. CDg l mt glycoprotein di dng homo dimer
(aa) hoc hetero dimer (a0) c mt trn mng t bo Tc cha
chn v 1/3 cc t bo T chn. CDe lin kt vi cc phn t
HLA-I mang mnh peptid khng nguyn ni sinh ca cc t bo
ch trong hot ng tip xc trnh din khng nguyn ni sinh.

Hnh 3.12. Cu trc ca cc BCR v TCR

a. S cu trc BCR v hai hetero Iga - Igp.
b. S phc h TCR ap/CDj. S ch r hai chui chc
n&ng o v p v hai n v chc n&ng ca phc h CDj
Ee v
c. M hnh t chc ca phc h TCR/CD*.
d. Ba kiu th th ca lymphoT.
(Theo J.p. Revillard, 1994)
 49

Vu
V,.
S cc S cc
gen to
50 57
gerc *o
ra tnh
a dng 70
I
(3 s> ra m/i
a dng
cc cc
12
m nh a m nh p
'*I
> i

Cc locus ca chui a v ngi

.V-V) &rY*3 tyj-0f2 4J.-A3 c* w c
B HN M K tl.K+ f-H bh H I I IMH
Locus ca chui p

v - y cy 0|i2 J|2 _ _ Cpv?

5*
: flllllH I Hl III r
Locus ca chui Y

V-Vy _J1_ Cr1 C2

H N K |-|I IJ 4 H ^
H nh 3.13. S lng cc mnh gen khc nhau c
dng to ra tnh a dng ca TCR ap ()
S sp xp ca cc locus gen cho cc chui a, 3, V, 5 ca
TCR(B).
50

Tm tt chng III

1. S nhn bit cc epitop ca khng nguyn c m bo bng

cc paratop nm trn phn t khng th hay cc immu
noglobulin ho tan (Ig) hoc cc th th di dng slg mng t
bo lympho B (BCR) v cc th th ca lympho T (TCR).
2. Cc phn t nhn bit khng nguyn c hnh thnh t cc
chui polipeptit, mi chui c t 2 n 5 khu vc (domain),
c m ho bng cc gen sp xp v t hp li trong cc t
bo B (i vi cc gen H, K, X ca Ig) v trong cc t bo tuyn
c (Thymocytes-t bo tuyn c s bit ho thnh lympho T)
i vi cc gen Y, , p v a ca cc TCR.
3. Tnh a dng cc k phong ph ca cc th th cha ng
par atop (trn 109 loi phn t khc nhau) c th c c nh
cu trc heterodime ca hai dng chui polipeptit (VH + VL,
Va+Vp, Vy + V), nh kh nng ti t hp trong cch sp xp
li cc gen V-J, V-D v D-J, nh tnh a dng ca cc mnh
gen ni J, cc vng N (Cc vng ni V-J v V-D-J ca TCR, V-
D-J ca cc chui nng Ig) v cui cng nh t bin soma
cc dng t bo B, nhng khng xy ra t bin trong dng t
bo T.
4. Nghin cu cc gen ca Ig v TCR c th a n nhng ng
dng thc tin trong Hnh vc nghin cu min dch bnh l v
mt s bnh ung th.
5. Cc cm bit ho khng nguyn (CD) l nhng phn t
protein hoc glycoprotein mng t bo c trng cho tng loi
t bo bit ho chc nng. Chc nng ca chng l gip cho
s nhn bit v tng tc, p ng min dch.
 51

Chng IV. Cc phc h ph hp t chc ch yu

4.1. M u

Nh chng ta bit cc chng trc, cc th th (recep

tors) nhn bit khng nguyn ca cc lympho B (BCR) s tng
tc theo khng gian vi cc epitop ca phn t khng nguyn.
Trong khi cc th th ca lympho T (TCR) tng tc vi cc
peptit ca khng nguyn c lin kt t trc vi cc phn
t ca phc h ph hp t chc ch yu (MHC - Major histocom
patibility complexes). Cc phn t protein ca phc h MHC
c m ho bi mt h thng gen ca phc h MHC nm trn
mng t bo trnh din khng nguyn APC (Antigen presenting
cell).
Vic pht hin ra cc sn phm protein ca MHC c tnh cht
ngu nhin v do tnh cc k a hnh ca cc phn t ny c mt
mi t bo ng vt. T ngi ta c th hiu r vai tr ca
chng trong qu trnh thi b cc mnh lai ghp. Khi nghin cu
c tnh ch't h thng s kim tra di truyn ca qu trnh thi b
cc khi u chut, Peter Gorer (1936) xc nh r cc khng
nguyn c m ho bi mt locus ca MIIC. Khng nguyn ny
c mt hng cu v cc t bo khc cho php kh nng thi b
hoc chp nhn cc mnh lai ghp ngha l kim tra kh nng
ph hp t chc ca m lai ghp. Cc cng trnh nghin cu tip
theo ca nhiu nh bc hc nh Georges Snell, Barij Benacerraf,
Hugh Mac Devitt cho php hiu bit cc gen cc locus khc
nhau ca lp I v lp II ca MHC. Cc cng trnh ca Jean
Dauset t 1958 cp ti vic nghin cu MHC ca loi ngi
v c gi l h thng HLA (Human Leucocyte Antigens) cho
thy chc nng sinh hc ch yu ca cc phn t HLA l trnh
din peptit khng nguyn cho cc lympho T.
52

4.2. Cu trc chung ca h th n g HLA

HLA ca ngi hoc MHC ca ng vt c c tnh bo th cao

t t c cc loi. l mt h thng nhiu gen, nhiu alen v
biu hin ng tri. H thng HLA l mt tng th cc gen nh
khu trn mt mnh cnh tay ngn ca nhim sc th s 6, chim
khong mt phn nghn ca genom ca ngi (bng p21.3). Cc
locus ny c nhm li thnh hai lp: lp I bao gm gia cc
gen HLA-A, B v c v lp II c t nht t 23 n 25 gen ca vng
HLA-D (hnh 4.1).
Ngoi cc gen m ho cho cc phn t ca HLA lp I v lp II,
ngi ta cn tm thy cc gen khc ca MHC kim tra mt s
giai on trnh din khng nguyn. l cc gen TAPl v TAP2
m ho cho mt cht vn chuyn peptit, cc gen LMP2, LMP7
m ho cho cc yu t ca th proteasom cha cc proteaz, cc
gen ca protein sc nhit (HSP70-2 v HSP70-1 v.v...). Cc pro
tein ny c chc nng lin kt vi cc protein b sc nhit loi
tr chng ra khi c th. Ngi ta cng tm thy phc h MHC
cn c cc gen C2, BF, C4A, C4B m ho cho cc thnh phn ca
b th, cc gen TNFa v TNFp m ho cho cc yu t hoi t ung
th. Tt c cc gen ny u c tnh cht a hnh, u biu hin
ng tri v lin h cht ch vi nhau.
- Tnh a hnh ca cc gen trn th hin tnh a alen. T
dn n kh nng t hp cao trn mi nhim sc th v con s
t hp cc kiu gen c th vt qu 1010. S khc nhau v alen
c th tng ng vi kh nng t bin ca mt hoc nhiu
baz, hoc thng xuyn c s thay th khong cch gia cc
trnh t m ca gen, lin quan n c ch bin i gen.
- Tnh biu hin ng tri th hin mi mt alen trn mt hap-
lotip. Mt ngi thng thng l d hp t cho mi mt locus
v mt nhm HLA ca ngi c xy dng t nhiu ch
ci trong mi ch ci c trng cho mt locus v c
truyn li t cha v m.
- Mi lin quan hp th hin ch tt c cc gen u c
truyn li thnh mt mng t cha m ca nhng a tr. Nu
ngi ta gi a v b l cc haplotip ca cha, c v d l cc hap-
lotip ca m th mi a tr u c di truyn t mt hap-
lotip ca cha v mt haplotip ca m v s c 4 kiu tr em l
ad, ab, bc v bd. Do xc sut cho cc HLA khc nhau
nhng a tr l 25%.
 53

4.3. Cu trc cc phn t v h gen ca HLA

Cc phn t lp I ca HLA dc hnh thnh t s kt hp ca

mt chui nh p2 microglobulm (B2m) v mt chui nng a.
Chui nh P2m c m ho bng mt gen nh khu nhim sc
th s 15. Phn t chui nh P2m c cu trc hnh cu c v
chc bao gm 99 gc axit amin c t chc thnh 2 l gp p lin
kt vi nhau bng mt cu disunfua (gia sistein 25 v 81).
Chui nng a c hnh thnh t 3 khu vc ngoi bo l a l, a2
v a3, mi khu vc c m ho bng mt exon. Ngoi ra chui a
cn c mt vng xuyn qua mng t bo v mt vng nm trong
t bo cht (Hnh 4.1). Cu trc 3 chiu ca chui a to ra mt
rnh gia cc khu vc a l v a2, c y rnh l mt l gp p v
cc b rnh to nn xon a.
Chnh dng cu trc vng rnh ny to kh nng tng tc
c hiu vi cc peptit ca cc phn t khng nguyn ca bn
thn hoc cc khng nguyn l khng phi ca bn thn.
Phc h gen ca HLA lp I c biu hin ch yu l HLA-A,
HLA-B v HLA-C. Ngoi cc gen HLA-A, B v c to ra sn phm
trn, ngi ta cn nhn bit c mt s gen khc nh HLA-E,
F, G c chc nng kim tra s tng hp cc protein ca lp I.
Cc gen HLA lp II (vng HLA-D) bao gm t 23 n 25 gen
c nhm li thnh ba phn vng ch yu l DR, DP v DQ.
Mt s gen c tnh a hnh, mt s gen l n hnh. Cc phn t
HLA lp II c hnh thnh t hai chui polipeptit a v p, mi,
mi chui u gm hai khu vc ngoi bo. Cu trc ba chiu ca
chng c th c dng gn ging vi cu trc ca cc phn t lp
I. Cc vng tn cng N ca phn t c nh khu kh xa bn
ngoi mng t bo v c tnh t chc a hnh. bn trong t bo,
cc phn t HLA lp II lin kt vi mt chui polipeptit khng
bin i c m ho bi mt gen nh khu nhim sc th s 5.
Mt hoc c hai phn t DR c biu hin theo th n bi
(haplotype). Trong tt c cc trng hp, chui a c m ho bi
mt gen DRA khng mang tnh a hnh. Chui p c m ho bi
mt gen DRBl cho mt phn t u tin v c m ho bi mt
trong cc gen DRB3, DRB4, DRB5 i vi phn t th hai.
Trong mt th n bi no , khng th cng mt lc tn ti
c ba loi gen DRl, DR8, DR10 v cng khng th c thm mt
phn t th hai. Cc chui a v p ca phn t DQ c m ho
54

bng cc gen DQAl v DQA2 tng ng. Cc gen DPAl v DPBl

m ho cho cc chui a v p ca DP. s n phm ca cc gen DMA
v DMB l chui ap heterodime, khng ging vi cc heterodime
ca cc gen DP, DQ v DR ng thi rt him khi biu hin trn
b mt t bo. Cc gen DOB v DNA t c phin m cc lym-
pho v c th m ho cho mt phn t HLA-DO. (Hnh 4.2)

HLA-I HLA-II

Mng VVVVVVYVVYVVV
J V jZ j*"iLJL>A \Mt<-?-!tL tlci
ft li_
__t I_
_ il>
_>v i ? t T V

Vng t bo cht

Hnh 4.1: Sd cu trc phn t HLA-I v HLA-II:

HLA lp I, chui nng a xuyn qua mng lin kt khng
cng ho tr vi chui nh p2-microglobulin; HLA lp II,
c hai chui u xuyn qua mng v lin kt khng cng ho
tr vi nhau. (Theo M. Peakman v D. Vergani, 1997).
 55

Tm ng (centromer)
a)
N him sc th 6

Lp II Lp III Lp I

['
Off
-m
Ctr*
' Iv p
**4 I t
i i n t c ? .IH S f It Nt-A- '
i . 4A t
a -m -A
DP DQ DR C4BC4AB1C2 HSPTNF B c A

c> J I /
M IN I

V ; V - 1 I | tt v - l A
Hi ' A.it tit A1 A. a TAt't m V H -' A i' B 0 1 /(I O'

DP DM DQ DR

Hnh 4.2. S v tr v cu trc gen ca HLA nhim sc th

s" 6 (theo M. Peakman v D. Vergani, 1997)

a) V tr cc cm gen trn nhim sc th 6.

b) S sp xp cm gen lp I, lp II, lp III.
c) Chi tit bn gen vng lp II: DP, DM, DQ, DR. cm gen
lp II c cha cc gen LMP2 v LMP7 m ha cho 2 peptit tham
gia vo ch bin khng nguyn ni sinh, TAPI, TAP2 l cc gen
m ha cho protein vn chuyn peptit khng nguyn.
(xem hnh 8.1)

4.4. S p h n b, iu ho b iu h in v ch c n n g ca
cc phan t HLA

Cc phn t HLA lp I: c mt phn ln cc t bo ca c th

(t 104 n 5.105 phn t/mt t bo) c bit nhiu cc t bo
lympho v i thc bo). C t hn t bo gan cha r t t hoc
bng khng hng cu, t bo thn kinh trung ng, mt 8 loi
t bo biu m ca ty v tuyn nc bt, v.v... Mt s t bo ung
th khng c cc phn t lp I. T l tng hp v biu hin trn
mng ca cc phn t HLA lp I tng ln nh tc ng ca inte-
feron a v p.
Chc nng ca cc phn t HLA lp I trnh din cc peptit
khng nguyn cho cc lympho T cha ng phn t CD8 bc l
trn b m t t bo. Cc lympho T ny gi l Lympho T- CD8*
56

cha ng mt glycoprotein dime, lin kt c hiu vi cc phn

t HLA lp I trong tng tc min dch. Cc peptit khng
nguyn c trnh din bt ngun t khng nguyn l do qu
trnh phn hu protein ni sinh (endogenic proteolysis) din ra
trong t bo trnh din khng nguyn (APC). Chng hn cc
thnh phn t bo vi khun, cc protein virus. Qu trnh phn
hu khng nguyn l din ra proteasom l phc h cha ng
cc proteinaz ca APC. Cc peptit c trnh din c kch thc
khong 9 gc axit amin c vn chuyn vo khoang li ni cht
kt hp vi cc phn t lp I v vn chuyn ra mng t bo ca
APC.
Cc phn t HLA lp II bnh thng bc l hn ch mt s t
bo ca c th. Mt ca chng c bit cao cc t bo chuyn
ho (105 phn t/ mt t bo) trong qu trnh trnh din khng
nguyn cho cc t bo lympho T-CD4\ Cc t bo trnh din
khng nguyn c th l cc lympho B, cc t bo c thu (t bo
biu b Langerhans, t bo khe hch lympho), cc t bo mono,
i thc bo, t bo biu m ng h hp, t bo ni m thnh
mch v c lympho T. S bc l cc phn t HLA-lp II s tng
ln di nh hng ca inteferon , ca IL4, IL13, TN Fa v p v
gim xung di tc dng ca prostaglandin PGE-2. Biu hin
bt thng ca cc phn t HLA lp II mng t bo thng lin
quan n s thiu ht min dch nghim trng.
Chc nng quan trng ca cc phn t HLA lp II l tng tc
c hiu vi lympho T-CD4* sau khi cc phn t HLA lp II
lin kt vi peptit khng nguyn. Nh vy tng tc kiu tam
phn t (trimolecular interaction) gia TCR, peptit lin kt vi
phn t lp I hoc lp II m bo cho kh nng tng tc min
dch c hiu v c hiu qu.
Chc nng chung ca cc phn t MHC l du hiu b mt
cho cc lympho T gy c t bo v cc lympho T b tr nhn
bit. Cc du hiu b m t MHC cng tham gia vo qu trnh bit
ho cc t bo lympho T. Mt vai tr quan trng ca mt s phn
t MHC Hn quan n h thng ni tit ca c th. Chng hn
dng t bo ung th Daudi khng bc l khng nguyn lp I v
khng c s tng hp P2 microglobulin (p2m) s khng c cc th
th tip nhn insulin vo th th t bo.
Con s l thuyt v cc nonapeptit khc nhau l 5,1x10". S
lin kt ca cc nonapeptit ny vo phn t HLA s dng t 1
n 5 gc axit amin cc v tr tn cng hai u ca peptit. Phn
gia cua peptit tng tc vi paratop ca TCR. Phn ny c th
ni ln so vi rnh lin kt peptit c bit trng hp ca cc
phn t HLA lp II v cc phn t HLA lp II c th lin kt VI
cc peptit khng nguyn c chiu di ln hn. Cc chui bn ca
peptit dc c nh vo cc ti v ni vo cc xon a v y gp
ca rnh. Cch cu trc nh vy chi cho php mt peptit hoc
mt lng rt nh cc peptit l khng phi ca bn thn c kh
nng c nhn bit bi cc t bo T ca mt c th (hoc cc
phn f IVHC ni chung) qui nh. (Hnh 4.3 v hnh 4.4)

Hnh 4.3: S cu trc rnh lin kt MHC-I. Cc peptit c

lin kt vi rnh MHC1 bng cc phn u tn cng ca chng

I
L
Hnh 4.4: S cu trc rnh lin kt MHC-II. Cc pep*
tit lin kt vi rnh MHC-II bng s tng tc dc theo
chiu di cua rnh lin kt
58

4.5. H t h n g H L A li n q u a n n q u n t h c h n g t c
v cc bnh l

S kt hp gia mt alen ca mt locus v mt alen ca locus

khc i khi xy ra mnh hn so vi s kt hp ngu nhin. S
m t cn bng ca mt mi lin kt cc alen thng c trng cho
mt qun th chng tc. Chng hn s kt hp gia cc gen HLA
ca lp III xy ra tng ng vi cc dng chng tc BFS, C2C,
C4A3 v C4B1 c mt ti 40% chng tc chu u (Caucasoid)
v ch c 12% chng tc da en. T cc nghin cu v s
phn b gen ca HLA s cho php tm hiu lch s c dn ca
mi vng v s di c ca cc qun th ngi.
Ngi ta cng nhn thy c gn 40 loi bnh l c lin quan
vi h thng HLA. Mt s bnh gy ra do ch mt gen HLA nh
bnh huyt sc t t pht, thiu ht enzim hydroxylaz-21, thiu
ht b th C2 hoc C4. cc ngi ng hp t mang gen bnh
l th triu chng bnh thy r c t l mc bnh l 1/100.000
ngi. Mt s bnh khc c lin quan n mt gen c kh nng l
DR2 gy ng m mt. Mt s alen ca lp II cng gy ra bnh t
min. Bnh vim khp t sng lin quan n mt khng nguyn
HLA-B27 c xc nh bng phng php huyt thanh thuc
mt phn t ca HLA lp I gy ra.

4.6. Cc phng php n gh in cu h th n g HLA

- Phng php huyt thanh hc phn loi HLA da vo cc

phn ng ca cc lympho mang cc khng nguyn HLA trn
mng t bo c th phn ng vi cc khng th v b th ca
chng. Ngun khng th c th l d khng huyt thanh (allo-
antiserum) nhn c bng cch gy min dch cho ngi
(truyn mu hoc ghp m l ...) hoc to khng th n dng.
- Phng php ho sinh bao gm vic phn tch in di phn
vng ng in (isoelectrofocahsation), in di hai chiu, xc
nh s khc nhau v khi lng phn t v s tch in ca
cc phn t HLA c tch ra bng cch kt ta vi khng th
khng HLA.
- Phng php sinh hc phn t c th nh loi tnh a hnh v
chiu di ca cc mnh gen gii hn (RFLP - Restriction frag
 59

ment Length polymorphism). Cc mnh gen c tch ra c

kch thc khc nhau bng in di, sau c chuyn thm
trn tm nitroxenluloz v c nhn bit bng cch lai vi mt
mu d c hiu vi mt gen HLA (k thut Southern). Cc
phng php hin i xc nh locus ca lp II da vo vic s
dng cc mu d oligonucleotit c hiu vi mt alen hoc
nhm cc alen (HLA oligotyping) v c hiu vi mt trnh t
chung ca tt c cc alen. Cc mnh gen s c nhn ln
bng PCR nh mt. on mi v tnh a hnh c pht hin
bng cch lai phn t hoc phn tch trnh t ADN. Cc
phng php ny rt chnh xc, c th thc hin trong 4 gi
vi my c so mu.
- Phng php t bo da vo s tng tc c hiu gia cc
phn t HLA v cc th th ca lympho T.
Phng php i hi s dng phn ng trn lympho c s
dng cht tin thn phng x H3 timidin o s sinh sn ca
cc lympho thch hp.
60

Tm tt chng IV

1. Phc h MHC, ngi gi l HLA l mt tng th bao gm cc

gen nm phn cnh tay ngn ca nhim sc th s 6, c tnh
cht a hnh, lin kt cht ch vi nhau (c truyn li ton
b t mt c th n bi halotip ca cha m n con ci) v u
biu hin ng tri.
2. Cc phn t HLA lp I (HLA-A, B, C) biu hin a s cc t
bo ca c th, trong khi cc phn t lp II (HLA-DR, DP,
DQ) phn b hn ch hn, c cc t bo trnh din khng
nguyn cho cc lympho TCD4+.
3. S biu hin cc khng nguyn HLA c iu ho c hiu
bng cc xitokin khc nhau v bin i theo cc iu kin sinh
l v bnh l.
4. Cc phn t HLA ca lp I v lp II c nh cc peptit khng
nguyn ca bn thn hoc khng phi ca bn thn bng cc
v tr a hnh ca chng. Phc h peptit - HLA tng tc vi
TCR, trong HLA lp I lin kt vi lympho TCD8+ v HLA
lp II lin kt vi lympho T-CD4*.
5. H thng HLA cho php thit lp mt giy thng hnh hay
chng minh th sinh hc cho mt c th; nh c th tm
hiu lch s mt qun th chng tc v nguyn nhn ca mt
s bnh l c Hn quan, c bit l cc bnh t min do mt s
allen bnh l kt hp vi nhau c th ng hp t.
 61

Chng V. B th

5.1. Khi nim

B th (complement - vit tt l C) l dng hp cht bao gm trn

bn mi loi protein (khong 5% protein ho tan ca huyt tng)
v cc protein mng (cc th th v cc yu t protein iu ho) c
kh nng tng tc ln nhau v phn ng vi mng t bo sinh
hc. Chc nng ca b th l :
- Tham gia vo qu trnh thc bo cc vi sinh vt.
- Trung ho cc virus v loi b cc phc h khng nguyn khng
th.
- iu ho p ng min dch.
Hot ng ca b th phn ln ph thuc vo s tng tc ln
nhau gia cc protein b th v cc th th t bo c hiu, ng
thi c khuynh hng hot ho nhanh chng v din ra ti ch.
iu c thc hin bng c ch khuch i v kim sot c hiu
qu. Hot ng ca b th c thc hin bng ba con ng:
1. Con ng c in (classical pathway) c hot ho bng phc
h khng th - khng nguyn ngha l ch xy ra khi khng th
kt hp vi khng nguyn.
2. Con ng bn cnh (alternative pathway) c hot ho trc
tip bng mt s polixacarit ca vi khun m khng cn c mt
khng th. C hai con ng hot ng ca b th u cn phc
h tn cng vo mng hoc phc h phn hu mng t bo vi
khun (C5b-9) v cc ion Ca2t v Mg2*. Do gn y ngi ta
cho rng c 2 con ng trn u khi ng cho mt con ng
thc 3 l con ng tn cng mng (Hnh 5.1).
3. Ngi ta cng tm thy con ng hot ho b th nh lectin MB
(gn ging c ch hot ho c in). Lectin MB c vai tr hot ha
62

b th thi k c th th u, th hin chc nng p ng min

dch bm sinh.

5.2. Cc p rotein ca b th

Thnh phn ca cc protein tham gia vo con ng c in v

phc h phn hu mng (phc h tn cng mng) l nhng b
th c k hiu t C l n C9. Hp cht Cl c to thnh t 3
tiu n v l Clq, C lr v C ls (xem hnh 5.1). Cc mnh peptit
do enzim phn hu c k hiu l C3a, C3b. Ch i k hiu cho
mt phn t b mt hot tnh, v d C3bi. Cc loi protein ca
con ng bn cnh xen k c k hiu bng cc ch ci in.
Chng hn p l propecdin, yu t" B l C3 tin hot ho, yu t D
l C3 tin hot ho convectaz. Trng thi hot ng ca cc phc
h b th c k hiu c gch ngang trn. V d: C4bC2a.
Cc protein ca b th c khuynh hng t pht hnh thnh
cc phc h thun nghch bao gm nhiu phn t. l trng
hp i vi Clq, C lr v C ls khi c mt ion Ca2+ v i vi C4,
C2. Trng hp i vi C3 v yu t B, cn phi c ion Mg2* v
i vi hp cht C5, C6, C7, C8 v C9 l 5 hp cht c th kt
hp vi nhau hnh thnh phc h tn cng mng (Membrane
Attack Complex- MAC).
c tnh hot ng rt c bit ca b th l lin kt vi b
m t ca cc vt th c hot tnh sinh hc nh phc h khng
nguyn-khng th, cc t bo, cc vi khun, virus, k sinh trng
v.v... Khi cc yu t C3 v C4 b phn hu s to ra mt v tr lin
kt vi mng trong thi gian rt ngn (di 10 phn nghn giy).
Nh lin kt ny lin quan n mt cu tio-este bn trong
tng i khng n nh v c kh nng c nh mt vt th
bng mt lin kt cng ho tr. Nu thiu mt cht tip nhn b
th ng lc, phn t b th t do trong tun hon mu nhanh
chng b mt hot tnh. V trn b mt mng t bo ca chnh
bn thn c th c axit sialic nh l mt tc nhn bo v chng
li s lin kt ca C3b nn rt ngho v tr tip nhn b th. Tri
li, mng t bo vi sinh vt hoc t bo ng vt khc bit v
chng loi pht sinh kh giu v tr tip nhn b th, s to iu
kin tt cho s lin kt vi b th.
Cc protein b th c tng hp gan, cc t bo biu m
rut (Cl), cc t bo mono v i thc bo. Thi gian bn hu
 63

ca C3, C4 v B l 24 gi nn chng cn c tng hp li hay

i mi.
Cc thnh phn C2, C4 v B c m ho bi cc gen ca b
th c tnh a hnh alen.

Hnh 5.1 Phc h b th Clq-Clr-Cls.

a. S phc h C lq (C lr Cls)2, trong Clq gm 6 tiu n v c

u trn tng t 6 bng hoa tuy lp v 6 ci ui collagen lin kt vi
2 phn t C lr v 2 phn t Cls. Cc u trn C lq lin kt vi vng Fc
ca cc Ig.
b. nh hin vi in t phng i 500.000 ln ca phc h C lq (C lr
C ls)2 (theo K.B.M.Reid).

5.3. Cc tin trnh hot ho b th

Nh trnh by hnh 5.2 s hot ho b th din ra theo

hai con ng v theo y chuyn. Thnh phn u tin ca b
th c hot tnh phn gii protein s phn hu c hiu thnh
phn th hai thnh hai mnh peptit v mt trong chng li c
hot tnh phn gii protein c hiu i vi thnh phn th ba.

5.3.1. Con ng hot ho c in

Con ng ny c thc hin bng s tng tc ca Cl vi

mt phn t IgM lin kt vi khng nguyn hoc khng
nguyn lin kt vi hai phn t IgG (IgGj v IgG3) (hoc IgG2
nhng km hiu qu hn). Trong phc h Cl ch ring tiu n
64

v Clq kt hp vi khng th. Rt him khi s hot ho c

khi ng trc tip nh cc cht nh protein phn ng c, cc
lipopolixacarit, hoc mt s virus.
Phn t C lq c cu trc trng ta b hoa 6 bng tulip, (hnh
5.1) c phn gia hnh si dng colagen v 6 tiu n v hnh cu
lin kt vi cc vng Fc ca IgG v IgM. Khi c mt ion Ca2\
Clq hot ho C lr v Cls. C ls c hot ho s phn hu
ng thi C4 v c C2 ko theo vic hnh thnh cc mnh C4b v
C2a. C4b v C2a hnh thnh mt phc h gi l C3 convectaz c
in tc l mt enzim lng phn t n nh khi c mt ion Mg2*
tip tc phn hu C3 thnh hai mnh C3a v C3b. Phn t C3b
li kt hp vi phc h C4b2a thnh phc h mi l C4b2a3b c
kh nng phn hu C5 vi iu kin l C5 c c nh vo phn
t C3b.
S hot ho theo con ng c in c iu ho bng Cl-
INH (cht c ch Cl). Cht c ch Cl-INH km hm s hot ho
C lr v C ls khi n kt hp vi cc enzim C lr v C ls v lm phn
li cc enzim ca Clq. Nu thiu ht bm sinh Cl-INH s dn ti
cc bnh ph mch. Mt lot protein lin kt vi C4 cng c tc
dng iu ho l C4bp (C4 binding protein). Cui cng hot ng
ca phc h C4b2a cng c kim sot bng cc protein c mt
trn b mt ca nhiu loi t bo: CD55 (DAF), CD35 (CRl) v
CD46 (MCP) (hay cn gi l protein cofactor ca mng t bo
CD46) (xem hnh 5.2A).
Nhng protein b mt t bo trn lm gii hn s hot
ho b th cc t bo ging nhau.
Cc protein C lr, Cls, C2, B, H, C4bp, MCP, DAF, CR1, cng
nh CR2 C6 v C7 u c hnh thnh t cc n v c trnh t
lp li t 60 n 70 axit amin, trong con s khc nhau thng
l 2 axit amin (i vi C lr v Cls) v khc nhau ti 56 axit amin
l C4bp.

5.3.2. Con ng hot ho b th nh lectin MBL

Lectin MB l lectin lin kt vi Mannan (Mannan Binding
lectin) c cu trc rt ging Clq bao gm phc h c 6 u vi
cc trc si di thuc dng Collectin (lectin dng Collagen), kt
hp vi 2 loi Zymogen protease serin l MASPl v MASP2. Khi
MASPl v MASP2 kt hp vi si trc lectin MB s to ra phc
 65

h ging nh C lr v C ls lin kt vi Clq trong con ng hot

ho c in.

Khi phc h MB lectin - MASPl - MASP2 lin kt vi b mt

tc nhn gy bnh s phn hu C2 v C4 v to ra C3 convertase
ging nh vai tr ca C lqrs trong con ng hot ho c in.
Ngi thiu ht lectin MB th hin kh nng d b nhim trng
rt cao giai on sm ca tui th u. iu chng t vai tr
quan trng ca lectin MB ca con ng hot ho b th trong c
ch bo v vt ch cn non tr trong giai on p ng min dch
bm sinh.

5.3.3. Con ng hot ho bn cnh v cc yu t hot ho

b th

Con ng ny s dng C3, cc yu t B v D v cng s dng

cc polixacarit nh inulin, zimozan (ca nm men), cc endotoxin
vi khun v mng hng cu th. S hot ho theo con ng
lun phin s d dng khi c thm khng th. Mi ln c hot
ho, con ng lun phin s c tng nhanh bng mt vng
khuch i t ti s hnh thnh C3 convectaz. C3 convectaz
c n nh nh propecdin (mt loi protein gy ra s c nh
C3 convectaz v lm n nh n). Khi c mt ion Mg2* C3b v yu
t B hnh thnh mt phc h lng phn t C3bB (hnh 5.2B).
Yu t D nh mt proteaza serin lm phn hu yu t B trong
phc h C3bB hnh thnh phc h convectaz C3bB. Convectaz
C3bB s phn hu C3 hnh thnh cc phn t mi l C3b s
lin kt vi mng t bo vi khun. Sau C3 l C5, C5 s to phc
h vi C3b v tr thnh c cht ca C3bBb. Nh mt peptit
nh c gii phng ra l C5a, trong khi mnh peptit C5b s
lin kt vi mng t bo. C5b li lin kt vi C6, C7 v tip theo
l C8 v mt phc h c hnh thnh s gy ra s thay i phn
t C9. mt thnh phn b th cui cng ca dy phn ng a n
s trng hp C9 (bao gm 10 - 16 phn t to polyme hnh ng).
66

C4 Carboxypeptidaz N C3 Carboxypeptidaz N

C4a C3a
&
' U C4b _ ' C3b^__Yu t'
> ^ - C l q r 2 s 2 D A F - - * + ----- *C4b2
/ C2a 0 "

Cl-INH
/6 @
C2b
C4b2a3b
C2 C5 convertaz

(B)

(A) v theo con ng bn cnh (B).

K hiu (-) l iu ho km hm, (+) l iu ho kch thch
ClINH: cht c ch Cl
DAF: yu t" thc y s ph hu C4b (decay-acceberating Factor)
 67

Con d ng c in Con dng bn cn h

C4b2a3b C3bBb3b

(C)

-* C5

C5b
C6, C7
P ro tein s
v
SP-40,40

C5b67 o

Hnh 5.3 Hot ho b th giai on tn cng mng

K hiu (-) l iu ho km hm
(+) l iu ho hot ho
68

Cc phc h vi b th c phn li v ci vo lp kp lipit ca

mng t bo vi khun v trng hp li thnh phc h tn cng
mng c dng hnh ng. Phc h tn cng mng C5b-9 k hiu
MAC (membrane attack complex) s to ra mt ng hm
xuyn qua mng c ng knh 10 nm to iu kin thm d
dng cc cht in li v nc nh Na+ hoc H20 . Dng Na* v
H20 to ra p sut thm thu lm ph v mng t bo vi khun.
Cc yu t H v I tham gia vo s iu ho vng khuch i.
Yu t H lin kt vi C3b cnh tranh vi yu t B ko theo s
phn li nhanh chng phc h C3 convectaz C3bBb v lm mt
hot tnh ca n. Hn na H lin kt vi C3b cn c vai tr l
cofactor enzim ca yu t I, cho php yu t I phn gii C3b
thnh C3bi bt hot. Chnh yu t' I cn c tc dng phn hu
C3bi thnh C3c ho tan C3d C3d c nh vo mng t bo vi
khun. Nh trn ni cc protein mng nh DAF v CRl cng
c vai tr kim sot hot ng ca phc h C3 convect C3bBb.
Yu t" c ngun gc thn: yu t thn (nephritic) (C3NeF) l mt
t khng th (autoantibody) IgG c hng chng li C3 convectaz.
T khng th ny lm bn phc h C3 convectaz v to cho n
bn vi tc ng ca yu t H.

5.3.4. Phc h tn cng mng (MAC)

C5 convertase c to ra nh cc con ng hot ho c in:

hot ho, hot ho bn cnh v hot ho nh lectin (MBL) s
tham gia vo giai on sau ca hot ho b th hnh thnh
phc h MAC. C5 convertase phn gii C5 thnh C5a v C5b. C5
tip tc lin kt vi C6 v C7 to phc C5bC6C7 ci vo mng t
bo vi sinh vt tip nhn C8. Phc h C5-8 khng c kh nng
phn hu mng vi sinh vt m cn phi lin kt vi C9. C9 l
protein b th s lin kt vi phc C5-C8 v t n s polyme ho
hnh thnh mt dng cc l cm su vo mng, c kch thc
vi ng knh 100, to cc knh cho nc v cc ion t do xm
nhp mng vi sinh vt v ph hu chng. Mi knh xuyn mng
 69

c th bao gm t 12-15 phn t C9 v c b sung thm mt phc

h C5bC6,78 c th thy c di knh hin vi in t.

5.4. Hiu
qu
* sinh hc
ca s hot
ho b th

Nhng hiu qu sinh hc ch yu ca s hot ho b th l:

1 G y cm ng phn ng vim bng vic gii phng ra cc ana-
phylatoxin - c t" gy phn v.
2 T o ra hin tng opsonin ho cc vi sinh vt hoc cc t bo
l nh tc dng ca C3b, C3bi v cb cho php c nh cc vt
th l vo cc th th CRl v CR3 ca cc thc bo (t bo a
nhn trung tnh, cc t bo mono v i thc bo). Hin tng
opsonin ho ng vai tr bt buc i vi kh nng thc bo.
3. T o ra s phn hu mng t bo vi khun hoc cc t bo
mu (gi ci) v cc virus c v lipit.
4. T o i u k i n trnh din khng nguyn cho cc lympho B
c thc hin bi cc t bo nang hnh tua c cc th th CRl
CR2 v CR3 mc cc trung tm mm pht sinh v sn
xut cc tn hiu sinh sn (CR2) v cc tn hiu bit ho (CRl)
i vi cc lympho B. S lin kt ca khng nguyn vi C3b
cn cho php s thm nhp v s trnh din khng nguyn cc
t bo lympho T.

5.5. B th v cc c c h trn th ot ca vi sin h vt

Rt nhiu v sinh vt to ra s hot ho b th bng cc con

ng c in hoc con ng bn cnh nhau nh cc proteaz ca
chng hoc nh s hot ho plasmin ca mu.
Tuy nhin, tri vi vai tr ch yu ca b th l thc hin c
ch bo v chng li nhim trng, nhiu loi vi sinh vt to ra
h thng i khng vi tc ng ca b th nhm trn thot h
thng min dch. Cc c ch trn thot vi sinh vt c th nh
sau:
- Hnh thnh lp v bc (capsul) ngn cn kh nng hot ho b
th theo con ng bn cnh (chng hn Streptococcus pneu
moniae, Haemophilus influenzae ...)
70

- Lm c nh phc h tn cng mng MAC cch xa thnh t

bo vi khun, hoc to i khng kh nng ci vo mng ca
phc h MAC.
- Tit ra protein ho tan c nh C3b cch xa vi k h u n .
- Phn hu cc thnh phn protein lin kt vi b mt ngoi
mng t bo, lm cn tr s tip xc vi cc th th CRl, CR2,
DAF thm nhp vo t bo t bo vt ch hoc trn thot
khi tc ng ca b th (chng hn Trypanosoma cruzi, Can
dida albicans hoc cc virus herpes).
 71

Phc h Ag - Ab mannoza ca b mt b mt vi khun

yi khun (LPS, Zimozan .)

iC l
C4
1
LMB - MASP
C4
I
C3
B
C2 C2 D

_________
I-
C3 - CONVBRTASE

C 4a\ C3a, C5a

I
C3b
I
Cc thnh phn b
th khc: C5b, C6,
C7, C8, C9

_ ... ... , _ i
Cht truyn dn Lin kt vi th th b Phc h MAC phn
peptit gy vim, th trn b mt I hc hu cc tc nhn vi
huy ng thc bo bo khun v t bo
ch
i
Opsonin vi khun v
loi b phc h min
dch

Hnh S.4. S tm tt mi quan h v h qu

ca ba con ng hot ho b th
72

5.6. Cc h th n g khc ca h u yt tng tham gia vo

cc c c h bo v v c ch vim

B th l mt trong bn h thng cc protein ca huyt tng

kim sot hin tng bo v v c ch vim. Ba h thng khc l
h thng tip xc, h thng ng mu v h thng tiu si huyt
(fibrinolysis system).
H thng tip xc bao gm cc yu t Hageman HF (tc yu t
XII), prekalikrein, yu t XI v cc kininogen c phn t lng
thp (LMwK) v cc kininogen c phn t lng cao (HMwK). H
thng ny c hot ho bng cc cht v c nh silic, amian, cc
tinh th pirophotphat canxi v.v hoc bng cc hp cht hu c
nh endotoxin vi khun, polixacarit sunfat, heparin, gly-
cozamino glycan v.v... v cc cht c b mt in tch m. S kt
t (aggregation) ca cc thnh phn ny ni chung din ra mt
v tr bn ngoi mch mu ko theo vic hot ho cc chui phn
ng enzim phn gii protein, gii phng kalikrein, mt proteaza.
S phn gii protein bng cc proteaza trong h thng tip xc
ca qu trnh ng mu a n gii phng nhiu mnh peptit
hot ng nh yu t Xlla, xa, aHFa, pHFa tham gia tip tc
tng tc vi yu t IX v b th (gii phng C5a). S hot ho
h thng tip xc c th xy ra hoc c khuch i nh cc t
bo a nhn trung tnh v lm tng hp prostaglandin (mt dn
xut c hot tnh dc l ca axit arachidonic) v hot ho cola-
genaza lm tng tnh thm cc mao mch v gim huyt p ng
mch. H thng ny c s dng trong qu trnh sc nhim
khun cc phn ng phn v v r t nhiu phn ng vim. iu
ho s hot ng ca h thng tip xc c thc hin nh Cl-
INH (i vi HFa, xa, kalikrein). Phc h antitrom bin III,
heparin, a l -antitripsin (i vi kalikrein, xa) v cx2 anti plas-
min.

5.7. Cc bnh l pht sinh do thiu ht b th bm sinh

Nhng s thiu ht ng hp t ca Clq, C4 (kiu ng hp

C4A, QO, BQO) v c bit l C2 (vi tn s 1/100.000) thng
ko theo cc bnh lupus ban h thng. S thiu ht di truyn
mt phn C4 (C4A v/hoc C4B) thng gp cc bnh nhn
 73

mc bnh t mien (lupus han , hi chng Gougerot Sjogren,

bnh tiu ng type I, (tiu ng ph thuc insulin), bnh
vim gan t min.
S thiu ht C3, B, D v propecdin ko theo s nhim khun
ti pht. S thiu ht C5, C6, C7 hoc C8 lun km theo nhim
khun gram m Neisseria sp. Bnh ph n do lon thn kinh
chc nng mch (angioneurotic oedem) l do gim s lng Cl-
INH (chim 85% trng hp) hoc do gim chc nng ca Cl-
INH (chim 15%). T l mc bnh trng hp ny l 1/150.000.
Cc bnh nhn c s suy sp t l C4 v C2. C th tim truyn
tm thi Cl-INH tinh ch v mt hot tnh trong trng hp
b chn thng hoc sau gii phu.
S thiu ht cc yu t H v I d gy ra nhim trng ti pht
v i khi gy bnh m ay, bnh thiu mu do tan huyt, bnh
vim thn tiu cu, trng hp ny t l C3 suy gim mnh.
Thiu ht DAF v cc cht c ch khc ca phc h tn cng
mng gy ra bnh hemoglobin niu v m, lm tng kh nng
thiu mu do b th ph hu hng cu.
74

Tm tt chng V

1. B th l mt tng th cc protein c kh nng c hot ho

lin tc nh con ng hot ho bn cnh (theo kh nng min
dch khng c hiu) hoc nh con ng hot ho c in (c
mt cc khng th IgM, IgG,, IgG3 hoc IgG^. Bn cnh
mt con ng hot ho b th nh lectin MB c kh nng lin
kt vi mannoza ca b mt tc nhn gy bnh (vi khun nm
V..V..) t ko theo s hot ho b th to ra hiu qu
opsonin vi khun v loi b Ag- Ab.
2. S hot ho b th c iu ho v kim sot bng mt tng
th cc protein iu ho, ho tan nh Cl-INH, C4bp, yu t' I,
yu t H hoc cc th th mng t bo DAF, MCP, CRl.
3. S hot ho b th gi vai tr quan trng trong qu trnh vim
(to ra cc c t gy phn v anaphylatoxin C3a, C5a) qu
trnh opsonin ho cc vi khun (vai tr ca (C4b, C3b, Cbi,
CRl v CR3) v lm phn hu cc vi sinh vt bng phc h
tn cng mng - MAC).
4. Nhiu vi sinh vt pht trin cc bin php khc nhau to ra s
n trnh hot ng ca b th v ch c th b thc bo khi c
mt nhiu khng th c hiu.
5. S thiu ht bm sinh mt s loi b th hoc cc cht km
hm dn n mt s bnh l, cho thy r vai tr sinh hc
ca mi loi protein b th.
6. Mt s protein khc nm trong ba h thng cn li ca huyt
tng l h tip xc, h ng mu v h tiu si huyt u c
vai tr trong c ch bo v v c ch vim ca c th.
 75

Chng V. Phn ng khng nguyn - khng th

v cc k thut ha sinh min dch

6.1. Phn ng khng nguyn - khng th

6.1.1. Cc c tnh chung ca s lin kt khng nguyn -

khng th

S lin kt khng nguyn-khng th c ba c im l: phn

ng pht nhit, c tnh c hiu v thun nghch.
Phn ng pht nhit: Ngi ta xc nh khi mt v tr ca
khng th (paratop) kt hp vi mt epitop ca khng nguyn
tng ng l s kt hp b sung khng gian ging nh " kha v
cha kha" (hnh 6.1) S lin kt c thit lp v duy tr nh
cc lc hp dn c nng lng nh (vo khong < 10 Kcal/mol) v
khng phi l lin kt cng ha tr. Cc lc lin kt Ag-Ab c
th hin l:
- Lc tnh in gia cc nhm c o o v NH3+ i din nhau ca
axit amin trong cc chui polipeptit.
- Cc lin kt hydro gia cc nguyn t H+v N hoc o
- Cc lin kt k nc gia cc axit amin k nc.
- Lc Van der Waals do s di ng ca cc in t gia hai phn
t. Lc ny tnh n s khc nhau gia cc m my in t
ca hai phn t (hnh 6.2).
S lin kt gia cc khng nguyn-khng th l mt phn ng
pht nhit, gii phng ra nng lng t khong 2 n 40 Kcal/
mol. Ngi ta c th phn bit khng th "lnh" khi n kt hp
vi khng nguyn 37c v ta nhit mnh t 30 n 40
Kcal/mol. Trong khi khng th "nng (chng hn khng th
76

chng li Rhesus, phn ng tt 37(C nhng ta nhit thp (t 2

n 10 Kcal/mol)
- Tnh c hiu ca k h n g th c th hin ch mt v tr
paratop ca khng th ch kt hp vi mt epitop ca khng
nguyn. Do nu ngi ta bit c mt trong hai yu t ca
phn ng khng nguyn-khng th th c th nhn bit c
yu t th hai. Tnh cht ny c th c ng dng rt rng
ri trong nghin cu y hc, min dch v c trong lnh vc sinh
hc rng ln. Tuy nhin tnh c hiu ca lin kt khng
nguyn-khng th (Ag-Ab) ch l tng i m khng tuyt i
- Tnh cht thun nghch ca phn ng k h n g nguyn-khng
th c th hin ch: phc h Ag-Ab c th b phn li do
nhit, do mi trng axit (pH<3), hoc do mi trng c lc ion
cao. Do c th ra chit tch ring khng th in vitro
ngay c khi phc h Ag-Ab c hnh thnh in vio. V d
ngi ta c th ra chit in vitro hng cu ca ngi mc bnh
tan huyt t min nghin cu tnh c hiu ca cc t khng
th (auto-antibodies) chng li hng cu.

/ / \ i V J_ J /' 'v
- \ \ s1./^
i - - i y ('
A i I \ \
i

* 1*4 khng
c n u i V
nng
vV
. V
n Bg uu y n
_
\ T s
---- ----- .. <i> i

H nh 6.1: V tr lin kt ca khng th. Phn t khng nguyn

nm lt trong rnh ca v tr lin kt ca phn t khng th b
sung theo v tr khng gian (theo Roitt, Brosto v Male, 1990)
 77

K hng th

L in k t
r K hng
nguyn
tt-

hydro
I

L c t n h i n Z1 -

Lc V an d e r ? / )
W aa ls s

Lc k nc

HO r a <

Hnh 6.2: Cc lc h t gia cc phn t khng nguyn v khng th

6.1.2 Cc c im v cht lng v s lng ca phn

ng khng nguyn - khng th

6.1.2.1. c im v cht lng

Phn ng khng nguyn-khng th c th hin bng i lc
lin kt gia chng. i lc lin kt ny th hin bng cu trc
khng gian b sung ln nhau gia epitop v paratop. S b sung
cng ph hp th i lc lin kt khng nguyn-khng th cng
cao. S lin kt khng nguyn-khng th l mt phn ng cn
bng, c th biu din nh sau:
Ag + Ab <=>Ag - Ab + nhit lng
[/lg - /16]
Hng s kt hp K=
[AgAb]
K biu hin bng nghch o ca nng 1/mol
S "ph hp" hay "thm kht" (avidity) ca mt khng th i
vi mt khng nguyn c hiu to iu kin nhanh chng xut
hin mt phn ng kt ta, hoc ngng kt. Phn ng ny ph
thuc vo hng s kt hp, ph thuc vo ha tr ca khng th
78

v s lng ca cc epitop, nhit pH v lc ion ca mi trng

phn ng. Cc iu kin trn cn c ch trong thc
nghim.

6.1.2.2. c im v s lng
Vic nh lng mt khng nguyn c th thc hin c nh
cc khng huyt thanh a ha tr (polyvalent antiserum) hoc
khng th n dng, bng cch xy dng mt ng chun theo
nng ca dung dch khng nguyn bit. Tuy nhin, vic
nh lng khng th trong huyt thanh ni chung khng th
chnh xc v:
- Cc khng nguyn u c nhiu epitop khc nhau.
- Cc khng th c hiu vi mt khng nguyn hp thnh mt
h khng ng nht bao gm nhiu phn t c i lc khc
nhau
Ch ring khng th n dng, ng nht v c tnh vt l v
ch lin kt vi mt epitop l c th dng nh lng chnh xc
khng nguyn. Thng thng vic nh lng khng th hoc
khng nguyn ch mang tnh cht bn nh lng. C th l
ngi ta dng mt dung dch pha long lin tip hai ln mt cht
phn ng v gi nguyn nng ca mt cht phn ng b sung.
Kt qu nh lng c biu hin bng nng pha long cao
nht m vn cho phn ng kt ta (hoc ngng kt) dng
tnh.

6.1.3. Phn loi cc phn ng khng nguyn - khng th

Cc phn ng khng nguyn-khng th xy ra in vitro c th

c quan st trong thc nghim. c th l phn ng kt ta
hoc ngng kt ca phc h Ag-Ab, c th l s phn hy ca vt
mang khng nguyn (chng hn s tan huyt khi khng nguyn
mang hng cu tng tc vi khng th). Mt s phn ng Ag-Ab
c th khng quan st c in vitro. Khi ngi ta s dng cc
khng th nh du. T c th phn bit c cc kiu phn
ng Ag-Ab.
- Kiu phn ng min dch hunh quang (Immuno fluorescence)
khi khng th c nh du bng mt cht mu hunh
quang.
 79

- Kiu phn ng min dch phng x (radio immunological reac

tion) khi khng th c nh du bng mt dng v phng x.
- Kiu phn ng min dch enzim ELISA (Enzyme Linked Im-
numo Sorbent Assay) khi mt khng th c lin kt VI mt
enzim trong xt nghim.

6.2. Cc k th u t m in dch

Cc k thut c s dng trong nghin cu min dch cn c

vo tnh cht ca phn ng khng nguyn-khng th dng kt
ta hay ngng kt, hoc kh nng phn ng khng nguyn-
khng th lin kt vi b th, phn ng khng nguyn - khng
th c nh du hay lin kt vi mt enzim nht nh. Trn c s
, c hng lot cc phng php xt nghim min dch c
ng dng.

6.2.1.K th u t kt ta trong mi trng lng

6.2.1.1. Xt nghim kt ta vng

y l k thut n gin nht khi ngi ta s dng mt ng
nghim nh cha mt dung dch khng nguyn y ng
nghim. Tip theo cho t t mt dung dch huyt thanh min
dch v quan st vng kt ta gia hai lp tip xc ca phc h
Ag-Ab. K th u t ny vn dc s dng kim tra nhanh chng
s p ng min dch ca mt ng vt ang trong qu trnh gy
min dch hoc xc nh nhm Lancefield ca cc streptococ
cus. l xt nghim kt ta Lancefield.

.2.U. Xc n h c ca cc kt ta phc h Ag-Ab.

K thut ny thc hin rt d dng nhng cn mt my phc
tp c ngun nh sng bc x mnh v n sc c truyn qua
mt ng nghim cha mt khng nguyn v mt huyt thanh
min dch tng ng. Tia sng b nhiu x cng ln th mt
kt ta cng cao. Ngi ta nh lng trong vng d tha khng
th nh mt huyt thanh cho ng cong. Ngi ta c mt
80

quang hc (OD) theo ng cong chun suy ra kt qu nh

lng.
K thut ny c nhiu ng dng, c bit l nh lng cc
khng nguyn khc nhau c nng khc nhau trong cc dch
sinh hc (tnh ra mg/mol).

6.2.2. Xt nghim khuch tn min dch theo Ouchterlony

Phng php ny cho php nh tnh cc phn ng khng

nguyn-khng th trong mi trng thch agaroz. Mc ch ca
phng php l so snh v nhn bit hai khng nguyn hoc
pht hin s c mt ca nhiu khng th trong huyt thanh. C
mt s c im kt ta khc nhau cho php quan st c cc
dng cung kt ta ca phc h Ag-Ab trong mi trng thch
rn:
- Phn ng ging nhau: nu hai khng nguyn ging nhau hoc c
cc epitop tng t, cung kt ta vi khng th c c tnh lin
tc.
- Phn ng khng ging nhau: nu hai khng nguyn khc nhau th
chng s kt hp vi hai khng th to ra cc cung kt ta bt
cho nhau.
- Phn ng ging nhau mt phn: nu hai khng th c mt epitop
chung v mt epitop ring cho mi loi th s thy mt cung kt
ta b sung to ra nhnh cho khng nguyn th hai.

6.2.3. in di min dch khuch tn (Immunodiffusion

electrophoresis)
Khi dung dch phn tch cha mt hn hp nhiu khng
nguyn, s khuch tn kp khng nhn bit cc vt kt
ta, ngi ta phi s dng k thut in di kt hp vi khuch
tn min dch. C nhiu kiu in di khuch tn min dch nh:
phng php ca Grabar-Williams, phng php in di men
dch Rocket ca Laurell, in di pht hin min dch in situ.
 81

6.2.4. Cc p h n g p h p ng ng k t m in d ch (Im m uno -

a g g lu tin a tio n )

S ngng kt cng l do hnh thnh mt mng li gia cc

khng nguyn v cc khng th, cho php kt hp mt s
lng cc ht c hnh th to ra th ngng kt c th quan st
c bng mt thng. Mng li ngng kt ch c th hnh
thnh i vi cc khng th t nht c hai ha tr tr ln. Cc
khng nguyn c hnh th hu nh lun lun l a ha tr.
Phn ng nging kt nhy hn so vi kt ta, ngha l c th
pht hin mt s lng rt nh khng th. Phn ng ngng kt
min dch cng cho php bn nh lng v cho kt qu tt,
ngi ta nn pha long huyt thanh trnh cc kt qu m
tnh gi do qu d tha khng th.
Ngi ta phn bit s ngng kt ch ng hoc ngng kt
trc tip trong chnh cc phn t to hnh th mamg cc
quyt dnh khng nguyn c hiu (v d hng cu, bch cu,
tiu cu, tinh trng, vi khun, trng bch cu (toxoplasme). Tri
li, s ngng kt th ng hoc ngng kt gin tip, trong
phn t to hnh ch l gi th cho mt quyt nh khng nguyn
c c nh nhn to trn b mt ca n. Ngi ta thng s
dng cc ht bi bng nha polystyren hoc cc vi tinh th coles-
terol. Kiu lin kt vi mt phn t thay i ty theo bn cht
ca mt khng nguyn c nh ln chng. Cc nhn t gn nh
benzidin, axit tannic, glutaraldehyt lun lun c s dng
trong phn ng ngng kt. Mt s v d p dng k thut ngng
kt min dch l:
- Xc nh nhm mu ABO ca hng cu trn lam knh.
- Nghin cu cc cht gy ngng kt lnh 4c.
- Chn on bnh do Salmonella (Salmonellose) bng phn ng
ngng kt VVidal.

6.2.5 Cc phng php m in dch s dng b th

K thut min dch c s tham gia ca b th c th c thc

hin khi phn ng hot ha ban u c c nh vi mt phn
on b th C lq trn mnh Fc ca mt phn t IgM hoc mt
IgGj (IgG2 hoc IgG3) kt hp vi mt khng nguyn. S hot
ha phn ng c b th s dn ti s phn hy cc phn t mang
khng nguyn t bo.
82

6.2.5.1. K th u t p h n hy t bo bn g b th
K thut ny c thc hin i vi t bo hng cu, s dng
nhiu nh lng b th. y hng cu cu c s dng
kt hp vi cc khng th c hiu trong cc iu kin khng
ngng kt s c trn ln vi mi trng sinh phm xt
nghim. Cng tan hng cu (hemolysis) c nh gi sau
khi 30 pht 37c v li tm. Tip theo o m t quang hc
ca hemoglobin c gii phng ra. Ngi ta nh lng b th c
m t trong mi trng theo n v CH-50. CH-50 l k hiu hot
ng phn hy hng cu cu c lm nhy cm bng mt
loi khng th c hiu. Mt n v CH-50 l s" lng b th cn
thit lm phn hy mt na s lng hng cu huyn ph.

6.2.5.2. K th u t c nh b th
K thut ny ch cho php pht hin cc khng th c kh
nng hot ha b th. B th ca huyt thanh xt nghim cn
c lm bt hot t trc nhit 56c trong 30 pht. Phn
ng tip theo c thc hin theo hai giai on:
- Giai on th nht: huyt thanh xt nghim loi b b
th v cho thm 3 n v CH50 ca b th chut Cobaye
chun t trc. Nu huyt thanh cha cc khng th th s
kt hp vi mt khng nguyn v c' nh b th trong thi
gian (1 gi 37c hoc 18 gi 4c v tip theo 1 gi 37C).
- Giai on hai: thm h thng hin hnh c cu thnh t
hng cu cu kt hp vi cc Ig c hiu trong cc iu kin
khng ngng kt.
B th c c nh giai on u, ngi ta khng thy
hin tng phn hy hng cu. Tri li, nu huyt thanh xt
nghim khng cha khng th c hiu th b th cn li sn c
kh nng lm phn hy hng cu giai on hai ca phn ng.
Phn ng ny cn hai xt nghim kim tra: mt xt nghim
khng c khng nguyn v mt xt nghim khng c khng th,
ngha l cc kim tra cho phn ng khng th gii thch c khi
khng nguyn hoc huyt thanh ch c' nh ring b th.
 83

6.2.6. Cc k thu t m in dch s dng thuc th nh du

Cc cht nh du thng c s dng nht l: thuc th

hunh quang (fluoro chromes) nh fluorescein, rodamin, tng
ng cho mu vng chanh hoc mu cam di nh sng cc
tm hoc xanh tm. Cc cht nh du c th l dng v phng x
nh l25I, hoc 3H pht ra tng ng cc bc x gamma v beta.
Cc enzim nh photphataz kim hoc peroxidaz, c th lm bin
di mu c cht do chng phn hy, cng c dng rt ph bin
trong xt nghim min dch lin kt enzim, v d k thut xt
nghim min dch lin kt enzim ELISA (Enzyme Linked Immu
nosorbent Assay) c s dng rt ph bin hin nay, cho mc
chnh xc cao.

6.2.6.1. K th u t m in dch h u n h q u a n g
Cc thuc th hunh quang nh izotioxianat ca fluorescein
(Isothiocyanate flurescein) cho mu hunh quang vng chanh
hoc lisamin rodamin cho mu hunh quang cam c gn
c n g hp vi m t k h n g n gu yn , VI m t k h n g th hoc th ng
hay gn vi antiglobulin bng cc lin kt cng ha tr. C cc
dng xt nghim hunh quang trc tip v gin tip, dng b th
khuch i
- Trong xt nghim min dch hunh quang trc tip, ngi ta
dng mt khng th nh du trn mt lt ct m t bo hoc
trn mt lp t bo di trn lam knh. Sau khi ra ch bn, lt
ct c kim tra di knh hin vi c trang b hunh quang v
phn ng khng nguyn- khng th s c nh khu bng
vng hunh quang.
- Trong xt nghim hunh quang gin tip, ngi ta trc tin
huyt thanh xt nghim (cha khng th) vi mt lt ct t bo
cho khng nguyn t bo kt hp vi khng th c hiu ca
huyt thanh. Sau khi ra nhiu ln, ngi ta thm mt an-
tiglobulin c nh du hunh quang v tip tc ln th hai.
Ra tiu bn v c kt qu di knh hin vi hunh quang.
- Trong k thut xt nghim hunh quang gin tip c s dng
b th khuych i, ngi ta cn dng mt antiglobulin c
nh b th v thc hin phn ng theo ba giai on:
Giai on 1: m hoc t bo vi mt huyt thanh xt
nghim, sau ra loi b huyt thanh tha.
84

Giai on 2: tip vi mt antiglobulin v thm b th ti

c nh, sau ra tip.
Giai on 3: tip phc h phn ng vi khng th nh du
chng li b th C3 (Mt phn t khng th to ra s kt hp
trn t bo rt nhiu phn t C3b) Sau ra phc h phn
ng v c kt qu.

6.2.7. K thut m in dch phng x

K thut ny ngy nay thng c thc hin trong pha rn:

mt trong cc thuc th c c nh ln mt gi th chng hn
nh y ging ca mt tm nha polystyren (microtiter) tm
xenluloza hoc cc vin bi bng nha. Nguyn tc nh lng
min dch phng x l theo kiu cnh tranh. Phn ng khng
nguyn-khng th l phn ng cn bng thun nghch. Mt
khng nguyn nh du kt hp vi mt khng th c hiu c
th c i ch bng s d tha ca cc khng nguyn t do. S
lng khng nguyn nh du nm trn khng th sau khi thm
khng nguyn t do t l nghch vi nng khng nguyn t do
dng nh lng. nh lng mt khng nguyn trong mi
trng sinh vt, ngi ta khng th tng ng trong cc ging
ca tm nha "microtiter". Khng th c hp th ln y
ging ca tm nha. Sau khi ra, ngi ta ph thm cc vng
nha khng ph khng th bng cch vi mt mt dung dch
protein. Sau ra li v thm hn hp khng nguyn cn xt
nghim vi khng nguyn cng loi c nh du I25I nhng
bit trc s lng. 0 y c s cnh tranh gia khng nguyn
cn xt nghim v khng nguyn nh du c kt hp vi
khng th. Sau khi ra ln na, ngi ta o hot ng phng x
cn li trong cc ging bng my m tia gamma. Hot ng
phng x cng yu th s lng khng nguyn cn xt nghim
cng c c nh ln khng th nhiu hn. Cn phi lm xt
nghim kim tra vi ging "trng" khng cha khng th y v
vi cc ging khng c mi trng xt nghim.
Nng khng th c suy on khi so snh vi ng th
chun xy dng vi dung dch khng nguyn c nng bit.
nhy ca xt nghim mc vi chc nanogram.
Trong mt s k thut xt nghim phng x, ngi ta c th s
dng khng th c hiu nh du phng x l25I. Ngi ta c th
s dng k thut xt nghim min dch phng x cnh tranh d
nh lng cc cht c S ( ) lng rt t trong cc dch sinh vt nh:
hocmon, (polipeptit, steroit) prostaglandin, cc du hiu ung th,
vitamin, IgK tng s.

6.2.8. K th u t m in dch lin k t enzim (ELISA)

Xt nghim min dch lin kt enzim (Enzyme Linked Immu

nosorbent Assay) hin nav c s dng rt ph bin trong cc
nghin cu chn on cc bnh ca ngi, ng vt v thc vt.
Nguyn tc ca phng php v c bn khng khc vi phng
php xt nghim min dch phng x. Trong phu'ing php ny
khng th thng lin kt vi mt enzim nht nh, thng l
photphataz k.m hoc peroxidaz.
- Nu xt nghim nh lng mt khng nguyn th khng th
c hiu vi n khng nh du s dvtc gn vi gi th rn
(thng l cc ging ca tm microtiter c 96 ging bng nha
polystyren). Khng th c hiu ny c to ra chng li
phn t khng nguyn cn nghin cu. Bc th hai l thm
dung dch nghin cu cha khng nguyn lin kt vi
khng th c hiu. Bc th ba l cho thm khng th c
hiu vi khng nguyn nghin cu nhng c gn cr.g
hp vi mt enzim (photphataza kim hoc peroxidaza). Tip
theo, o hot enzim bit kh nng phn hy mt c cht
t khng c mu bin thnh sn phm c mu v c o
bc sng hp th thch hp. V d c cht ca enzim phot-
phataza kim khng c mu l paranitrophenylphotphat sau
phn ng enzim s bin i thnh paranitrophenol c mu
vng chanh, c pht hin bc sng 405nm.
- Nu xt nghim nh lng mt khng th th khng nguyn
c hiu c gn trc tin vo y ging microtiter. Tip
theo cho khng th cn nghin cu vo to phc lin kt
Ag-Ab. Sau cho thm antiglobulin chng khng th (chng
li khng th nghin cu) dc gn cng hp vi mt enzim v
qui trnh xt nghim ging trng hp trn.
86

Tm tt chng VI

1. Phn ng lin kt gia khng nguyn v khng th l s kt

hp c tnh cht b sung gia cu trc khng gian ca mt epi-
top trn phn t khng nguyn v vng tip xc tng ng
paratop ca phn t khng th. S lin kt ny mang tnh
cht khng gian bng cc lc lin kt khng cng ha tr.
2. S lin kt gia khng nguyn - khng th c 3 c im l
phn ng pht nhit, c tnh c hiu cao v thun nghch.
Tnh c hiu ca khng th l tng i v khng tuyt i.
Do c th c nhng phn ng cho nhiu hoc t vi cc
khng nguyn c cu trc tng ng vi mc "ph hp"
khc nhau.
3. Cc k thut xt nghim v nh lng trong ha sinh min
dch l da vo nguyn tc tng tc c hiu gia khng
nguyn v khng th. C nhiu dng khc nhau nh: khuych
tn, ngng kt min dch kt hp in di min dch, xt
nghim min dch lin kt enzim v min dch phng x.
 87

Chng VII. Cc c quan v t bo ca h min

dch, bit ha v chc nng

H min dch c pht trin cao ng vt c v v chim,

chim 1/60 trng lng c th ca ngi. Cc c quan ca h
min dch c th c phn chia nh sau:

7.1. C quan ngun

C quan ngun bao gm chung cho h thng to mu. Cc t

bo ngun ca ty xng c th sinh ra hng lot dng t bo
khc nhau nh dng hng cu, dng megacarioxit, dng bch cu
ht, dng mono v i thc bo, dng t bo lympho. Ngay trong
tun th 10 ca i sng phi thai trong d con, ngi ta
nhn thy cc t bo ngun u tin trong xng cng vi s to
mu ty xng vo tun th 20. ngi, mt phn cc t bo
ngun lympho ri ty xng i theo con ng tun hon mu
n tuyn c "luyn tp" v chn thnh cc lympho T, trong
khi mt phn khc tip tc pht trin ti ch (Xem hnh 1.2,
chng I).

7.2. Cc c quan s cp

C quan s cp cn gi l c quan lympho trung ng. C quan

ny cng xut hin sm trong i sng phi thai trc khi c c
quan th cp. Qu trnh tng sinh cc t bo lympho nhng c
quan s cp c lp vi tt c cc kch thch khng nguyn. Vai
tr ca cc c quan ny l: Cho php cc t bo ngun lympho
giai on u tin c bit ha v sinh sn, c "hc tp"
dung np cc thnh phn cu trc ca bn th n c th, ngha
l hc cch nhn bit "ci bn thn".
88

7.2.1. Tuyn c (Thymus)

y l c quan lympho trung ng quan trng v l c quan

lympho - biu m c cu to t hai thy hp li. Tuyn c nm
vng trung th t trc v pha trn. S bit ha ca cc t bo
lympho din ra phn v v phn ty ca tuyn c khc bit
nhau. Trong vng v, cc t bo lympho c gi l cc t bo
tuyn c v c s lng rt ln v c bao quanh bng cc t
bo biu m (Epithelial cell). Cc lympho phn ty dng c
bo tu (Medullary thymocytes) ca tuyn c b phn tn rt
nhiu so vi phn v. Qun th lympho tuyn c r t nhy cm
vi hocmon corticoit v b ph hy ti 95%. Ch c 5% lympho
bn vi hocmon ny l c th chn sinh l v c chuyn vo
tun hon mu.
Vai tr sinh l ca tuyn c c biu hin kh sm, trong i
sng phi thai ca ng vt. ng vt b ct b tuyn c s
khng c p ng min dch t bo i vi lympho T gy c hoc
lympho tham gia vo qu mn mun. Trong trng hp ny,
ng vt c th dung np mnh ghp ngoi lai khng ph hp t
chc.
Tuyn c c tc dng nh mt c quan cho php bit ha lym-
pho T theo hai cch sau:
- Lm bin i ti ch cc lympho T cha bit ha thnh cc
lympho T c th th TCR i vi khng nguyn.
- To ra cc yu t th dch c th gi l cc yu t "thymosine",
thymopoetin tip tc gy nh hng ln hot ng ca lympho
T trong khu vc ph thuc tuyn c ca cc c quan lympho
ngoi vi v hon thin tin trnh bit ha cc lympho T.

7.2.2. Ti Fabricius v ty xng

Ti Fabricius l mt c quan lympho biu m nm mt sau
ca l huyt ca loi chim cho php s bit ha cc t bo lym-
pho B.
ng vt c v v ngi khng c ti ny. n nay, ngi
ta thy rng s chn ca cc t bo ngun lympho thnh t bo
lympho B c thc hin trong ty xng. Bng chng l cc t
bo pro.B v pre.B bt ngun t t bo ngun CD34* c nhn
ln khi tip xc vi cc t bo vch ngn v mng li ca xng
 89

v tip nhn cc xitokin t nhng t bo ny cho qu trnh bit

ha ca chng. Cng ging nh t bo T tuyn c, cc lympho
B b cht mt phn ln ty xng do qu trnh apoptosis v b
cc i thc bo nut. Qu trnh apoptosis l mt c ch cht
theo chng trnh ca cc t bo.

7.3. Cc c quan lym pho th cp

Cc c quan lympho th cp cn gi l c quan lympho ngoi vi

bao gm cc hch bch huyt, l lch, hch amidan hay hch
hnh nhn, cc tm Peyer (l nhng m lympho ri rc sut
chiu di ca rut, tp trung phn rut tha v phn tn cng
ca rut non.), cc m bch huyt lin kt vi nim mc (tuyn
nhy) ca ng h hp, ng tiu ho v ng tit niu.
c tnh chung ca c quan lympho th cp l pht trin chm
hn so vi c quan s cp. Cc c quan ny tip tc chc nng
nui dng cc lympho T n t tuyn c v lympho B n t ty
xng theo con ng tun hon mu. nhng c quan ny, cc
t bo lympho B v T biu hin c tnh chc nng ca chng
khi tip xc vi mt khng nguyn, mt s vng ca c quan
lympho th cp, ngi ta tm thy mt s" hch bch huyt c t
bo bao quanh hnh thnh cc nang lympho, trong chim u
th l cc nang lympho B.

7.4. N gun gc cc t bo ca h m in dch

Mt phn ln cc t bo ca h min dch u c ngun gc to

mu, ch ring cc t bo lympho T v B c cc th th b mt
(TCR v BCR) chu trch nhim v tnh min dch c hiu hoc
min dch thch ng trong i sng c th. Tuy nhin mt s ln
cc t bo to mu u tham gia trc tip vo vic cm ng, iu
ha v bc l p ng min dch c hiu cng mt lc m bo
tnh min dch khng c hiu. l nhng t bo a nhn nh
bch cu trung tnh, bch cu a axt v bch cu a kim, cc t
bo mast, cc tiu cu, cc t bo dng mono v i thc bo.
Mt s t bo khng to mu cng tham gia vo qu trnh cm
ng hoc biu hin phn ng min dch nh: t bo nang phn
90

nhnh (dendritic follicular cell) ca cc c quan bch cu ngoi

vi, cc t bo ni m. (xem hnh 1.2, chng I)
V ngun gc, t t c cc t bo ca h min dch u xut pht
t t bo ngun bit ha lin tip to ra hai dng t bo ch
yu l:
Dng t bo bch cu sinh ra cc t bo lympho
Dng ty xng dn ti cc thc bo v cc kiu t bo to
mu khc nhau.
n nay ngi ta cho rng ch ring dng t bo NK (t bo
dit t nhin - Natural killer) l trc tip bit ha t t bo
ngun ty xng.
Nh vy cc t bo ngun ty xng c th bit ha sinh ra
hng lot cc t bo to mu khc nhau nh dng nguyn bo
hng cu sau ny to ra hng cu, dng t bo nhn khng l
(megacaryocyte) sau ny sinh ra cc tiu cu i vo mu. Cc
dng mono sau ny c th bit ha thnh cc i thc bo
(macrophage), dng t bo c ht (granulocyte) sau ny bit ha
thnh cc t bo trung tnh (chim 60 - 70% bch cu), t bo a
axt (chim 3% bch cu). Cc t bo a kim chim 1% bch
cu, t bo mast nh khu m. Cui cng dng t bo lympho
sau ny bit ha thnh cc loi qun th lympho B v lympho T.
(xem hnh 1.2).
V chc nng ca mt s' t bo thuc dng ty xng, c th
tm tt nh sau:
Cc t bo trung tnh c kh nng di chuyn p ng tn
hiu ha hng ng. Nh cc th th ca t bo nh CD35,
C D llb, CD 18, th th tip nhn Fc nh CD32 v CD64 nn
chng c th c nh v nut cc vt th hoc cc vi sinh vt
c opsonin ha bi b th v khng th. Chng cng c th gy
tn thng m t bo trong cc phn ng min dch bnh l nh
b th v khng th.
Cc t bo a axt c mu hng hoc khi nhum eosin cn
gi l "bch cu i toan" c chc nng gy c, c sn xut vi
s" lng ln chng li s nhim bnh k sinh trng, tham gia
vo cc phn ng d ng do IgE hoc do tc ng ca c t
ngoi sinh.
Cc t bo a kim (Ba) c nhum mu bng cht mu kim
tnh, giu enzim arylsunfataz, p glucuronidaz, histamin v heparin.
Cc t bo mast (Ma) c hai dng, mt dng nh khu tt c
cc m lin kt, giu histamin v heparin. Dng th hai nh
 91

khu tuyn nhy rut, phi, cha nhiu th th ca IgE

(2,5xlOe/l t bo). C hai d n g t bo Ba v Ma c th th i VI
IgE c th to ra s kt t vi khng nguyn lin kt vi IgE ko
theo vic gii phng cc cht ha gii trung gian nh cht ha
gii lipit, cc xitokin. Do cc t bo a kim v t bo mast c
vai tr quan trng trong c ch bo v chng li k sinh trng v
tham gia vo cc phn ng d ng cng vi khng th IgE.
Cc t bo dng mono v i thc bo (macrophage) bo gm
mono ca mu v i thc bo ca m. H thng t bo ny bao
gm nhiu dng: i thc bo ca phi, i thc bo m lin kt,
cc t bo Kuffer ca gan, i thc bo ca lch v m bch
huyt, i thc bo ca xng (osteoclaster), ca m thn kinh
v.v... Ngoi ra cn mt s dng t bo khng thc bo (nonphago-
cyte) i km theo h thng ny nh khu cc hch bch huyt
v tuyn c (thymus).
Cc mono v i thc bo cha mt s ln cc enzim l dng
peroxidaz v lyzozim tham gia vo cc phn ng vim, to ra
hin tng dung hp t bo gia chng, t ti cc t bo khng
l, nhiu nhn (hin tng syncytium) nh cc t bo Langer-
hans.
S bit ha cc t bo n nhn (mono) mu thnh cc i
thc bo ca m km theo vic tip thu c tnh chc nng nh
gy c cho t bo v chc nng dit vi khun bng cch sn
xut ra cc dn xut hot ha oxy v gc nitrozil (NO).

7.5. Cc t bo thuc dng lympho, bit ha v chc nng.

7.5.1. c im chung ca s bit ha cc t bo lym pho

Cc t bo lympho bao gm hai dng qun th l lympho T v

lympho B, u bt ngun t cc t bo ngun to mu (haemato
poietic stem cells) c mt giai on trung gian ging nhau l t
bo ngun lympho (lymphoide stem cell) nhng cha c xc
nh r. Hai dng lympho ny khc vi cc dng t bo khc
ch c s bit ha theo hai giai on: giai on u c lp vi s
kch thch ca mi trng, giai on tip theo ca s hot ha
chu nh hng ca cc khng nguyn hoc do s tng tc idio-
92

typ. iu cho php to ra s thch ng ca p ng min dch

c hiu i vi cc kch thch ca c th v ca mi trng cha
khng nguyn.
Ngi ta cn phn bit s bit ha din ra c quan trung
ng v c quan ngoi vi. i vi t bo T s bit ha xy ra
tuyn c, i vi t bo B xy ra ty xng. Qu trnh bit ha
ny c tnh cht khng thun nghch, c c trng bi s sp
xp li cc gen biu hin cc th th tip nhn khng nguyn
trn mng t bo ca mi loi qun th: TCR hoc BCR. Giai
on bit ha c quan trung ng l mt qu trnh la chn
dng nh cc phn t ca MHC kt hp vi peptit ca khng
nguyn (i vi lympho T) v nh cc epitop ca khng nguyn
tng tc vi BCR (i vi lympho B). S la chn dng cho php
loi b mt phn ln cc lympho (c bit l lympho T) v loi b
cc lympho B t phn ng. Lympho B "t phn ng" b loi b
bi v trn b mt ca chng c cha th th "cha chn mi" bao
gm chui nng IgM ghp cp vi chui nh gi X (pseudo-X).
Mt khc, mt s lympho B do c s sp xp li cc mnh gen
nn sn xut ra cc t khng th (autoantibody) chng li cc
khng nguyn ca bn thn (autoantigen) th cn phi b loi b.
C ch loi b th hin khi lympho B nhn bit cc t khng
nguyn lin kt vi t bo k bn c t khng th, s truyn
tn hiu cho t bo ny "t st" theo c ch apoptosis (l mt qu
trnh cht ca t bo lp chng trnh).
Giai on ngoi vi ca cc qu trnh bit ha xy ra cc c
quan bch huyt ngoi vi v ph thuc vo cc tn hiu ca cht
hot ha c to ra do s tng tc ca BCR vi cc epitop, v
do s tng tc ca TCR vi cc peptit lin kt vi phn t MHC.
Cc phn t khc ca mng t bo ca h min dch cng gy ra
nhng tn hiu cng phi hp cn thit cho s hot ha.

7.5.2. S bit ha ca lympho T v du hiu khng nguyn

bit h

Lympho T dc bit ha t t bo tin thn ty xng CD34\

CD44+ di chuyn v tuyn c. y chng tr thnh t bo c
lp v l nhng nguyn bo sau phn chia v bc l cc phn
t khng nguyn CD2, CDl, CD5 . Tip theo cc t bo bc l
phn t TCR, phc h CD3. Cc t bo khc bc l thm phn t
 93

CD4 v CD8. Ch CD l vit tt t ch "cm bit ha" (Cluster

of Differentiation) v con s mang theo l th t nh loi quc
t.
Qu trnh chn ca lympho T c th c tm tt theo bng
sau:
Bng 1: Qu trnh chn ca lympho T

Cc yu t Cc dng t bo Vi tr bit
ha
bit ha
T bo ngun min dch M to mu
T bo tin thn T
Cc yu t' bit
ha ca tuyn
^
T bo c v
N
T bo c ty
Tuyn c

c
Lympho T cha chn
Yu t' bit ha Lympho T chn Mu v c quan
tuyn c (C thm quyn min dich) bch huyt

. i
Bit ha tip theo chc nng

Chc nng ghi Chc nng iu ha Chc nng hiu

nh (T b tr : Th v T c ch :Ts) qu
(T ghi nh) (T gy c : Tc
v T hiu qu
qu mn mun)

Qu trnh chn la m tnh v dng tnh i vi qun th

lympho T cng din ra tuyn c v c trnh by tm t t
hnh 7.1
94

T khi thu

i vo tuyn c

Protimoxit
LP V
CD4 CD8-
X
khng cha TCR APOPTOSIS

cha TCR
a ,p
LP TU
CD8*

\
OVIHI '
TOt $ ( p e p tit
% H ,q

t bo
biu m
CD4*

CHN DUNG TNH CHN M TN

i ra vn g ngoi vi, tr
th n h cc t bo lym-
pho chn, k t hp
BN NGOI TUYN c c h iu vi M HC,
khng c c tn h t
p h n ng

Hnh 7.1. S la chn m tnh v dng tnh ca lympho T

tuyn c. lp v cc t bo tuyn c bit ha gm c CD4* v
CD8* (la chn dng tnh), nhng ch tn ti ring cho tng
qun th ph ch bc l mt dng CD4+8 hoc CD4 8+ do tc dng
loi b (la chn theo m tnh) ca cc phn t phc h MHC.
(Theo Miller, 1993).
 95

7.5.3. S b i t ha lym pho B

Lympho B dc bit ha t cc t bo ngun lympho CD34 ca

gan phi thai v t ty xng ca ngi trng thnh. S bit
ha lympho B xy ra lin tc trong i sng c th v khc vi
s bit ha ca lympho T hai c im:
S bit ha lympho T xy ra tuyn c v gim dn n tui
dy th.
S bit ha lympho B ca ng vt c v xy ra ty xng,
ca chim xy ra ti Fabricius. Tin trnh bit ha ca lympho
B c th tm tt nh sau: T t bo ngun ty xng bit ha
thnh lympho B khi thy (pro B) sau thnh tin lympho B
(pre B) v tip theo l bit ha thnh lympho B cha chn c bc
l IgM b mt (mlgM). Giai on tip theo l lympho B chn mi
bc l IgM v IgD b mt (mlgM v mlgD). Nu lympho B
chn khng gp khng nguyn s b phn hy. Lympho B chn
khi gp khng nguyn li tip tc c bit ha thnh nguyn
bo B (B-blaste) v t bo plasma (plasmocyte). Ch c t bo
plasma mi c kh nng tit khng th c hiu vi khng
nguyn l. Mt khc, nguyn bo B c th tr t bo B ghi nh
(memory - B) khi gp li khng nguyn l c th nhanh chng
hnh thnh t bo trong p ng min dch dch th c hiu (s
hnh 7.2).
96

Khng nguyn fPlfi*

f
rz> \m o
t bo plasma

Nguyn bo B V __
6 ghi nh
_______ I^nn^o
khng nguyn_____ J -ngA

Hnh 7.2. S qu trnh bit ha lympho B.

(theo J.P. Revillard, 1994)

7.5.4. S bit ha cc dng t bo khc theo chc nng

min dch

7.5.4.1. Cc t bo dit t nhin (N K Natural Killer)

Cc t bo dit t nhin bao gm mt qun th khc nhau ca
cc t bo bch cu c c tnh gy c. Ngoi chc nng gy c
chng cn bc l th th CD16 c i lc cao vi Fc v th th
CD56. Phn ln cc t bo NK u c hnh thi ca cc lympho
bo ln c ht LGL. Mt s trong chng li c du hiu bit ha
ca dng t bo T nh cc th th CD8, CD2, TCRX.5. Mt dng
 97

th ba ca cc t bo NK khng c du hiu bit ha c trng

cho c dng t bo T v B nn c gi l t bo lympho khng c
c tnh "Null lymphocyte".

7.5.4.2. Cc tiu cu. (Thrombocytes)

Cc tiu cu xut pht t cc t bo nhn khng l tham gia
vo qu trnh cm mu (haemostasis) cng nh cc phn ng
vim v chng nhim trng. Chng cng bc l cc phn t lp I
ca phc h MHC, cc th th ca IgG (CD32) ca IgE (CD23),
cc th th ca yu t' VIII, ca vitronectin (CD51), CD41 v
CD42; ca xitoadezin cho php lin kt i vi cc fibrinogen, fi-
bronetin v vitronectin trong chc nng ng mu v cm mu.
98

^ VHch vm
hng (V.A)
Hch amian

Tuyn c
__ Lch
Cc tm peyer ca rut non
Rut tha
Mch bch huyt
Tu xng

Hnh dng mt hch bch huyt

Mch bch
huyt ti
Mch ni
m trn
Trung
tm mm

Lp v
V\. \t I

i Lp cn
i vV \
V*SN \ Mch bch
v/ huyt i

Hnh 7.3. V tr h thng m t bo min dch ca c th ngi

7.5.4.3. Cc t bo trnh din kh n g nguyn A P C A ntigen

p resen tin g cell)
T bo trnh din khng nguyn bao gm hai loi :
Trnh din khng nguyn cho lympho B l nhng t bo nang
c dng thy hoc bch tuc (dendritic cell) ca hch bch huyt,
ca lch. Chng s c nh khng nguyn trn mng t bo bng
th th ca b th C3 v trnh din cho cc t bo B. Cc khng
nguyn c th vn c lu gi lu di trong nhiu thng trn b
 99

mt t bo nang c thy. Cc t bo nang c thy khng c

ngun gc to mu.
Trnh din khng nguyn cho lympho T c dm bo bng tt
cc cc t bo mono, i thc bo v cc dn xut ca t bo tua.
Cc khng nguyn dc trnh din di dng cc pept lin kt
vi cc phn t ca MHC lp I s trnh din cho cc t bo lym-
pho TCD8\ lin kt vi cc phn t ca MHC lp II s trnh din
cho cc t bo lympho TCD4*.
t uyn c, cc t bo APC bao gm cc t bo biu m ca lp
v tuyn c, cc t bo tua v cc i thc bo nm gia lp v
v ty ca tuyn c. cc m t bo khc, APC l cc t bo tua
Langerhans ca biu m. Cc t bo ny khc vi cc t bo thc
bo (phagocytes) l khng c th th i vi b th v bc l cc
phn t ca CDl v CD4 hoc c cc th th i vi Fc. Cc t
bo ny bt gi khng nguyn v ch bin thnh cc peptit lin
kt vi cc phn t MHC lp II, sau vn chuyn v pha vng
hch bch huyt. Cc APC cn li l cc t bo khe. Khc vi cc
t bo Langerhans, cc t bo khe rt t tng hp v i mi cc
phn t MHC lp II.
- Cc t bo c thy ca m lin kt cng c chc nng ging cc
t bo ca Langerhans.
- Cc t bo B cng tham gia trnh din khng nguyn cho t
bo T bng cch chng nhn bit khng nguyn nh BCR, sau
to phc h BCR-Ag. Phc h BCR-Ag s c nhp bo v
khng nguyn s c phn hy thnh cc peptit nh en-
dosom. Tip theo cc peptit khng nguyn c lin kt vi cc
phn t MHC lp II gy ra s hot ha lympho T. Bn thn
Lympho T khi c hot ha nh trn s tng hp cc lym-
phokin kim sot s hot ha ca lympho B. l mi quan
h tng h trong p ng min dch qua trung gian t bo v
tp ng min dch dch th.
- Cc t bo mono v i thc bo cng bc l cc phn t MHC
lp II v trnh din khng nguyn cho cc lympho TCD4+.
- Cc t bo ni m (endothelial cell) v biu m (epithelian
Cell) cng c th l cc APC v bc l cc phn t MHC lp II
khi c kch thch bng gamma inteferon (IFN y)
100

7.5.4.4. Cc t bo lympho T g y dc. (Tc)

Cc lympho Tc nhn bit cc t bo ch (c th l nhng t
bo b nhim trng hoc virus, cc t bo ung th...) bng s
tng tc phn t gia TCR vi mt peptit kt hp vi mt
phn t ca MHC. Trong trng hp TCD8* xy ra s tip xc
vi cc phn t MHC lp I v trng hp TCD4+ c s tng
tc vi phn t MHC lp II.
Cc t bo NK v LAK (t bo git c hot ha bng lym-
phokin: lymphokine activated killer cell) cng ging nh i thc
bo khi c hot ha s ph hy cc t bo ung th hoc t bo
gi bin dng. Ngun gc ca s tng tc c hiu ny vn cn
cha c sng t.
 101

Tm tt chng VII

1. Cc c quan ca h min dch bao gm

- C quan ngun sinh ra cc t bo to mu v cc t bo ca h
min dch
- Cc c quan trung ng hay s cp, cc c quan ngoi vi hay
th cp. T cc c quan ny cc t bo ca h min dch c
sinh ra, c luyn tp nhn bit c "ci bn thn v ci
khng phi ca bn thn" c bit ha v thc hin cc chc
nng min dch.
2. Cc t bo tham gia vo phn ng min dch bao gm mt
phn l cc lympho T v lympho B c cc th th b mt nhn
bit khng nguyn ring cho mi qun th, v mt phn khc
l tng th cc t bo ph tr c chc nng cm ng, iu ha
v gy hiu qu min dch c hiu v khng c hiu.
Cc t bo tham gia vo phn ng min dch u bt ngun t
ty xng to mu. S bit ha ca chng c kim sot bng
tng th cc xitokin v cc yu t tng trng ph hp vi s
sinh sn v s chn ca chng.
3. Cc loi t bo a nhn trung tnh v a axit c nhng c
im khc nhau v chc nng phn bit nhau. T bo a nhn
trung tnh c i sng ngn, c chc nng-kim sot s nhim
trng v cc phn ng qu mn vi s tham gia ca b th v
khng th.
4. Trong khi cc t bo a axt r t c, kim sot s nhim k
sinh trng, gy ra tn thng t bo trong cc bnh d ng.
5. Cc t bo a kim v cc t bo mast ca m lin kt v m
nim mc (tuyn nhy) tham ga vo phn ng min dch ph
thuc IgE trong cc bnh d ng v nhim k sinh trng.
6. Cc t bo APC c vai tr rt quan trng trong p ng min
dch c hiu qua trung gian t bo. l cc APC cho lympho
B v cc loi lympho T.
7. Chc nng trnh din khng nguyn c thc hin nh nhiu
kiu t bo, gy ra hin tng thc bo, phn hy t bo v
gy c cho t bo ch.
 103

Chng VIII. S tng tc gia cc t bo min

dch v iu ho p ng min dch

8.1. S tng tc gia cc t bo c thm quyn min dch

Cc t bo lympho bt ngun t cc c quan lympho s cp sau

khi c bit ho v luyn tp min dch u l nhng t bo
chn, c thm quyn min dch ngha l c chc nng min
dch nht nh. C th l chng c kh nng nhn bit mt loi
epitop nh mt th th slg (Ig b mt ca t bo B) hoc nh
TCR ca t bo T c quan lympho th cp. S tip xc vi epi-
top ca cc t bo to ra mt giai on mi cho s chn ca cc
t bo c thm quyn min dch gip cho chng tr thnh nhng
t bo p ng min dch c hiu qu. S chn mi ca cc t bo
cn gip cho s hp tc gia cc loi t bo c thm quyn min
dch i vi nhau v cho php c th thch ng nhanh chng vi
mi trng xung quanh. C cc loi t bo tham gia vo s hp
tc trong p ng min dch t bo l:
1.Cc t bo trnh din khng nguyn (APC) l i thc bo,
thc bo n nhn, t bo dng bch tuc hay cc t bo c tua
(Dendritic Cell) v mt s loi t bo khc nh Langerhans
ca biu m, c cc t bo B. Cc APC c chc nng ch yu l
trnh din cc khng nguyn cho cc lympho T b tr (Th) v
lympho T hiu qu (Tc).
2. Cc t bo lympho b tr T-CD4 ng vai tr cm ng gy ra
p ng min dch.
3. Cc t bo lympho T hiu qu cn gi l Tc (T gy c) c vai
tr loi b cc t bo b nhim virus hoc t bo bin dng ung
th. Tc lun lun biu hin cm bit ha CD8*.
4. Cc t bo c thm quyn min dch nh lympho B (tit ra
khng th) lympho T CD8* (chuyn bin thnh cc t bo gy
hiu qu tit ra lymphokin gy c) v c hai loi t bo u
104

phn chia tng cng khi c p ng min dch. Bn cnh

cn c mt c ch kim sot rt chnh xc gii hn s hp
tc p ng min dch. l s km hm p ng c hiu qu
theo kiu c ch ngc (feedback), nh vai tr ca Ts
(T. suppressors).
Khi c khng nguyn xm nhp, c ch hp tc v iu ho
p ng ng thi xy ra cho php loi b khng nguyn nhng
ng thi cng c qu trnh chp nhn khng nguyn. Tuy
nhin, s loi b khng nguyn xy ra u th i vi cc khng
nguyn l v s p ng min dch b km hm c to ra i
vi cc t khng nguyn (autoantigen). Ngi ta c th phn bit
hai giai on hp tc t bo l:
- Giai on cc i thc bo bt gi khng nguyn v trnh din
peptit khng nguyn cho cc lympho T b tr (Th). l s
hp tc cc i thc bo v lympho T b tr.
- Giai on gii phng cc yu t hot ho (lymphokin ca Th)
v hot ho cc lympho-B tit ra khng th. l s hp
tc gia Th v lympho B.

8.2. S trn h d in k hn g n gu yn

8.2.1. Trnh din khng nguyn ni sinh

Khng nguyn ni sinh khng nguyn ca bn thn v cng

l nhng khng nguyn ca virus nm bn trong t bo cht
(Cytosol) ca t bo b nhim s c ch bin bng vi th pro-
teasome, mt phc h gm 28 tiu n v trong c hai tiu n
v l LMP2 v LMP7 c vai tr tiu ho khng nguyn ni sinh
(LMP2 v LMP7 c m ho trong phc h gen HLAII, xem
hnh 4.2). Pettt khng nguyn c ch bin s c TAP1 v
TAP2 vn chuyn vo khoang li ni cht lin kt vi rnh
ca HLAI mi c tng hp nhng cn nm khoang li ni
cht. Vic lin kt ca peptit khng nguyn vi HLA I c s gip
ca cc phn t bo mu Calnexin, Calreticulin v mt pro
tein tr gip cho TAPI l TAPASIN. Sau ch ring phc h
HLAI-peptit khng nguyn c ng gi bng bc mng v c
vn chuyn ln b mt t bo ch b nhim trnh din cho t
bo T-CD8+. nhng t bo khng b nhim virus ni bo, cc
peptit ca protein bn thn lun lun lp y rnh lin kt ca
 105

MHCI (HLAI) v bc l trn b mt mng. Khi t bo b nhim

virus ni sinh, lng MHCI lun c tng hp d tha sn c
khoang li ni cht sn sng lm nhim v trnh din khng
nguyn nhim ni sinh.
8.2.2. Trnh din khng nguyn ngoi sinh

Khng nguyn ngoi sinh l khng nguyn b bt gi bi cc

i thc bo v cc t bo B.
S hp tc cc lympho T vi cc i thc bo, t bo mono cn
cc qu trnh sau:
- Bt gi khng nguyn ch bin thnh peptit phn t nh v
trnh din peptit khng nguyn cho cc lympho T b tr c
hiu mc cc phn t MHC lp II.
- Nhn bit gia cc t bo nh phn t MHC lp II ca i thc
bo v lympho T.
- Hot ho lympho T nh cc cht truyn dn sinh hc ho tan
nh IL1 v IL6 do i thc bo hot ho tng hp ra.
C ch phn t v t bo ca s trnh din KN c th hin
hai dng sau vi hai dng lympho T: TCD4 v TCD8.
Cc khng nguyn ny c nut (endocytosis) v c bc
trong bc mng (vesicle), sau dung hp vi lysosome v b tiu
ha, ch bin thnh cc mnh peptit khng nguyn trong mi
trng axit ca bc mng. Trong lc , cc phn t MHC lp II
(HLA-II) cng c tng hp trong khoang li ni cht nhng
lun lun c lin kt vi mt protein bo mu (chaperon) c
tn gi l chui li. (Invariant chain). V vy MHCn khng th
kt hp c vi bt k protein mi c tng hp li ni cht.
Chc nng th hai ca chui li l hng dn cho MHCI lin kt
vi bc mng c pH axit cha peptit KN cn trnh din. Phc h
MHCII-Ii, sau s c tip cn vi mt s protease a axit v
c bit di tc ng ca HLA-DM lm phn hy, tch ri chui
li ra khi MHCn lin kt vi peptit KN. Phc h MHCII-
peptit KN s c bc l trn b mt mng t bo APC trnh
din cho t bo TCD4* (hnh 8.2).
Cc i thc bo cng c th bt gi nhiu khng nguyn nhd
cu trc kt dnh khng c hiu (v cng c th nh cc khng
th c i lc cao vi t bo). Khng nguyn b bt gi s c
ch bin nh qu trnh phn gii protein ni sinh thnh cc
mnh peptit khng nguyn nh v cc peptit khng nguyn nh
106

s lin kt vi cc phn t HLA lp II- v c c nh trn b

mt t bo APC. Epitop ca khng nguyn s c nhn bit c
hiu bi mt TCR ca lympho T b tr. Mng t bo cha CD c
c tnh nhn bit cc phn t HLA II (DR, DQ, DP). S lin kt
gia hai loi t bo (Th-i thc bo APC) cn c tng cng
bng lin kt ca cc phn t khng c hiu nh CD2-LFA3,
LFA,-ICAM. (ICAM: Intercellular Adhesion Molecule v LFA:
Leukocyte Function Antigen c gi l cc integrin thuc h cc
glycoprotein heterodime ca mng t bo c chc nng lm kt
dnh gia cc t bo vi nhau v gia cc t bo vi cht nn
ngoi bo). Hnh 8.1. trnh by s s trnh din khng nguyn
v vai tr ca cc cm bit ho CD4.
C ch phn t v t bo ca s trnh din khng nguyn th
hin cc c im sau:
- S tip xc gia i thc bo v Th c th quan st c cc
hch lympho khi c s xm nhp ca mt khng nguyn mc
hnh thnh cc m i thc bo hot ho bao quanh cc
lympho T.
- S hp tc i thc bo-Th cng cn mt tn hiu ho hc di
dng cc cht truyn dn sinh hc nh: IL v IL6. Ngoi ra,
cc protein ny cn c nhiu cht khc nh hot ho ACTH
(Adrenocorticotrophic hormone, mt hocmon kch thch tuyn
thng thn), yu t gii phng tuyn di i, lm tng glu-
COZ ca mu. mc lympho T, ILl gy cm ng tng hp
ILj (l mt yu t cn thit cho s tng sinh ca cc lympho T)
cng nh to cm ng bc cc th th ca Th vi ILj. ILX
cng gip cho 8 chn mi cc lympho B.
Cc t bo khc cng c vai tr APC l cc t bo tua bc l cc
khng nguyn HLA lp n v khng nguyn CD6. Ngy nay,
ngi ta cho rng cc t bo tua c vai tr rt quan trng trong
cm ng v duy tri p ng min dch.
Tm li, chc nng ca cc i thc bo l trnh din khng
nguyn, nhn bit lympho T, tng hp IL v trong cc trng
hp bnh l c th m bo vai tr ca cc t bo ho sng
(keratinocytea), t bo hnh sao (astrocytes), t bo gian mch
(mesangial cells). iu ng ch l 8 trnh din KN c tnh
chn lc c hiu i vi hai loi t bo TCD4* v TCD8* (hnh
8.3).
 107

___ Pept.it
/ k h n g n g u y n
M n g sinh
cht Io
>1

B m y (olg

Calnexin* Calreticulin
Peptit

(LMP2-7)
Proteasome

Hnh 8.1. S trnh din khng nguyn ni sinh

(Theo Peakman v Vergani, 1997)
108

' M H C -II

Hnh 8.2. S trnh din khng nguyn ngoi sinh

(Theo Peakman v Vergani, 1997)
 109

(B)
T bo tr n h din T bo ch
(A)
A psn!t< c0

c
P h n t
M H C l p II
cD
V~ P h n t M HC
lpl
^ 5 (\
P e p tit M( \ \
k h n g n gu y n CD4

T h th t bo T CD8

y r ir * U ru s vTC K in k ifM s

T bo Tyrozinkinaz Tyrozinkinaz T bo
T CD4 T CD8+

Hnh 8.3. Vai tr ca cc cm bit ho CD4 v CD8

trong trnh din khng nguyn
(Theo Peakman v Vergani, 1997)

8.3. Hp tc lym pho Th - lym pho B

c im chung ca s hp tc lympho Th-lympho B l lm
cho lympho B bin dng v c hot ho tng hp cc khng
th IgM hoc lympho B c th tr thnh cc t bo mang IgG,
IgA hoc IgE ca mng v bit ho tip tc thnh cc t bo
plasma sn xut cc Ig khc nhau, ng thi bin thnh cc
lympho B ghi nh min dch.
Giai on hp tc Th-B xy ra theo hai c ch c quan h cht
ch vi nhau. l hin tng c hiu khng nguyn v hin
tng khng c hiu khng nguyn. C hai hin tng ny vn
110

cn ang c bn lun v s tn ti v bn cht ca n. Trong

c ch ny, ngi ta cho rng s c mt ca i thc bo s lm
d dng cho s hp tc gia lympho Th v lympho B. i thc
bo c th trnh din khng nguyn cho cc lympho T v cho n
mt tn hiu hot ho lm nhy cm cc cht truyn dn sinh
hc ca lympho T. S tng tc trc tip gia lympho T v lym-
pho B xy ra ng thi vi vic nhn bit khng nguyn vi s
tham gia ca TCR v cc Ig b mt hoc HLA lp II ca lympho
B. Hin tng ny c m t di tn gi l cu khng
nguyn. Lympho B sau khi bt gi khng nguyn nh cc Ig b
mt c th bc l khng nguyn mc mng t bo tng t
nh mt APC. S tng tc Th-B cng c th c tng cng
bng cc phn t kt dnh nh CD4 ca lympho Th v HLA lp
II ca lymphoB. Hin tng tng tc khng c hiu khng
nguyn c s tham gia ca cc intelkin. Cc lympho Th tit ra
mt lot cc intelkin trong vi mi trng cha lympho B hot
ho t c hai hiu qu sau:
- Lm tng sinh t bo B: lymphokin ng vai tr l cc yu t
tng trng t bo B (B cell growth factor: BCGF) v i hi t
bo B phi c cc th th BCGF. S hot ho ny nh IL1 hoc
cht kch thch phn bo (mitogen) IL2, inteferon a, v IL4 l
nhng yu t tng sinh t bo.
- Lm bit ho t bo: lymphokin lm bin i t bo B tit IgM
thnh cc t bo B tit cc Ig khc nh IgG, IgA, IgE. l cc
yu t bit ho t bo B (B cell diferentiation factor BCDF).
Ngy nay ngi ta bit IL2 ng thi ng hai vai tr l
lm tng sinh t bo v gy ra bit ho t bo, IL4 ng vai tr
kch thch vic sn xut IgG, IgE, IL5 lm tit IgA. Inteferon
gy ra bit ho t bo ging tc dng ca IL6. Cc BCGF cng
tham gia kim hm tng hp chui nng ca cc Ig.
S p ng min dch i vi khng nguyn c tnh cht khng
ng nht bi v cc khng nguyn c th nhiu dng khc
nhau nh: protein l dng ho tan, cc khng nguyn l nhng
t bo (l khng nguyn ph thuc tuyn c), cc hp cht
polime nh polixacarit ca vi khun (l khng nguyn khng
ph thuc vo tuyn c) c kh nng kch thch lympho B, khng
cn s c mt ca i thc bo v lympho T. trng hp ny
cc khng th c tit ra ch yu l IgM.
 Ill

S hp tc gia lympho Th v mt lympho T khc cng c th

lm bin i lympho T ny thnh dng c hiu qu, c kh nng
gy ra p ng min dch trc tip i vi mt khng nguyn
dc a lp li vo c th. Cc lympho T c hiu qu ny c th
chuyn bin thnh cc dng lympho Tc, hoc thnh lympho T
tit cc lymphokin.

8.4. S iu ho p ng m in dch

Mt khng nguyn l khi xm nhp vo c th s gy ra p

ng min dch dch th (sn xut ra cc khng th) v p ng
min dch qua trung gian t bo.
T lu, ngi ta bit rt r kho d tr ca h min dch rt
a dng v c th thch ng vi bt k mt khng nguyn no.
Mt con th hoc mt con chut c kh nng tng hp ra cc
khng th khng ch chng li cc virus v/hoc vi khun c mt
trong mt sinh thi m cn chng li tt c cc phn t protein
c cu trc rt khc nhau nh anbumin, insulin ca nhiu ngun
gc khc nhau hoc thm ch mt cht mi c tng hp
phng th nghim khng tn ti trong t nhin.
C ch no c th gii thch cho kh nng sn xu't ra cc loi
protein b sung cho cu trc ca khng nguyn l rt phong ph
? c nhiu gi thuyt gii thch cho c ch iu ho p ng
min dch. Ngi ta cho rng p ng min dch c biu hin
ba dng: iu ho p ng min dch th dch, tc l iu ho
vic sn xut cc khng th ho tan, iu ho p ng min dch
qua trung gian t bo v cui cng l kh nng iu ho nh s
tng tc min dch thn kinh - ni tit vi s tham gia ca
nhiu loi hocmon v cc cht dn truyn xung thn kinh.
112

8.4.1. iu ho p ng min dch bng cc khng th v

mng li idiotip

8.4.1.1. Khng th i lc cao hay khng th bao vy

Cc khng th c sn xut ra t lympho B c th thay i
trong p ng min dch th dch. Tht vy, lc u, khi mt
khng nguyn l xm nhp, ch xut hin mt s t cc lympho B
nhy cm vi khng nguyn . Dn dn s p ng min dch
tng ln do tng sinh mt dng t bo B v lm bin i khng
nguyn l. Sau t lu c s cnh tranh kt hp vi khng
nguyn lm xut hin kh nng chn lc ch mt dng t bo B.
Cc khng th i lc cao ch c sn xut ra t mt dng t bo
B. Khi c khng nguyn l xm nhp tr li th chnh khng th
c i lc cao s kt hp nhanh chng vi khng nguyn v cnh
tranh vi cc th th cng loi ca lympho B. Cc khng th i
lc cao i vi khng nguyn l c gi l cc khng th bao vy
hay khng th phong b Tc dng iu ho p ng min dch
th dch s to ra hin tng khng cn ti kch thch h thng
min dch. Nh kh nng ny trong thc t, ngi ta ng
dng khng th bao vy cha mt 8 bnh nh tan huyt tr
s sinh (liu php huyt thanh anti-Rh(D) -hoc liu php huyt
thanh khng un vn v.v...
mt kha cnh no , cc khng th i lc cao li c tc
dng tiu cc, c th che ph cc t bo bin dng ung th, ngn
cn khng cho cc lympho T gy c cho nhng t bo ny. Bn
cnh , mt s loi khng th i lc cao c th ngn nga kh
nng thi b cc mnh ghp t bo, cng c th c ng dng trong
k thut cy ghp m t bo.

8.4.1.2. Khng th izotip

S iu ho p ng min d'.:h th dch ng ch l iu ho
tit khng th izotip: Trong c th, t l cc lp Ig l mt con s
tng i n nh. Trong trng hp bnh l, nh bnh u tu, ch
mt dng Ig n dng c sn xut ra km theo vic gim tng
hp cc Ig ca cng mt izotip. Mt izotip l s khc bit cu
trc ca cc vng khng bin oi cc chui peptit cu to nn
Ig, m bo cho s a dng h cu trc ca cc lp, cc di lp
v cc kiu Ig. Tt c cc izotip ca cc Ig u c mt mt c
 113

th bnh thng ca cng mt loi. S iu ho izotip c

nghin cu r trong trng hp IgE do cc t bo T c th th Fc
ca IgE chi phi (RFce). Cc lympho Te tng hp cc yu t lin
kt vi IgE (IgE binding Factor: IgEBF) hoc lm tng tng hp
IgE hoc km hm tng hp IgE.

8.4.2. iu ho idiotyp v mng li idiotyp

iu ho khng th theo kiu idiotip v mng li c
hnh thnh t cc thc nghim ca H. Kunkel (1963), J. Oudin
v sau c N.K. Jerne (1974) tp hp li thnh quan nim
chung cho rng mi mt khng th Abl hoc mt th th T c
c trng bng mt paratop (Pj) b sung cho mt epitop (e) v b
sung cho cc epitop nm cc phn bin i ca phn t khng
th v c gi l cc idiotop (ij). Mi idiotop ij tng ng vi mt
paratop (p2 anti i) c mt trn mt khng th Abz (hoc mt th
th T). Bn thn Ab2 li c cc idiotip i2 c nhn bit bi cc
paratop (p3 anti ij) ca khng th Ab3 v.v... chnh l dy mng
li idiotop. S p ng min dch ko theo lm gim khng
nguyn xm nhp v lm tng khng th Abi c nhn bit
bng mt khng th Ab2 (anti idiotip). Dn dn epitop lin kt
vi t bo sn xut Ab s khng cn na (khng nguyn gim)
nhng khng th anti-idiotip li tng (Ab2 tng). Cc t bo sn
xut Ab b c nh bi Ab2 s lm ngng vic sn xut Ab. Do
Ab2 c tc dng iu ho vic sn xut Ab,. Nu tip tc tim
khng nguyn s lm tng tiu th Abj v do ti kch thch
cc t bo sn xut khng th ny s lm ph v trng thi cn
bng, li cun theo vic sn xut Ab) v tip theo l Ab2 v t
ti trng thi cn bng mi.
S tng tc idiotip-paratop hnh thnh nn mt mng li
thng tin phn t v t bo, ng thi to ra kh nng iu ho
gia cc yu t ca h thng min dch vi cc epitop ca cc
khng nguyn ca bn thn v khng nguyn l. L thuyt ny
biu hin r l mt trong nhng pht trin phong ph nht
ca lnh vc min dch hc v y hc.
114

8.5. iu ho p ng min dch nh cc t bo ympho T

Ngi ta phn bit nhiu kiu lympho T km hm hay trn p
tng tc gia chng vi nhau, cc lympho T km hm c hiu
khng nguyn v khng c hiu khng nguyn.

8.5.1. Cc lympho T trn p c hiu khng nguyn

S hot ho cc lympho T c ch c hiu khng nguyn
c nghin cu chut nh sau:
i thc bo cha cc phn t MHC lp II gi l IJ (tn hiu
nhn bit km hm) lm hot ho mt T km hm khc cng
cha IJ. Lympho T km hm TS| ny c gi l lympho T c ch
cm ng (inducer). TS tip tc hot ho TS2 cng mang tn hiu
IJ* v TS2 c gi l TS2 truyn dn (transducer). TS2 tip tc
hot ho TS3 v TS3 c gi l t bo gy hiu qu iu ho T c
ch. S nhn bit gia cc t bo trong qu trnh hot ho ny
ca cc t bo T c ch s c m bo bng tn hiu IJ do MHC
lp II m ho. Trong khi s nhn bit c hiu khng nguyn
s c m bo bng cc th th khng nguyn ca cc t bo T
c ch. C th l TS c mt idiotip, TS2 c mt anti idiotip, TS3
c th c anti-antiidiotip. Do , s iu ho c th c kim
sot bng t bo TS2 c anti-idiotip c kh nng bao vy cc t
bo T b tr v cc t bo T gy hiu qu. Bng s kt hp gia
antiidiotip vi cc idiotip, lympho TS3 s kim sot hot ng ca
cc t bo c cng idiotip vi n c lin quan n p ng min
dch bng mt c ch cnh tranh gia cc t bo c cng mt
khng nguyn hoc bng tc ng ca mt yu t c km hm
c hiu do chng tit ra.
Theo Dorf v Benacerraf, c th cc i thc bo cn thit cho
s hot ho cc lympho T c ch trong khi trnh din khng
nguyn.

8.5.2. Cc lympho T c ch khng c hiu khng nguyn

C nhiu loi lympho T km hm biu hin hot ng khng
c hiu i vi khng nguyn. Cc lympho ny c th c hot
ho bng cc tn hiu khc nhau nh ConA, histamin, cc pros
taglandin D2 (PGEa), v mt s phc h min dch khc. Cc t
bo T-km hm khng c hiu khi c hot ho bng ConA s
tit ra mt yu t ho tan gi l SIRS (Soluble Immune Response
 115

Suppressor). Yu t km hm p ng min dch ny sau khi

c ci bin nh i thc bo s c kh nng hot ho dy
chuyn cc lympho T km hm dng c hiu. Yu t ny cng
ng vai tr quan trng, lm xut hin cc quyt nh khng
nguyn IJ trn mng i thc bo. Cui cng rt c th hot
ng ca cc lympho T c ch c kim sot trc tip bng cc
lympho T-gy hiu qu.

8.6. iu ho p ng min dch bng kim tra di truyn

Cc thc nghim du tin ca Benacerraf v cng s (1974)

chng minh s iu ho p ng min dch c kim tra bng
cc yu t di truyn. Vic s dng cc dng chut cng ngun gc
gen (chut cobaye ng sinh) cho php xc nh chc chn s tn
ti ca mt gen hoc mt nhm gen lin quan vi s p ng
min dch. Cc gen ny c k hiu l Ir (Immune response
gens). Sau ny, ngi ta chng minh cc gen Ir lin quan vi
MHC v s kim tra di truyn i vi p ng min dch ch yu
lin quan vi cc lympho T. Cc protein do Ir m ho ch c
bc l cc t bo ca h min dch nh: cc lympho, cc i thc
bo, cc t bo c tua v.v... l nhng t bo biu hin cc phn
t MHC lp II. Nhiu nghin cu chng minh cc t bo T v
B tng tc ti u vi nhau ch khi chng l nhng t bo biu
hin cc protein lp II ca MHC. Chc nng ca cc protein ny
l gip cho cc t bo T nhn bit khng nguyn.
Ngi ta cng cho rng c mt s gen khc khng lin kt vi
locus ca MHC nhng cng c kh nng iu ho p ng min
dch. Chng hn, thiu cc gen cu trc m ho cho cc th th T
hoc B, c th xy ra hin tng biu hin kiu hnh khng p
ng min dch. Mt s nghin cu khc cng cho php xc nhn
cc gen c lp vi MHC to ra s nhy cm vi mt s bnh
truyn nhim. Tuy nhin c ch tc ng ca nhng gen ny vn
cha c chng minh r rng.
116

8.7. iu ho p ng m in dch nh s tng tc

m in dch-thn kin h ni tit

8.7.1. Vai tr h thng thn kinh

Trong c th, h min dch cng chu nh hng tc ng ca
h thn kinh ni tit (hnh 8.4)
H thn kinh c th thc hin vic kim sot h thng min
dch nh trc thn kinh di i - tuyn yn.

Tn hiu nhn thc

Cht truyn
dn thn kinh, Intelkin, xitokin
cc peptit thn v khng th
kinh v cc
hocmon

Hnh 8.4 S tng qut s tng tc min dch

thn kinh ni tit

Tuyn di i kim tra trc tip vic bi tit cc hocmon tin

yn nh hocmon sinh trng hoc prolactin, hoc c nh hng
n cc tuyn ch th cp nh v thng thn, tuyn gip,
tuyn sinh dc. Nh thu sau ca tuyn yn, cc dy thn kinh
di i gii phng trc tip cc hocmon vazopresin v oxitoxin
i vo dng mu. C th nu mt s v d in hnh v s km
hm cc chc nng min dch thng qua vic s dng cc hocmon
glycocorticoit. Cng tng t, nu mt s cn bng gia estro-
gen-progesteron s c kh nng gy ra cc bnh t min, lm
thay i tnh phn ng min dch trong mt s giai on sng
nh thi k thai nghn v sn ph.
 117

Cc nghin cu gii phu thn kinh cho thy ton b cc c

quan lympho th cp nh tuyn c, lch, hch bch huyt, cc
m peyer u c cc dy thn kinh giao cm v i giao cm
(parasympathic) dn ti hoc tip xc vi cc t bo biu m
tuyn c hoc trc tip tip xc vi cc t bo lympho. Chc
nng chnh xc ca cc h thng mng li thn kinh khng ch
tham gia vo vic kim tra tc dng mu trong cc m t bo,
s lu hnh ca cc lympho, s bi tit cc yu t iu ho min
dch m cn c vai tr i vi s bit ho cc t bo lympho.
Cc th th ca colin v adrenalin (dng P) c xc nh
trn b mt cc t bo tuyn c (thymocytes) v cc lympho T
hot ho. Cc cht hip ng tc dng cht ng vn dc hc
(pharmacological agonistes) kiu p adrenalin, thng qua AMP
vng, c tc dng km hm s sinh sn t bo lympho v s hot
ho chng, c bit km hm s bc l th th i vi IL-2.

8.7.2. Vai tr ca cc cht thn kinh ni tit khuch tn

Vic pht hin cc peptit trong cc nron v cc t bo khc
nhau c chc nng ni tit dn n mt khi nim v cht
ni tit khuch tn. l cc neuropeptit hoc mt s enzim
ca t bo thn kinh nh enolaz, mt s' protein kt hp cc ht
tit nh cromogranin, hp cht tasikinin (tachykinine) cn gi l
cht p ph bin trong h thn kinh trung ng ngoi vi phc h
gangliozit ca mng, mt s hocmon nh oxitoxin, vazoprexin,
nrophixin, P-endophin.
Cc nghin cu mi y cUng minh c tnh kch thch
m in dch ca c h t p i vi s Sinh sn ca cc t bo T, i vi
s thoi bin cc ht (degranulation) trong t bo mast, kch
thch sn xut ILl v yu t' hoi t ung th (TNF) ca cc i
thc bo. Trn mng t bo ca cc t bo T b tr v T gy c,
ngi ta pht hin c cc th th c hiu khng gian i vi
cht p. Vic pht hin ra hm lng cao ca tasikinin ti hot
dch khp c b vim gi vai tr quan trng ca peptit ny trong
bnh thp khp.
Ngi ta cng xc nhn ngui c s tng hp ti ch cc
hocmon oxitoxin v vazoprexin tuyn c khi tm ra ARN thng
tin m ho cho cc hocmon trn c mt dch chit ca tuyn.
Rt c th hai hocmon ny l cc yu t quan trng tham gia vo
giai on hot ho sm ca qu tr \h bit ho cc lympho T.
118

Ngi ta cng pht hin c nhiu th th nhn bit cc

hocmon sinh trng nh IGF, v IGF2 (yu t sinh trng ging
insulin: Insulin like Growth Factor) mng t bo lympho T
hot ho. Hn na cc ARN thng tin m ho cho cc IGF) v
IGF2 cng c pht hin tuyn c phi thai cho thy cc yu
t sinh trng c tng hp ti ch c quan min dch v
chng c vai tr quan trng trong s bit ho v chn t bo T.

8.7.3. Tc ng kim sot ngc ca s tng tc min

dich
ni
tit
Cc ILj c kh nng hot ho trc thn kinh ni tit di i
tuyn yn - tuyn thng thn trong qu trnh tit CRF (corti-
cotrophic releasing factor) tuyn di i v tit ACTH
(Adrenocorticotrophic hormone) tuyn tin yn. ILl cng kch
thch s tit hocmon tirotrophin, hocmon sinh trng v hocmon
LH (hocmon kch thch t bo k pht trin to ra hocmon sinh
dc).
Cc hocmon ACTH, p endophin cng c th c tng hp
trong mt s t bo lympho di dng cc dn xut peptit ca
chng.
Tm li, s iu ho hot ng sng ca c th sinh vt bc
cao ph thuc vo s cn bng v s phi hp cht ch gia hai
h thng thng tin gia cc t bo l h thn kinh ni tit v h
min dch. Trong qu trnh tin ho, mt s cc peptit c hot
tnh sinh hc c la chn l nhng vecto ca s truyn tin
gia cc t bo. Hn na cc peptit tin thn cng c th b ct
ra thnh cc mnh peptit khc nhau v mt s chng c tc dng
sinh hc ngc li. C ch ny cho php tng cng kh nng
thng tin ca mt genom, bi v ch mt gen cng c th tr
thnh mt n v m ho cho nhng tn hiu thng tin khc
nhau.
 119

Tm tt chng VIII

. S tng tc gia cc t bo c thm quyn min dch c

Ihc hin bng cc loi t bo l cc APC, cc t bo lympho T
b tr (T||), cc lympho T gy c (T-CD8+) v cc lympho B.
Mi kiu t bo u c chc nng min dch ring bit v hp
tc vi nhau thng qua cc phn t MHC lp II gia t bo b
tr c hiu v i thc bo.
2. Ngi ta phn bit hai giai on hp tc ca cc t bo c
tham quyn min dch l: giai on hp tc i thc bo v cc
lympho T b tr v giai on hp tc gia lympho T b tr v lym-
pho B.
3. S iu ho p ng min dch c th c thc hin bng cc
khng th theo con ng to ra cc khng th c i lc cao vi
khng nguyn hay khng th bao vy, hnh thnh cc dng
izotip ca khng th v c bit l theo c ch idiotip v mng
li idiotip.
4. iu ho p ng min dch theo con r.g s dng cc t bo
T-c ch c hiu khng nguyn v khng c hiu khng
nguyn cng c thc hin thng qua cc phn t lp II ca
MHC ( ngi l HLA) nh tn hiu IJ c hiu nhn bit km
hm ca lympho T-km hm, hoc bng cc tn hiu ho hc
khng c hiu nh histamin, prostaglandin E2 v.v...
5. iu ho p ng min dch lun lun c kim tra v di
truyn ca cc gen Ir m ho cho cc phn t protein lp II
ca MHC cc lympho T.
6. iu ho p ng min dch ph thuc vo s tng tc gia
hai h thn kinh ni tit (cc hocmon, cc cht dn truyn
thn kinh) ln cc chc nng ca h min dch v tc ng
ngc chiu ca cc cht iu bin min dch nh ILl, xitokin ln
h thng thn kinh ni tit.
Chng IX. Min dch bnh l qu mn

9.1. Khi n im ch u n g v m in dch bnh l

H min dch ca mt c th p ng li vi cng mt khng

nguyn ln tip xc th hai thng mnh hn rt nhiu so vi
tip xc ln u. p ng ny mang tnh c hiu nhng c th
din ra qu mc v a n s tn thng nghim trng cc m
t bo. S p ng min dch qu mc thng c gi l hin
tng qu mn cm (Hypersensibility), hay qu mn, nu nh
khng nguyn l c s' lng qu ln hoc s p ng min dch
t bo v th dch qu mnh. Cooms v Gell phn bit 4 kiu
qu mn, nhng Roitt v cc cng s a thm mt khi nim
qu mn th 5. Nm kiu qu mn l:
- Kiu ly qu mn phn v (Anaphylactic hypersensibility)
- Kiu 2, qu mn gy c t bo (Cytotoxic hyper sensibility)
- Kiu 3, qu mn do cc phc h min dch (Immunocomplex
hy per sensibility).
- Kiu 4, qu mn qua trung gian t bo, hay qu mn mun
(Delayed type hypersensibility)
- Kiu 5, qu mn do kch thch (Stimulating hypersensibility).
Bn cnh hin tng qu mn, min dch bnh l cn cp
ti cc kha cnh min dch ca cc bnh t min, min dch
chng nhim trng vi khun v virus, s thiu ht ca bnh suy
gim min dch mc phi (AIDS) v min dch chng ung th,
tng sinh min dch. Sau y chng ta ln lt xt n cc kha
cnh min dch bnh l ni trn.
122

9.2. Cc hin tng qu mn

9.2.1.Qu mn phn v do IgE

Thut ng phn v (anaphylaxis) ln u tin Richet v Por
tier (190*2) nu ra khi h tim chng cho ch mt loi dch chit
t xc tu ca loi hi qu. Vic tim nhc li ln th hai thng
lm cho ch b cht khi con vt b sc phn v (anaphylactic
shock). Sau ny Von Pirquet (1907) nu ra th ut ng d ng
(Allergy) ch tt c cc hin tng bin i ca vt ch khi
tip xc ln th hai vi cng mt khng nguyn. Thut ng d
ng tr nn ng ngha vi qu mn cm (hypersensibility).
Ty theo cc loi ng vt, sc phn v c th gy ra try tim
mch v cn co tht ph qun, lm ngt th v dn n t vong.
Trong trng hp ny, trnh ci cht t ngt, ngi ta c th
tim vo tnh mch adrenalin (epinephrin) ngn s co c trn
v chng li s gin mch. Hin tng phn v cng biu hin
di da dng ban nga hoc ni my day tc th do s gin
mao mch v tch ly hng cu di da.
C ch ca cc phn ng qu mn IgE l cc khng th tham
gia cc phn ng qu mn ngi ch yu do IgE, c th trong
mt s" trng hp c thm IgG4. Cc IgE s c nh vo cc th
th c i lc cc l RFcel c mt rt nhiu co t bo mast v
a kini v cc th th c i lc yu hn l RFccII (hoc CD23)
ca cc t bo a axt, ca tiu cu v cc i thc bo.
Nng IgE trong huyt tng kh thp (100 -- 200ng/ml hoc
50-100 n v quc t) v c i sng ngn khong 2-3 ngy. Tuv
nhin cc IgE ny c th tn ti lu di nhiu thng khi c c
nh trn cc th th i lc cao ca t bo mast. Cc khng
nguyn gy d ng (gi l allergene) lt qua da hoc tip xc vi
mng nhy c th to cu ni lin kt gia cc IgE d c' nh
sn trn th th mng v lm hot ha t bo mast. Nh vy
nh to thnh cu ni gia cc th th qua trung gian IgE, cc t
bo mast c hot ha v phn hy cc ht trong t bo, gii
phng ra cc cht ha gii trung gian, c bit l histamin. Cc
t bo mast tham gia vo qu trnh qu mn do IgE l nhng t
bo m lin kt v mng nhy. Lympho T cng c tc dng
kim sot ton b phn ng qu mn kiu I (typ Hl) thng qua
 123

cc xitokin gy vim ca chng. Mt khc, lympho T dc

hot ha s sn xut cc yu t gii phng histamin. Cc t bo
a axit cng b hp dn n ni phn ng d ng nh cc yu t
hot ha tiu cu PAF (Platelet Activating Factor), cc xitokin
IL-5, IL-3 c sn xut t cc lympho. Cc t bo trung tnh
cng dc hp dn vo v tr phn ng nh cc intelkin IL8,
LTB4, c bit cc i thc bo cng c kh nng c nh IgE
nh th th RFcell v RFcel ca chng v s tit ra cc cht ha
gii lin kt vi khng nguyn gy d ng.
Cc cht ha gii tham gia vo qu mn phn v quan trng
nht l histamin c nh vo u mt dy thn kinh gy ra s co
c trn ph qun, rut, d con, vch thnh mch mu lm tng
tnh thm mch mu, gy ph n v gy phn ng my ay
trong da, gy tit nc nhy qu mc ph qun.
Seretonin cng c hiu qu hot ha mch mu tng t nh
histamin v c mt tiu cu nhng khng c t bo mast. Vai
tr ca n i vi phn ng qu mn yu hn so vi histamin.
Cc yu t ha hng ng t bo trung tnh cng nh yu t
hoi t ung th a (TNFa) cng c vai tr i vi t bo mast ca
mng nhy. Mt s yu t ha gii c ngun gc mng t bo nh
yu t hot ha tiu cu (PAF - axete), cht chuyn ha ca axit
arachionic c phn chia thnh prostaglandin (PGD, c
trng cho t bo mast). Mt s cht ha gii c tit ra mun
hn l IL-3, IL-4, IL-5 v TNFcx (tumor necrosis factor).

9.2.2. Qu mn c hiu kiu II v III do IgM v IgG

Hai kiu qu mn ny u s dng cc khng th IgM v IgG

gy tn thng cc t bo v cc m t bo khi cc khng th ny
lin kt c hiu khng nguyn, lm hot ha h thng b th v
tng tc vi cc th th ca Fc.
Hin tng qu mn kiu II bao gm phn ng ca cc khng
th chng li mt khng nguyn t nhin hoc mt cht ngoi lai
(exogene) c nh trn b mt mt t bo ch hoc mt m t
bo. Phn ng lin kt khng nguyn-khng th (Ag-Ab) ny li
ko mt phn ln cc t bo mu tham gia vo phn hy t bo
ch v bng c ch hot ha b th v s dng phc h tn cng
mng t bo hoc bng qu trnh opsonin ha to iu kin hp
124

dn cc i thc bo tiu ha t bo ch. l c ch qu mn

gy c t bo.
hin tng qu mn kiu III, s hnh thnh phc h Ag-Ab
c th gy tn thng v tr hnh thnh nn chng hoc phc h
ny tun hon trong mu v bm vo thnh mch mu to ra
nhiu dng bnh l do cc phc h min dch Ag-Ab v ni chung
u gy tn thng m t bo (vim mch v vim tiu cu thn
chng hn). l phn ng Arthus.

9.2.2.1. C c h ca hin tng qu m n kiu II v III

l phc h khng nguyn - khng th (do IgM, IgGl hoc
IgG3) hot ha b th theo con ng c in hnh thnh
phc h tn cng mng. Cc t bo ch tip theo s b ph hy
bng s hoi t v b i thc bo tiu ha. Cc phn ng qu
mn kiu II v III c th xy ra vi mt s lng nh khng th
IgM hnh thnh lin kt vi Clq. T bo hng cu rt nhy
cm vi kiu phn ng ny nhng cc t bo c nhn thch hp
vi c ch c s tham gia ca phc h tn cng mng.
S hot ha b th cng ko theo s opsonin ha cc t bo
ch nh cc thnh phn b th C3b v C3bi. Cc t bo hng
cu v tiu cu b opsonin ha cng b i thc bo vng ty
l lch, gan v phi tiu ha.

9.2.2.2. Cc bnh lin quan dn qu m n kiu II ngi

9.2.2.2.1. Cc phn ng truyn mu ca nhm ABO

Nm 1900, Landsteiner pht hin ra ngi c 4 loi nhm
mu ch yu l A, B, 0, AB. S khc nhau gia cc nhm mu l
do cc khng th c trong huyt thanh v khng nguyn nm
trn mng hng cu ca mi nhm mu qui nh v c th c
trnh by theo bng 9.1. T kh nng cho v nhn ca cc
nhm mu c trnh by s di y (S v di)

 125

Bng 9.1 : Thnh phn khng nguyn v khng th ca

cc nhm mu ABO v nguyn tc cho v nhn mu

Nhm Khng Khng th trong Kh nng Kh nng

mu nguyn huyt thanh cho nhn
mng hng
cu
A A Khng th chng B A, AB A, 0
B B Khng th chng A B, AB B, 0
AB A v B Khng c khng th AB A, B, 0,
AB
0 Khng c Khng th chng A A, B, AB, 0
v B 0

V di truyn hc h thng nhm mu ABO c locus gen nm

nhim sc th s 9 v c lp vi cc locus ca cc h thng khc.
H ABO bao gm ba kiu ln cc alen l A, B v 0. Cc gen A, B
ng tri, cn gen 0 th v nh hnh.
V c tnh min dch v ha sinh ca nhm mu ABO, ngi
ta thy nu ch c hai khng nguyn A v B th kiu hnh ca
hng cu s c 4 loi l A, B, AB v o ty theo c th c hoc
khng c cc khng nguyn A v B. Cc t bo hng cu rt giu
s lng cc v tr khng nguyn A hoc B trn mng (t 300.000
n 1.000.000 v tr trn mt t bo). Cc khng nguyn ny
cng c tm thy mc bch cu, tiu cu v nhiu c quan
nh da, thn, tuyn nc bt, d dy v.v... Do h thng nhm
mu cn c vai tr quan trng trong vic cy ghp cc c quan,
c bit l da v thn. Thc t, h ABO cn phc tp hn bi v
c ti hai dng gen A: gen A, xc nh khng nguyn Aj, gen A2
ch xc nh ring cho khng nguyn A vi mt s lng v tr
khng nguyn A c trn mng kh nh (ch khong 300.000 v
tr cho mt t bo hng cu). Trong khi , gen A) xc nh cho
mt s lng ln cc v tr khng nguyn trn mng ln hn
nhiu (1.000.000/t bo hng cu). H nhm mu ABO cn lin
quan cht vi h thng khc ca hng cu l Rh. Cc gen ca hai
h nm 2 locus khc nhau, trn hai loi nhim sc th khc
nhau. Do trong nhm mu 0 mc d khng c khng nguyn
A v khng nguyn B trn mng hng cu nhng vn c khng
126

nguyn H. C th tm tt s tng hp cc khng nguyn ca

nhm mu ABH nh sau:

1/ Gal NAc (P 1,3) - Gal(P 1,3) - Glu NAc(p 1,3)-Gal

(Hoc p 1,4)
Cht tin thn khng nguyn nhm mu
Gen H (ucosyl transferaza)
Cht tin thn nhm mu + Fucoza--------- Khng nguyn H

2/ Khng nguyn H ------- > Khng nguyn H lin kt vi

+ (al-3) GalNAc (ctl-3) GalNAc
Gen A (N-axetylgalactozamil-transferaza) Khng nguyn A

3/ Khng nguyn H ------- > Khng nguyn H lin kt vi

+(al*3) Gal (al-3) Gal
Gen B (galactozamil transferaza) Khng nguyn B

4/ Trong c th c khng nguyn A v B u c hai enzim ca A v B

cng hot ng.
Khi truyn mu, nu c khng th ngoi lai (alloantibody) c
th gy ra s tan huyt v ngng kt hng cu. Triu chng
bnh th hin l gy st, cao huyt p, au tht lng v kh th,
gy nn ma. S phn hy t bo hng cu (hemolysis) l o qu
trnh opsonin ha hng cu c s tham gia ca b th theo con
ng hot ha c in v c tc ng ca i thc bo vng
lch. Tuy nhin, nh cc quy tc an ton truyn mu, cc ri ro
trn c th khc phc d dng.
9.2.2.2.2. Bnh tan mu do khng ph hp kh ng nguyn Rhesus
Nu ngi cha mang khng nguyn Rhesus (Rh+) trn mng
hng cu, ngi m khng c khng nguyn ny (R h) th a con
ca h c R h \ Khi mu ca thai nhi c dp chuyn sang mu ca
ngi m ln mang thai u tin s gy ra phn ng min dch
to khng th c th m chng li hng cu ca mu thai nhi (Rh\
hoc yu t D). ln mang thai sau, khng th IgG chcmg yu t'
 127

D s xut hin vt qua hng ro nhau thai gy ra s phn hy

hng cu ca thai nhi.
Bin php phng tr bt buc l tim khng th anti-D cho cc
ph n Rh trc khi c thai mang R h\ Khng th ny s
opsomn ha hng cu ca thai tun hon trong mu m v s
gy ra s loi b chng nhanh chng khi mu ca m v khng
gy cm ng tng hp khng th IgG anti-D.

9.2.3. Qu mn trung gian t bo hay qu mn mun

Qu mn mun (kiu 4) c Gell v Coombs phn loi l do

vic sn xut ra lymphokin ca lympho T c hiu vi mt khng
nguyn gy ra s di chuyn, hot ha v tch ly ti ch cc
bch cu dn nhn.
Ngi ta ni min dch qua trung gian t bo hoc qu mn
qua trung gian t bo l ch cc phn ng sau y do cc
khng nguyn khc nhau gy ra c trnh by theo bng sau:

Bng 9.2 : Thnh phn cc khng nguyn

v cc phn ng min dch do chng to ra

Khng nguyn Phn ng min dch

Vi khun, virus Qu mn mun
Nm men, nguyn sinh, ng vt, S chng chu ca t bo do tip
k sinh trng. thu c
Protein (+ t cht dy ) Qu mn mun.
Hapten (+ protein ca bn thn) Qu mn do tip xc, gy vim da.
Khng nguyn cy ghp Thi b manh ghp ngoi lai
Khng nguyn ung th Thai b khi u
Khng nguyn m t bo Gv ra mt s bnh t min

9.2.3.1. D ang qu m n do tip xc

Qu mn tip xc thng dc gi l cc phn ng eczema gy
ra s vim da do tip xc vi cht gy d ng. Phn ng ny cng
c th do hapten nh cc kim loi nng (niken, crom) v rt
128

nhiu cht ha hc t nhin nh nha m cao su, sn t nhin,

nha tng hp, thuc nhum, mt s dc phm, mt s sn
phm ca thc vt nh pentadexylcatechol ca cy o ln
ht, cht c cy sn (Sumac fauxvernis)...
Biu hin ca bnh qu mn l v tr tip xc vi mt hapten
s gy tch ly cc t bo bch cu n nhn bao quanh cc tuyn
m hi, tuyn b nhn, nang lng v sau xm nhp vo biu
b. sau 48- 72 gi. Kim tra t bo hc cho thy r cc t bo n
nhn chim u th l 0D4* v mt phn nh CD8\ cc t bo
Langerhans CD1\ Cc t bo T dc hot, ha ti ch bng cc
khng nguyn do cc t bo Langerhans trnh din s tit ra cc
lymphokin nh ILv, IL|. GM-CSF. c bit l IFNy v IFNa. Hai
xitokin cui cng gy cm ng biu hin cc phn t kt dnh
gia cc t bo v cc phn t HLA-DR ca t bo ha sng
(keratinocyte). Tip theo cc t bo ha sng tit ILl. IL6,
GM-CSF cng hot ha lympho T. Cc t bo biu m (epithelial
cell) cng hot ha v gy di ng cc lympho T theo c ch gn
nh cc t bo ha sng.

9.2.3.2. Qu m n mun kiu tubecculin

Phn ng ny c khi ng bng mt s lng rt nh lyni-
pho T CD4\ T CD8+ c hiu vi mt khng nguyn. Cc lym-
phokin ch yu tham gia vo phn ng qu mn l cc yu t
km hm s di ng ca i thc bo (M1F). TNFa, tip theo
IFNy to nn yu t hot ha i thc bo. Cc xitokin gy ra
ha hng ng IL8. NAP.l tc ng vo co mono v tng s
biu hin ca cc phn t kt dnh ca cc lympho. mono v biu
m.
Dng qu mn ny do s nhim trng vi khun v virus gy
ra (ln u tin c m t cho qu trnh nhim vi khun lao
(Micobacterium tuberculosis) nn c gi l qu mn kiu
tubecculin.
Biu hin cho qu mn l phn ng ban ti ch khi tim
di da cht tubecculin l mt cht gy nga, sn phm t phn
ca vi khun lao sau mt thi gian khong 48 gi. Tip vng
da dy cng ln. Du hiu c trng nht l s tch ly ca cc
lympho v cc mono c ngun gc mu v dc chuyn thnh i
thc bo ca m. Khc vi qu mn do tip xc. dng qu mn
nv xy ra vng su di da. m khng phi lp biu b da.
 129

9.2,3.3. Qu m n u h a t
Qu mn to u ht xy ra do b nhim vi khun. c bit
trong bnh lao, ngi ta pht hin thy cc u ht trong cc vng
phi b tn thng.
Trong bnh phong, ngi ta thy c cc u ht c to ra t
cc t bo biu m, b nhiu t bo lympho xm nhp. Mt s"
bnh nhim k sinh trng sn mng (Schistosoma) cng c dng
qu mn mun to ra cc u ht.

9.2.4. Qu mn do kch thch (Kiu V)

Dng qu mn ny xy ra khi c mt dng khng th, chng

hn mt khng th c sinh ra do t bo tuyn gip b kch
thch cc bnh nhn Basedow. Khng th ny c th gi l t
khng th (autoantibody) tc ng ln th th mng t bo tuyn
gip, kch thch t bo tuyn gip lm thay i cu hnh khng
gian th th ca hocmon TSH (Thyroid stimulating hormone) v
do gy bin i tng hp AMPv. Hon cnh cng tng t xy
ra vi cc lympho B khi c s kch thch ca mt khng th
to ra chng li cc Ig trn b mt t bo B.
130

Tm tt chng IX

1. S p ng min dch qu mn kiu I biu hin dc tnh phn

v ti ch hoc sc phn v ni chung do khng th IgE gy ra.
C ch ca phn ng l hnh thnh cu ni ca cc th th ca
IgE cc t bo mast to ra s bi tit ca cc cht ha gii
min dch cc t bo ngi.
2. Cc dng biu hin chnh ca bnh l sc phn v, vim mi d
ng, kh th d ng, eczema d ng. mn nga ban d tng
m, my day, ph mch v cc d ng tiu ha.
3. S tng hm lng IgE huyt thanh l mt du hiu khng c
nh v khng c hiu cho d ng nhng c th lin quan n
biu hin lm sng ca d ng.
4. Mt s cc yu t di truyn v mi trng (v d s nhim
kh quyn) c th gy ra bnh nhng ngi d cm nhn d
ng.
5. p ng qu mn kiu II v III u do cc khng th IgM v
IgG gy ra theo c ch hot ha b th, gii phng cc peptit
ca b th (C3a, C5a) v c gi l anaphylatoxin, gy phn
hy mng t bo v co c trn. Hng lot t bo tham gia hin
tng qu mn kiu II v III l tiu cu, bch cu a nhn
trung tnh, bch cu a axt, t bo mono v i thc bo.
6. Min dch chng vi sinh vt l mt c ch tng hp qua trung
gian t ba v c ch tc ng phn t ca cc sn phm t
bo.
7. Min dch ung th nghin cu hin tng bt thng trong
sinh sn ca cc dng t bo min dch. Nguyn nhn di
truyn ca bnh l do s t bin ca cc gen gy ra hin
tng ri lon trong iu ho ca chu trnh t bo (ng ch
l gen p53 m ho rho protein p53 v gcn J)21 ras).
8. Mi loi b n h u n g th u do mt k h n g n g u y n c hi u qui
nh. Ngi ta cng pht hin c mt s h cc gen ca
khng nguyn ung th. Vic hiu bit cc khng nguyn ung
 th c th gip cho vic phng nga v chn on ung th c
bit l ung th c ngun gc virus.
9. Tham gia vo min dch chng ung th gm cc kiu t bo
nh NK. LAK, cc i thc bo, cc t bo a axt v.v. ..
10.Hi chng tng sinh min dch l s ri lon v chc nng ca
cc t bo h thng min dch v to ra nhng sn phm c
bit l cc khng th n dng v cc protein c trng. Bnh
tng sinh min dch cng do nguyn nhn cc gen gy ung th
tc ng n chu trnh t bo c bit l s dt bin ca cc
gen v cc nhim sc th.
 133

Chng X. Min dch chng vi sinh v min

dch ung th

10.1. M i n d c h c h n g vi s in h v t

Min dch chng vi khun v chVig nm s dng mt c

ch tng hp qua trung gian t bo v c ch phn t, ngy cng
c pht trin theo s tin ha ca cc loi, ng thi thch
ng i vi h sinh thi vi khun V? vt ch.
Trong s cc c ch ny, quan trng nht l s p ng min
dch t nhin tc l min dch khng c hiu. l h thng b
th, cc thc bo, cc xitokin. y l s p ng tc thi nhm
bt gi v ph hy tc nhn gy bnh. Trong khi phn ng
vim, cng l s p ng t nhin cho php trnh c s lan
truyn ca vi sinh vt. Tnh min dch thch ng c hiu s
dng tt c cc c ch min dch t nhin c hiu qu v s min
dch thu c, c luyn tp trong i sng cho c th sinh
vt c th sng st, i mt vi mt th gii y ry vi sinh vt
v cc tc nhn c hi. Trong c im min dch tip thu c
c tnh ghi nh min dch cho php chng ta thc hin phdng
php tim chng phng bnh.
Ngrii ta phn bit hai dng vi sinh vt xm nhp vo c th l
vi sinh vt pht trin ngoi bo v vi sinh vt pht trin ni bo.
Cc vi sinh vt pht trin ngoi bo d trYi thot khi tc ng
ca b th v cc thc bo nhng l ch tc ng ca cc khng
th c hiu. Trong khi cc vi sinh vt pht trin ni bo (vi
khun v k sinh trng) ch c th b ph hy nh s hot ha
ca i thc bo, bng cc xitokin do lynipho T tit ra tiong
trng hp p ng min dch c hiu.
10.1.1. Cc c ch t nhin v thch ng d loi tr vi sinh
vt nh lp da v luyn nhy

Hng ro vt l v hi! hc:

Da v tuyn nhy hoc nim mc* l mt h sinh thi phc tp
m bo cho ro chc nng bao v ca c th nh: loi tr vi sinh
vt bnh !. chc niig thng tin th hin qua phn min
dich c- liu vi cc vi khun xm nhp, chc nn^ l)*K v hng c
ch hoi sinh.
* Lysozym ca bo (iiai t bo v mt s ehcVt tit c kl nang
dirt vi khun xm nhp.
Vai t r Iiiin dch ti ch in^ rut (h yu l )iK) v ('(
th chng li (tc t vi khun nh trong bnh a cluiy v bnh t
(cholera)

10.1.2.Phn ng vim ti ch v h thng clng li nhem

tr n g

Ngay kill vi khun vt qua lp ro bo v (da v tuyn nhv).

chng s khi dng bng cc phn ng vim. Ha yu t quan
trng lin lip c hiu qu chng li nhim khun l: b th. cc
xitokin v cc t bo tlc bo. Chc nng bo v cliig li nhim
khun ca b th dc chng minli l 05, C6. 07, C8 hoc
propccdin trong trng hp nhim cu trng Neisseria menin
gitidis v N. gonorrhoea. Cc xitokin Iil* TNFa, ILltt v ILl
IL6, IL8, IFNy cng gy kch thch cc phan ng vim ti ch v
h thng. Mt s protein (lc bit l protein phn ng c (Clip)
cng tham gia phn ng vim.

10.1.3. p ng min dch dc hiu chng nhim khun

p ng min dch dc hiu chng nhicm khun dc th hin
cc c ch ch yu sau:

10.1.3.1. Sn xut cc khng th chng lai cc p o lix a ca ri

l cc cpitop ca cc t bo vi khun v nm
S p ntf ( i cc* t bo B thng l vi dng (oli^oclonal)
ngha l c mt vi dng sinh ra cc IgM, IgG i khi c ca gA, 6
ngi. S pht trin mt kho d tr t bo B chig li cc poly -
 1:*r>

xacarit ca vi khun Streptococcus pneumoniae ngi c c

diem xut hin mun, khng trc 2 hoc 3 tui.

10.1.3.2. p ng ca cc lym pho T

Cc lympho Ta( nhn bit cc poptil t protein ca vi khun
do cc A1V (c lp II hoc l|) 1 ca MHC) trnh din. Thng
thng, cc protein tit hoc l sn phain thoi la ( lia vi sinh
vt <kui (luc trnl (ii cho ro lvmpho TC1)1\ S,o\ ra. ngi
ta cn tm thy cc tiu qun th lymphoTCI)8*uH xut hin. (lc
hiu vi cc khntf nguyn e kt h(|) vi (c phan t lp I ca
MHC Cc khng nguvn ca vi khun (' th CIC to ra theo c
ch nut bng cch cun mn^' sinh chat (Coiling p h a g o c y t o s i s )
ra t bo thc bo. sau c*l bii thm l peptit v k't l) vi
prottMi lp I ca HLA. l trng hp ca Borrelia burgoor-
fori c m t.

10.1.3.3. Cc c c h hiu qu s d n g x ito k in

(Yu* lympho T gy hiu qu chng nhim khun pht trien 1)011
ngoi hoc bn trong t bo bng nhng tn hiu ha hc. c
bit l cc xitokin. Han thn cc xitokin li c th gy cm ntf
v khuyrh (li s sn xut xitokin ca cc i thc bo v ra
cc t bo NK. Pn cnh d. cc khng th c th c (lnh ln b
mt vi khun, hot ha b th v to diu kii opsonin ha v
hin tng thc bo. Cc xitokin ILl, II.(, TNFcx, IKXy lm tn
tnh chng chu ca vt ch. FNy lun ioc sail xut ti nhim
trng t cc t bo NK, tip theo l t lympho Ty| v lymplio
Tap.
Ngoi ra, ngi ta cn thy c cc protein sc nhit (hsp: lcat
shock protein) cng phi hp tc diM vi cc t bo T (lc liu
vi chng trong vic bo v chng li cc vi sinh vt khc nhau.
Protein sc nhit c kha nng kch thch chn lc cc t bo TyS
v rt c th qun th Ty c chc nng loi b cc t bo bt
thng (t bo b nhim khun hoc cc t bo ung th).
Cc* siu khng nguyn (supcrantigcne) nh d c nh
ngha l cc phn t c kh nng lin kt vi cc phn t !n II
ca MHC v vi cc trnh t peptit ca mt s h TCR (Vp), c
tc dng hot ha nhiu ng t bo T v kch tlnVli vic ^iai
phng cc lvmphokin IL2, IFNy v TN Fu. Cc du hiu nhim
136

c siu khng nguyn t cu khun Staphylococus c

quan st thy l st, a chy, ph mch no, ph mch phi v
thn, do nhim c thc phm.

10.2. Min dch ung th

10.2.1. Khi nim ung th, cc gen ung th v km hm ung th

Ung th (Cencer, tumour) l mt bnh ca cc c th a bo,

trong cc t bo phn chia bt thng v khng c iu
ha, dn n s bit ha khng bnh thng (cn gi l neopla
sia).
Ung th xut hin ni chung l do s tch ly li cc t bin
ch yu cc ng vt c xng sng bc cao. Ung th cng ng
ngha vi s hnh thnh cc khi u (tumour) c nghin cu
kh chi tit cc loi ng vt c vit l ngi, nhng cc
khi u cng xut hin thc vt (v d bnh khi u bt thng
ca cy do vi khun Agrobacterium tumefaciens gy ra, bnh
"Crown gall").
Ba c im ca t bo ung th l:
1. Tnh bt t trong sinh trng ngha l t bo phn chia v hn
v khng bit ha.
2. T bo b bin dng khng tun theo s kim sot ca cc yu
t sinh trng.
3. T bo bin dng c kh nng di c (metastasis) ngha l di
cn xm nhp vo cc m t bo bnh thng khc v pht
trin thnh mt qun th t bo ung th mi, to khi u.
Bnh thng t bo khng bin dng ung th c cc gen c
gi l gen tin ung th (proto-oncogene) thc hin cc chc nng
bnh thng l to ra cc sn phm iu ho s sinh trng v
bit ha t bo. Nu t bo b nhim virus mang gen gy ung th
(oncogene), cc gen tin ung th ny b t bin tr thnh cc
gen gy ung th (oncogen) c hot ng qu mc v khng bnh
thng. Cc proto-oncogene ny cng c th b t bin do nhiu
tc ng mi trng nh phng x, ha cht.
S tng sinh khi u c bn cht n dng, nhng cc t bo
mi sn sinh t mt dng li rt a dng v kiu gen (genotype)
 137

hiu hin qu mc mt s gen, mt i mt s nhim sc th... v

da dc?ng ve kiu hnh. S bt thng v di truyn t cc t bo
ung th do tip thu dc dn n c tnh tng trng v
hn, lm ngng bit ha, lm mt kh nng km hm tip xc v
tng kh nng di cn cc t bo ung th bt thng n khu tr
nhng m t bo c bit no y.
Cc sn phm ca cc gen tin ung th t bo bnh thng
kim sot cc tn hiu hot ha v sinh sn t bo. l cc th
th ca cc yu t tng trng, cc protein truyn tn hiu ho
hc (chang hn: serin treoninkinaz, protein G...), cc protein
tham gia bo v chng oxit ha Bcl-2 hoc cc yu t dch m (C-
myc). Cc gen tin ung th c th c hot ha do t bin. S
t bin gen ras c thy nhiu cc khi u ca ngi lm
km hm cu hnh khng gian hot ng ca protein p21ras lm
hot ha t bo. Tc ng ca gen ung th gy ra s chuyn
on nhim sc th (nhim sc th 14 v 18), gy ra s biu hin
qu mc ca Bcl-2 (protein anti-oxydant) lm mt i hin tng
cht theo chng trnh (apotosis) ca lympho B trung tm
ngun.
Trong khi , cc gen km hm ung th (anti-oncogene) hoc
(tumor suppressor) c pht hin khi phn tch cc t bin
ca cc dng ung th. Cc gen ny m ha cho cc protein ca
khung t bo, hoc protein iu ha chu trnh t bo, hoc sa
cha ADN. ng ch l gen p53 m ha cho protein p53 b
nh ch hot ng trn 50% cc khi u ca ngi. Protein p53
rt t biu hin cc t bo b sc (stress), b thay i cu trc
ADN. T khng gip cho vic sa cha ADN trc khi phn
chia t bo. S t bin gen p53 dn n tch ly mt dng pro
tein bt hot, lm mt kh nng sa cha ADN v cho php t
bo b bien dng c tnh sng st. Nh vy, gen km hm ung
th c vai tr km hm sinh trng t bo v sn phm ca
gen ny l nhng cht iu ha sinh trng t bo.

1.2.2. p ng m in dch c hiu chng ung th

10.2.2.1. K h n g nguyn un g th
Ngcri ta pht hin ra cc khng nguyn c hiu ca cc
khi u ca ngi. Tip theo ngcli ta cng nhn thy cc phn
138

ng hn hp gia cc lympho T vi cc khng nguyn ca khi u

cng c nhn thy. Trong cc trng hp ung th. cc
lympho T dc sinh sn ch yu l dng lympho T CD4* v mt
phn l cc lympho T CD8* c hiu vi cc t bo ung th tit
ra TNFa. Boon v cc cng s (1994) pht hin c mt h
cc gen ca khng nguyn ung th melanoma v gi l MAGE
(melanoma associated genes). T mu ca bnh nhn mang bnh
melanoma MZ2, h tch c cc lympho T CD8+ c hiu vi
khi u MZ2-E.
Cu trc peptit ti u c sn xut t gen MAGE-1 c
xc nh t dng t bo MZ2-E bao gm 9 axit amin (nonapeptit)
l mt epitop T lin kt vi HLA-Al. Cc khng nguyn ung th
khc cng c xc nhn, chng hn cc t bo ung th dng
B bc l khng nguyn CD19 v CD20, dng T bc l CD25.

10.2.2.2.Khi u do virus gy ra
Rt nhiu kh u thc nghim v mt s khi u ca ngi do
virus ung th gy ra, dng virus ARN v ADN, v d virus Ep-
stein-Barr (EB.V) c kh nng gy ung th vm hng. Cc virus
B gy vim gan (HBV), virus c (HCV) cng c kh nng gy ung
th gan. ng th c t cung do mt s dng papilloma virus ca
ngi (HPV 16 v 18). Cc retrovirus HTLV-1 thng tham gia
vo ung th bch cu T (leukemia) ngi trng thnh. Tn s
ca ung th tng rt cao cc bnh nhn thiu ht min dch
(i vi ngi ghp m, b bnh AIDS), rt c th do c ch gii
km hm min dch, (Nossal,1993).

10.2.3.Min dch t nhin chng ung th

Tham gia vo min dch t nhin chng ung th gm ba kiu

t bo:
- Cc t bo NK: Cc t bo ny c kh nng phn hy in vitro
cc dng ung th biu hin yu hoc khng biu hin cc phn
t MHC. S tng tc c hiu phn t cho php phn ng
gy c cho t bo ung th cn cha sng t. Cc t bo LAK,
t bo dit c hot ho bng lymphokin (Lymphokin acti
vated killer Cell) nhn c nh nui cy lympho khi c mt
IL2 c kh nng phn hy in vitro cc t bo bt ngun t mt
khi u.
 139

Cc i thc bo: Chng dc hot ha in vitro nh cc xitokin

nh IFNy v cc sn phm c ngun gc t vi khun v c kh
nng phn hy in vitro cc t bo ung th. Tnh dc hiu
tng tc phn t trong phn ng gy c i vi cc t bo
ung th cng cha c bit r. TNFa c sn xut ra t cc
di thc ho hot ha c kh nng ph hy nhiu dng t bo
ung th.
- Cc t bo a axt: c hot ha bng IL5 v cc cht ha gii
khc c tnh c cao i vi cc m t bo hnh thng v i
vi k sinh trng sng trong cc t bo khi u.

10.2.4. Liu p h p m in dch v m in dch phng tr ung th

Vic nhn bit cc khng nguyn ung th c hiu l mt kh

khn nn a s cc bin php min dch cha bnh mi ch da
vo s kch thch khng c hiu cc phn ng min dch. Tuy
nhin ngi ta cng s dng cc phn ng min dch c hiu
khng nguyn cho vic d phng cc khi u c ngun gc virus.
V c cc vacxin chng virus vim gan B, v ang c m rng
cho cc vacxin FBV, HCV, HPV-16... Cc liu php th nghim
tim chng vacxin vi ung th melanoma ang c tin hnh
vi cc peptit khng nguyn ung th. Th nghim trn c p
dng cho cc bnh nhn kiu hnh HLA-A1. Cng c the thc
hin bin php gy min dch bng cc peptit MAGE-1 vi s c
mt ca t cht hoc bng cc vect biu hin trnh t m ha cho
khng nguyn ny (v d retro virus, BCG...)
Ngi ta cng c nh s dng khng th n dng chng li
khng nguyn ca mt s bnh ung th. Cc khng th ny c
th c ci bin bng cch gn vi mt ng v phng x hoc
mt loi thuc, dc t vi khun hoc c t thc vt nhm tiu dit
cc t bo ung th.
Cc xitokin, IFNa cng ang c s dng cho nhng kt qu
kh quan trong vic phng tr mt s bnh ung th. Ngoi ra,
ngi ta cng s dng c nhng t bo LAK ca ngi bnh c
nui cy khi c mt IL2, sau tim tr li cho ngi bnh.
Mt nguyn tc cha bnh ung th khc ang dc nh gi l
s ng mt s dng phn t nh cc dn xut ca vitamin A
(axit retinoic) hoc mt s khng th cho php gy ra s bit ha
140

sm cc t bo ung th v t to ra qu trnh sinh l ph hy

cc t bo ung th bng c ch apoptosis.
Cc liu php ha hc v phng x, kt hp vi vic xy dng
li h thng to mu bng cch cy ghp cc t bo ngun
(CD34\ T h y l+) ca bn thn bnh nhn (ghp cng ngun:
autogre) cng c p dng.
Mt bin php khng phi l lin php min dch l nu c th
ct b cng sm cng tt khi u dng cha di cn <ung th v)
khi pht hin sm bnh l ko di thi gian sng.

10.3 Hi chng tng sinh m in dch v cc bnh ung th

10.3.1.Khi nim

Hi chng tng sinh min dch l nhng bnh tng cng qu

trnh sinh sn ca t bo dng lympho (t bo T v B). Nghin
cu hi chng ny lm tng thm s hiu bit v h min dch,
cho php phn tch v chn on s lan truyn dng t bo n
dng, cc qun th v cc phn t xut hin mt s lng rt t
trong c th bnh thng. Vic nghin cu cu trc cc phn t
Ig trong cc bnh tng sinh min dch cho php hiu bit cc Ig
n dng trong bnh l trc khi pht minh ra phng php sn
xut cc khng th n dng ng dng cho y hc.
Nghin cu hi chng tng sinh min dch gip cho vic phn
loi chnh xc hn cc bnh l v t bo hc v di truyn t bo,
tm hiu c mi quan h gia hi chng bnh ny vi cc loi
virus (E-BV, HTLV-1...).

10.3.2.Tnh n dng ca bnh tng sinh min dch lympho

Trong a s" trng hp ung th, sinh sn t bo mang tnh

n dng. iu ny c chng minh nh mt dng t bo ca
bnh ch tit ra mt loi khng th dn dng c cu trc ging
nhau.
 141

10.3.2.1.Cc k h n g th dn dng ca huyt th a n h

Ce khng th dn dng c cu trc ging nhau, tch in nh
nhau v to ra mt bang protein r nt trong in di. Cc k
thut in di phn gii cao (lp mng agaroz) cho php pht hin
(c Ig n ng khng thy dc in di tiu chuan (hnh 10.1).
K thut phn tch in di min dch l cn thit, cho php xc
nhn thuc tnh ca ch mt chui L, chui Kappa hoc lambda
v cc izotip chnh xc (IgAl, IgA2, IgGl, IgG2...) ca mt chui
nng H trong cc bnh u ty (myeloma).

I 14 *
41ti \
:> : anti-lp

SM\
a n u
s? U1pi
jn! .
S*N " : ; Upl
. r .1
r!" * ntln
*
*'' '- ( li jl
I
anf*t.
s>
i
SMN

Hnh 10.1 nh in di min dch cho bit cc cung kt ta (c du sao)

ca huyt th anh bnh l (SP) khc bit vi cung kt ta bnh thng
(SN) khi s dng cc khng th khng chui nng v khng chui nh
khc nhau, y trnh by hai dng bnh l khc nhau (a*v b+)
142

*0 M < '
m w t - mm m*-F
^ ~~ m>
*** rflv
/
' > * 4 * 7 # t ,*

Hnh 10.2. nh in di huyt thanh trn gel

tm polyamid xc nh cc trng hp bnh u
tu dng IgG, IgA, IgM, cc chui nh X v K.

1. Huyt thanh bnh thng.

2. IgG X.
3. IgG (u tu).
4. IgA K (tng sinh macroglobulin).
5. IgA K(hai vch kp ca bnh u tu).
6. IgM K(Bnh ung th Waldenstrom).
7. IgM K(Bnh ung th Waldenstrom).
8. IgG X ca nc tiu bnh u tu ch thy r bng protein Bence Jones
type K.
9. Ba dng bt thng ca cc Ig mi tn ch IgM K, IgGj v IgG X (ung
th bch cu: leukemia).

10.3.2.2. Cc hu qu sinh l bnh

Cc Ig n dng ca huyt thanh c th gy ra s r'i lon
bnh l do nng qu cao trong huyt thanh, do tnh c hiu
v cu trc bt thng ca chng. Cc khng th dn dng c th
lm tng tc lng ca hng cu, lm tng hm lng protein
ca mu v to thnh cc cun bAng hng cu. Mt s" hi chng
tng sinh gy ra cc hu qu ng ch sau:
- Hi chng tng nht ca mu do cc IgM v IgG dn dng,
gy tn thng tim mch v tn thng y mt. Cc khng
th n dng c th lin kt vi cc th th Fc ca tiu cu gy
ra bin chng chy mu v nhim trng.
- Hi chng tn thng t bo v m t bo do s lng cn ca
cc chui nh ca Ig n dng, xy ra bnh ng thn do 11
ty. S tn thng cc ng dn trong thn do tch t qu ln
cc protein Bence Jones (PBJ) l dng dime ca chui nh
khng th n dng dng t do.
 143

- Cc bnh "Amylose" ng "cn tinh bt" do s tch ly mt s

dng protein (chui nng v chui nh ca Ig) v cc t bo
plasma n dng gy ra tn thng ti ch thnh mch mu,
li, tim v c xng, ng tiu ha v phi.
- Cc bnh ng cn chui nh v Ig n dng thn, ng tiu
cu thn, gan, tim v i khi cc m t bo khc. S ng
cn ny c pht hin bng cc khng th khng kappa hoc
khng lambda.

10.3.2.3. Mt s v d tn g sinh n dng ca t'bo B

10.3.2.3.1 Bnh u tu nhiu ch (mltiple myeloma)

u ty nhiu ch hay a u ty l s tng sinh c tnh dng t
bo lympho B. kiu hnh t bo plasma. Bnh ny dn dn tn
thng xng, rng xng lan trn hoc ti ch, i khi gy
xng. Phn tch biu u ty v sinh thit xng cho thy r s
xm nhp cc t bo plasma c hnh thi khc nhau, gy ra bnh
suy ty km theo thiu mu.
C hai triu chng bin chng ca bnh a u ty l: tn
thng thn, tn thng ng dn ca thn v tiu cu thn, ng
cn trng amyloz, gim tng hp cc Ig bnh thng lin quan
n d ha qu mc (hypercatabolism) trong cc bnh u ty ca
IgG. Bin chng tip theo l nhim trng. Biu hin ca bnh l
au n ti ch v lan truyn.
V nhng c im ha sinh min dch, ngi ta phn bit
4 dng u ty khc nhau l:
- Khng th dn dng ton b, cha trong huyt thanh ch yu,
c t hoc khng c trong nc tiu.
- Khng th dn dng +PBJ xut hin trong huyt thanh nhng ch
yu l PBJ, trong nc tiu n dng ch c Ig n dng v khng
c PBJ (PBJ l protein Bence Jones, mnh dime chui nh IgG)
- C PBJ, c hoc khng c g n dng trong huyt thanh.
Trong nc tiu c Ig n dng.
- ty "khng bi xut" Ig n dng v PBJ.
10.3.2.3.2. Ung th bch cu (leukemia) hay bnh mu trng
Bnh mn tnh c u th nam gii c tui trn 50. Khi bnh
chuyn sang dng c tnh ca nguyn bo lympho B v nguyn
bo lympho T c tin lng xu th bnh nhn s bieu hin r
khng nguyn chung cho bnh bch cu nguyn bo lympho. C
144

th dng khng th n dng c hiu khng li khng nguyn

ny (khng th J5) cho xt nghim ELISA pht hin bnh.
c im ca bnh l tng sinh n dng t bo B c mt
thp IgM v IgD trn mng t bo. Ung th bch cu dng mn
tnh (chronic lymphoid leukemia-CLL) him thy la tui di
50 v thng tr nn lnh tnh, nhng cui cng cng c 20%
bnh nhn th hin khng th n dng trong huyt thanh s c
tin lng xu, tr thnh c tnh.
Hai dng bin chng ch yu ca bnh CLL l s thiu ht
min dch th cp km theo vic gim st sn xut khng th v
pht sinh cc bnh t min, c bit l bnh tan hng cu t
min (hemolytic autoimmune disease)
10.3.2.3.3. u lympho hay lymphoma
Ngi ta phn bit hai dng lymphoma: dng u lympho khng
phi Hodgkin v bnh lympho-Hodgkin. u lympho khng Hodg
kin l dng biu hin ch yu do t bo B to ra mt kiu Ig c
ch mt dng chui nh (kappa hoc lambda) Tri li trong tng
sinh dng B phn trn, ngi ta thy r biu hin ng thi c
hai dng chui nh l K v X. Bnh nhn b lymphoma Hodgkin
c c im l kin trc ca c quan lympho b ph hy v xut
hin cc t bo khng l, cha hai nhn gi l t bo Reed-
Sternberg.
Bnh ngng kt hng cu lnh l do tng sinh bch cu ty
xng, tit ra mt Ig n dng huyt thanh, c hot tnh t
khng th (autoantibody) chng li hng cu ca bn thn.
Lymphoma Burkitt (BL) hu nh lin quan vi virus Epstein-
Barr, biu hin hm v phn bng.
10.3.2.3.4. Bnh macroglobulin Waldenstrom
c im ca bnh l tng sinh dng t bo B vi nhiu kiu
hnh t t bo B hnh dng nh cho n cc t bo plasma (nhiu
dng trung gian ca B). IL6 ng vai tr quan trng trong vic
duy tr dai dng s chn ca dng B v s tng sinh dng B din
ra ty xng, hch bch huyt v c l lch. Xt nghim ha
sinh min dch cho thy xut hin mt lng ln macroglobulin
c khi lng 400.000 dalton bao gm cc IgM n dng v a-2
macroglobulin trong huyt thanh ngi bnh. Hi chng ca
bnh l tng nht ca mu, mu mu nht v c bin chng
thiu mu do tan hng cu v chy mu xut huyt.
10.3.2.4. S t n g sin h dng lyrnpho T
S t n g s in h bc h cu c tnh dng lym pho T hay b n h m u
t r a n g dng T (T.Cell leukemia) xy ra ngi tr n g t h n h c
bit c n h i u N h t Bn v T ru n g M. Bnh do loi r e tr o v ir u s
HTLV-1 u
( H u m a n T.Cell le ukemia v i r u s l ) gy ra. ly m pho T r t
th n g x u y n n m v tr biu b c to t h n h t cc ly m pho
T C D 4 \ T C D 8 + bit ha. Cc lvm pho T n y khi tip xc VI
hiu b s gii p h n g ra cc lymphokin (GM-CSF, IFNy, T N F a ).
Biu hin b n h ly l do tc ng ti ch ca cc xitokin ln biu
b v lp da tr o n g h a y c h n b (derma).

10.3.2.5. N guyn n h n di truyn v nguyn n h n t bo

ca bnh.

Rt nhiu khi u ca cc lympho B pht sinh km theo s mt

kh nng iu ha ca mt tin gen gy ung th (proto-
oncogene) C-myc hay cn gi l gen tim n lin quan n ung
th. Gen C-myc c vai tr nht nh trong vic chuyn trng thi
CiJG ca chu trnh t bo lympho v c th vi nhiu dng t
bo khc. S tng cng biu hin ca gen ny s bo trc s
hot ha lympho.
Ngi ta nhn thy s iu ha biu hin qua gen C-myc b v
phm s lm cn tr t bo tr li trng thi ngh G0 trong chu
trnh t bo v bt buc t bo sinh sn lin tc. S ri lon tng
sinh t bo B thng km theo hin tng chuyn on ca locus
C*myc trong cc nhim sc th. c bit l trng hp u lym
phoma Burkitt, ngi ta lun lun thy c s chuyn on ca
oncogen C-myc vi cc trnh t iu ha locus IgH (t4;18 c
75% cc trng hp) hoc cc locus IgK hoc IgL (t2;8 hoc t8;22
c ti 25% trng hp). Gen C-myc l gen "pht trin sm" c
chc nng hot ha t bo biu hin qu mc cc t bo khi
u t di s kim sot ca cc yu t phin m cc Ig. C th
minh ha c th s chuyn on gia cc nhim sc th 8 v 14,
trong c cha gen C-myc locus ca chui nng i gy ra bnh
lymphoma Burkitt (Hnh 10.3).
146

Nhim sc the K Nhim sc ihc 14 Nhim sc th' X Nhim sc th 14

C-myc

Hnh 10.3. S chuyn on ca gen C-myc locus ca chui

nng trong bnh lymphoma Burkitt. (theo I. Roitt. 1990.)

Sau y l tng kt mt s v d v s chuyn on ca cc

nhim sc th trong cc hi chng tng sinh min dch.
Bng 10.1. S chuyn on cc nhim sc th gy ra bnh tng sinh
min dch (theo Kaplan v Delpech - Biologie molculaire et Mdicine,
trang 479 - Paris 1993)

Gcn th N h i m K iu u n g Chuyn don G en N h i m

nht sc th th sc
th 2 th
Lympho li
Ly m pho l 8 Lymphoma t(8:14)(q24:q32) ltfH 14
Burkitt
C-myc 8 Lymphoma t(2;8)(qll;q24) IgK 2
Hurkit
C-myc 8 Lymphoma t(8:22)(c|24;ql 1) |R|- 22
BurkiM
bCl - 1 11 Leukemia 1(1 l;14)(c|13;q32) \\\ 14
lymphoma
bCl - 2 18 Lvmphoma 1.(14:18)(<|32:<|21) ItfH 11
nang
Pbx 1 1 l^*uk(*mia I(1:19)(c|2:*:qi:i) E2A 19
lymphoma
IL :* f> U uk(ima t(5:H)(q:n;c|.T2) Ik H 11
Ivmphonia
Lympho T
tai - 1 1 Leukemia f(11:H)(c|1.):q32) TR(M) 14
lymphoma
Tan - 1 9 i/cukcmia t(7;19)(q.M:q34) TRC-B 7
nguyn
bo
TKC 11 Ix'ukomia 1(7:1 l)(<|35:q 13) TRC l 7
 147

lymphoma
( nyc H Leukemia 1(8; 11)(q24:ql \ ) TKC-A M
lymphoma
Hox 11 10 Leukemia 1(11:14)(<|25.<jl 1) TRC 1) 14
lymphoma
rbtn 1 11 lx*ukomia TRC-I)
lymphoma
TCKA M Leukemia inv(14)(q11:q.T2) Ir H 1
lymphoma

10.3.2.6. Bnh tn g sinh min dich lin quan n chui

nng
Cc bnh ny c c dim l huyt thanh ca bnh nhn c
mt loi Ig n dng nhng khng c cc chui nh (dng Ig c
cu trc bt thng). Bnh th hin ba lp Ig ch yu l IgM.
IgG v IgA (c bit l IgA,). Trong huyt thanh ngi bnh, cc
phn t Ig c chui nng b ng ha rt cao, ngha l kt hp
vi nhiu loi gc ng. l c im quan trng v s bin
i cu trc ca cc chui nng Ig. Bnh ca chui nng y thng
din bin di dng tng sinh min dch v biu hin ca bnh
t min. Trong khi d bnh ca chui nng a th hin s tng
sinh dng nguyn bo lympho IgA,. xm nhp vo rut non v
cc hch mng treo rut, lm teo nhung mao rut, dn dn hu
qu suy dinh dng do hp th dinh dng km.

10.4. Mt s c im lm sng ca ung th

10.4.1. Ch th u n g th (T um our m a rk e r)

T lu cc nh khoa hc sinh hc v V hc mong mun tm ra

cc ch th ung th pht hin cng sm cng tt s chuyn
dng c tnh ca t bo unf th. C mt s hp cht ho sinh
c pht hin c quan h cht ch v di khi c tnh c hiu
i vi mt s bnh unf Ih xem nh l nhng ch th ung th.
C1 th ung th c dinh ngha l nhng i phn t khi xut
hin mt bnh ung th. c nng thay di theo chiu hng
tng ln lin quan s pht sinh v tng trng ca nhng khi u
c tnh mt bnh nhn.
Ch th ung th c th chia lm hai dng: ch th t bo v ch
th th dch.
148

- Ch th ung th dng t bo bao gm cc khng nguyn trn b

mt cc t bo, cc th th hormon v th th yu t tng
trng, nhng bin i di truyn (bin i gen) ca t bo.
- Ch th ung th dng th dch bao gm cc cht ho sinh dc
pht hin nhng nng qu mc bnh thng c mt trong
huyt thanh, nc tiu v cc th dch ca c th.
Chng c cc t bo hoc m ung th tng hp v tit ra, t
khi u b ph v hoc c to ra t cc phn ng ca c th
i vi khi u.

10.4.2 P h n loi ch th u n g th th eo k h n n g c h i u
bnh.

- c hiu cao khi ch th ung th khng c pht hin i

tng kho v u lnh tnh.
- C nhy cao l d pht hin giai on sm khi ch c mt
t bo ung th xut hin.
- c hiu c quan ngha l ch xut hin mt c quan b ung
th.
- Xut hin tng quan vi giai on ung th v kch thc khi u.
- Tng quan vi tin lng v thi gian sng.
- C gi tr d bo.

10.4.3 Mt s ch th ung th lin quan vi bnh

1. CEA l mt glycoprotein 180 kDa cha 60% ng (carbohy

drate) l mt trong nhng khng nguyn ung th thai, thng
xut hin nng cao trong huyt thanh bnh nhn ung
th trc trng, v mt s bnh ung th ng tiu ho (bnh
thng, ngi kho khng ht thuc l, nng CAE < 3-5
ng/ml) ngi ht thuic tng t 3-10 ng n 20 ng/ml. CAE
c sn xut trong s pht trin phi v thai. Sau khi sinh,
CAE ngng sn xut nn ngi trng thnh c nng rt
nh.
Ngi ta tm ra c t nht 14-16 gen thuc h gen C/EA m
ho cho CEA, v cc cht Lng t CEA hoc cc protein lin
quan n qu trnh mang thai (BGP).
2. AFP (Alpha Fetoprotein) l mt glycoprotein 70 kDa cha
khong 2,5% ng, c tng hp gan v ti non hong
 149

ca thai v c U ) vo luivt thanh tun th 13 ca thai

k. Sau khi sinh, nng AFP trong huyt thanh tre s sinh
gim dn v ngi trng thnh, khoe mnh ch cn 3-5
ng/ml. 90% bnh nhn ung th biu m gan tin pht c nng
AFP tng ln hn 1000 ng/ml, i khi t 10.000 n
1.000.000 ng/ml (Abodov, 1971 Saito, et al 1990, Taketa. et
a 1990).
iu ng lu l AFT thai k c mc glycozyl khc
vi AFP ca ung th gan v mt SC) dng AFP bnh l khc.
Taketa v cng s (1990), ch ti c im ny v s
dng lectin nhn bit c hiu AFP glycozyl bnh l
pht hin v phn bit bnh ung th vi cc AFP bnh
thng thng khc.
3. HCG (Human Chrionic Gonandotrophin) l mt asialo glyco
protein (glycoprotein khng cha axit sialic) c khi lng
phn t 46 kDa, bao gm hai tiu n v a v p lin kt khng
cng ho tr vi nhau. Tiu n v (3 ca HCG c hot tnh c
hiu ring cho HCG, trong khi tiu n v a ging hocmon LH
(hocmon th vng: Luteinising hormone), giai on u ca
thai k, HCG c t bo l nui phi (Trophoblaste) v nhau
thai tng hp. HCG c chn on c thai (pht hin c hiu
s c mt tiu n v p. Tuy nhin, khi nng chui p t do
tng cao trong trng hp ung th bung trng hoc tinh
hon. Cc xt nghim ch dnh ring cho tiu n v p t do
cho nhy 100% i \'i ung th t bo nui thai v nhy
70% i vi ung th tinh hon khng ht. Trong bnh ung th
nhau thai lun lun xut hin HCG, v khng xut hin AFP;
nhng bnh ung th ti non hong th ngc li: AFP
dng tnh v HCG m tnh. Nng HCG c th tng len
trn 1 triu IU/ml bnh ung th t bo nui dng nang sn
(40 -50% ung th biu m thai dng nang sn). Nng
HCG tng ng vi giai on pht trin khi u v tin lng
bnh ung th t bo nui v t bo mm. Ngi khoe bnh
thng c nng HCG di mc 5 IU/ml.
4. CA 15 - 3 l khng nguyn ung th c t bo ung th v
mt s" t bo biu m tit vo mu v dch c th. CA 1 5 - 3
c pht hin nh hai khng th n dng l 115 - D8 v
DF3. CAI 5-3 c dng pht hin theo di, iu tr v pht
150

hin s di cn trong ung th v. 70% bnh nhn n ung th

v b di cn u c nng CA 15-3 tng. Gi tr nng
CA15 -3 tng ln cnp xut hin trong ung th bung trng,
ung th tu, rut kt v ph qun. Tuy nhin nng cao cng
thy bnh s gan, vim gan v mt s bnh phi, bnh v
lnh tnh.
5. NSE (Enolaza c hiu nron thn kinh: Neuron - Specific
Enolase) l mt isozym ca enolaza bao gm hai polypeptid
gn nh ging nhau, mi chui 39 kDa. Trong qu trnh ng
phn(glycolysis).
NSE xc tc cho s bin i 2-photphoglycerat thnh phot-
phoenolpyruvat v tham gia vo sinh tng hp hexoza. NSE cn
ion M f+ v Mrr* nh l nhng cofactor v b km hm bng
phosphofluoride.
V NSE nh khu mc t bo nn vic pht hin thy n
trong huyt thanh ch ra hin tng hoi t t bo ung th. Do
, NSE l mt ch th khng thch hp lm cho vic pht hin
giai on sm ca ung th. Cng c th s dng ch th NSE
phn loi m hc. Ung th t bo nh ca biu m ph qun pht
hin rt nhanh, c th c x l ho tr liu. Vic phn loi m
b bnh da vo NSE c th to iu kin d dng cho cch la
chn phng php cha tr. Tuy nhin, cn phi hp vi vic xc
nh ch th CEA. Khi nng NSE tng cao qu ll,8ng/ml s
cho tin lng xu, nhng nu nh hn ll,8ng/ml, thi gian sng
lu di hn.
Ch , v NSE c tm thy trong t bo plasma, tiu cu
nn ngi b bnh tan huyt, nng NSE cng cao.
Cng c th thy NSE tng ln c ngha nu mu ly ra
qu 60 pht trc khi ly tm tch huyt thanh.
6. PSA (Khng nguyn c hiu tuyn tin lit: Prostate - Spe
cific antigen) l mt glycoprotein 34 kDa c hnh thnh m
tuyn tin lit c mt c trng thi bnh c tnh v lnh
tnh. V vy PSA khng thc s l ch th dc hiu ung th c
quan. Tuy nhin PSA cng ng gp cho vic d ho v bnh
ca tuyn tin lit giai don khi pht sng lc cc ri ro
i tng nam gii trn 50 tui.
V chc nng sinh hc, PSA l mt proteaza serin gip ch
qu trnh Lm lng Linh dch bng c ch ct fibronectin ca tinh
dch. 0 bnh nhn ph i tuyn tin lit lnh tnh(bemgn hy-
perplasia), nng PSA cng tng trong huvt thanh v c
pht hin nhy hn so vi PAP(Prostatic acid phosphatase).
S sn xut PSA c th b c ch bng cch iu tr vi anti -
androgen.
7. PAP (Photphataza axit ca tuyn tin lit: Prostatic Acid
Phosphatase) l mt glycoprotein 100 kDa c sn xut t ly*
sosome ca t bo biu m(epithelian cell), photphataza axit
bao gm 5 isozvm c mt nhiu loi t bo v dch c th
khc nhau nh. tiu cu, hng cu, h thng li ni m (gan,
lch), tu xng v t bo m tuyn tin lit. Tuy nhin
tuyn tin lit, isozym bng 2 c trng cho m c gi l
PAP nhng khng c hiu cho ung th v nng ca n cn
tng ln bnh ph i tuyn tin lit lnh tnh. Ch th PAP
cng c dng xc nh v theo di iu tr bnh ung th
biu m tuyn tin lit (Prostate Careinoma). Nng PAP
tng ln huyt thanh ch r s tin trin ca bnh ung th.
Trong khi ngi khoe bnh thng nng PAP l 0
0,2ng/ml.
Chc nng sinh hc ca PAP l xc tc cho s thu phn cc
monoeste ca axit photphoric trong tinh dch. iu kin hot
ng ti u pH 4,5 - 6. cn ch l PAP rt nhy cm vi
nhit , d bin tnh, cn xc nh hot tnh ngay sau khi ly
mu v ba qun mu trong iu kin lnh. Tri VI PSA, vic
sn xut PAP khng b anti - anrogen km hm.
8. P2-M (Beta 2 - Microglubulin) l thnh phn chui nh ca
HLAI c mt hu nh tt c cc t bo cha nhn, c bit
nng d cao b mt cc t bo ympho. ^2-M c khi lng
11,8 kDa v dc phn lp nc tiu ca bnh nhn cha
protein niu. Bnh thng, ngi kho cng pht hin c
trong huyt thanh c 3,4 ig /ml, nc tiu c 0,154 |ig/ml.
Trong khi cc bnh nhn ung th dng lympho (bnh a
u tu, leukaemia), nn^ 32-M tng cao, ch r thi gian sng
st ngn.
Trong cc trng hp bnh lnh tnh (vim cu thn, ng thn,
bnh nhn AIDS , bnh nhn ri lon chc nng min dch) ch
th [32-M cng l mt gi tr cn c coi trng. iu ng ch
l (V2-M ca nc tiu km n nh, ph thuc vo pH.
152

Tm tt chng X

1. Min dch chng vi sinh vt l mt c ch tng hp qua trung

gian t bo v c ch tc ng phn t ca cc sn phm t
bo.
2. Min dch ung th nghin cu hin tng bt thng trong
sinh sn ca cc dng t bo min dch. Nguyn nhn di
truyn ca bnh l do s t bin ca cc gen gy ra hin
tng ri lon trong iu ho ca chu trnh t bo (ng ch
l gen p53 m ho cho protein p53 v gen p21 ras).
3. Mi loi bnh ung th u do mt khng nguyn c hiu qui
nh. Ngi ta cng pht hin c mt s" h cc gen ca
khng nguyn ung th. Vic hiu bit cc khng nguyn ung
th c th gip cho vic phng nga v chn on ung th c
bit l ung th c ngun gc virus.
4. Tham gia vo min dch chng ung th gm cc kiu t bo
nh NK, LAK, cc i thc bo, cc t bo a axt v.v...
5. Hi chng tng sinh min dch l s ri lon v chc nng ca
cc t bo h thng min dch v to ra nhng sn phm c
bit l cc khng th n dng v cc protein c trng. Bnh
tng sinh min dch cng do nguyn nhn cc gen gy ung th
tc ng n chu trnh t bo c bit l s t bin ca cc
gen v cc nhim sc th.
6. Mt s c im lm sng trong bnh dch ung th c ch
l cc ch th ung th (Tumour marker). S dng cc ch th
ung th dng pht hin sm bnh, tin lng v theo di
iu tr ung th c hiu qu nhm mc ch ko di thi gian
sng ca bnh nhn.
Chng XI. Min dch bnh l: thiu ht min dch
v hi chng suy gim min dch mc phi (AIDS)

11.1. Khi nim

S thiu ht min dch thng biu hin trng thi bt thng

ca mt, hay nhiu yu t ca h min dch dn n cc bnh l
khc nhau nh nhim trng v i khi dn n ung th. C hai
dng thiu ht min dch l thiu ht nguyn thy hay bm sinh
v thiu ht th c'p. Thiu ht min dch bm sinh do nguyn
nhn di truyn, thiu ht min dch th cp do yu t bn ngc i
nh thuc, chiu x, dinh dng km v do nhim trng.
V bnh l, ngi ta phn bit cc kiu thiu ht min dch
nh: thiu ht Ig hoc protein ca b th, thiu ht cc t bo
dng thc bo hay dng lympho T hoc lympho B.

11.2. Thiu ht m in dch nguyn thy ca cc t bo B

Cc bnh nhn thiu ht min dch chc nng ca t bo B

thng b nhim trng (ng h hp ti din i vi cc vi
khun vim phi cng nh cc bnh nhim trng ng rut.
Cc kiu bnh l do thiu ht t bo B l:

11.2.1. Bnh khng c - globulin trong mu

Biu hin t bo v ha min dch ca bnh l: t hoc khng

c cc t bo B trong mu, hch bch huyt rt nh v khng c
hch amidan, khng c IgA, IgM, IgD v IgE v rt t IgG trong
huyt thanh. Ngi ta gi bnh ny l agamma globulin trong
mu do t bin gen XLA, gen ny m ha cho mt protein l ti-
154

rozinkinaz c hiu ca dng t bo B. Mt dng bin i ca

bnh ny km theo s thiu ht hocmon sinh trng.

11.2.2. Thiu ht IgA, cc phn lp IgG v tng IgM

S thiu ht IgA thng gy nhim trng h hp v ng

rut v d bin chr.g thnh cc bnh t min. Gn 50% bnh
nhn b thiu ht IgA d xy ra hin tng sc khi b nhim
trng mu.
S thiu ht cc phn lp IgG in hnh nht l IgG,, IgG.; v
IgG4. S thiu ht ny lin quan vi nhim trng gy bnh m.
S thiu ht IgG v IgA km theo s tng IgM cng gy
nhim trng vi khun to m, tng sn hch bch huyt v gim
mnh bch cu trung tnh.
Nguyn nhn ca bnh l t bin gen m ha cho glycopro
tein gp39, mt cu t gn ca CD40 (Xq27).
Cng c trng hp biu hin bnh gim y - globulin trong
mu (hypogamma-globulinemia) thng thng l gim hm
lng IgA huyt thanh. Mt s trng hp ca bnh trn l do
nhim virus Epstein-Barr.

11.3. Thiu ht m in dch nguyn thy ca cc t bo T

S thiu ht min dch cc t bo T thng biu hin cc

dng bnh khc nhau:

11.3.1. S pht trin bt thng ca t bo ngun lym pho

giai on sm ca s bit ha

Bnh thiu ht nguyn thu dng lympho T mang tnh di

truyn bm sinh, biu hin hi chng Di - George v c
chng minh bng th nghim ct b tuyn c, gy s pht trin
bt bnh thng ca dng lympho T. Bnh ny cn lin quan n
s thiu ht di truyn adenozin deaminaz. S thiu ht enzim
trn ko theo vic tch ly cc cht trao i gy c cho t bo
ngun lympho nh dATP v dGTP. Cc cht c ny km hm
enzim ribonucleotit reductaz l enzim cn thit cho s tng hp
ADN v s nhn ln ca t bo.
 155

11.3.2. Biu hin thiu ht cc phn t phn lp II ca MHC

Bnh th hin do thiu ht mt phn cc t bo lympho T

CD4* gy ra s bt hot cc gen ca phn t lp II. Mt s dng
hi chng thiu ht lympho T c km theo s bt thng biu
hin cc phn t lp I ca phc h MHC.

11.3.3. Hin tng m t iu ha gin mao m ch do di tru y n

Bnh ny do thiu ht cc t bo T km theo thiu ht IgGv,

IgG, v IgA lm mt kh nng iu ha gin mao mch ca tiu
no v mt. V t bo hc v sinh hc phn t, ngi ta thy
thng xuyn t gy cc nhim sc the 7 v 14 vng ca cc
gen TCR v Ig. T lin quan n sai st trong vic sa cha
ADN.

11.3.4. Thiu ht cc protein kt dnh bch cu

Hi chng ny thng gi l thiu ht kt dnh bch cu (Leu

cocyte Adhesion Deficiency: LAD) lin quan n thiu ht biu
hin cc protein mng di h p2 ca cc integrin. Integrin l
mt h cc glycoprotein mng c cu trc heterodime c chc
nng ch yu l kt dnh gia cc t bo, bn trong t bo v
ngoi bo. Nguyn nhn ca bnh l do cc t bin ca gen m
ha cho chui p (CD 18), lm mt i s c mt cc dng het-
erodime CDlla/CDl8, CDllb/CDl8 v CDllc/CD18.

11.4. T hiu hut

m in dich
cc thc
bo v b th

Dng thiu ht min dch thc bo thng th hin cc bnh

sau y:
- Gim bch cu trung tnh do bm sinh thng ko theo d
nhim trng Staphylococus aureus v cc mm bnh gram m.
- S thiu ht bch cu ht (granuolopenia) cng gy ra mt s
bnh thiu nng ca bch cu a nhn nh gim kh nng ha
hng ng v di ng ca cc bch cu thc bo.
156

- S thiu ht cc yu t b th c bit l C l-N H ko theo bnh

ph mch bi v Cl-INH tham gia vo s iu ha tng th cc
phn t trong c ch ng mu v vim.

11.5. S th iu ht m in dch th cp v AIDS

S thiu ht min dch th cp thng c biu hin cc

bnh sau:

11.5.1. Cc bnh v mu v ung th

l cc bnh v mu mn tnh dng B trong c bnh

macroglobulin Waldenstrom, bnh u ty, bnh u lympho Hodg
kin l do thiu ht qu mn mun. Cc bnh nhn thng b
nhim vi khun, virus hoc nm vi sinh vt. Tuy dc im min
dch th dch bnh thng nhng s thiu ht min dch t bo l
mt trong nhng yu t d bo trc ng thi vic sn xut
IL10 t pht tng ln.

11.5.2. Thiu hut

m in dich
do ri loan
trao i cht

Tnh trng dinh dng km protein thng gy ra s thiu ht

min dch th cp cc nc ngho. Hin tng ny gy ra s
bin i bt thng ca cc t bo T v lm tng t l y globulin
trong mu.
Thiu ht min dch t bo c th gy ra bnh suy thn. Hi
chng h thn v cc bnh ng rut cng do s thiu ht min
dch km theo hin tng gim y globulin trong mu.

1.5.3. Bnh AIDS v con ng ly truyn

Thiu ht min dch do HIV (Human Immunodeficiency Virus)

l loi bnh do virus gy ra s suy gim min dch cho ngi
c pht hin M trong nm 1981, n nay lan ra khp th
gii. Theo d on ca t chc y t th gii (WHO), n nm
2000 s c khong 26 triu ngi b nhim HIV trn ton th gi)
v mi nm c khong 1,8 triu ngi trong s s cht v cn
 157

b n h s u y gim min dch mc phi (AIDS: A cquired I m m u n o

Defficiency S y n d ro m e ) do HIV gy ra. H in t ng cc nc
c h u A v c h u Phi trong n h n g n m u ca th k XXI cn
b n h n h i m HIV c chiu hng gia t ng. V vy c n p h i c
n h n g bin p h p k h o a hc hu hi u v tin h n h n g h i n cu loi
th u c v vacxin c hi u q u n g n n ga s tin tr i n b n h
t r o n g cng ng d n c.
H IV c h a i loi k h c n h a u l HIV-1 (gy ra 98% b n h lan
t r u y n ) v HIV-2 chim u th v n g t y c h u Phi, t lan
t r u y n t r n t h gii. HIV l cc r e t r o v ir u s c b m y di t r u y n
th u c h L en tiv iru s.
S ly t r u y n v iru s c th xy ra th e o bn con ng s a u y:
- Con ng tim truyn do dng chung kim tim chch ma ty.
- Ly nhim bng con ng truyn mu ca ngi bnh cho
ngi khe.
- Con ng tip xc tnh dc.
- Ly truyn bnh t ngi m mc bnh sang thai nhi qua nhau
thai.

11.5.3.1. Tin trin ca cc du hiu sinh hoc v bnh l

S tin trin ca bnh c theo di bng cc du hiu ca vi-
rus, nh lng khng th khng HIV v o cc thng s" lin
quan n s thiu ht min dch.
11.5.3.1.1. Pht hin virus: pht hin virus, ngi ta o
protein p24 lu hnh trong mu, (l protein ch yu ca v cap-
sit virus) phn lp virus t mu hoc t cc lympho tun hon
bng cch nui cy t bo v o p24 hoc o hot ng transcrip-
taz ngc trong dch ni ca mi trng nui cy. Ngi ta cng
s dng phng php pht hin genom tin virus hoc ARN vi-
rus bng cch khuch i enzim trc tip hoc gin tip (phng
php PCR v RT-PCR).
11.5.3.1.2. Nghin cu khng th chng HV: Vic nghin cu
ny c thc hin bng k thut ELISA i vi cc protein khc
nhau ca virus. Phng php ny c s dng thng thng
pht hin cc i tng c huyt thanh dng tnh. Tip theo l
k thut phn tch chuyn thm min dch protein (Western
blot) bt buc cn c lp li i vi mu huyt thanh th hai.
S dng khng th khng cc protein ca lp v v cc protein
GAG.
158

Du hiu min dch: du hiu quan trng l vic gim dn dn

s lng lympho T CD4+ trong mu v mt s du hiu khc
nhau nh tng hm lng P2 microglobulin huyt thanh, tng
neopterin huyt thanh v nc tiu, tng nng IgG v IgA
trong huyt thanh.
11.5.3.1.3. Qu trnh tin trin ca bnh: Ngi ta chia lm ba
thi k tin trin bnh.
- Thi k s nhim-, din ra trong mt s tun nhim HIV biu
hin s lng khng nguyn p24 tng ln v khng th khng
p24 theo cng tng ln, s p ng ca T gy c (Tc) cng
tng ln. Trong nhng tun u nhim HIV, s lng lympho
T CD4+ gim xung nhng sau li tng ln.
- Thi k th hai: ko di t 1 n 12 nm c gi l pha khng
c triu chng xut hin, hay pha tim n. Trong thi k ny
s lng khng th n nh mc cao, khng nguyn p24
thng kh pht hin nhng virus HIV c th c pht hin
bng PCR hoc RT-PCR trong cc lympho ca mu v trong
cc m bch huyt.
- Thi k th ba tip theo xut hin khi s lng lympho T CD4*
gim nhanh xung di mc 200 t bo/ml mu. Lc hi
chng lm sng ca bnh suy gim min dch xut hin. Trong
giai on ny, ngi ta c th pht hin khng nguyn p24, t
l phn trm cc t bo b nhim virus v i khi c th thy
gim t l khng th khng cc protein GAG (p24, pl7), ng
thi t l chung ca cc t bo T (T CD4\ T CD8+) cng gim
xung. Hi chng suy gim min dch mc phi c xc nhn
bng s xut hin cc mm bnh nhim trng "c hi", s xut
hin cc khi u trn da Kaposi (Sarcome kaposi); l khi u
biu m mch, b ha sng c mu ta trn da. Biu hin
thi k tin AIDS c th l st, gim trng lng c th, m
hi ban m.
giai on AIDS, cc mm nhim bnh "c hi" c th do cc
nm Candida, Cryptococus gy bnh phi, cc bnh Crypto-
sporidiose km theo a chy, cc bnh vim phi do Pseumocystis
carinii, nhim lao Microbacterium, bnh trng bch cu
(Toxoplasmose), nhim virus trn da nh Herpes simplex, nhim
Salmonella, Streptococcus, cc mm vi khun to m phi,
xng hoc mch mu. v.v...
 159

11.5.3.1.5. Cu trc ca virus HIV

Li pit k p
( m n g vi ru s)

capxit

Hnh 11.1. S cu trc HIV (theo J.P. Revillard, 1994)

V virus c hnh thnh t lp lipit kp ging mng sinh cht

ca t bo, cha cc glycoprotein (gp) 120 kDa, bc l ngoi mng
v mt gp nh 41 xuyn qua mng, c hai phn t glycoprotein
u bt ngun t phn t tin thn gp 160. Gp 120 lin kt d
ng vi phn t CD4 ca lympho T CD4*. v capsit cn gi l
lp bc gm bn loi protein p24, pl7, p9 v p7, u bt ngun t
protein tin thn p53 kDa c m ha bng gen gag ca virus.
Cc c th b nhim HIV s sn xut ra mt khng th chng li
protein gag v p24. Bc capsit cha hai phn t ARN genom ca
virus v 3 loi enzim transcripta'/ ngc, proteaz v integraz
(loi endonucleaz lp rp).
T chc genom ca virus gm 3 gen cu trc, ch yu chung
cho cc retrovirus, cng nh cc gen iu ha khc nhau ring
cho HIV. C/c gen cu trc l gen gag, to ra nhiu sn phm
pl7, p24, p7 v p9 lin kt vi ARN. Gen pol m ha cho cc en-
zim khc nhau nh po (proteaz), p66 v p51 (transcriptaz
ngc) v p34 (endonucleaz integraz) gen env m ha cho cht tin
thn gp 160 (gm gpl20 v gp41)
160

cc u tn cng 5' v 3' ca genom virus c cc trnh t lp

li o ngc LTR (long terminal repeats) cha ton b cc tn
hiu cn thit cho s phin m (transcription) ca provirus v
cho s gn kt vo cc gen ca t bo. iu ng ch l mt s
trnh t iu ha ca cc LTR cng ging vi cc trnh t iu
ha ca t bo. Cc gen iu ha l gen tat (trans activator) m
ha cho protein 14 kDa cn cho s ti bn virus. Protein ny tc
ng mc ca trnh t khi ng TAR nm trong vng LTR,
c chc nng loi b s km hm sao m. Gen rev m ha cho pl
20 kDa lm n nh v vn chuyn cc bn sao kch thc ln
mARN cn cc m ARN ny li m ha cho cc pl cu trc ca
HIV. Gen nef (negative regulator factor) m ha cho pl 27 kDa
(s c photphoril ha v kt hp vi axit myristic iu bin
s biu hin phn t CD4 ca mng t bo). Gen vif (virion infec-
tivity factor) m ha cho pl 23 kDa tham gia vo s chn v s
bin thi ca virus. Gen vpu c hiu cho HIVl m ha cho pl
16 kDa ng vai tr gii phng cc virion t t bo b nhim. Gen
vpx c hiu ca HIV2 v SIV (virus gy bnh AIDS kh) m
ha cho p l 14 kDa tc ng mc c hiu i vi vt ch
nhim bnh. Cui cng gen vpr m ha cho p l 15 kDa c vai tr
lm tng tc ti bn v hiu qu tc nhn bnh l ca virus
i vi t bo T.
11.5.3.1.6. Qu trnh nhim virus v chu trinh ti bn
Th th ch yu ca t bo vt ch i vi cc HIVl v HIV2
l phn t CD4. S tng tc virus i vi CD4 th hin i lc
cao gia khu vc (domain) N tn cng DI ca CD4 v mt vng
c hnh thnh t 4 phn khng i ca phn t gpl20. Phn
t gpl20 c hai vng rt ging cu to ca HLA-DR v mt vng
khc c cu trc ging khu vc VH ca cc Ig. S tng tc phn
t gpl20 - CD4 ko theo s ci t vng k nc ca gp41 vo
lp mng k nc v to ra s dung hp virus-t bo vt ch.
Mi mt t bo lympho T CD4+ca ngi c mt s lng CD4
nhim virus (khong 1000 phn t/ t bo (pht hin bng
Cytofluorometry- php o hunh quang t bo). Virus HIV c th
nhim d dng vo t bo vt ch nh cc con ng sau:
- Khng th chng gpl20 to iu kin thch hp cho virus xm
nhp t bo.
- Cc th th ca C3 (ca tbo thc bo, lympho B v t bo nang
c thy) c th lin kt vi virus c opsonin ha bng b th.
 161

- Gangliozylxeramit ca b mt mng t bo (dng biu m rut,

m o) v t bo thn kinh c th lin kt vi phn t gpl20.
1.5.3.1.7. p ng min dch chng H IV trong qu trnh nhim
Khng th: sau khi nhim virus t 3 n 12 tun thy xut
hin khng th trung ha tng i yu khng li vng V3 ca
phn t gpl20 l khng chc chn (in vivo) v khng th khng
th phn hy c virion khi c mt b th.
Cc lym pho T gy c
S p ng ca cc lympho T CD4* i vi cc peptit ca HIV
d dng nhn thy v chnh s hot ha lympho T CD4 in vitro
gy ra s ti bn cc virus. Ngi ta cng thng bo s c mt
ca cc lympho T CD4 gy c c hiu vi cc peptit NEF v
nhiu cng trnh chng minh r lympho T CD4 gy c c
hiu vi gpl20.
ng ch l p ng ca lympho T CD8+ gy c xut hin
lc s nhim v tn lu lu di trong thi k khng xut hin
triu chng bnh v ch bin i vo lc cui ca qu trnh bnh.
Cc lympho T CD8+ rt c th ng vai tr kim sot s ti bn
ca virus trong thi k khng biu hin triu chng bnh v c
th tham gia vo cc hin tng min dch bnh l.
S gim hot tnh CD8 giai on cui cng ca bnh AIDS
trng vi s vic cc t bo CD8+ CD57+ b km hm do c t t
bo gy ra.
11.5.3.1.8. V sao b bnh AIDS do H V hin nay kh cha khi
HIV gy tnh bt thng v s lng lympho T CD4+
Ngi ta thy c hin tng gim mnh s lng v gim
nht thi cc t bo lympho T CD4+ ca mu. Trong thi k lm
sng cha biu hin triu chng bnh AIDS, s lng qun th
t bo ny gim dn dn. Tip theo, cc phn ng qu mn mun
gim xung bt bnh thng in vivo. S tng hp IL2 v IFNy
cng gim. S ti bn virus ko theo hiu qu bnh l t bo trc
tip. T l cc t bo b nhim virus trong thi k cha c triu
chng bnh khong t 1/100 n 1/10.000 (trong mu) v trong cc
hch bch huyt c t l ny cao hn.
Mt c im quan trng l cc lympho T CD4+ b nhim virus
c th dung hp vi cc lympho T CD44 bnh thng hnh thnh
cc t bo ln nhiu nhn, lm tng hiu qu bnh l. Hin
tng ny gi l Syncytium.
162

Mt c ch bnh l khc l cc lympho T CD4+ b nhim c th

trnh din cc peptit virus kt hp vi cc phn t HLA lp I s
l t bo ch b tiu dit bi cc lympho T gy c. Mt khc cc
lympho T CD4+ khng b nhim c th nut cc phn t gpl20
ha tan (ng vai tr APC) v trnh din cc peptit ch bin
kt hp vi phn t lp II, gy ra kt t cc phn t CD4 cng
vi khng th khng gpl20. Hu qu ca hin tng trn l to
ra tn hiu mt ng (anergy) v to ra ci cht apoptosis cho
chnh cc t bo T CD4.
*S bt thng ca cc i thc bo, cc t bo B v nhng t
bo khc:
S nhim virus i vi cc t bo trnh din khng nguyn c
th lm yu i chc nng ca nhng t bo ny, ng thi to
iu kin cho s phn hy chng bi tc dng ca cc t bo Tc.
Cc t bo B th hin kh nng sn xut tng ga ma v alpha
globulin (IgG, IgA) v lm thay i t l cc di lp IgG khi b
nhim virus. S p ng khng th chng li p24 chim u th
lu di trong qu trnh tin trin bnh.
Ngi ta cng thy r s thiu ht chc nng dit vi khun
ca cc t bo trung tnh, chc nng ca NK cng suy yu.
Tt c nhng s thiu ht min dch trn do HIV gy ra s
to iu kin d dng cho cc vi sinh vt c c hi xm nhp vo
c th ngi bnh.
Cui cng, h gen ca HIV l ARN lun lun t t bin, nn
vic to vaccin phng tr bnh chng HIV ang gp nhiu kh
khn v qu trnh nghin cu vaccin cn ang l nhim v quan
trng ca cc nh khoa hc y hc v sinh hc phn t.
 163

Tm tt chng XI

. Nhng s thiu ht min dch bm sinh l cc bnh him thy

phn ln do cc t bin gen m ha cho cc phn t c chc
nng ch yu ca h min dch.
1. S thiu ht cc Ig ko theo bnh nhim trng.
. Nhiu bnh thiu ht min dch s c cha bng liu php
ghp t bo ngun to mu, hoc liu php di truyn d cho
kt qu tt trong mt s trng hp.
Ngi ta phn bit s thiu ht min dch th cp vi s thiu
ht min dch bm sinh. S thiu ht min dch th cp do
nhiu nguyn nhn nh ung th bch cu dng B, cc bnh u
lympho Hodgkin, do trao i cht ri lon, do nhim trng cc
vi sinh vt, c bit l virus gy suy gim min dch HIV.
f. Hi chng suy gim min dch mc phi (AIDS) ngi l do
nhim virus HIV1 v HIV2, nhng ch yu l HIVl (98% lan
truyn bnh) S tin trin ca bnh c th chia lm ba thi k:
thi k s nhim, thi k tim n (ko di t 1 n 12 nm) v
thi k hi chng suy gim min dch vi thi gian ngn tnh
theo nm thng.
(. S p ng min dch chng virus HIV trong qu trnh nhim
c th hin bng khng th chYig li cc glycoprotein ca
lp v virus nh gpl20, cc lympho T gy c, T CD4+, c bit
l T CD8\
Hu qu ca vic nhim virus HIV l gy ra s thiu ht min
dch, c bit l s gim bt bnh thng v s lng ca lym-
pho T CD4* trong mu, gim chc nng min dch ca nhiu
loi t bo ca h min dch v gy ra p ng min dch th
dch bt bnh thng ca cc t bo B. T dn n cc
nhim trng c hi, xut hin nhiu bnh khc nhau.
Chng XII. Dung np min dch v bnh t min

12.1. D ung np m in dch

12.1.1. Khi nim

Dung np min dch (immunological tolerance) cho php c

th trnh phn ng vi cc thnh phn ca bn thn trong thi
k c th mi sinh ra. Ni mt cch khc nh c ch dung np
min dch cc t bo lympho c th phn bit c ci bn thn
v ci khng phi ca^n thn.
Nhng th nghim u tin ca Medawar v cng s (1953)
cho bit khi tim cho chut non A cc t bo ca chut trng
thnh CBA s ngn cn s thi b mt mnh ghp da ca chut
ny trn chut A trng thnh.
Cc khng nguyn ho tan cng c th to ra s dung np. V
d albumin huyt thanh b (BSA) c tim cho th mi sinh s
ngn cn vic sn xut ra khng th chng li BSA th trng
thnh. S dung np min dch cng c th c to ra cc ng
vt trng thnh nhng i hi phi tim mt lng khng
nguyn rt ln. Weigle v cng s chng minh rng tc ng
ca khng nguyn nng thp s luyn tp cc lympho T,
trong khi , nng cao ca khng nguyn gip cho vic luyn
tp i vi cc t bo B v T. Nh vy tnh phn ng ca mt
ng vt i vi mt khng nguyn phn nh mi quan h hp
tc gi cc t bo B v T trong vic sn xut ra mt khng th.
Mt phn t khng nguyn c dung np nu bn thn n
khng b ci bin bng cc i thc bo trc khi n c trnh
din cho cc t bo lympho.
166

12.1.2. Cc c ch to ra dung np min dch

Ngi ta nu ra cc loi c ch gii thch sau y:

12.1.2.1. S y n l n g m in dch
Ngi ta thy r h min dch dung np vi cc thnh phn
ca bn thn c th v hin tng ny gi l s yn lng min
dch. Cc thnh phn ca bn thn ch c th tr thnh cht gy
min dch (immunogene) nu chng kt hp vi cc phn t lp
II ca MHC. Tuy vy, cc phn t trong tun hon mu c th b
bt gi bi cc lympho B, b ci bin v kt hp vi cc phn t
lp II ca MHC nhng nng thp s khng to ra i lc
gi tn hiu cho cc t bo T. Nhng t bo B thng xuyn
yn lng.
S yn lng min dch cng c th do khng c cc gen m ho
cho cc th th ca t bo lympho chng li mt s" quyt nh
khng nguyn ca thnh phn bn thn.

12.1.2.2. C c h loi b dng

Ngi ta c nhiu bng chng cho thy c mt c ch loi b
tt c nhng t bo c hiu vi bn thn m khng lm thay
i phn cn li ca kho d tr cc t bo lympho. V vy, chnh
cc khng nguyn ca bn thn (autoantigen) tham gia la
chn loi b cc dng. Thin hng c bit ca c th s sinh l
kh nng dung np nn trong qu trnh pht trin h min dch,
cc t bo lympho c mt giai on tip xc vi autoantigen
v gy ra ci cht cho cc dng lympho t phn ng. l c ch
loi b dng.
Mt s bnh t min ca ngi km theo s tng cao nng
ca cc t khng th (autoantibody) c hiu gy ra bnh l. Tuy
nhin cng c mt sbnh t min lin kt vi cc t khng th
nhng vai tr gy bnh ca cc t khng th khng r rng. Mt
s bnh vim mn tnh khng kt hp vi cc t khng th c
hiu li do hiu qu bnh l cu cc lympho T- t phn ng.
Cc quan st lm sng bnh t min cho php phn bit s
khc nhau ca bnh nh cc bnh c hiu vi c quan hoc vi
m t bo (v d bnh vim tuyn gip, chng nhc c, bnh
Pemphigus v cc bnh t min h thng nh lupus ban ri
 167

rc. Sau y l danh sch cc bnh t min d c nghin cu

(bng 12.1)
Bng 12.1. Cc bnh t min ch yu (theo J.F. Bach 1993).
/. B nh t m i n k h n g c hiu c qu a n
Lupus ban ri rc.
Vim nhiu khp dng thp khp.
Hi chng Sjogren.
Thiu mu do b tan hng cu, bnh gim bch cu, gim tiu
cu t min.
Bnh x cng lp da b (Sclerodermia).
Vim da c.
2. B n h t m in c h i u c q u a n

C quan Bnh t min bit r Bnh t min cn nghi

vn
Tuyn ni tit Vim tuyn gip Thiu nng b my sinh
dc
Bnh Basedow
Tiu ng tui tr
ph thuc insulin.
D y Thiu mu Biermer
rut
Thn Hi chng
Goodpasture
C Chng nhc c
Bnh thp khp c.
Da Bnh Pemphigus Bnh vy nn.
Bnh tri tc.
Gan Vim gan c tnh
Vim gan mn tnh.

12.2.2. Cc t khng nguyn tham gia

Vic hiu bit cc t khng nguyn (autoantigene) ca bnh t
min c ngha rt quan trng, cho php hon thin cc xt
nghim pht hin chn on c hiu v d bo hng diu tr.
Ngy nay, ngi ta c" gng nhn bit cc phn t khng nguyn
nh cc ngn hng bc l ADN b sung (c-DNA) trc ht l cc
epitop B v cc peptit kt hp vi cc phn t MHC c trng
168

cho bnh. Ngay c khi c c cc t khng th tng i c

hiu cho mt loi bnh th vic nghin cu nguyn nhn ca
bnh cng gp nhiu kh khn bi v cc t khng th dng
nh c nh trn cng mt cu trc cng c th nhn bit cc
khng nguyn khc nhau. Chng hn t khng th chng
Laminin, chn colagen IV hoc t khng th chng khng
nguyn bnh Godpasture u c" nh ging nhau trn cc lp t
bo y tiu cu thn.
Ngi ta cng nhn thy 4 autoantigen khc nhau c mt ti
cc khp ni t bo biu m, 4 loi bnh Pemphigus khc nhau.

12.2.3. Cc nguyn nhn ca bnh t min

12.2.3.1. Nguyn nhn d i truyn

Bnh t min do nhiu yu t' gy nn: nh cc du hiu di
truyn, cc yu t mi trng.
Hin tng di truyn bm sinh gy ra cc bnh tiu ng ph
thuc insulin, x cng mng thn kinh, bnh vim nhiu khp
dng thp khp, bnh lupus ban ri rc....
Phn ln cc bnh t min l do kiu hnh HLA qui nh. Mi
quan h gia kiu hnh HLA vi bnh t min c th c gii
thch l do chc nng trnh din cc peptit ca bn thn HLA .
Mt s cc nghin cu mi y cng c cho gi thuyt trn.
Mt nguyn nhn di truyn tip theo l nhng t thiu ht
bm sinh cc thnh phn ca b th nh C2, C4, CRl, (CD35)
chng hn 0,3% c s thiu ht d hp t dng C2; 40% c th
ng hp t b bnh lupus ban ri rc. C th gen TNF v cc
protein sc nhit c vai tr trong mt s" bnh t min.

12.2.3.2. Cc nguyn nhn m i trng

Rt nhiu nghin cu cho rng cc vi sinh vt gy ra bnh t
min, chng hn virus bnh si, virus Epstein-Barr gy bnh
vim nhiu khp. Mycobacterium cng gy bnh vim nhiu
khp.
Ngi ta cn nhn thy s thay i ca cc vng a l khc
nhau, nh t' c a (atopy) cng gy ra t l mc bnh t min
khc nhau. V d vng Bc bn cu c s lng ngi mc bnh
 169

vim a khp, bnh tiu ng typ I nhiu hn cc vng khc.

Mi quan h gia vi sinh vt v bnh t min c th l gin tip
nhng tc nhn nhim khun thng gy ra cc bnh vim th
cp. V d bnh vim lot d dy thng lin quan n vi khun
Helicobacter pylori, triu chng lit nh kiu co tht do retrovi
rus HTLV-1 gy ra.

12.2.4. Cc c ch hiu qu ca bnh t min

12.2.4.1. Vai tr bnh l ca k h n g th

Nghin cu cc loi bnh t min cho php xc nhn r c ch
gy tn thng ca khng th chng li cc th th. Chng hn
trong bnh nhc c (Myasthenia), s c nh ca khng th ln
th th c th gy ra s ph hu chc nng vn ng ca t bo.
Khi lin kt vi th th t khng th bao vy tc ng ca cht
truyn dn sinh hc (Mediator), l cht i khng (antagoniste)
hoc thay th cht truyn dn sinh hc ng vai tr hip ng
tc dng hoc hp vn (agoniste), kt hp cnh tranh vo th
th, t khng th cng c th khng c hiu qu sinh hc. Tuy
nhin t khng th c th iu bin th th khng cho n bc l
trn mng t bo. Cui cng t khng th khi kt hp vi th th
mng s kch thch t bo kt hp vi b th v hp dn t bo
git n ph hu t bo v m theo c ch gy c t bo.
Trong bnh u nng tuyn gip Basedow, t khng th chng
li th th ca TSH s phn ng vi vai tr ca mt cht hp vn
(agonist) lm tng AMPV ni bo v kch thch s tng hp
hocmon tuyn gip. Mt s t khng th biu hin hot tnh en-
zym (c gi l abzym) phn hu lin kt photphodieste gy tn
thng AND trong bnh lupus ban h thng.

12.2.4.2. Vai tr ca lym pho T t p h n ng v cc x ito k in

Vai tr gy bnh ca lympho T cha c chng minh trc
tip. Tuy nhin cc nghin cu v xitokin TNFa, ILj, ILg c
sn xut nhiu cc t bo mng hot dch trong bnh vim a
khp cng gi vai tr du hiu bnh ca cc xitokin ny.
Nhng nghin cu v c ch v nguyn nhn gy bnh t min
c th gip cho vic iu tr cc bnh t min. Chng hn ngi
170

ta ra phng hng tim chng peptit cng vi cc t bo

T, hoc ca cc th th dng T gy bnh kch thch in ivo s
p ng Tc chng li dng t bo bnh l.
Mt hng khc l dng t khng nguyn tng hp cnh tranh
vi khng nguyn bnh l ca c th trong lin kt vi phn t
lp II HLA. K thut ny c hiu qu khng ch phng nga
bnh m cn cha bnh cho mt s m hnh ng vt. Nhiu cng
trnh mi y chng minh cch iu tr cho ung mt dng t
khng nguyn s cho php loi b bnh vim no tu d ng,
bnh vim khp colagen typ II v mt s bnh d ng khc.
Trong trng hp bnh vim no tu cch iu tr trn lm
xut hin cc lympho TCD4\ TH2 tit ra IL4, IL10, chng li
hu qu gy bnh ca lympho TH1, ng thi lm xut hin
TCD8+ c hiu vi mielin, lm gii phng TGFp c hiu qu km
hm khng c hiu i vi t khng nguyn.
Ngi ta cng ang nghin cu dng khng th n dng lm
cht km hm min dch cha mt s bnh t min trn m
hnh ng vt. s dng khng th n dng cha bnh cho
ngi cng ang c nghin cu lm gim tnh sinh min
dch trong ng dng cy ghp m, cy ghp c quan v xc nh
c ch tc ng ca khng th trong cc bnh t min.
 171

Tm tt chng XII

1. Cc C ch dung np t nhin i vi cc thnh phn ca bn

thn c tip thu trong qu trnh pht trin h min dch.
C ch ny biu hin mc khc nhau ca cc lympho T v
B (c ch yn lng min dch, c ch loi b dng, c ch km
hm ca lympho T, s mt ng, biu hin s hp tc gia t
bo T v B trong dung np min dch).
2. Cc bnh t min ngi bao gm nhiu dng khc nhau nh
cc bnh vim mn tnh, bnh ti nhim vi sinh vt, bnh t
min h thng v c hiu cc c quan.
3. Bnh t min l do nhiu gen gy ra, c bit chu s kim
sot ca cc gen MHC v cc gen b th.
4. Cc yu t mi trng nh nhim trng vi khun, virus v yu
t c a c vai tr nht nh trong cc nguyn nhn gy bnh
t min.
5. Cc c ch hiu qu ca bnh t min nh vai tr ca khng
th, lympho T t phn ng, cc xitokin c th gip cho vic tm
hiu bnh t min, tm ra phng hng iu tr bnh.
 173

Chng XIII. S tin ha min dch ca cc loi

ng vt

13.1. M u

Theo cc nghin cu v c sinh hc v tin ha, nhiu nh

khoa hc nh Grass, Devillier (1965); Carrol (1988); Margulis,
Schwartz (1988) cho rng, loi ngi v phn ln cc loi ng
vt khc u thuc v mt ngnh ln cc ng vt c dy sng
(Chordata). H min dch ca chng th hin ba c im sau
y:
1. S c mt m hch biu m lympho vng hu lin kt vi
cc khe mang.
2. S c mt cc m ty lympho kt hp vi ng tiu ha.
3. C kh nng nhn bit cc khng nguyn ngoi lai (alloanti-
gene) v phn ng chng li chng.
Trong khi s khc nhau ch yu gia cc ng vt dy sng
v c xng sng vi cc ng vt khng xng sng l ng vt
khng xng sng khng c phn ng ca khng nguyn l vi
mt cht ha gii c hiu kiu khng th immunoglobulin,
ngoi tr ng vt da gai (Echinoderma). Cc phn ng bo v
ca cc ng vt nh bt bin, giun, thn mm, nhuyn th, cn
trng loi cu gai c hnh thi khc nhau. Hn na, mc d c s
pht hin hin tng thc bo ca Metchnikoff vo nm 1882
ng vt ngnh da gai (sao bin) nhng s lng cc cng trnh
nghin cu v tnh min dch ca ng vt khng xng sng
vn cn hn ch v mang tnh l t cho n nhng nm 60 ca
th k 20. Tuy nhin ngnh chn khp (Arthropoda) l ngnh
ng vt khng xng sng chim 90% s loi ng vt bit,
s lng cc nghin cu v tnh min dch kh phong ph v tp
trung theo ba hng chnh: cc t bo tham gia vo tnh min
dch, cc cht ha gii min dch v cc phn ng min dch.
174

13.2. Kh nng m in dch ng vt khng xng sng

13.2.1 Cc biu hin t bo ca h min dich

Cc t bo ca h min dch ng vt khng xng sng c

th hnh thnh theo hai nhm l cc t bo c nh v cc t bo
tun hon mu.
Cc t bo c nh i khi tp trung li nhng thng rt hay
phn tn ton b c th. cc cn trng, cc trung tm sinh
mu thng c chc nng l ni sn sinh ra cc t bo tun hon
mu ng thi c c chc nng l c quan thc bo v l ni tng
hp ra cc phn t khng khun. Ngi ta cng m t cc
hch sinh mu cc loi rn nc thuc lp gip xc (Crustacea)
v nhuyn th (Mollusca). Ngoi ra cn trng cc t bo mng
bao tim tp trung li thnh tng m hch thc hin chc nng
m bo (endocytosis). 0 rn nc c cc i thc bo c nh
thnh tng nhm t 4 n 5 t bo dc theo mch mu v khe
mang. Cc t bo tun hon mu xut hin ng vt chn
khp v thn mm, trong khi bch cu xut hin cc nhm
khc ca ng vt khng xng sng. 0 cn trng c hai dng t
bo mu l t bo mu khng ht v c ht. T bo mu c ht
kiu 1 tham gia vo hin tng thc bo v hin tng kt t
(coagulation), t bo c ht kiu 2 hoc c ht in hnh c th
to ra th so v cc bao bao vy vt th l v tng hp mt
phn lyzozim ca mu tiu ha vt l. Cc t bo c ht kiu
3 hoc dng t bo plasma - i thc bo cha cc th lyzoxom.

13.2.2 Cc cht ha gii ha hc

Tuyt i a scc ng vt khng xng sng u khng c

khng th. Nhng chng cng tng hp mt s dng phn t c
hot tnh c i vi vt th l hoc c mt s cht hip dng tc
dng vi cc t bo min dch, tham gia vo phn ng kiu
opsonin ha. Cc cht c i vi cc vt th l c mt ng
vt khng xng sng c th l cc lyzozim, cc phn t gy tc
ng phn hy mu ca ng vt c xng sng, cc cht gy
phn hy vi khun c thn mm, da gai, giun t l nhng pro-
 175

teir. c kch thc nh t 2.10' - 4,8.10' alton. Mt s cht khc

nh melanin c tng hp cn trng v rn nc c tc dng
chng li k sinh trng v cc tc nhn gy bnh. Hu ht cc
ng vt khng xng sng c th tng hp lectin (agglutinine)
v cc enzim xc tc cho phn ng tng hp melanin phi hp
tham gia vo c ch bo v min dch t bo. l nhng phn
t c kh nng to iu kin cho s nhn bit v/hoc lm kl
dnh nhng t bo ca vt th l. Chc nng ca cc lectin vn
cha c chng minh y . Tuy nhin ng vt thn mm
ngi ta chng minh cc lectin c th ng vai tr trong vic
nhn bit ci khng phi ca bn thn nh cc t bo mu ca
chng to lin kt gia cc th th trn mng t bo ca mt s
t bo mu l v cc t bo vt th l.
H thng phenoloxydaz (PO) ca ng vt khng xng sng
cng l mt dy phn ng a n hot ha prophenoloxydaz
(Pro PO) trong mu ng vt chn khp tip theo cc PO l xc
tc cho chui tng hp melanin. Chang hn s hnh thnh
quinon l hp cht gy c chng k sinh trng.
Cc hp cht glycan hoc ni c t endotoxin cng vi cc ion
canxi tham gia vo phn ng kt t dch huyt (hemolymphe)
cc giai on u, c th so snh vi h thng b th ca cc ng vt
c vu.

13.2.3 Cc phn ng min dch ng vt khng xng sng

Ngi ta thy mt s cht dng attaxin c cn trng ch c

hot tnh dit mt s dng vi khun gram m trong khi cc cht
xecropin (ccropine) c ph dit khun rt rng i vi cc vi
khun gram dng v vi khun gram m. S tng hp xecropin
c cm ng tc thi bng cc mm bnh c mt trong h tun
hon mu ca cn trng (Insecta).
Cc phn ng min dch qua trung gian t bo ca ng vt
khng xng c mt tt c cc ngnh ca chng. l hin
tng kt t (coagulation) vi s tham gia ca cc yu t th dch
v t bo. ngnh chn khp, hin tng kt t huyt tng l
do s kt ta ca mt dng protein c hiu. Hin tng kt t
cn km theo vic bi tit v hot ha mt s yu t ca t bo
lm bin dng cc t bo mu c ht kiu 1 v 2 to tip xc vi
176

vt th l, gii phng cc yu t nhn bit ca h thng

phenoloxydaz c mt cn trng. Kt t l giai on u tin,
giai on nhn bit ca phn ng min dch ng vt khng
xng sng.
Kh nng thc bo c thc hin bng cc t bo c nh v
cc t bo tun hon mu xy ra theo mt qu trnh tng t
nh cc ng vt c xng sng. Tuy nhin, nhng s tip xc
min dch lun c thc hin c tnh ngu nhin, rt him ch
ng theo kiu ha hng ng. Cc t bo ny hnh nh khng
c th th c hiu v khng c s tham gia ca globulin min
dch. Nng lng tiu th dnh cho hin tng thc bo l do
qu trnh ng phn k kh. S hnh thnh th bao (capsules)
v th hch (nodules) l mt phn ng c bit c mt ng vt
khng xng sng nh cn trng v gip xc nh rn nc din
ra theo ba giai on. Giai on u l nhn bit khng nguyn
nh m t trn. Giai on th hai l tch ly t bo tun
hon mu v chnh cc t bo ny l thnh phn ca th bao,
bao bc quanh vt th l (vt k sinh chng hn) hoc to ra th
hch trong trng hp vi vi sinh vt. giai on ba cc t
bo tun hon mu i khi bin i su sc, to ra lp v lm c
lp vt th l v loi b n ra khi c th cn trng. Trong cc
th bao v th hch, ngi ta lun lun thy c mt cc cht
melanin, mt s cn trng thuc b hai cnh (Dptera), cc t
bo mu ch c chc nng tng hp melanin v khng tham gia
qu trnh hnh thnh th bao. Mt s cn trng k sinh trn cc
cn trng khc vo lc trng tim cc ht virus ADN vo
h tun hon vt ch v gy km hm hon ton phn ng min
dch ca vt ch, cho php u trng ca cn trng k sinh pht
trin. l kh nng km ch min dch ca cn trng.

13.3. K h nng m in dch ca ng vt dy sng v

c xng sng

13.3.1 Cc ng vt hi tiu

Ngnh c dy sng (Chordata) gm 3 ngnh ph l ngnh ph

sng ui (Urochordata) hay cn gi l ngnh c bao (Tunicata),
 177

ngnh ph sng u (Cephalochordata) v ngnh ph c xdng

sng tin ho hn c (Vertebrata). ng vt hi tiu thuc v
Urochordata l ngnh ph dy sng s khai. Mt s t bo mu
ca hi tiu c c im ging amip v c chc nng thc bo, c
vai tr quan trng trong c ch tit v p ng min dch. T bo
mu ca Tunicata bao gm t 5 n 8 kiu t bo trong t
nht c 3 kiu c th so snh vi cc ng vt bc cao. l cc
t bo lympho, cc t bo bch cu v cc t bo khng bo. Cc
t bo ny hnh thnh t do trong tun hon mu hoc hnh
thnh cc m hch lympho kt hp vi m lin kt hoc c
tm thy ng tiu ha, c bit c nhiu vng mang. H min
dch ca ng vt dy sng s khai c c im gn vi cc ng
vt khng xng sng nhng tin ha hn v c mt s c
im ging vi ng vt c xng sng. Chng hn Tunicala c
cc du hiu b mt t bo Thy-1 ging vi cc globulin min
dch c a n g v t c xng sng.

13.3.2 Cc ng vt c xng sng bc thp

Cc ng vt c xng sng bc thp l lp c khng hm hay

c ming trn (Cyclostomata) bao gm c hp v c xem
nh ng vt s khai nht ca ng vt c xng sng vn cn
st li. Loi c ny c trung tm to mu s khai vch ng tiu
ha v cc vng sau ny s xut hin lch v tuyn c. Ngoi
ra cc loi c ming trn xut hin tin thn (pronephros).
Lp c sn (ChondrichthyesJ gm c ui, c mp v c chime
c h min dch c cu trc phc tp hn mc d vn cn s
khai, c ui ngi ta thy c tuyn c s khai c phn bit
phn v v phn ty v c mt l lch vi phn ty trng v ty
. Cc ng vt ny c kh nng thi b mnh ghp ngoi lai v
kh nng tng hp cc khng th. C ui l ng vt c xng
sng u tin c cc t bo plasma ging ng vt c v v chim.

13.3.3 c im m in dch ca cc lp c xng

Lp c xng c ngun gc xut hin rt sm t i c sinh,

hnh thnh nn lp c Osteichthyes bao gm nhiu phn lp vn
cn tn ti cho n nay. lp ny ngi ta thy trung thn cha
cc m to mu vi nhiu t bo lympho v cc i thc bo
178

melano tp trung thnh tng cng vi cc t bo c ht. Cc

t bo plasma cng xut hin nhiu trong l lch nhng khng
thy hch bch huyt. So snh vi chim ngi ta thy lp c
ch c mt c quan lympho s cp l tuyn c. Thn, lch, cc
to mu c tm thy mt s nhm c u nm cc khoang
sn ca u. Bao tim hoc cc tuyn sinh dc ng thi l trung
tm bit ha v sinh sn v l ni d tr cc dng t bo mu.
V c tnh min dch th dch lp c, ngi ta thy r s
tng hp cc khng th c khi lng phn t cao, kh gingvi
IgM ca ng vt c v. C th l protein min dch ging IgM
ny c chui nng khong 70 kDa, chui nh 22-25 kDa c mt
huyt thanh cc loi c, tr c ming trn. Khi tim hng cu
nhm mu 0 ca ngi gy min dch cho c hp
(Petronizon marius), ngi ta thy c s tng hp cc phn t
khng th c khi lng 320 kDa (9S). Cc Ig ny c 4 tiu n v
75 kDa kt hp khng cng ho tr vi nhau v c cu trc bc
hai th hin 50% dng xon a (Litman et al, 1970). 0 c chime
(c sn), c ui ngi ta cng pht hin IgM dng pentame (17
- 19S) v cng c dng monome (7S). Cc IgM ca c xng cng
c phn chia thnh cc di lp, trong cc chui Hu khc
nhau v tnh khng nguyn. c tr (Ictarurus punctatus) (cat
fish), ngi ta tm thy hai izotip chui nh L. 0 phn lp c phi
(Dipneusti), hai lp Ig khc nhau v tnh khng nguyn c
pht hin l IgM pentame (H = 70kDa, L = 23kDa) v cc Ig
monome (H = 38kDa, L = 22 - 23kDa) v i khi c thm dng
IgN (Marchalonis, 1977)
Tm li, mc d cc kt qu nghin cu v tnh min dch ca
c cho thy mt s nt tng ng vi ng vt c v nhng cng
c nhng s khc bit c bn sau y:
- Khng chng minh c ngun gc tuyn c ca cc t bo
lympho (khng cha cc Ig b mt). Do cha bit c hiu
qu ca s ct b tuyn c i vi s tng hp khng th.
- Cha c chng c v c ch t bo ca vic x l v trnh din
khng nguyn.
- c bng chng v s tn ti ca cc khng nguyn ca
MHC lp I v lp II c chp (Hashimoto et al. 1990). [The
Fish immune system, Acad. Press (Iwama george & Nakenishi
Teruyuki (1996)].
 179

Cc cht truyn dn sinh hc do cc t bo h min dch ca c

tit ra nh cc xitokin cng c bit dn trn 20 nm trc
y. V d, khi c hi b nhim virus ca bnh nhim khun gy
chy mu do virus VHSV, ngi ta nhn thy trong huyt thanh
c xut hin nhanh chng mt, yu t" c c tnh ging interferon
biu hin hot ng cao nht sau 2-3 ngy c b nhim virus
(Dekinkelin v Dorson, 1973). Dng t bo mono ca c chp
(Cyprinus carpi) v c tr cng sn xut nhiu yu t ging IL|.
Cc t bo lympho hn hp v cc bch cu ca c chp v c tr
khi b kch thch bng lectin PHA u c kh nng tit ra mt
yu tc hot tnh tng t IL2.
Ngi ta cng pht hin c nhiu loi b th c mt lp c
ging vi Cl, C2, C3, C4 v C8-9 ng vt c v. Khong 6
thnh phn b th pht hin c cho thy h thng b the
c tng i pht trin (Jensen et al, 1981).

13.3.4. c im m ien dch ca ng vt bin nhit

Ngay t i c sinh ngi ta tm c du hiu pht sinh

ca cc ng vt lng c (Amphibia). Cho n nay cc loi lng
c vn cn tn ti v c phn chia lm 3 b: b lng c c
ui (Urodela) b lng c khng chn (Apoda) v b lng c
khng ui (AnouraJ. Cc loi b st cho n nay cng tn ti v
c chia thnh cc b: b ra, b c su-thn ln v b rn.

13.3.4.1. Tnh m in dch t bo ca ng v t bin n h it

Nu nh c quan min dch s cp tuyn c ca ng vt lng
c c ui cha bit ho r rng gia phn tu v phn v th
cc ng vt lng c khng ui v ng vt b st, tuyn c
bit ho r rng gia phn v v phn tu. Cng tng t, phn
tu v tu trng lch ca ng vt lng c c ui vn
cha c s bit ho r rng. Trong khi ng vt lng c
khng ui, s bit ho cu to ca lch r rng v tng t
nh cc loi b st v ng vt bc cao. 0 cc ng vt lng c
v b st, h thng cc hch v m bch huyt lin kt vi ng
tiu ho cng hnh thnh. c bit Urodela v lng c
khng ui u hnh thnh m hch amian mc khc
nhau. Ring cc loi b st, cc m hch lympho vng hu
hnh thnh r nt. Tu theo cc loi lng c khng ui, phn
180

tu xng c biu hin mc cao thp khc nhau. cc

loi lng c khng ui, vic ct b tuyn c cn phi c thc
hin rt sm t 4 - 7 ngy sau khi th tinh th mi c kh nng
gi li cc mnh ghp m t bo ngoi lai. iu ny cho thy vai
tr quan trng ca tuyn c i kh nng min dch lai ghp t
bo ca ng vt lng c. Phc h ph hp t chc ca lng c
khng ui cng c c im tng i pht trin. Cc khng
nguyn lp II ca MHC biu hin lng c khng ui.
Trong khi cc khng nguyn lp I v II u biu hin b st.

13.3.4.2. Tnh m in dch th dch ca dng v t bin n h it

Cc khng th tng t IgM c tng hp ng vt lng

c v b st. Thm vo ngi ta miu t cc Ig c khi
lng phn t nh tng t IgG c mt cc ng vt lng c,
cng nh dng IgY (dng monome) lng c khng ui v c
ui, ng vt lng c khng ui, mt dng IgM hexame,
IgY (monome), IgX (polyme) thuc (Izotip IgM) c miu t.
Cc IgY ca ng vt lng c khng ui c c tnh khng
nguyn gn ging vi cc IgG ca b st, chim v gn ging IgA
ca ng vt c v. cc ng vt bin nhit nhit, khng c cc
di lp (subclass) IgG, khng c IgE v IgD nh cc ng vt c
v.
Tm li, tnh phn ng vi cc yu t ngoi lai c pht
trin cc ng vt c xng sng bc thp, mc d cn s khai
nhng cng th hin kh nng tin ho ca cc loi ng vt.
Nh , cc c th ng vt gi c tnh bn vng ca c th v
qun th loi, nhn bit c "ci bn thn" v thi b "ci
khng phi ca bn thn", to ra ng lc tin ho cc loi.

13.3.5 c im m in dch ca cc loi chim

13.3.5.1 Cc c quan v t bo m in dch

13.3.5.1.1 Ti Fabricius
Khc vi cc loi ng vt c v, cc loi chim, c mt c quan
min dch c bit l ti Fabricius. C quan min dch ny l ni
cc t bo lympho B chn. Hn na, cc loi chim khng c cc
tuyn bch huyt ring bit. Ti Fabricius l mt c quan lym-
 181

pho c dng ti nm vng sau, pha trn hu mn. Khoang ti

c ph kn bng khong 15 np gp s cp v 7 np gp th
cp. Cc np gp ny dc vin bng mt lp biu m, cc t bo
nhy (t bo nim mc). Lp biu m che ph nhiu nang lym-
pho, c s lng t 8000 - 12000. Bao quanh nang l mt mng
li mch lympho to i cc hng, cung cp mt s ln cc t
bo lympho. Trong cc nang ca ti Fabricius c mt lp t bo
biu m kt hp vi cc nang to ra lp ngn cch gia phn tu
v phn v ca nang. Cc lp tu v lp v ca nang cha ng
mt s t bo plasma, cc lympho v cc t bo hng cu li (re
ticulocytes). Ton b b mt ca vch ngn cc khoang ca ti c
din tch tng ng 10 cm2 trong c 10% l lp t bo biu
m lin kt vi nang. Ti Fabricius ng vai tr va l c quan
lympho trung ng va l c quan lympho ngoi vi v cha ng
c t bo plasma sinh khng th v cng cha ng cc lympho
T, nm vng ph thuc T ca ti [Glick et al (1956); Sorvari et
al (1975); Murthy et al (1984)]. Cng tng t nh tuyn c, ti
Fabricius ca g con c kh nng tit ra mt hocmon l bucxin
(bursine) t cc t bo nm bin gii lp tu v lp v ca nang
lympho
13.3.5.1.2 Tuyn c
Theo Kendall (1980), tuyn c ca chim bao gm t 12 n 18
thu tch bit v phn b i xng bn cc mch mu c. Mi
thu li c phn chia thnh cc thu nh c cu trc phn v
v phn tu. Cu trc hin vi ca cc thu nh tng t nh
tuyn c ca ng vt c v. Tuy nhin, cng c mt s c im
sai khc l tuyn c ca cc loi chim c chc nng nh mt c
quan lympho ngoi vi bi v khong 7% cc t bo lympho c
tuyn c l lympho B (sau khi trng n). Hn na, sau khi gy
min dch, ngi ta thy c cc trung tm mm v mt s" t
bo sn xut khng th. Tuyn c ca loi chim ging ng vt
c v v cng l mt tuyn ni tit. Dch chit tuyn c cng gy
cm ng bit ho cc t bo T, in vivo v in vitro.
13.3.5.1.3 Cc c quan lympho th cp ca chim
Cc c quan lympho th cp ca chim gm lch, cc hch nh
bch huyt, m bch huyt ca ng tiu ho, m bch huyt cnh
mi. chim trng thnh, lch l c quan sn xut khng th
(Ig) v t kch thc pht trin ti a trong 6 tun tui u
tin. c bit lch ca chim c mt s o nh (mt s cm) c
lp ca cc t bo B.
182

Nhn chung, cc loi chim khng c cc hch bch huyt ring

bit, ngoi tr mt s loi thuc h ngan ngng (Anseridea). Cc
m bch huyt y th hin l nhng hch nh (nodules) nm
ri rc theo chiu di mch mu, hoc mt s c quan. Tri li
m lympho ng tiu ho cc loi chim kh pht trin. l ti
Fabricius, m amian ca rut tt (manh trng) v cc tm
Peyer dc theo ng tiu ho. Ti Fabricius ng c hai vai tr
(th cp v s cp) v vai tr min dch cc b i vi chim non.
M lympho cn mi nm vng gn mi v gn mt chim. M
ny c hnh thnh ngay t nhng ngy th 17 - 1 8 ca qu
trnh p trng l do s xm nhp ca cc t bo lympho xut
pht t nim mc (tuyn nhy) mt v cc xoang mi. Ngi ta
tm thy y ch yu l cc lympho B v rt t lympho T.
13.3.5.1.4. Cc t bo ca h min dch chim
H min dch chim bao gm cc t bo lympho T v lympho B.
Cc lympho T cng c phn bit l lympho T b tr (T||), lym-
pho T km hm, lympho T gy c v cc lympho T lin quan n
cc phn ng qu mn mun. Cc du hiu b mt ca cc t bo
T cn t c sng t. Ngi ta s dng khng th n dng
v nhn bit c khng nguyn b mt CT3, gn ging phc
h CD3 ca ng vt c v. Khng nguyn CT3 c mt khong
20% t bo c v ch yu cha nhiu cc lympho ca lch v
mu.
Cc t vo B ph thuc ti Fabricius, khi trng n, c khong
2xl07. Cc t bo B nhanh chng phn chia ti v t s lng
gp i trong mt ngy. Tuy vy, ch khong t 1 n 10% s t
bo ny ri ti i v pha cc c quan lympho ngoi vi. S cn li
b cht hoc bit ho in situ. Cc du hiu b mt ca t bo B
bao gm hai nhm l cc khng nguyn c hiu cho tt c cc
lympho B. Nhm u tin c 4 loi khng nguyn b mt l CB-
1, CB-2, B3 v HNK-1. Khng nguyn CBj c th ng vai tr
tng trng v lm chn cc lympho B. Khng nguyn CB2 c
mt cc lympho v cc t bo biu m ca ti v cha r vai tr
ca n. Khng nguyn B3 c t bo B vng tu, cc t bo
biu m rut v ti hu. Nu thiu B3 g b bnh thiu ht gama
globulin trong mu. Khng nguyn HNK-1 c mt cc t bo B
ca c quan lympho ngoi vi v ng vai tr lm chn cc lympho
B ca ti.
Pink v cc cng s s dng khng th n dng nghin
cu khng nguyn chung cho cc t bo B v nhn thy chng
 183

u cha cc Ig. Cc t bo cn li ca h min dch chim bao

gm cc di thc bo, t bo bch cu ht (gm cc t bo a axt
gi: pseudo-eosinophile biu hin hot ng thc bo v vim,
cc t bo a axit thc th, cc t bo a kim), cc t bo tiu
cu, t bo mast, cc t bo NK v K (l nhng t bo c c tnh
ph thuc khng th: ADCC).
13.3.5.1.5. Cc khng nguyn MHC v nhm mu
g, MHC bao gm 3 loci l B-F (cc khng nguyn lp I), B-L
(cc khng nguvn lp II) v khng nguyn a hnh B-G (khng
nguyn lp IV), ch c bc l trn b mt hng cu v lin kt
cht vi locus B-F. Nghin ca MHC ca g cho thy c nhiu
im ging VI ng vt c v v tnh cht a hnh, v cu trc
v chc nng v s biu hin t bo. Tuy nhin, ng vt c
v khng c khng nguyn B-G. Chausse v cc cng s
nghin cu v cu trc phn t ca phc h B v chng minh
tnh a hnh v di truyn ca cc phc h BL, BF v BG.
Vic pht hin vai tr ca cc khng nguyn lp I v lp II ca
MHC g cho php hiu c s bin dng di truyn ca tnh
chng chu mt s bnh ca g.
13.3.5.1.6. Cc globulin min dch (Ig)
chim, ngi ta tm ( 3 lp Ig l: 7slg, IgM v "IgA"
(tng t IgA) v khng pht hin c cc di lp. Ngi ta
cho rng rt c th c cc Ig gn ging IgD v IgE ca ng vt
c v. (Chen et al 1982).
- Chui nng ca 7slg c thm mt khu vc chc nng so vi
chui nng gamma (IgG) ca ng vt c v. H s lng ca
7slg l t 7,3 n 7,4 s. 7slg l mt globulin min dch ch yu
ca huyt thanh, c nng t 5 n 7 mg/ml. ng ch l
c s sai khc nhiu gia 7slg v IgG ca ng vt c v.
- Cc IgM ca chim c khi lng phn t 890kDa v h s lng
17s. Do khi lng phn t kh cao nn IgM ca chim khng
th vt qua lp biu m ca vi trng v do khng c mt
non hong. C 5 allotip ( t M-1,1 n M-1,5) ca IgM nh
khu cc khu vc chc nng thuc vng CH khc nhau.
- Cc IgA "tng t" - c cu trc ging vi cu trc ca IgA ca
ng vt c v. Chng c nhiu cc cht tit v cc dch sinh
vt v tn ti hai dng (monome v polyme). Theo s lng
monome kt hp, h s lng ca cc IgA tng t bin i t
9 n 16s v c khi lng phn t t 350 n 900 kDa. IgA
184

ca chim tp trung nhiu mt (3 -12mg/ml) v c tit vo

khc rut t trng t l l,7mg/ml, ni c th chng li s
xm nhp ca vi khun v virus. Cc IgA ca mt chim cng
c mt mnh tit c khi lng 60 kDa. Mnh tit ny c cc
t bo gan tng hp v gn vi IgA trong qu trnh i t mu
vo mt.
13.3.5.1. 7. Cc b th ca chim
B th ca chim cng c vai tr bo v th dch chng li
nhim trng. Ging nh cc ng vt c v, thnh phn C3 ng
vai tr quan trng trong min dch v l phn t quan trng
nht ca s hot ho b th. g, C3 c tinh ch, c khi
lng phn t 190 kDa bao gm hai polypeptit a v p, c khi
lng tng ng bng 118 v 68 kDa. im ng in ca chng
bin i t 6,4 n 6,6. Nng ca C3 t 0,4 n 0,5mg/ml v
bng mt na nng C3 c trong mu ca ng vt c v. C3
ca chim ging ng vt c v v cu trc v chc nng. B th
ca chim c th c hot ho theo con ng c in v con
dng lun phin. Theo con ng lun phin, yu t B c vai tr
quan trng khc vi yu t B ca ng vt c v l c tnh a
hnh cao (BS, BF v BF/s), v khng kt hp vi tnh a hnh ca
MHC. Yu t B l mt glycoprotein c khi lng 90 kDa v c
th tham gia vo s hot ho b th theo con ng c in.
Ngi ta cho rng yu t B tham gia vo phn ng tiu huyt
min dch (immunohemolysis) ging vai tr ca C2 ca ng vt
c v. Do C3 cng c vai tr ca C4 bi v ngi ta khng tm
thy C2 v C4 cc loi chim. c bit chim, ngi ta thy c
Cl- esteraz tc ng ln yu t B. Hot ng ca b th c
pht hin ngy p trng th 13 v t cc i vo khong 3
n 4 tun tui. Ngi ta cn cha bit r nhiu iu v hot
ng ca b th ca cc loi chim.

13.3.6. c im h min dch ca b linh trng

Nghin cu c im min dch ca b linh trng khng ch
gip cho vic tm hiu mi quan h tin ho min dch gia cc
loi ng vt bc cao so vi loi ngi; ng thi cn ng gp
cho cc nghin cu y sinh hc thc nghim ca cc bnh loi
ngi nh bnh ung th, bnh truyn nhim, thiu ht min
dch trong c AIDS v cc bnh t min. Theo Sibley v Ahl-
 185

guist (1987), 98% thng tin di truyn (genom) ca ngi giig

cc loi kh cao cp Chimpanz, 92% ging kh thng thng
lc a chu Phi v 85% ging kh Nam M.
Cc c im min dch ca linh trng c nghin cu
rt k trong nhng cng trnh ca cc tc gi nh Benirschke
(1986) [Primates: the Road to self sustaining population.
Springer Verlag, New York], Kalter (1987) [Monographs in pri-
matology. Vol 2. Alan Liss, C O . New York]. Hin nay, b linh
trng bao gm 13 h l: T u p a lid a e , D a u b e n to m d a e , In d ru la e ,
L e m u r id a e , L orisidae, Tarsiidae, C allitricidae, Cebidae, Cer-
copithecidae, Colobidae, H ylobatidae, P o ng id a e v H o m in id a e .
(hnh 13.1).
C th tm tt mt s c im quan trng v c quan min dch,
tnh min dch t bo v dch th ca b linh trng v mt s
c im ca chng.

13.3.6.1. Tu x ng ca b lin h trng

y l c quan min dch s cp, l ngun to ra tt c cc t
bo mu c chc nng tun hon mu ca c th. Ln u tin,
cc tc gi Stasney J. v Higgins GM m t thnh phn tu
xng ca kh Rhesus (M acaca m u la tto ), vo nm 1936 (The
bone marrow of the monkey. Anat. Rec., (1936) 67: 219) v cho
bit tu xng ca kh Rhesus gm 39% l cc t bo hng cu,
53% l cc t bo bch cu a nhn, 4,5% l cc t bo lympho,
6% l cc t bo mono. Khi so snh VI loi ngi, ngi ta thy
kh Rhesus c s" lng d tr cc t bo ngun to hng cu ln
hn.
Tu xng ca loi kh ui sc chu M (Marmoset) thuc chi
C a llith r ix c hnh thi khc thng c nghin cu kh chi
tit. S biu hin ca MHC v vai tr ca n trong cy ghp tu
xng c nghin cu.
186

H nh 13.1. Cc h thuc b linh trng hin nay (theo Kalter, 1987)

13.3.6.2. Min dich t bo

Tnh min dch t bo ca qu trnh pht trin c th (onto-
genesis) ca loi kh (Macaca nemestrina) c cc tc gi
Terao, Rose, Scakett v Clark nghin cu trong thi gian gn
 187

y (Development of lymphocyte subset in pig - tailed macaque.

Human. Immunol. 1988, 21:33). Cc tc gi trn cho bit kh
mi sinh, cc t bo c hnh thi dy c v c du hiu khng
nguyn c trng cc t bo B IgD\ cc t bo T CD4\ Lp220\
T CD8*. Khi tui kh cng cao, du hiu tng ng i VI cc
lympho c thay i, c th t bo B khng biu hin IgD (BlgD ),
T CD4\ Lp220 . Ngi ta cng pht hin c 3 tiu qun th
T C D 8 l TCD8+ ,CDl8br\ TCD8bn CDl8m,,\ TCD8mal, C D l8b",
nhng cha r s pht trin ca chng tng ng vi chc nng
c hiu min dch nh th no. Cc t bo TCD4* kh Macaca
trng thnh c s lng cao hn so vi kh cn non. c im
ny ging VI ngi nhng khc vi kh Chimpanz.
Chc nng p ng min dch ca cc t bo T v B kh u
ch (Babuoin) c nghin cu v ngi ta nhn thy kh
ging ngi. Trong khi , khng c mt loi linh trng no th
hin p ng min dch mnh nh loi ngi.
Cc nghin cu khc cho thy cc t bo n nhn ca mu
ngoi vi (PBMC) ca loi ngi c kh nng sinh sn ti u khi
c lectin kch thch nh con A hoc PHA. Trong khi , iu ny
khng th hin trng hp kh Rhesus.

13.3.6.3. T n h m in d ch th d ch
Tnh min dch th dch ca cc loi linh trng c
nghin cu trong nhng nm 60 ca th k 20. Ngi ta s
dng khng nguyn ngoi lai chng minh s tn ti ca cc
globulin min dch nh IgG, IgM, IgD, IgA, IgE trong huyt
thanh ca cc loi linh trng. Vic kim tra cc phn lp IgG,
cc tip kappa v lambda ca chui nh v tnh d th ca IgA
cng c thc hin trong cc nghin cu v c Damian
v Greene tng kt y trong ti liu ca h (The immumol-
ogy of non human primates, in: RN Finnes, Ed. Pathology of
semian Primates Karger Basel, 1972, tr.342).
188

C th a ra mt s dn liu so snh bng sau:

B n g 13.1. T l Ig huyt thanh ca ngi v cc ng vt linh
trng trng thnh, mg/ml (theo Demian v Greene, 1972)

Cc loi IgM IgG IgA

Chimpanz 0,59 - 2,4 11,3 - 18,0 0,97 - 2,12
Kh Orang Outang 0,20 - 0,9 10,5 - 13,3 0,90 - 1,9
Kh u ch Babouin 0,30 - 1,8 11,0- 13,3 0,1 -4,1
Macaca mulatta 0,80 - 2,0 12,0 - 30,0 0,3 - 0,9
Macaca arctoides 1,00- 1,2 8,5- 11,1 3,1 - 4,3
Ngi 0,60 - 1,5 7,7 - 13,5 1,8- 2,8

Cc nghin cu v thnh phn b th ca cc loi linh trng

cho thy, khng huyt thanh ca d khng li cc thnh phn b
th ca ngi u c th-phn ng vi tt c thnh phn b th
ca kh bc cao, ngoi tr yu t Clq. Cc loi kh c chu Phi v
chu c c tnh thiu ht khng nguyn cc b th Clq, C ls
v C9. Cc loi kh Nam M thiu ht tt c cc thnh phn b
th, ngoi tr C5, C6 v yu t' B ca propecdin. cc ng vt
thuc b bn hu (Prosimia), ngi ta khng pht hin c bt
c mt thnh phn b th no trong huyt thanh, v chc nng,
hot ng b th ca cc loi ng vt linh trng c th so snh
vi loi ngi, tr cc ng vt bn hu, l ng vt bc thp
nht ca linh trng.

13.3.6.4. Phc h p h hp t chc ch yu ca linh trng

Kh nng phn bit c "ci bn thn" v "ci khng phi
ca bn thn" l c tnh quan trng ca tt c c th a bo bc
cao. Kh nng nhn bit ny c c l nh sn phm ca cc
gen ca MHC (Gtze D. The MHC in man and animals. Springer
- Verlag. Inc. New York. 1977). S phn bit gia "ci ca bn
thn" v "ci khng phi ca bn thn" c thc hin d dng
nh tnh a hnh ca cc sn phm gen ca MHC ngay trong
mt loi. Cc khng nguyn ca MHC ngay trong mt loi. Cc
khng nguyn ca MHC thuc v mt h ln ca cc immu
noglobulin, lun lun c mt b mt t bo. ng ch l tnh
 189

a hnh ca cc sn phm gen l do s t hp ca mt s lng c

gii hn ca cc gen. Cc gen ca MHC ngi v chut c
nghin cu chi tit [Dausset J , Pla. M. complexe majeur d'histo-
compatibilit de l'homme. Flammarion Mdecine Sciences Paris
(1985). Hood et al. Genes of the major histocompatibility complex
of the mouse. Ann. Rev. Immunol, 1983, 1: 529 - 568]. cc ng
vt linh trng, phn ln cc cng trnh nghin cu v MHC c
lin quan n kh Rhesus (Macaca mulatta) v kh Chimpanz
(Pantroglodytes).
13.3.6.4.1. H th n g R h L A ca R h e s u s
V ngun gc, nhng sn phm ca cc gen ca MHC Rhesus
(cn gi l RhLA) u c xc nh v huyt thanh hc bng
c tnh ca t bo lympho i vi khng huyt thanh ngoi lai
nhn c nh cch gy min dch cho i vi mt c th ca
cng mt loi. Theo phng php ny, Balner v cc cng s
H Lan, cng nh Neefe v cng s M xc nh c
khong 27 gen c kim tra bng 2 locus phn bit nhau v di
truyn. Cc locus ny rt ging cc locus A v B ca HLA lp I
ca ngi. Cho n nay, ngi ta cha tm c locus tng
ng vi locus HLA-C c mt kh Rhesus. Phn tch ho sinh
v cu trc phn t ca nhng sn phm ca cc gen RhLA lp I
cho thy c nhiu c im rt ging chut v ngi. Cc khng
nguyn ny c to thnh t 2 chui polipeptit c khi lng 44
kDa v 12 kDa. Chui nh tng ng vi p.2 microglobulin ca
ngi.
Cc sn phm ca cc gen RhLA lp II cng c m t t
1974, c k hiu l Ial. Hin nay ngi ta gi l locus DR
ph hp vi s phn loi i vi cc gen lp II-HLA ca ngi.
on gen DR ca kh rt ging DR ca ngi v chut v bao
gm 8 khng nguyn khc nhau. ngi, bn cnh khng
nguyn ca DR, ngi ta tm ra khng nguyn HLA-D v
chng minh rng cc sn phm gen ca locus D c xc nh
khi nui cy hn hp cc t bo lympho, tng ng vi cc khng
nguyn ca DR. Cc gen p ng min dch IR (Immune Re
sponse) c m t chut cng c chng minh kh v
ngy nay l nhng gen ca lp II ng vai tr quan trng trong
vic cm nhn i vi cc bnh khc nhau ngi v ng vt.
Ngi ta cng tm c hai hoc ba gen trong chng c h
thng RhLA. Ngoi ra, cc gen m ho cho cc yu t ca b th,
190

c bit l yu t a hnh Bf cng nm MHC. S c trnh

by hnh 12.2 l bn gen ca h thng RhLA nm nhim
sc th 6 v c so snh vi kh Chimpanz v ngi.
Lp II Lp I
Ngi
D/DR B

Bf C2 C4
Chimpanz
D/DR B

C2
Bf
Rhesus

D/DR B

C2
Bf

Hnh 13.2. Bn gen ca MHC ca ngi, kh

Chimpanz v Rhesus (Theo Balner, 1981).

13.3.6.4.2. H thng ChLA ca Chimpanz

H thng ChLA ca Chimpanz cn t c nghin cu so vi

RhLA. Cc khng nguyn lp I ca ChLA c xc nh r v
ging nh Rhsus (Jonker M. Van Vreeswij w, 1981). Vng DR,
hin nay cn cha bit r, nhng cc kt qu phn tch v huyt
thanh hc v .nh phng php nui cy phc h t bo lympho
chng minh vng D/DR ca Chimpanz ging vi ngi.
Ngi ta cng chng minh r tnh a hnh ca mt s yu t
b th ca Chimpanz nh Bf, C2, C3, C6 v C8. Hn na, cc
nghin cu cho thy cc yu t" C2, Bf lin kt cht ch vi ChLA,
trong khi , cc yu t C3, C6 v C8 khng lin kt vi ChLA
(hnh 12:2). Mi y Mayer v cc cng s cho bit, cc gen
ChLA lp I c phn tch mc trnh t cc nucleotit ca
 191

chng. Khi s dng mu d (probe) ADN ca ngi m ho cho

v tr ca lp I, Mayer v cng s phn tch mt th vin gen
ca ADN ChLA tm hiu alen A v alen B v chng rmnh
rng mt s alen ca ngi c nhiu c tnh ging vi cc alen
ca Chimpanz. T cc dn liu trn, cc nh nghin cu kt
lun rng, tnh a hnh ca MHC tn ti trc khi xy ra s
phn ho tin ho theo hai hng Chimpanz v loi ngi.
13.3.6.4.3. H thng CyLA ca kh Cynomolgus (Macaca facicularis)
Keever v Heise (1985) nghin cu MHC ca kh Macaca
facicularis, v tm ra t nht 35 c im c hiu khng nguyn
ca lp I CyLA. Cho n nay, ngi ta bit 14 c im
c cng nhn l ph thuc vo locus CyLA -A, 10 c im ph
thuc locus CyLA -B v 6 c im ph thuc CyLA -C. T ,
ngi ta nhn thy tnh a hnh ca h thng CyLA ln hn h
RhLA v c cu trc ging vi loi ngi.
Tm li, vic nghin cu cc c im min dch ca cc ng
vt linh trng khng phi ngi hin nay l iu rt cn thit
nhm tm hiu s tin ho min dch loi ngi. Nh cc k
thut sinh hc phn t v min dch phn t, cc nh khoa hc
c th iu ch cc xitokin, nhm nng cao kh nng iu chnh
cc t bo lympho in vitro v in vivo. Cc kt qu nghin cu
trn m hnh linh trng cho php to bc chuyn tip qu
gia nghin cu khoa hc c bn v ng dng thc tin y hc i
vi loi ngi iu tr cc bnh nhim trng, cc bnh qu
mn, ung th, s cy ghp c quan v cc bnh thiu ht min
dch, c bit l AIDS.
192

Tm tt chng XIII

1. S khc nhau ch yu gia ng vt dy sng, c xng sng

v ng vt khng xng sng l ch: ng vt khng xng
sng khng c cht ho gii ca c th kiu khng th kt hp
vi khng nguyn l xm nhp t bn ngoi. Trong khi ,
ng vt dy sng c cc m hch biu m lympho, cc m
lympho- tu kt hp vi mt s c quan nh khe mang hoc
ng tiu ho, ng thi c kh nng nhn bit khng nguyn
l v phn ng chng li chng nh cht ho gii kiu khng
th s khai hoc khng th thc s.
2. Lp c xng l ng vt c xng sng bt u c c quan
lympho s cp nh tuyn c, thn, lch. Tuy nhin, cc c
quan ny cn s khai v ng lun c vai tr l trung tm bit
ho, sinh sn v d tr cc t bo lympho v t bo mu,nh
nhng c quan lympho th cp. Kh nng p ng min dch
c cng biu hin thp. Khng c bt k bng chng no ni
v c ch trnh din khng nguyn, v khng c MHC lp I v
lp II. Khng th ca c cng ch dng ging IgM nhng c
kh lng phn t thay i, cha phn thnh nhiu lp khc
nhau nh ng vt c v, nhng h thng b th gm 6
thnh phn, tng i pht trin.
3. Tnh min dch t bo v min dch th ca ng vt bin
nhit (ng vt lng c) c nhng tin b hn so vi cc
ng vt bc thp l:
- c c quan min dch s cp nh tuyn c, lch, tng t b
st v ng vt bc cao.
- c bit lng c pht trin phc h ph hp t chc lp I
v lp II v biu hin r b st.
- c tnh min dch th dch th hin r, bao gm mt s
khng th nh IgM, IgG, IgA tng t, mc d cha c IgE
v IgD.
 193

4. H min dch ca cc loi chim c tin b cao:

c c quan lympho s cp bit ho r nh tuyn c v c
bit ti Fabricius, l ni bit ho ca cc t bo lympho B, mt
c quan ring bit cho cc loi chim.
- c c quan lympho th cp bit ho nh lch, hch bch
huyt, m bch huyt. Cc t bo min dch nh lympho T v
lympho B bt u c biu hin bit ho theo chc nng ring
bit.
- H MHC, cc khng th v b th biu hin r chc nng
min dch.
5. ng vt linh trng khng phi ngi c h min dch tin
ho cao VI nhiu c im ging loi ngi; mc d cng c
mt s c tnh ring cho mi h v mi loi. Do cc kt qu
nghin cu h min dch ca linh trng s a ti nhng ng
dng thc tin sinh y hc rt to ln cho loi ngi.
 195

Chng XIV. Phng v cha bnh bng liu php

min dch

14.1. Vi n t lch s

Da vo s quan st v kh nng chng chu bnh u ma

ca ngi b mc bnh ln u v sng st Edward Jenner
Anh (1796) ch ra vacxin s khai t mn m ca b b bnh
u ma iu tr cho ngi. Ln u tin, cc th nghim y
to ra kh nng chng chu bnh ca ngi vi bnh ny.
Louis Pasteur (1885) p dng nguyn tc tim chng trn
cha lnh bnh di cho mt thanh nin tn l Joseph Meister
b ch di cn t trc. Ngy nay vic gy min dch tch cc
c gi l tim chng (vaccination) k nim pht minh ca
E. Jenner mang li hiu qu rt to ln nhm phng nga cc
bnh do c t" vi khun v virus gy ra. Cc th h vacxin lin
tip ra i v ngy cng c hon thin v c xem nh cc
cht gii c t (anatoxin). l vacxin ch t c t bch hu
v un vn x l nhit hoc focmon, hoc vacxin t vi khun
nguyn vn b git, vacxin gim bt c t nh BCG, poliovac,
vacxin si, st vng, vacxin ch t cc tiu n v khng nguyn
(vacxin hepatit B). Nm 1967, t chc Y t th gii (WHO)
chnh thc t ra mt chng trnh tim chng m rng, c h
thng trn ton th gii nhm ngn nga nhiu bnh dch cho
loi ngi.
Vic pht minh ra c tnh khng c ca cc khng th chng
li c t vi khun bch hu ca Von Behring vo u th k XX
m ra hng s dng rng ri huyt thanh min dch ca cc
loi ng vt nh th, nga, cha bnh nhim trng. l
ngun gc ca liu php min dch (Immunotherapy), tc l
phng php cha bnh trn c s min dch. Hin nay, cc th
h khng th c s dng trong liu php min dch ln lt
196

c ci tin. Lc u l khng th a dng ca ngi c tinh

ch t hn hp huyt thanh ca nhiu c th cho mu. Tip theo
l vic to ra khng th n dng ca Kohler v ca Milstein
(1975) m ra kh nng ng dng trong nghin cu y hc v
liu php min dch. Nhng th h khng th n dng ngy
cng c hon thin nh khng th lai ghp gen ca ngi v
chut (chimaeric humanised rodent monoclonal antibody), khng
th c hiu lng tnh (bispecic antibody)...
Ngy nay cc nh khoa hc v y hc cng nghin cu v
a vo nhiu phng php cha bnh trn c s min dch nh
liu php t bo, liu php gen, cc cht km hm, kch thch
min dch v iu ho min dch cha cc bnh nhim trng,
bnh t min, bnh suy gim min dch bm sinh hoc mc phi,
ng thi liu php min dch c ng dng trong cy ghp
thay th cc c quan.

14.2. Tim ch n g, v acx in p h n g v cha bnh

14.2.1. Nguyn tc tim chng v sn xut vacxin

Tim chng (vaccination) ng ngha vi gy min dch ch
ng nhm gip cho c th c kh nng to ra mt c ch bo v
chng li 8 xm nhp ca mt c th xm lc hoc c t ca
n. Gy min dch ch ng hay tim chng khai thc c tnh
c hiu v ghi nh trong p ng min dch s cp (sn xut ra
khng th gM c i c thp ban u) v p ng min dch th
cp (sn xut vi tc nhanh ra mt lng ln khng th IgG
v IgA c i lc cao). To ra kh nng ghi nh min dch nh tc
dng ca khng nguyn dng vacxin khi gp chng hoang di
th s p ng min dch s c thit lp trong c th. Cc
vacxin ng vai tr l nhng khng nguyn ca cc tc nhn gy
bnh c lm gim bt c tnh hoc b bt hot hoc l cc
tiu n v (subunit.) ca cc c t' vi khun hoc virus. c
im quan trng ca tim chng vacxin l phi m bo c
mc an ton tuyt i, khng gy bnh nhng to ra cho c
th tip thu c tnh min dch khi c tc nhn hoang di xm
nhp. Hin nay, mi loi vacxin c s dng u c nhng kha
 197

cnh li ch v bt li. Chng hn cc vacxin c ch to theo

kiu lm gim mc c (poliovacxin) c s dng theo ng
ming, c li ch bo v v phng bnh tt v thng ch s dng
mt liu cn thit. Hn na vacxin s lm tng tnh min dch
qun th v c th truyn tnh min dch t ngi ny sang ngi
khc. Tuy nhin, iu bt li ca vacxin kiu gim c tnh c
th l s bin i c tnh d dn n xut hin kiu vi sinh vt
hoang di mi v v th vacxin lun lun phi bo qun lnh.
Trong mt s trng hdp, vacxin kiu gim c t cng khng
th c dng cho ngi thiu ht min dch t bo T v tnh
trng thai nghn.
Cc vacxin c ch to theo kiu git cht tc nhn gy bnh
c li ch l an ton cao, n nh hn khi vn chuyn i xa v bo
qun d tr d dng. Tuy nhin, iu bt li ca chng l km
hiu qu hn so vi vacxin kiu gim bt c tnh do s lng cc
liu dng nhiu hn v khng to ra c tnh min dch qun th.

14.2.2. Cc dng vacxin ang c n ghin cu v s dng

14.2.2.1. Cc vacxin vi kh u n
Cc vi khun c th c git hoc lm mt hot tnh iu
ch tc nhn gy min dch hu ch. Vi khun c nui cy in
vitro. Cc vacxin vi khun bao gm :
a)Vacxin gim bt c tnh nh BCG (Bacille - Calmette -
Gue'rin) i vi bnh lao.
b)Vacxin gy bt hot tnh (hay vi khun b git):
- Bordetella pertussis i vi ho g
- Salmonella typhi v s.paratyphi i vi bnh st thng hn.
c) Vacxin l cc tiu n v hoc c t:
- Neurotoxin ca Clostridium tetani lm mt hot tnh bng
x l ha hc c iu ch vacxin un vn.
- c t ca Corynebacterium diphtheriae lm mt hot tnh
bng x l ha hc c iu ch vacxin bch hu.
- Polixacart thnh t bo vi khun Haemophilus influenzae typ
b c iu ch vacxin vim mng no.
- Polixacarit thnh t bo vi khun Neisserm meningitidis A v
c c iu ch vacxin vim mng no ty.
198

Ni chung, ngi ta c th x l nhit, ha cht nh focmon,

phenol git vi khun cho mc ch iu ch vacxin.
Cc vacxin c iu ch c dng ton b t bo vi khun lin
quan n vn sn xut trong nui cy t bo c th a n
nhng hiu qu ph tri ngc khng mong mun, T , ngi
ta nghin cu pht trin mt loi vacxin gm cc tiu n v
v thng gi l vacxin khng cha t bo (acellular vaccines). V
d, Bordetella pertussis l tc nhn gy bnh ho g, c mt c t
v mt cht ngng kt hng cu t b m t lng mao vi khun
(fimbrial haemagglutinin) c vai tr quan trng lin kt vi cc
t bo biu m ca vt ch. Vacxin kt hp gia hai loi protein
c tinh sch trn v lm mt hot tnh l mt dng
vacxin mi c nhiu u th. Tng t nh vy, ngi ta sn xut
ra mt loi vacxin st thng hn khng cha t bo bt ngun
t polixacarit v t bo Vi (tc l khng nguyn gy c Vi).
Mt loi vacxin mi c gi l vacxin Hib. c iu ch t
polixacarit v vi khun Haemophilus influenzae typ b kt hp vi
protein c t un vn (tetanus protein). Vacxin ny c hiu qu
ln, ngn chn bnh nhim trng Haemophilus meningitis,
thng gy t l t vong cao.

14.2.2.2. Cc vacxin k sin h tr n g

K sinh trng l nhng c th a bo v k sinh nhiu vt
ch trung gian trong vng i ca chng. Thm vo nhiu k
sinh trng lun lun thay i c ch tinh vi nhm trn thot s
p ng min dch ca vt ch. l nhng vn kh khn
cho vic iu ch mt dng vacxin k sinh trng. Bnh st rt do
k sinh trng Plasmodium sp. Hng nm git cht 1,2 triu
ngi v lm ly nhim bnh n 800 triu trn th gii. Bnh
sn mng Schistosoma lm ly nhim 200 triu ngi, bnh ng
hay bnh chagas Nam M do cc k sinh trng Trypanosoma
cruzi ly nhim cho 12 triu ngi V.V. .. Do s nghim trng
, ngi ta cn phi ch to ra cc loi vacxin k sinh trng.
c mt s s kin cho thy rng vic gy min dch chng
li cc k sinh trng c nhng kt qu nht nh. Trong nhng
nm gn y, ngi ta t c nhng tin b quan trng
trong lnh vc iu ch vacxin chng bnh st rt. Bng chng
cho thy l cc t bo T gy c (Tc) c kh nng git cc k sinh
trng mc gan. Trong nm 1991 Hill v cc cng s
 199

Oxford chit xut ra cc peptit khng nguyn t rnh ca cc

phn t HLA - B53 lp I qun th ngi Gambia chng chu
c bnh st rt c tnh. Cc kt qu nghin cu chng minh
rng qun th Gambia chng chu bnh st rt c tnh c xut
hin s p ng min dch ca t bo T gy c HLA-53 vi pep-
tit khng nguyn ca cc k sinh trng st rt LSA-1 (Liver-
stage specific Antigen-1: khng nguyn c hiu giai on
gan). iu ny gi cc nh khoa hc iu ch mt loi vacxin
trn c s cc peptit t LSA-1.

14.2.2.3. Cc vacxin viru s

Cc vacxin virus c iu ch cc dng virus sng nhng
gim c tnh hoc dng virus b git hoc cc tiu n v
khng nguyn virus.
- Vacxin sng lm gim c tnh nh vacxin st pht ban,
vacxin bi lit (poliovac-Sabin), vacxin quai b, bnh si.
- Vacxin virus b git (lm bt hot tnh): vacxin bi lit dng
tim (vacxin Salk), vacxin cm, vacxin ch di.
- Cc vacxin gm cc tiu n v: vacxin hepatit B, vacxin cm.
Mt nguyn tc c bn cho vic ch to vacxin gim c l cc
virus ARN d dng c lm gim c t hn so vi virus ADN v
ARN d c kh nng b mt hot tnh. Do vacxin gim c t
ch c th c p dng cho cc virus d dng mt hot tnh v
chc chn b mt hot tnh.
to ra cc vacxin gm cc tiu n v khng nguyn, ngi
ta cn hiu bit v chn phn khng nguyn ca virus gy ra
p ng min dch ca t bo T v v tr hay ch khng nguyn
to ra cc khng th trung ha c hiu qu nht. C th l
khng th trung ha c khuynh hng nhm vo cc protein b
mt ca virus, trong khi cc t bo T p ng nhm trc tip
chng li cc thnh phn bn trong virus. Thm vo , cc tiu
n v trong vacxin cn phi c mt tt c cc chng ca virus
th vacxin mi c tnh vn nng.
Trong mt tng lai khng xa, vic s dng cng ngh ti t
hp ADN c th a ti sn xut mt s vacxin c tnh an ton
cao, nht l trnh c c tnh ca virus. Cc vacxin ti t h p
c th c ng dng sn xut vacxin gm cc tiu n v ca
khng nguyn (c th l vacxin chng bnh st rt v chng vim
gan siu vi trng), khc phc c kh khn phi nui cy t
200

bo. Cc vacxin ti t hp c th c ch to phi hp cc tiu

n v c chn lc, nhm to cho vacxin c epitop u th min
dch, c th kt hp vi a s cc allotyp ca HLA lp II kch
thch p ng cc t bo T b tr (TJ, cng nh kt hp vi cc
phn t HLA lp I kch thch t bo T gy c CD8, hoc to
ra cc khng th trung ha theo mun.

14.3. Liu php min dch khng th v c t min dch

Khng th n dng c t hp t chui bin i ca chut

kt hp vi vng khng bin i ca khng th ngi c gi l
cc khng th lai ghp CDR (t ch : "vng xc nh b sung" :
Complementarity Determining Region), y cc gen ca vng
xc nh b sung ca khng th chut lin kt vi khng nguyn
(cc gen ca VH v VJ c ghp ni vi cc gen CH v CL ca
ngi v c bc l trong mt vect. Sau ngi ta a vo cc
t bo ng vt c v tng hp ra khng th lai ghp c hai
ngun gc gen (Chimaeric Humanised Rodent Monoclonal Anti
body). Khng th lai ghp hai ngun gc gen iu tr c hiu
qu bnh vim khp mn tnh.
Mt dng khng th khc l khng th hai chc nng c hiu
(bi-specific antibody). Cc khng th ny c hai cnh tay lin kt
c hiu vi hai khng nguyn khc nhau. Mi mt v tr lin kt
khng nguyn c th nhm vo mt loi khng nguyn ung th.
V mt s khng nguyn ung th cng c th bc l cc m t
bo bnh thng nn vic lin kt lm tng gp i kh
nng nhn bit, lm tng tnh c hiu lin kt ca khng th.
Ngi ta nhn thy hu nh tt c cc t bo ung th mu c
tnh c bit l cc t bo plasma c tnh u mang du hiu
khng nguyn in hnh nh CD v CD20. Mt s lympho T ung
19

th cng biu hin cm bit ha b mt CD25 mc cao,

Ngi ta s dng cc khng th n dng m t tnh cht
v nhn bit s khc bit ca cc cm bit ha khng nguyn
ny. Cc khng th n dng c th c cng hp vi cht ng
v phng x Iod (I131) trong liu php min dch phng x, hoc
cng hp vi cc cht c nh rixin (lectin t Ricinus communis)
hoc c t bch hu, trong liu php min dch c t. Cc
khng th nh vy c th c xem nh l nhng "u n thn
 201

k", c th tm dit cc t bo ung th v cc t bo lympho t

phn ng trong cc bnh t min.
Hin nay. vn d s dng khng th n dng kiu u n
thn k mang cc c t vn cn ang c th nghim lm
gim bt c tnh ca phrtng php ny. Thm vo , cc khng
th s dng c ngun gc khc hu nh d tp trung mc d
gan v lch. Cc cht c nh rixin c bn cht l glycoprotein
cng c hp th gan, c th gy c cho gan. trnh iu
ny ngi ta dang th nghim vi cc cht c khng cha cc
gc ng.
Cc c t min dch kt hp mnh Fv ti t hp (Recombinant
Fv mmunotoxins) l mt sn phm ca cng ngh ti t hp
ADN v cng ngh khng th rt mi y (t 1994 - 1998)
c s dng th nghim lm sng chng li cc khi u rn, cc
bnh ung th mu (Leukemia, lymphoma, cc bnh Hodgkin)
ngi.
Theo Reiter Y v Pastan I (1998) cc c t min dch ti t
hp bao gm cc mnh khng th n dng Fv (mnh VH, VL
ci bin) c kt hp vi mt c t vi khun rt mnh l
exotoxin A ca vi khun Pseudomonas (vit tt l PE). tng
thit k immunotoxin ti t hp xut pht t c s l nhiu t
bo ung th bc l qu mc khng nguyn ung th c trng
(sn phm ca Oncogen) trn b mt t bo ca chng v thuc
min dch chng ung th cn phi nhn bit c hiu loi tr
t bo ung th m vn gi nguyn vn cc t bo bnh thng.
Do , mt na phn t ca c t min dch l khng th nhn
bit c hiu t bo ung th v mt na khc l cht c PE.
Cht c PE l mt protein cha 3 khu vc: Domain I gm cc
axit amin l-> 252 lin kt vi th th a2 - macroglobulin c mt
c t bo ung th v t bo bnh thng; Domain II (gm cc
axt amin 253 -* 364) c chc nng cho php lm chuyn ri
phn trnh t cui c (gm on trnh t axit amin t 280 - 613)
vo phn xitosol ca t bo. Trnh t cui c ny cha domain III
(bao gm cc axt amin t 396 -> 613) khi trong t bo s tham
gia vo qu trnh ribozyl ho yu t ko .di F2 cng vi ADP, lm
ngng s tng hp protein, gy cht t bo. Dng cht c PE -38
l PE b ct xn domain I v phn trnh t (gm cc axt amin
365 ->379) ch c tc dng gy c nhng khng nhn bit t bo
d dng c sn xut ti t hp trong E.coli v c dung hp
202

v i truyn vi manh khng th trc tip chng li khng

nguyn ca cc t bo ung th. T , c t min dch ti t hp
c tnh chn lc v tm dit t bo ung th c hiu qu. Mnh
khng th c sn xut ti t hp trong E.coli cng l kt qu
ca nhng cng trnh nghin cu v pht trin mnh m ca
cng ngh ti t hp khng th n dng t nhng nm 1991 n
1996 (Winder, Milstein, Raag, Whitlow, Reiter, Pastan). Sau khi
thit k gen sn xut cc mnh scFv, dsFv (ch bao gm V|| v V|
lin kt vi nhau bng mt peptt nh hoc bng mt cu disunfua),
cc mnh khng th ti t hp c dung hp vi phn tn cng N
ca PE - 38. Cc vecto biu hin c t min dch scFv hoc dsFv l
mt plasmid c s" lng bn sao ln, c Studier v Moffatt
thit k v m t t nm 1986. Cc khng th ti t hp ang c
nghin cu cho liu php min dch ung th trnh by bng 14.1.
Bng 14.1. Cc ch cho liu php min dch (Reiter, Pastan 1998)

K h n g nguyn Kiu k h n g nguyn D ng u n g th K h n g th

u ng th th i t k

CD 19/20/22 Cc k h n g nguyn bit ho L euk em ia t RFB4

ung th bo B

T h th E G F T h th V, no, phi

erbB 2 T h th c hiu u n g th V, d dy e23

/ Oncogen

T h th IL-2 Th th bc l qu mc L eu k em ia t A nti-Tac
bo T

T h th IL-4 Th th bc l qu mc Thn

T h th IL*6 T h th bc l qu mc a u tu.
mieloma

Lewis Y K h n g nguyn p h t trin V, d dy, B3, BI

C acbohydrat rut kt

T h th EGF Th th c hiu u ng th Gan, no MR1, YlO

t bin / Oncogen
 2(W

r c 111 a Ml k h n g the ti t hp c n g dc n g d n g cho vic

ph! hin v (lit tr t bo u n g t h khi c h n g cc kt hp vi
cc c h t n h d u phng x n h I o d 12: hoc F IH. C h a n g h n
ngii ta diu ch m n h k h n g th (lsFv n h d u F 1K v I 11
b t n g u n t k h n g tl anti-Tac. N h c h n g ta bit, k h n g
th a n ti-T a e n h n bit v chng li tiu dn v a c a t h th IL-2
c m t n h i u t bo un g th. u im ca m n h d s F v l c cu
t r c nh nn p h n b v t h m lot n h a n h vo cc khi u m a n g
t h th IL 2. Do c th p h t h i n n h a n h cc khi u c kch
thc r t nh. Hn n a vic s d n g liu p h p m i n dch p h n g
x p h h u t bo u n g t h b n g cc m n h k h n g t h ti t hp
n h d u u n g t h dc hiu cao c t h loi b c cc khi u nh
v t bo u n g th, t gy c i vi n h n g t bo b n h thng.
Mt phng php mi khi s dng cc mnh khng th ti t
hp l liu php khng th kt hp enzim v thuc tin thn
chng ung th. l k thut ADEPT (antibody - directed
enzyme - prodrug therapy). Trong phng php ny khng the
ti t hp c cng hp ban u VI enzim v a vo c th
nhn bit cng nh nh v cc t bo ung th hoc ch ung th.
Sau cc thuc tin thn dit t bo ung th (prodrug) khng
c hot tnh s c cc khng th cng hp enzim bin thnh
thuc c hot tnh v hu dit t bo ung th. Enzim trong phc
h khng th enzim c tc dng khuych i c hiu tc dng
chng ung th ca thuc ti cc ch ung th. K thut ADEPT
c ng dng hu dit cc t bo c biu hin th th
EGF v th th erB2, mt s khng nguyn ca cc t bo ung
th biu m (Carcinoma, melanoma). V d phc h dsFv - p lac-
tamaz c iu ch chng li t bo ung th c th th erbB2 c
hiu qu cao hu dit t bo ny khi n lm bin i thuc tin
thn cephalosporin - doxorobixin thnh doxorobixin.
Liu php khng th d phng bt buc l khng th anti - D1
c tim cho tt c ph n Rh (d) mang thai nhi c khng
nguyn Rh*(D). Khng th ny s opsonin ha hng cu ca thai
nhi chy vo mu ca m v loi b chng v ngn cn s tng
hp khng th anti - D c th m.
204

14.4. S dng cc thu c km hm m in d ch

Cc thuc km hm min dch trc tin l cc Corticosteroid.

l cc gluco corticosteroid nh cortizon, hidrocortizon, pred-
nizon v prednizolon c s dng c hiu qu kim sot s
p ng min dch gy vim tn thng trong thc hnh lm
sng. Hydrocortizon xucxinat tan c trong nc, dng tim vo
tnh mch, trong khi prednizon c dng ng ming v c th
bin i thnh prednizolon nh cc enzim ca gan.
Hiu qu tc dng ca cc glucocorticosteroid l: thng qua
cc th th t bo cht, thuc c chuyn ti nhn t bo, lm
ci bin s biu hin ca gen, tc ng ch yu ca steroid n
chc nng min dch lin quan n mc tit cc xitokin. 0
liu lng s dng dc l, glucocorticosteroid km hm s gii
phng TNFct v IL-1 t cc t bo mono, lm gim s tng hp
IFN - Y v IL-2 ca lympho T. 0 liu lng s dng qu ngng
dc l, in vitro, thuc c tc dng km hm qu trnh thc bo
ca t bo mono v km hm kh nng git vi khun ca chng.
Ngi ta khng th qun tc dng ph ca thuc steroid l lm
tng kh nng nhim trng, km hm s sinh trng ca tr em,
lm tng ng huyt v tng huyt p.
Mt s hot cht sinh hc cng l nhng cht km hm min
dch nh cyclosporin v tacrolimus. Cyclosporin l sn phm ca
nm Tolypocladeium inflatium c xc nh u tin vo
nm 1976 trong khi tuyn chn cc tc nhn khng sinh. Sau
ny chng thng c s dng rng ri trong thc hnh lm
sng. Cyclosporin v tacrolimus (t nm mc Streptomces tsu-
kubaensis) mc d c cu trc khc nhau nhng u lin kt vi
cc protein ni bo l immunophilin. Cyclophilin l protein ca
t bo cht lin kt vi Cyclosporin, ngy nay c xc nh l
mt enzim c tn gi l peptidyl prolin cis - trans isomeraz (hoc
gi l rotamaz). Trong khi protein lin kt vi tacrolimus l
TBS. Phc h Cyclosporin - Cyclophilin v tacrolimus - TBS c
cng mt i lc vi t bo ch cha phosphataz gi l Calxi-
neurin v hot ng ca n ph thuc vo ion Ca2+. Calxineurin
nhn tn hiu thng tin th hai c sinh ra do nng Ca2*
tng ln sau khi c hot ha nh th th TCR s c tc dng
phn gii photphat (dphosphorylation) i vi yu t phin m
NF - ATC c mt trong t bo cht. T lm hot ha gen tng
 205

hp II-I 2 (hot dng ca NF - AT, cng phi hp vi yu t NF -

AT nam trong nhn). Tc dng ca phc h thuc khi lin kt
vi cc protein ni bo c hiu s nh hng ti s hot ha t
bo T bng cch km hm hot ng ca Calxineurin.

14.5. S d n g cc xitokin v an tixitok in

Xitokin l nhng rht tit ca t bo c tc dng vn nng n

giai on sm ca c ch vim v tc dng km hm min dch.
C 4 chin lc ch yu lm gim tc ng ca mt xitokin l:
bao vy s sn xut xitokin. ch bin xitokin ni bo to ra
mt dng protein c hot tnh b km hm, trung ha xitokin
trong tun hon mu v km hm th th c hiu nhn bit xi-
tokin.
Intelkin 1 l mt xitokin c tc dng trong giai on sm ca
vim v tn ti 3 dng IL-la, IL-ip (c hot tnh sinh hc) v
IL-1 ra (khng c hot tnh sinh hc). C hai loi th th nhn
bit IL-1 l IL-1RI v IL-1R II. Ngi ta iu ch mt s khng
th chng li IL-1 v cc dng ha tan ca th th ca n
trung ho s d tha qu ngng ca IL-1 trong tun hon mu.
Cc khng th chng li th th nhn bit IL-1 c s dng
cng vi IL-1 ra (dng ti t hp) s c tc dng bao vy s tip
nhn cc tn hiu trc khi vim qua trung gian tc ng ca IL-
1. IL-1 dng nh c vai tr ch yu trong cc qu trnh vim
trong cn bnh thp khp. Cc th nghim bao vy tc ng ca
IL-1 trn m hnh ng vt c tc dng lm gim bnh vim
khp. Mt ng dng khc l km hm tc ng ca IL-ip lm
gim trng thi c tnh ca mt s" bnh ung th mu. Ngi ta
chng minh c l IL-1 gy c i vi cc t bo o nh p.
V vy vic bao vy tc ng ca IL-1 trong m hnh th nghim
i vi ng vt b bnh tiu ng ph thuc insulin s lm
gim bt s tn cng ca cn bnh ny.
Intelkin 2 c vai tr quan trng trong hot ha cc lympho T.
Do , mt s bnh lin quan n lympho T nh bnh t min s
thi b c quan cy ghp khng mong mun c nghin cu.
V d, cc t bo c tnh lympho T bc l qu mc cc th th
IL-2, nn c th tin rng IL-2 l yu t sinh trng ca t bo.
Tri li, vic s dng tng cng chc nng ca IL-2, cng lm
tng cng p ng min dch chng li cc khi u.
206

Trong mt vi nm gn y, ngi ta s dng cc khng

th chng li chui a ca th th IL-2 (CD 25) bao vy s hot
ha t bo T. Hin nay cng c mt s phng php th
nghim trn lm sng khai thc kha cnh min dch ny
bng cch s dng cc liu php c t min dch v min dch
phng x.
Khng th t chut chng li chui a ca th th IL-2 (khng
th anti CD 25) c th nghim iu tr s thi b mnh
ghp c quan thn. Mc d khng cn nghi ng g v hiu qu
ca vic th nghim ny nhng khng the anti CD 25 (cn gi l
khng th anti -Tnc) cng l mt immunogen d gy p ng min
dch. Tuy nhin cc th nghim trn cng thc y vic iu
ch khng th lai ghp gen chng li CD 25 s khc phc c
kh khn trong iu tr lm sng.
Mt phng php mi to ra s hot ha IL-2 i vi cc t bo
gy hiu qu min dch cng c ng dng rng ri trong liu
php chng khi u. Phng php ny ln u tin c Steven
Rosenberg M s dng. l vic tch cc t bo lympho t
mu ngoi vi ca bnh nhn b ung th, sau hot ha v nhn
ln in vitro cc t bo ny cng vi IL-2 qua mt s ngy. Trong
nhng iu kin y, mt dng lympho khng phi T s c pht
trin c hnh thi lympho ht ln (LGL: Large G ranular Lym
phocytes). Trong cc m hnh th nghim ng vt, cc lympho
ny c c tnh rt cao chng li cc khi u thc nghim v c
th c gi l cc t bo git c hot ha bng lymphokin
(LAK: Lymphokine activated Killer). Liu php t bo LAK
c chng minh l lm thuyn gim mt phn hoc thuyn
gim hon ton trn 20% bnh nhn b mt s bnh ung th c
bit l ung th da c tnh (melanoma) v ung th biu m thn.
Tri vi liu php t bo LAK, ngi ta khng th iu tr trc
tip IL-2 bi v liu cao, IL-2 s gy c cho c th. Tuy vy,
tim IL-2 trc tip vo mch mu cng lm tng lng t bo
lympho, lm tng t bo git t nhin (NK) v lm tng hot
ng ca cc dng t bo kiu LAK. Hin nay M v Anh,
liu php trc tip v gin tip IL-2 cng bt u c s
dng cho mt s' bnh ung th (c bit l hai bnh k trn), tuy
rng hiu qu ri ro gy cht khng mong mun c th t ti
4%.
 207

I n te fe ro n dc xem n h l m t t h n h vin ca h m i n dch

b m sin h c t c d n g ch ng li virus. Ni c h u n g c hai kiu inte-
feron l i n te f e r o n I v II. I n te f e r o n I c h o t tn h k h n g v iru s
bao gm hai loi l inteferon ex (IFN - a) v inteferon (IFN - ).
C hai loi IFN - a v IFN - u c khi lng phn t xp x
18 kDa c tc dng chng li s sinh sn t bo (antiprolifera
tion), c bit l IFN - a, kch thch hot ng cc t bo git t
nh i n (NK) l m t n g biu hin cc p h n t HLA lp I, n h n g
khng lm tng bc l lp II. c bit, IFN - a l mt xitokin c
ng d n g i u tr chng u n g t h c h i u qu. n h t l u n g t h
m u c tn h . Cc p r o te in t i t hp b l ngun t gen IFN - 0.2 l
n h n g s n p h m th n g mi, bao gm IF N -a v IFN- a2b.
C mt s c ch gii thch hot ng chYig virus ca IFN - a
l: IFN-a km hm trc tip s tng hp cc protein ca virus,
lm tng kh nng nhn bit min dch i vi cc t bo b
nhim virus. Bng cch lm tng cng qu trnh bc l cc pro
tein ca HLA lp I (i vi IFN-a v P) v cc protein ca HLA
lp II (i vi IFN - a). Thm vo , cc IFN a v c tc dng
kch thch hot ng ca cc t bo mono, t bo dit t nhin, v
cc lympho T. c bit IFN-CX c cng nhn l thuc diu tr
ung th bch cu t bo tua (hairy cell leukaemia), mt dng
ung th lympho B bt thng. So vi cc t bo B bnh thng
cc t bo ung th B dng tua c s bc l cc th th IFN-a
tng ln t 4 n 8 ln. Hiu qu iu tr IFN-a i vi cc t
bo khi u l lm gim s tng hp ADN, gim tng hp protein,
do lm thuyn gim bnh a s cc bnh nhn v duy tr
hiu qu tr bnh t 1 n 2 nm.
IFN-CI cng c iu tr cho cc bnh nhn ung th biu m
t bo thn, ung th a c tnh, bnh nhim virus vim gan B v
c mn tnh (c th cha khi t 40 n 50% s bnh nhn).
Inteferon-y l Inteferon kiu II c sn xut t cc lympho T
CD4 T h1, T CD8 v cc t bo NK. N hot ho cho s biu hin
ca cc phn t HLA lp II, lm thc y s bit ho cc t bo
mono thnh cc i thc bo. Ring bn thn IFN-a hoc kt hp
vi yu t" hoi t ung th (TNF: Tumor necrosis factor) c tc
dng ph hu cc k sinh trng ni bo (nm bn trong i thc
bo) hoc kch thch t bo to ra cc dn xut oxy (H20 2> O cl,
OI', O B r) v cc mono oxyt nit ph hu t bo vi khun.
208

14.6. Liu php m in dch t bo

Cc bch cu khc alen, cng loi (allogenic leucocytes) c th

c s dng iu tr cc bnh nhn gim bch cu, c bit
trng hp nhim trng mu. iu bt li ca phng php l
hiu qu c tnh cht tm thi v thi gian sng rt ngn ca
cc bch cu a nhn, hn na vic tim truyn c th gy cm
ng tng hp khng th anti - HLA, ko theo s ph hu cc
bch cu v tiu cu c tim truyn.
Liu php t bo cng c s dng trong trng hp cy
ghp t bo ca bn thn (autograft) hoc cy ghp m khc alen
nhng cng loi (allograft). V d: Cy ghp tu xng, cy ghp
t bo ngun sinh mu cho tr s sinh thiu ht min dch c
tnh.
Liu php t bo c chp nhn, ban u c th nghim
trn chut nht c m hnh bnh tiu ng typ I, hoc trn
chut b bnh vim khp. Ngi ta nhn thy cc t bo T
chut mc bnh c th truyn bnh cho chut lnh, c x l
lm bt c tnh theo nguyn tc iu ch vacxin, sau c
tim truyn cho chut nh l mt vacxin. m hnh chut,
phng php ny cha khi bnh tiu ng cho chut,
ngi, vic th nghim lm sng liu php vacxin t bo hin
nay thu c nhng kt qu kh quan i vi cc bnh nhn
b bnh vim khp v cc bnh x cng nhiu dng m t bo.
Mt cng ngh mi cho php thc hin liu php min dch
tip nhn (truyn tnh min dch th ng t c th ny n c
th khc) l s dng s p ng min dch t bo lympho T
git cc virus nm bn trong t bo. Bnh nhn c cy ghp
tu xng khc alien khc phc c s nhim Cytomegalovirus
trong thi k b bnh gim bch cu, t cho php phc hi cc
t bo tu xng. Trong nhng nghin cu mi y, ngi ta thu
nhn cc t bo lympho T ca mu ngoi vi t c th cho tu
xng trc khi cy ghp v nui cy in vitro cng vi ngun
khng nguyn virus v IL-2. T s to c dng t bo gy
c (lympho Tc) v a vo bnh nhn tip nhn tu xng b
bnh gim bch cu. S p ng min dch cc t bo T chYig
li virus mu ngoi vi sau thi k liu php ghp t bo T t
kt qu tt v bnh nhn c cha tr theo phng php trn
khng b nhim Cytomegalovirus. Liu php ny c th tr thnh
 209

m t tr o n g n h n g ph ng p h p ch a b n h tng lai, bo v cho

cc b n h n h n ghp tu xng b th i u h t bch cu.

14.7. Liu p h p gen chng ung th

Trc ht, m un s d n g liu p h p gen chng u n g th, cc n h
k h o a hc c n h i u r trong qu t r n h p h t sinh u n g th, hin
t ng p n g m in dch chng u n g t h xy r a n h t h no?
c b n g c h n g cho t h y c hin t ng p ng m in dch chng
u n g t h m u . Cc t bo u n g t h c th t h a m gia p n g min
dch khi cc k h n g n g uyn u n g t h c tr n h din bi c h n h cc
p h n t H L A t r n b m t cc t bo khi u, hoc c n g c th
c t r n h d i n bi cc t bo t r n h di n k h n g n g u y n khc. Khi
cc t bo b tr (T||l) c t r n h din s ti t r a cc IL-2, lm
h u y ng cc t bo gy c (Tc) n h n bit t bo u n g t h v
p h n h u chng . T h a m gia vo q u t r n h p n g m in dch ny,
ngoi cc phn t HLA lp I/ hoc lp II, cc cm bit ho CD4
(ca Tj|), CD8 (ca Tc) cn c cc ng tn hiu (Co - signals) nh
CD28 v B7. Cc khi u ln t do pht trin l do cc t bo c
tnh trn thot khi s kim sot min dch. iu ny c th
xy ra khi khng nguyn c hiu ung th khng c bc l
trn b mt t bo ung th, do mt i cc phn t HLA, hoc do
khng c mt cc ng tn hiu tham gia trnh din khng nguyn,
dn n hin tng m't ng (anergy) ca cc t bo T||.
S mt ng ca cc t bo TH trong trnh din khng nguyn
l hin tng t bo T khng th nhn bit min dch v mt kh
nng p ng min dch.
Liu php gen min dch nhm mc ch vt qua c ch trn
thot min dch ca cc t bo ung th trnh by trn. C
th tm tt qu trnh thc hin liu php gen ch'ng ung th
nh sau: T bo ung th, hoc khi u c ly ra ngi bnh,
c nui cy v cc gen thch hp c th c ci t vo cc t
bo con chu (hay hu du) ca chng. C th c 4 cch ci t
gen nh sau:
a. tng cng kh nng nhn bit min dch, cn ci t cc
gen m ho cho cc phn t HLA.
b. Cc gen nhn bit khng nguyn ung th cng c ci t
theo mc ch trn.
210

c. ' tng cng hot ho cc lympho c hiu, cc gen m ho

cho s bc l cc ng tn hiu (chng hn B ?) cng c ch
ci t khc phc tnh trng mt ng ca t bo Th.
d. Nhm huy ng tng cng t bo T gy c (Tc), ngi ta ci
t gen m ho cho IL2.
e. khc phc tnh trng thiu ht hoc bt hot ca gen p53,
l mt gen c coi l km hm ung th, ngi ta v ang
nghin cu ci t gen ny vo nhng t bo khi u bit
ch xc nhng t bo khi u b ung th l do thiu ht gen
p53.
Sau , cc t bo ci bin s c hon tr li cho bnh
nhn theo liu php quy nh.
Trn m hnh nghin cu ng vt, liu php gen chng ung
th to ra nhng kt qu loi b tn gc cc khi u v bo v
chng bnh ti pht tr li. Liu php gen chng ung th ngi
c a vo lnh vc lm sng v ang ha hn mt tng
lai tt p nhm cha tr ung th mu v cc bnh ung th khc.
Chng XV. Min dch trong cy ghp

15.1. Khi nim v phn loi cy ghp

T h u t n g cy ghp ( t r a n s p l a n t a t i o n ) dc s d n g cho t h
t h u t cy g h p mt m t bo hoc mt c q u a n ni t n g (tng)
t mt c t h cho t h a y th m hoc c q u a n c a c th n h n
b p h h u chc n n g do b n h l hoc do c h n th n g v t l
n h m d u y tr cuc sng ca h. Ngi ta c n g s d n g t h u t ng
G r a f t n g h a l g h p cho cc m t bo k h n g c cc ng ni
m c h m u n h g h p da, ghp gic mc... Ngi ta p h n loi
t h n h cc loi cy g h p c h yu s a u y:
- Cy ghp t thn: (Autograft hoc Autologous transplant).
l kiu cy ghp cc m hoc c quan tng ca chnh bn thn
mt c th trong lm sng, vic cy ghp ny ph bin l cy
ghp da t v tr ny sang v tr khc. V d, cy ghp da ly t
phn khc ca c th ca mt bnh nhn b bng da mt.
Trong iu kin khng b nhim tx-ng, s cy ghp t thn
lun lun cho kt qu tt ngha l khng c b hin tng thi
b mnh ghp.
- Cy ghp cng gen: (Syngraft hoc Syngeneic transplant) l
cy ghp m t bo hoc c quan tng gia nhng c th ging
ht nhau v b gen di truyn. Trng hp ny c c gia hai
c th cho v nhn c sinh i cng trng (monozygotes) v
trong thc nghim lm sng him xy ra.
- Cy ghp d gen: (Allograft) c thc hin gia c th cho v
c th nhn c b gen khc nhau nhng cng mt loi. y l
trng hp cy ghp ang c nghin cu v p dng ph
bin trong lm sng. Tuy nhin, cy ghp khc gen hay d gen
thng dn n kt qu thi b mnh ghp hoc c quan ghp.
- Cy ghp ngoi lai: (Xenograft) c thc hin gia cc loi
ng vt khc nhau. y l trng hp cy ghp kh khn
212

nht nhng cng ang c nghin cu ng dng cho y hc

cha bnh.
Thnh cng ca cy ghp ch yu ph thuc vo phn ng
min dch ca c th nhn i vi khng nguyn cy ghp ca c
th cho, c mt c quan hoc mnh ghp. Trong rt nhiu
khng nguyn to nn tnh a hnh ca mt loi (cc allotype)
ngi ta chng minh rng, tng th cc khng nguyn c
m ho bi nhng gen ca phc h ph hp t chc ch yu
(MHC) l quan trng nht i vi qu trnh cy ghp. Chng hn
trong thc t truyn mu, mt dng cy ghp m c bit, cc
khng nguyn ca h thng nhm mu ABO v Lewis c vai tr
rt quan trng. Mt tng th khc ca phc h ph hp t chc
p h n h cc si u k h n g n g u y n ( s u p e r a n ti g e n : H M ls chut)
hoc cc khng nguyn c trnh din di dng peptit lin kt
vi cc phn t MHC ca c th cho hoc c th nhn, cng c
vai tr trong cy ghp.
Phn ng min dch ca c th nhn chng li cc khng
nguyn ca mnh ghp c thc hin bi cc t bo T v cc
khng th lm tn thng v gy ri lon chc nng sinh hc ca
mnh ghp. l cc phn ng thi b mnh ghp. Vic cy
ghp khc gen cng loi hay cy ghp khc loi u dn n thi
b mnh ghp. Tu theo c ch min dch bnh l v cng
phn ng thi b mnh ghp ngi ta c th chia ra mc thi
b ti cp, thi b cp thi b kinh nin hoc ko di.
Khi c th nhn khng c kh nng thi b mnh ghp d gen
do thiu ht min dch bnh l hoc do b km hm min dch v
nu mnh ghp hoc c quan tng c cha cc lympho T, th cc
lympho ny c th nhn bit khng nguyn ca c th nhn v
s gy ra phn ng mnh ghp chng li vt ch, vit tt l GVH
(Graft Versus Host reaction).

15.2. Cc c c h thi b m nh ghp

tm hiu cc c ch thi b mnh ghp, cc m t bo hoc

c quan b thi b c phn tch sinh thit (biopsy). Ngi ta
thy r cc mnh ghp b thi b th hin s thm nhp gy
sng vim ca cc t bo bch cu n nhn, c th l cc t bo
lympho v cc i thc bo. Nh cc khng th n dng, ngi
ta c h n g m i n h s c m t c a cc t bo TCl)4, TCD8. i th c
bo, ly m p h o B, t bo git t n h i n NK. c b n g c h n g cho
t h y cc c ch c h im u th tr o n g p n g s in h l m in dch
cng c p dng cho hin t n g thi b mnh ghp ging nh
tro n g p n g m i n dch vn c. S c n b n g gia cc t h n h vin
c a h t h n g m i n dch t bo v m i n dch dch t h c tc d n g
iu k h i n mc , quy m v s biu hi n c a q u t r n h t h i b
mnh ghp. Ngay khi mt t bo b tr TCD4 cha mt ln tip
xc V I khng nguyn (ngi ta gi l T||0. t bo "Ngy thc:
Virgin hoc n a iv e h e l p e r cell) gp p h i mt d k h n g n g u y n (al-
loantigen) c trnh din bi APC, t bo T||0 s bit ho tr
thnh T|l hoc T|2. Khi trong mi trng c IL-12 l sn phm
ti t c a i th c bo, cc T ho s bit ho t h n h Tl- C D 4 +. B a n
thn T1 cng c chc nng hot ho T- CD8* cng cc i thc
bo t h n g q u a k h n n g ti t IL-2 v IFN-y c a n. T u y n h i n ,
nu trong mi trng chim u th l IL-2 th cc t bo T||0 s
b i t ha t h n h cc t bo T|2 v nh cc IL4, IL 10 s c ti t
ra hot ha cc t bo lympho B v sn xut ra khng th.
Nghin cu cc protein v cc bn sao ARNm cc mnh ghp
trong qu trnh thi b cho thy s c mt ca IL2, IFN-y
nhng khng thy xut hin IL4. iu c th gi vai tr ca
Th1 l iu khin chng trnh thi b mnh ghp. Ngi ta bit
r IFN-y c vai tr huy ng v hot ho i thc bo, lm tng
cng qu trnh bc l cc phn t MHC cc mnh ghp, to
cho chng c bit nhy cm i vi cc lympho T gy c T
CD 8* c ngun gc t c th nhn. IL2 cng c vai tr hot ho
cc t bo Tc.
Tm li, cc yu t xitokin c vai tr c hiu tham gia vo qu
trnh iu ho s thi b cc mnh ghp. Tuy nhin, ngi ta cn
bit r c ch nhn dng cc d khng nguyn cc mnh ghp
s din ra nh th no? Trong iu kin cy ghp thc nghim
cng nh cy ghp lm sng c thc hin gia cc c th
khng c quan h gn gi v gen ca cng mt loi, cc khng
nguyn c gi l d khng nguyn quan trng s c m ho
bi mt phc h gen ca MHC (hoc HLA ca ngi). Chc nng
sinh l ca cc MHC l trnh din khng nguyn cho cc t bo
T. Vn quan trng l cc d khng nguyn c nhn bit nh
th no? Ngi ta nu ra hai kh nng nhn bit:
214

- Th nht: h min dch ca c th nhn bit mt MHC nguyn

vn v coi l mt s nhn bit trc tip d khng nguyn.
- Th hai: mt peptit bt ngun t MHC l (ca c th cho cng
c coi l allopeptit) c th c trnh din trong mt rnh
ca phc h MHC ca c th nhn. l s nhn bit gin
tip d khng nguyn. Ngi ta bit r cc t bo c th
nhn bit mt s lng cc phn t MHC ca c th chu vt
tri hn s lng cc allopeptit c ch bin (t 1000 n
10000). Do , cc d khng nguyn c nhn bit bi h
thng min dch ca c th nhn khng chi bao gm cc phn
t MHC ca c th cho m cn gm c cc phn t MHC cha
ng cc allopeptit c sn trong MHC ca c th cho. Chnh
nh cc phn t MHC ca c th cho mang sn allopeptit c
cu trc bn vng cng c kh nng kch thch s nhn bit d
khng nguyn ca c th nhn.

15.3. Phn loi cc phn ng thi b m nh ghp

Trong thc hnh lm sng c rt nhiu c quan tng c cy

ghp v phn ln u kiu ghp d gen. Do ngi ta lun
lun phi x l cc loi thuc km hm min dch v iu bin
min dch. S thi b mnh ghp c th c phn loi ty theo
quy m thi gian xut hin c ch thi b. Sau y l bng trnh
by s phn loi ca cc phn ng thi b mnh ghp.
Bng 15.1. Phn loi s thi b mnh ghp

Kiu thi ghp Thi gian cy C ch min dich c th

ghp xy ra
Thi b ti cp Din ra theo pht Cc khng th mi
hnh thnh
Thi b rt cp T 1 n 5 ngy Cc lympho T
Thi b cp tnh T tun th 2 Cc lympho T
Thi b ko di T nhiu thng Cc khng th, b th v
(trng din) n hng nm cc phn t bm dnh
 S tli 1)0 ti cap (lin ra trong co trng hp cy tfh(;|) khng
CUII^ nhm mu, (lc bit l khc nhm mu AIU). Ngi ra cn
bit r cc khng nguyn nhm mu AHO khng ch c mt trn
h mt t bo hng cu m cn c cc t bo biu m. Cc
khng t h ca c t h nhn cng tham gia chng li trc t i ) cc
phn t HLA lp I ca c th cho.
Trong thi b cp tnh cc lympho T ca c th nhn trc tip
nhn dng cc alloantigen theo c che nhn dng trc tip.
S thi b ko di hay trng din xy ra sau khi c s cy
ghp thnh cng. Nguyn nhn ca qu trnh thi b ny vn
cn cha c bit r v bnh l. Ngi ta cho rng c qu trnh
tn thng cc ni m mao mch, c th do mt yu t no
dn n bin chng sau ny. Ni m c th b ph hu do phc
h khng the khng nguyn ngoi lai c tch lu dn cc m
a n s hot ho b the. Cc xitokin nh IL 1, IL 6, TNF-y v
cc phn t bm dnh cng c xut hin trong qu trnh thi
b, c tc dng iu ho mc hot ng ca cc t bo ni m.

15.4. Mt s c im lm sng trong cy ghp

15.4.1. C th cho m nh ghp hoc c quan

i vi vic ghp thn, ghp tu xng v c bit l ghp cc

thy gan, cc nh phu thut yu cu c th cho trng thi
ang sng v c s chp nhn t nguyn. i vi cc loi cy
ghp khc, nu c th cho trng thi cht no (hn m xy
ra) th vic hi sinh (resanimation) i vi c th cho: tr gip
khng kh h hp, duv tr huyt p hiu qu s ng vai tr quan
trng trong kt qu cy ghp sau ny.
Mi c th cn c kim tra v nhm mu khng nguyn
Rhesus (Rh), phc h HLA-A, HLA-B, HLA-DR cng nh kh
nng truyn nhim cc bnh virus nh vim gan siu trng,
thiu ht min dch HIV.... Vic nghin cu khng th chng li
Cytomegalovirus (CMV: Cytomegalovirus thng nhim vo tu
xng hoc c quan ghp) l iu rt quan trng, phng ri ro
d xy n cho cc c the nhn.
216

15.4.2. C th nhn mnh ghp

Cc quy lut la chn ngi nhn phi lun lun tho mn
min dch nh phc h HLA. Cc mnh ghp c quan lun lun
cn c s ph hp khng nguyn nhm mu ABO. Ngi ta lun
tn trng s ging nhau v nhm mu trnh s tch lu qu
nhiu cc i tng c nhm mu o trong s cc c th nhn
ang i ghp. Trc khi cy ghp ngi ta cng xt nghim cc
phn ng cho bch cu (Cross - Match). l phn ng tm s
ph hp trc tip nhm pht hin cc d khng th (alloanti-
body) chng li hng cu hoc chng li cc bch cu gia hai c
th cho v nhn. Phng php ny c trnh by bng 15.2.
Bng 15.2 Minh ho phn ng Cross - Match bch cu

Cc thnh phn 1 2 Kim tra

Lympho T ngi cho
Huyt thanh ngi nhn Ab* Ab Ab* Ab
Huyt thanh th (b th + + - +
v khng th)
Cht mu (eosin Y) thm khng khng khng
mu
Phn ng Cross - Match + - - -

Phn ng Cross - Match dng tnh l mt chng ch nh cho

trng hp ghp thn, ch r s c mt ca khng th ca ngi
nhn chng li khng nguyn MHC lp I ca ngi cho.

15.5. Liu php km hm m in dch trong cy ghp

Ngy nay cc quy trnh x l cht km hm min dch ngy a

dng v thch ng vi cc ri ro trong thi b mnh ghp hoc
tu theo kiu c quan c cy ghp, tu thuc vo tnh phn
ng ca tng c th nhn. Ngi ta s dng rt nhiu cht
km hm min dch tm kim s hip ng trong cy ghp
(synergy) v lm gim thp s ri ro ca cc hiu qu ph khng
mong mun. Tt c qu trnh cy ghp c gim st lm sng
 217

v tfiam st sinh hc rt u dn nhanh chng pht hin cc

klun^ hong ca s thi b mnh ghp. Khi s dng cc cht
km hm min dch ngi ta cng lun lun theo di kh nng b
nhim trng c hi thng hay i km, c bit l nhim cy
tomegalovirus v nhiu loi virus gy bnh khc. Bn cnh
cc ri ro v ung th thng hay tng ln trong qu trnh cy
ghp thng c theo di v phng.
Mt s dng thuc km hm min dch c th c gii thiu
sau y:
Azathioprin: thuc ny chng trao i cht, tc dng nh l
cht i khng purin, c chc nng ging nh tc nhn chng
tng sinh t bo. Thuc c s dng trn hai thp k i VI
ngi.
Corticosteroid: c nhiu tc dng ln h min dch nh lm
gim s lng cc t bo lympho B tun hon, km hm s qua
li ca cc t bo mono, km hm s tng sinh v bc l cc gen
xitokin ca t bo T (cc ILl, IL2, IL6, INF-y v TNF-a). nh
hng ph ca thuc cng biu hin da, xng v nhng m t
bo khc.
Preclnizon: dc s dng tc thi trc hoc ngay trong lc cy
ghp vi liu lng gim dn. Methylprednizolon c iu tr
ngay khi chn on l c hin tng thi b mnh ghp v s
dng hng ngy ko di lin tip trong 3 ngy.
Mt SC) thuc km hm min dch khc cng c s dng ph
bin l: Cyclosporin A, Tacrolimus, Sirolimus. Sau y trnh by
tm tt mt s c ch tc ng ca thuc.
B n g 15.3. C ch tc ng ca thuc km hm min dch

Thuc Kiu tc (ng

Azathioprin Km hm s tong hp purin

Corticosteroid Hao vy s bc l cc gen xitokin

Cyclosporin A Bao vy con ng hot ho t bo T ph thuc ion C a2*

Tacrolimus Bao vy con ng hot ho t bo T ph thuc ion C a2*

Si roll nius Bao vy s tAng sinh t bo do IL-2 kch thch v bao vy cc tn

hiu ng kch thch qua tru n g gian CTLA-4

218

Mt s khng th dn dng v a dng: l thuc km hm min

dch cng c s dng d chng li s bc l phn t b mt
ca cc t bo lympho T nh TCD4\ TCD8* hoc tc dng vo
cc th th IL 2 (CD 25).

15.6. M ang th ai l trng thi t nhin ca cy ghp d

gen

Thai (thai nhi v cc phn ph) l mt dng m d gen bc l

cc phn t MHC c m ho bi mt kiu n bi (haplo-
type) ca ngi cha, nhng s pht trin ca n khng b ngn
cn trong thi gian mang thai ca c th m, mc d vn c s
thiu ht min dch. C ch ca nghch l min dch ny cho n
nay vn cha sng t.
Nhau thai c to thnh t cc t bo nui (cytotrophoblaste)
v hp bo nui (syncytiotrophoblaste) tip xc trc tip vi tun
hon mu ca ngi m. Trong thi gian mang thai, cc phn t
IgG ca ngi m cng c m bo vn chuyn vo h tun
hon ca phi m bo chc nng min dch ban u c tnh
cht vay mn ca thai. Cc t bo nhau cng bc l cc khng
nguyn HLA lp I (A, B, c v G) nhng c che ph bng mt
dng glycoprotein l sialomuxin. Cc t bo lympho ca m d
dng vt qua tun hon mu ca thai theo mt c ch cha
sng t nhng rt c hiu qu cho php trnh c hin tng
GVH. Cc t bo hng cu ca thai cng c th chuyn sang mu
m trong giai on cui ca thi k mang thai. Cc t bo nui
v c th c cc t bo lympho ca thai cng chuyn sang tun
hon mu m ngay trong 3 thng u tin v gy ra sn xut cc
khng th chng li HLA (lp I v lp II). Khng th chng li
HLA ca thai c pht hin 10% ca ngi mang thai ln du
v 30% ca ngi mang thai ln th ba. Tuy nhin, nhng khng
th ca ngi m thc t b hp th trn t bo nui v khng
gy bt k mt nh hng no ti thai nhi.
S ln ln ca t bo nui c iu ho bng cc xitokin c
kch thch bng cc IL3v yu t GM-CSF. Cc th nghim
chut cho thy IFN-y v TNF-a c tc dng km hm sinh trng
t bo nui gy ra hin tng xy thai. Cc hocmon ca nhau
thai c tc dng iu bin p ng min dch ca c th m trong
khong vi mi trng vng tip xc gia m v thai nhi. Khi
 219

(le, s ln^ rc th th tip nhn hocmon progesteron ca cc t

bo lvmpho CUM m gicm xuns mnh m. Trong khi d hot
n^ NK ca cc t bo mng rng ca d con tng len lc ban
(lau th thai, san d gim xung khi c thai v tng ln mnh
khi n^i m lao dng.
Vic nghin cu cc hin tng min dch trong khi c thai v
m ( u a n h min dch gia thai nhi v ngi m s gip cho vic
sa cha mt s bnh bm sinh (tim khng th d phng chng
Rhf(I)) chng xay thai) hoc mt s bnh ung th nhau, ng c
thai nghn...
 221

I. Cu hi n tp min dch c s

Chng I

1. V s mi quan h gia min dch t nhin (min dch bm

sinh) v min dch tip thu (min dch c hiu hoc thch
ng). T nu r thnh phn t bo a nhn, c tnh ca t
bo NK, thnh phn cc i thc bo v cc thnh phn min
dch th dch (b th, xintokin, khng th).
2. Thnh phn v c tnh ca cc t bo lympho Tv t bo
lympho B.
3. V s bit ho v v tr bit ho ca t bo lympho T.
4. V s bit ho v v tr bit ho ca t bo lympho B.
5. Thnh phn v chc nng ca cc Xitokin.
6. Trnh by tm tt l thuyt la chn dng trong min dch v
v s km theo gii thch.
7. Nguyn tc c bn trong liu php tim chng vacxin. Cho v
d v cc dng vacxin c s dng hin nay.

Chng II

1. nh ngha v khng nguyn.

2. Gii thch r tnh khng nguyn (antigenecity) v tnh min
dch ca khng nguyn (mmunologenecity). Khi gy min dch
cho ng vt nhn khng th, khng nguyn s dng cn c
nhng c im no?
3. Th no l mt hapten?
4. Nu c tnh sinh min dch ca mt s dng khng nguyn.
222

Chng III

1.V s mt phn t khng th v cho bit c im ca

chui nng, chui nh ca phn t khng th. Ch r v tr ca
Fab (mnh khng th kt vi khng nguyn), F(ab)2, Fc (mnh
peptit d kt tinh ca khng th. S lng cc cu lin kt
disunfua ca khng th IgG.
2. Phn loi cc khng th v chc nng ca tng loi khng th.
3. C s di truyn v tnh a dng ca khng th.
4. Thnh phn phn t, h gen v cc chc nng ca cc th th
lympho B (BCR).
5. Thnh phn phn t v cc chc nng ca cc th th lympho
T(TCR).
6. Nguyn tc v s sn xut khng th n dng (monoclonal
antibody) v khng th ti t hp.

Chng IV

1. V s v cu trc phn t HLA - lp I v HLA - lp II v so

snh s khc nhau v cu trc v chc nng?
2. V s v s nh khu ca cc gen m ha cho cc phn t
HLA - I, HLA - II v nu mt s c im chnh ca cc phc
h gen ny.

Chng V

1. Cc thnh phn protein ca b th.

2. V s con ng hot ho b th theo c ch c in (c ch
c hiu). Nu r cc b th tham gia v cc yu t iu ho
con ng ny. So snh vi con ng hot ho b th c lectin
MB tham gia vi con ng c in.
3. V s con ng hot ho b th theo c ch bn cnh (c
ch khng c hiu). Nu r cc b th tham gia v cc yu t
iu ho.
4. Hiu qu sinh hc ca hot ho b th l g? V s km theo
hiu qu tn cng ph v mngt bo vi khun v t bo ch
c hi.
 223

f). Nu mi quan h gia ba con ng hot ho b th.

(). Cc* hnh l pht sinh do thiu ht bm sinh cc loi b th.

Chng VI

1. Nu c tnh chung ca phn ng khng nguyn - khng th?

2 . c im nguyn tc ca phng php khuch tn min dch
Ouchterlony?
3. Nguyn tc v c dim ca k thut ELISA.

Chng VII

1. Thnh phn cc c quan min dch s cp (c quan lympho

trung ng) v vai tr sinh hc ca chng.
2. Thnh phn cc c quan min dch th cp (hay ngoi vi) v
chc nng sinh hc ca chng.
3. Thnh phn cc t bo trnh din khng nguyn (APC).

Chng VIII

1. Trnh by qu trnh hp tc gia cc i thc bo v cc lym-

phoT.
2. V s s trnh din khng nguyn cho cc dng t bo T.
Nu r c tnh hiu qu ca cc cm bit ho khng nguyn
CD4 v CD8.
3. Nu s hp tc gia lympho T b tr (Th) v lympho B v hiu
qu sinh hc.
4. So snh hai dng iu ho min dch bng cc lympho T c ch
c hiu v khng c hiu.
5. Nu r c ch iu ho p ng min dch bng c ch mng
li Idiotip.
6. Vai tr ca h thn kinh v ni tit trong iu ho p ng
min dch.
224

Chng IX v chng X

1. C ch min dch ca hin tng qu mn phn v c s tham

gia ca IgE.
2. C ch min dch v hu qu ca qu mn c s tham gia ca
IgM v IgG.
3. Nu hai loi bnh qu mn kiu II: bnh tan hng cu v
ngng kt hng cu do truyn mu v do khng ph hp
khng nguyn Rhesus.
4. Nu tm tt cc c ch min dch chng li s xm nhp ca vi
khun (vi khun, vi nm) v k sinh trng.
5. Quan im hin i v ung th.
6. Nu cc kiu t bo v cc yu t th dch p ng chng li
ung th.
7. Hi chng ung th ca dng t bo Lympho B: bnh u tu, ung
th bch cu, Bnh u lympho (lymphoma).
8. Hi chng u dng t bo lympho T.
9. Nguyn nhn t bin gen v t bin nhim sc th ca cc
loi bnh ung th. c im lm sng ca mt s bnh ung
th. Mt s ch th ung th,ng dng trong chn on v theo
di bnh.
10.Liu php min dch khng th chng ung th.
11.Trnh by liu php gen chng ung th.
12.Trnh by liu php s dng Xitokin chng ung th.
13.Trnh by liu php min dch t bo chng ung th.

Chng XI

1. Cc biu hin bnh thiu ht min dch (nguyn thu dng

lympho B do nhim trng ti din).
2. Trnh by biu hin thiu ht min dch nguyn thu dng
lympho T do yu t di truyn.
3. Trnh by cc con ng ly lan bnh thiu ht min dch mc
phi do HIV.
4. Trnh by cu trc ca virus HIV.
5. Nu cc giai on tin trin bnh l do nhim HIV ngi.
6. V sao khi nhim HIV, h min dch ca ngi b suy gim,
khng phng cu cha?
Chng XII

nh n g h a d u n g n p min (lch l g?
1. Trnh by cc c ch c th giai thch hin tng dung np
min dch.
2. n h n g h a v cc b n h t min, cho mt vi v d v b n h t
min.
3. Trnh by cc nguyn nhan gy bnh t min.
1. Nu mt s phng hng diu tr cc bnh t min.

Chng XIII

1. c im h min dch ca lp c xng.

2. c dim h min dch ca lp ng vt bin nhit.
3. c im h min dch ca lp chim.
4. c im h min dch t bo ca b linh trng (loi kh).
5. c im cc loi khng th v b th ca mt s> loi kh.
6. So s n h phc h p h hp VI t chc c h yu c a m t s linh
trng RhLA, ChLA, HLA.

Chng XIV

1. Nguyn tc min dch hc ca liu php cha bnh bng tim

chng (vaccination).
2. Nguyn tc chung ca sn xut vacxin.
3. Cc dng vacxin c sn xut hin nay trn th gii v Vit
Nam
4. C th sn xut vacxin cha bnh cho cc loi ng vt (gia
cm, thu cm) no c hiu qu ti nht? V sao?

Chng XV

1. C ch thi b cc mnh ghp.

2. Nu mt s' c im lm sng ch yu trong cy ghp.
3. V sao ni mang thai l trng thi t nhin ca cy ghp d
gen (allograft).
226

II. Mt s dng cu hi th min dch

Cu 1: Cho bit cc trng hp

A = IgG B = IgM
c = C hai loi trn D = Khng c loi no c
Hy ch chn mt ch ci cho p n ng ca cc cu hi sau:
1. C cha chui X v lin kt isult (S-S)
2. C cha chui a
3. C cha chui e
4. i qua mng nhau thai
5. C cha chui ni (J)
6. C cha chui mnh tit s

Cu 2 : Cho bit cc trng hdp

A = IgG B = IgM
c = IgD D = IgE
E = Khng c loi no
Hy chn ch mt ch ci cho p n ng ca cc cu hi sau :
1. Lp khng th quan trng trong bo v min dch, thng c
mt tuyn nhy ng h hp, ng tit liu tinh dc.
2. Lp khng th chim t l cao nht trong huyt thanh ngi
trng thnh.
3. Lp khng th c vai tr quan trng trong d ng typ I.
4. Lp khng th xut hin u tin trong tin ho v p ng
m in dch s cp.
5. Lp khng th c thi gian bn hu di nht.
6. Lp khng th t bit r chc nng nhng lun c mt trn
mng t bo B chn v khng c trn mng t bo B ghi
nh.

C u 3 : Cho bit cc trng hp

A = C3b B = C4b
c = Cho c hai loi trn D = Khng c loi no c
 227

H y chn c h i m t c h c i cho p n n g c a cc c u h i sau:

1 Tham gia vo con ng hot ho c in.
2. C lin kt vi ion canxi (Ca2+) trong qu trnh hot ho.
3. Tham gia vo con ng hot ho bn cnh.
4. C kh nng to ra hot ng ca anaphylatoxin.
5. Phc h b th c,qrs s b phn li l do:
A: C s tham gia ca Cl-inh.
B: B mt lon Canxi v c s tham gia ca Cl-inh.
C: B mt ion Magie D: c ba loi trn

C u 4 : Cho cc trng hp ch ci sau v dng n la chn

cho cc cu hi di
A = 1,2 v 3 l ng B = 1 v 3 l ng
c = 2 v 4 l ng D = 4 l ng
E = Tt c l ng
a) Hy ch n p n n g n h t cho cc cu hi:
- Cho bit c quan lympho trung ng?
- Cho bit c quan lympho ngoi vi (a phng)?
1. Tu xng (Borne marrow)
2. Lch (Spleen)
3 Tuyn c (Thymus)
4. Hch bch huyt (Lymphonodes)
b) Hy ch n p n n g n h t cho c u hi:
Nhng t bo min dch sau y loi no tham gia vo h t bo
min dch?
1. Bch cu c ht.
2. T bo lympho.
3. T bo mono.
4. i thc bo.
c) Hy ch n p n n g n h t cho cu hi:
Cc t bo ngun a nng c sinh ra t c quan (hoc cc c
quan no)?
1. Gan phi.
2. Ti non hong.
3. Tu xng ca ngi trng thnh
4. Lch ca ngi trng thnh
228

d) Hy chn p n ng nht cho cu hi:

Cc t bo lympho B ca ngi v chim c gio dng v
trng thnh t cc c quan no?
1. Ti Fabricius hoc vng tng ng tu x n g ca ng vt
bc cao.
2. Hch bch huyt.
3. Tu xng.
4. Lch.

C u 5: Hy chn ch mt ch ci cho p n ng cc trng

hp sau:
A = Ig G B = Ig M
c = C hai loi IgG v IgM D = Khng c loi no c
1. Khng th no c cha chui 8 .
2. Khng th no c cha chui .
3. Khng th no c cha chui K.
4. Khng th no c cha chui J.
5. Khng th no c cha mnh tit s.
6. Khng th no i qua mng nhau thai.
7. Cc khng th no c nhng c tnh sau:
- C cha cc chui nng ging nhau.
- C cha cc chui nh ging nhau.
- C cha gc ng saccacharide.
- Di ng trong in trng ging nhau.

C u 6: Cho cc trng hp sau:

A : Vng bin i ca chui nng.
B : Vng khng bin i ca chui nng,
c : C hai trng hp trn.
D : Khng c trng hdp no.
Hy chn ch ci cho p n ng i vi gen no m ha cho
cc vng ca phn t khng th:
1. Gen J.
2. Gen D.
3. Gen L.
4. Gen m ho vng c ca mnh Fc.
5. Cc gen exon m ho cho cc domain VHl.
6. Cc gen exon m ho cho cc domain VH3 v VH4 ca IgM.
7. Cc gen intron ca cc Ig.
 229

Cu 7 : Cho cc trng hp:

A : T- CI)V B : T bo B
( \ c hai loi trn D: K hng c loi no
1. Lin kt vi t bo trnh din khng nguyn (APC) cha MHC
l p I.

2. Lin kt vi t bo trnh (lin khng nguyn (APC) cha MHC

lp II.
3. T bo no tit ra cc khng th.
4. T bo no tit ra IM.
f). T bo no ti t ra y u L sin h tr n g BCGF.
6. T bo no sn xut ra IFN-y.

Cu 8 : Cho cc trng hp sau. hy chn mt ch ci:

A:CD4f B:CD8+
C: C hai loi trn D: Khng c loi no.
1. Loi t bo no tham gia vo qu trnh tip nhn s trnh din
khng nguyn.
2. Loi t bo no tham gia vo qu trnh tip nhn s trnh din
khng nguyn ni sinh.
3. Loi t bo no tham gia vo qu trnh tip nhn s trnh din
khng nguyn ngoi sinh.
4. Loi t bo gy c Tc c cha cm bit ho khng nguyn CD
no.
5. Loi t bo no c vai tr quan trng trong nhim khi pht
virus HIV -1.
Cu 9 : So snh cu trc phn t, chc nng min dch v h
gen ca phc h HLA.
CulO : C ch t bo hc v phn t ca s trnh din khng
nguyn.
C u l 1 : Chng minh s a dng ca khng th bng c ch di
truyn v ti t hp gen.
Cu 12 : C ch t bo hc v phn t ca s trnh din khng
nguyn.
Cu 13 : Nu ng dng ca cc xitokin (cytokinee) trong cha
bnh truyn nhim v bnh ung th.
Cu 14 : Nu ng dng khng th ti t hp trong cha bnh.
Cu 15 : Phn tch cc c ch thi b mnh ghp.
Cu 16: V sao trong cy ghp tng (m t bo hoc c quan)
cn phi s dng liu php km hm min dch.
PH LC

 233

Ph lc I. c im cu trc v chc nng ca

cc khng nguyn CD
iC th'xem thm trn: The HCMD Website, httu.y/www.hlda 8 .org lin
q t r i n dri rc gen v di liu crt s v bn cht protein ca cc CD)

Khng Biu hin t Trng Cc chc nng Cc ln Mi quan

nguyn bo lng khc he ho hng
CD phn
(kDa)
GDI Cc t bo 43 - 49 Phn t ging Immu
a,b,c,d tuyn c v, MHC lp I, kt noglobulin
cc t bo hp vi P2-
Langerhan, microglobulin.
cc t bo C vai tr
tua, t bo B chuyn ho
(CDlc), biu trong vic trnh
m rut, c din cc khng
trn, mch nguyn cht bo
mu (CDld)
CD2 Cc t bo T, 45 -58 Phn t dnh TI 1 , Immu
cc t bo bm, lin kt vi LFA-2 noglobulin
tuyn c, cc CD58 (LFA-3).
t bo NK Lin kt vi Lck
ni bo v hot
ho t bo T
CD3 Cc t bo y: 25- Kt hp vi th T3 Immu
tuyn c, cc 28 th khng noglobulin
t bo T 5:20 nguyn t bo T
e: 2 0 (TCR). Cn thit
cho biu hin b
mt t bo v
truyn tn hiu
nh TCR.
CD4 Cc tp hp 55 ng thu th T4, L3T4 Immu
con t bo cho cc phn t noglobulin
tuyn c. Cc MHC lp II.
t bo T:TI 11 Lin kt vi Lck ..... I
234

v TH 2 tren be mt te
(khoang 2/3 bo chat mang.
cc te bo T Thu the cho
ngoai vi), gpl20 HIV - 1 v
hach cu dan HIV-2.
nhan, dai
thirc bo.
CD5 Cc te bo 67 f l , Ly 1 Ihn the
tuyen rc, cc thu don
te bo T, tap (an xc
hap con cc thi)
te bo B
CD6 Cc te bo 1 0 0 - 130 Lien ket vai r 12 Thu the
tuyen rc, cc CD 166 thu don
te bo T, cc (an xc
te bo B a thi)
benh bach
cu man tinh
CD7 Cc te bo 40 Chua r, domain Immu
Biu tao mau da te bo cht lien noglobu
hien nng, cc te ket vai PI 3 lin
benh bo tuyen lie, kinaza bng lien
[y cc te bo T ket cheo. La
d'u hieu cho
benh bach cu
cap tinh te bo T
v benh bach
cu te bo
nguon da nng
CD 8 Cc tp hop a:32-34 Dng thu the T 8 , Im m u

con te bo : 32-34 cho cc phn tir Lyt2,3 noglobu

tuyen rc, cc MHC lap I. Lien lin
[6 bo T gay ket vai Lek trn
dc te bo b^ mat mang te
(khoang 1/3 bo cht
cc te bo T
ngoai vi)
CD9 Tien te bo 24 Lm trung gian Protein
B, cc bach cho sir ket tu vt qua
cu dan tieu cu v hoat mang 4
nhn, te bo ho nh ln, cng
ira axit, bach FcyRIIa, c the dirac goi
cu ira kiem, dng vai tr l protein
 235

tic'll call, cc trong s dch xu v 11

t hao T hot chu ven t ho. mng 4
ho, no v (TM4)
cc t ho
than kinh i
Hiioai
c hin.
1
c trn c
mach. ....... , , 1
1
Cl) 10 11CI thn t 100 Proteina/a kim Hndopep-
bo B v I , loi km. L du ti(iaza
iiii
hiri cc t ho hiu cho bnh trung
benh tim tuy bch cu cp tnh,
1 ly xng. tnh tin t bo khng
B (ALL) nguvn
bch cu
cp tnh
ph bin
(CALLA
)
CDl la Cc t bo 180 Di n v a L LPA-l Integrin a
lympho, bch ca integrin
cu ht, cc LFA-1 (kt hp
hch cu dn vi CD 18); lin
nhn v di kt vi CD54
thc bo (ICAM-1),
CD 102 (ICAM-
2), v CD50
(ICAM-3)
|C D 1 Ib Cc t bo 170 Di dn v a M Mac-1 Integrin a
dng tu v ca integrin (cht kt
t bo NK CR3 (kt hp dnh t
vi CD 18): lin bo)
kt vi CD54,
thnh phn b
th iC3b, v cc
protein trong
cht nn ngoi
bo
C D llc Cc t bo 150 Di n v cxX CR4, Integrin a
dng tu ca integrin CR4 p 150, 95
(kt h(tp vi
CD 18): lin kt
vi fibrinogen.
236

C D lld Bch cu 125 Di n v a D Integrin a

ca integrin, kt
hp vi CD 18;
lin kt vi
CD50
CDwl2 Bch cu dn 90-120 Cha r
nhn, bch
cu ht, tiu
cu

CD13 Cc t bo 150-170 Proteinaza kim Amin-

bch cu n loi km opepti-
nhn tu daza N
CD14 Cc t bo 53-55 Th th cho
bch cu dn phc h
nhn tu, c lipopolysacarit
trng cho v protein lin
MNP kt lipopolysa-
carit (LBP)
CD15 Bch cu Trisacarit tn ^ewisx
trung tnh, cng c biu (Le*)
bch cu a hin trn cc
axit, bch glycolipit v
cu n nhn nhiu glycopro
tein b mt t
bo
CD 15s Bch cu, t Ligand (cu t Sialyl- Poly-N-
bo ni m gn) cho Lewis* acetyl-
CD62E, p (sLe) lactosa-
min
CD15U CD 15 sunphat Cc cu
trc
cacbohy-
drat
CD 16 Bch cu 50-80 Thnh phn ca FcyRIII Immu
trung tnh, th th Fc i lc noglobu
cc t bo thp, FcyRIII, lin
NK, i thc lm ung gian
bo cho s thc bo
v tnh gy c t
bo do t ho ph
thuc khng th.
 237

CDw 17 Bch cu Lactosyl cera-

trung tnh, mide, mt gly-
bch cu n cosphingolipid
nhn, tiu b mt t bo
cu
CD 18 Bch cu 95 Di dn v in- Integrin
tegrin P2, kt
hp vi C D lla ,
b,c v d
CD 19 Cc t bo B 95 To thnh phc Immu
hp vi CD21 noglobu
(CR2) v CD81 lin
(TAPA-1), ng
th th cho cc
t bo B- do-
main nm trong
t bo cht lin
kt vi tyrozin
I kinaza v PI3-
kinaza t bo
1
cht.
CD20 Cc t bo B 33-37 Cc oligomer Cha 4
CD20 c th to on pro
thnh mt knh tein
ion Ca2\ c th xuyn
ng vai tr mng
trong iu ho
qu trnh hot
ho t bo B
CD21 Cc t' bo B 145 Th th i vi CR2 Protein
trng thnh, cc thnh phn iu
cc t bo b th C3d, virut khin b
tua nang Epstein -Barr. th (CCP)
Cng vi CD19
v CD81, CD21
to ng th th
di vi cc t
bo B
CD22 Cc t bo B a:130 Lin kt vi Sia- BL-CAM immu
trng thnh : 140 loconj ugate noglobu
lin
238

CD23 Cc t bo B 45 L th th i lc PccRIl Lectin

trng thnh, thp cho IgE, dng c
cc i thc iu ho s tng
bo hot ho, hp IgE, l cu
bch cu a t gn cho ng
axit, cc t th th CD 19:
bo tua nang, CD21: CD18
cc tiu cu
CD24 Cc t bo B, 35-45 Cha r Th
cc bch cu tng
ht ng
ngi
ca
khng
nguyn
bn nhit
chut
(USA)
CD25 Cc t bo T 55 Chui a ca thu Tac CCP
hot ho, cc th IL-2
t bo B v
cc bch cu
n nhn
CD26 Cc t bo B 110 Exopeptidaza, Dipepti- Glycopro
v T hot ct cc dipeptit dyl pep- tein
ho; cc i X-Pro hay X- tidaza IV xuyn
thc bo Ala u N t cc mng
polypeptit dng II.
CD27 Cc t bo 55 Lin kt vi Thu th
tuyn c CD70, c th TNF
thuc tu hot ng nh
xng, cc t mt cht ng
bo T, NK, kch thch i
mt s t bo vi cc t bo B
B v T.
CD28 Cc tp hp 44 Hoi ha ac t bo Tp 44 Immu
con t bo T, T nguyn thu, l noglobu
cc t bo B th th di \i cc lin v
hot ho 11 hiu dng kch CD 8 6
thch (till hiu 2 ), lin (H7.2)
kt vi CD80 (B7.1 )
vCD86(B72)
 2;u)

('1 ) 2 () Bach cau 130 Dirai dan vi m- Integrin \\

tcgrin (U, kct
hap vai CI)4()a
cV intemin VLA-
1

1C I)>0 Cac te bao T, 120 Lien kct vai Ki - 1 Thu the

B, NK hoat CD30L INI
hoa , cac (CD 153), ('1)30
bach can dan lien ket cheo
nil an tang cirang sir
nhan di cua te
bao B va 1
('1)31 Cac bach cau 130-140 La phn tir ket PECAM- Immu
dan nhan, dinh, la trung 1 noglobu
cac tieu can, gian tirang tac lin
bach cau hat, giira bach can
tap hap con te bao noi mo va
tc bao T, cac te bao ni m
te bao tc bao te bao noi m.
ni mo
CD32 Cac bach cAu 40 La thu the L'c ai FcyRII Immu
dan nhan, lire thap di vai noglobu
bach can hat, cac immu lin
cac te bao B, noglobulin ket
bach cau ira hap vai nhau:
axit plurc he mic'n
dich
CD 3 3 Cac te bao 16 67 Lien ket vai Sia- Immu
tien dang loconjugate noglobu
tuy, cac bach lin
cau dan nhan
CD34 Cac tien te 105-120 La cau tu giln Mucin
bao tao mau, cho CD62L (L-
ni m mao selectin)
mach
CD35 Hong cau, te 2 50 I hu the bo the CR1 CCP
bo B, bach I, lien ket vai
cu dan nhan, C3b va C4b, lam
bach can trung gian cho
tiling tinh, sir thirc bao
bach can ira
axit, cac te
1 bao tua nanc
240

CD36 Tiu cu, 88 Phn t kt dnh GPIV,

bch cu n tiu cu: bao GPIIIb
nhn, cc t gm s nhn tiu cu
bo ni m bit v s thc
bo ca cc t
bo cht c
chng trnh
CD37 Cc t bo B 40 -52 Cha r, c th Protein
trng thnh, lin quan n s xuvn qua
cc t bo T truyn tn hiu, mng 4
trng thnh, to thnh phc ln
cc t bo h vi CD53,
dng tu CD81, CD82 v
MHC lp II
CD38 Cc t bo B 45 NAD glycohy- T10
v T s cp, drolaza, lm
cc t bo T tng s nhn i
hot ho, t bo B
bch cu
CD39 Cc t bo B 78 Cha r, c th
hoat ha, cc lm trung gian
t bo NK cho s kt dnh
hot ho, i ca cc t bo B
thc bo ,
cc t ba
tua
CD40 Cc t bo B, 48 Lin kt vi Thu th
i thc bo, CD 154 TNF
cc t bo (CD40L), l th
tua, cc t th cho tn hiu
bo biu m ng kch thch
c bn i vi cc t
bo B, kch
thch s sinh
trng, s bit
ho, s ng m
isotype ca cc
t bo B, v s
to thnh cyto
kine bi cc i
thc bo v cc
t bo tua
 241

CD4I Tiu cu, t Dimer: Integrin alb, kt Pllb Integrin a

bo nhn GPIIba: hp vi CD61 d
khng l 125 to thnh GPIIb,
GPIIbb: lin kt vi fi
22 brinogen, fi-
bronectin, yu t
von Willebrand,
Jtirombospondin
CD42 Tiu cu, t a: 23 Lin kt vi yu a; CiPIX on lp
a,b,c,d bo nhn b: 135, t von Wille b: GPIba giu Leu-
khng l 23 brand, thrombin, c: GPIbp cine
Biu hin c: 2 2 cn thit cho s d: GPV
bnh l d: 85 kt dnh tiu cu
cc v tr tn
thng
CD43 Bch cu, 115-135 C cu trc ko Leu- Mucin
ngoi tr cc (bch cu di, di khong kosianin
t bo B ngh trung 45 nm v c th sialo-
tnh) l cht chng phorin
95-115 dnh
(cc t
bo T)
CD44 Bch cu, 80 - 95 Lin kt vi axit Khng Protein
hng cu hyalurronic, lm nguyn lin kt
trung gian cho Hemes,
s kt dnh ca Pgp-1.
cc bach cu
CD45 Tt c cc t 1 8 0 -2 40 Tyrozin phot- Khng Fibronectin
bo to mu (nhiu phrta7a, lm lng s nguyn dng III
ng truyn n hiu qua ph bin
dng) th th khng bach cu
nguyn ca cc t (LCA),
bo B v T, c nhiu T2 0 0 ,
ng dng do s B220
phn ct lun phin
CD45 Tp hp con 180 ng dng ca Fibronectin
RO t bo T, tp CD45 khng dng II
hp con t cha exon A, B,
bo B, bch c no
cu dn
nhn, i
thc
--- . bo
242

CD45 Cc t bo B 205 - 220 ng dng ca Fibronectin

RA v tp hp CD45 cha exon dng II
con t bo A
T(t bo T
nguyn
thu), bch
cu n nhn
CD45 Tp hp con 190 - 220 ng dng ca 1200 Fibronectin
RB t bo T, t CD45 cha exon dng II
bo B, bch B
cu n
nhn, i
thc bo,
bach cu hat
CD46 Cc t bo c 56/66 L protein ng MCP CCP
nhn to mu (cc bin yu t mng,
v khng to th phn lin kt vi C3b
mu ct) v C4b cho php
phn hu chng
nh yu t I
CD47 Tt c cc t 47 - 52 Phn t kt IAP, Siu h
bo dnh, th th MER 6 , immu
thrombospondin OA3 noglobulin
CD48 Bch cu 40-47 Cu t gn gi Blast-1 Immu
inh cho CD244 noglobulin
CD49a Cc t bo T 200 Integrin a l , kt VLA-1 Integrin a
hot ho, hp vi CD29,
bch cu n lin kt vi co-
nhn, t bo lagen, laminin - 1
thn kinh, c
trn
CD49b Cc t bo B; 160 Integrin a2, kt VLA-2, Integrin a
bch cu n hp vi CD29, GPIa tiu
nhn; tiu lin kt vi co- cu
cu; t bo lagen, laminin
nhn khng
l; cc t bo
thn kinh,
biu m, ni
m; t ho
hu xng
U M ')i C.ac t bo B, 125,30 Integrin (x3, kt VLA-3 Integnn a
nhin t ho hp vi CD29,
(lnh hm lin kt vi
laniinin -5, fi-
bronectin, cola-
gen, cntactin,
invasin :
n m i Phn h rng 150 Integrin 4, kt VLA-4 Inlegrin (X
bao gm cc hp vi CD2(),
t bo B, t lin kt\ vi fi-
bo tuyn c, bronectm, MAd-
bch cu dn CAM-1
nhn, hch VCAM I
cu ht, cc
t ho tua
CD49e Phn b rnc 135, 25 Intcgrin , kt VI.A Inteurin a
c
bao gm cc hp vi CD29,
t bo T ghi lin kt \i fi-
; nh, bch bronectin, inva-
cu dn sin
nhn, tiu
cu
CD49f T bo 125, 25 Integrin a 6 , . t VLA - 6 Integrin a
lvmho T, hp vi CD2
bch cu dn lin kt wi
nhn, tiu laminin, invasii.
cu, t bo merosinc
nhn khng
l, nguyn
bo dinh
dng
CD50 T bo tuyn 130 Lin kt vi KAM -3 Immu-
c, cc t bo CD1 1 a/CD 18 noglobulin
B, cc t ho integrin
T, bch cu
dn nhn,
bach cu hat
244

CD51 Tiu cu, t 125, 24 Integrin aV , kt Th th Integrin a

bo nhn hp vi CD61, vi
khng l lin kt vi vi tronectin
tronectin, yu t'
von Willebrand,
fibrinogen, v
throm-
bospondin; c
th l th th
cho cc t bo
cht c chng
trnh.
CD52 T bo tuyn 25 Cha r, l ch CAMPA
c, cc t bo cho cc khng TH- 1 ,
T, cc t' bo th m c s HES
B (khng c dng lm suy
t bo yu cc t bo T
plasma), t tu xng
bch cu n
nhn, bch
cu ht, tinh
trng (sper
matozoa)
CD53 Bch cu 35-42 Cha r MRC Protein
0X 44 xuyn qua
mng 4 ln
CD54 Cc t bo 75-115 Phn t kt dnh ICAM-1 Immu
to mu v ni bo, noglobulin
khng to (ICAM)-l, lin
mu kt vi integrin
CDlla/CD18
(LFA-1) v in-
tegrin
CD1 lb/CD18
(Mac-1), th th
i vi rhino-
virut
CD55 Cc t bo 60-70 Yu t tng cng DAF CCP
to mu v phn hu (DAF),
khng to lin kt vi C3b,
mu phn hu conver-
taza C3/C5
 245

CD56 Cc t
bo 135 - 2 2 0 ng dng ca NKH - 1 Immuno-
NK phan t kt dnh globin
t bo thn kinh
(NCAM), phn
t kt dnh
CD57 Cc t bo Oligosacarit, H N K -1 ,
NK, Tp hp c tm thy Leu-7
con cc t trn nhiu gly
bo T, cc t coprotein b mt
bo B, v t bo
bch cu n
nhn
CD58 Cc t bo 55 - 70 Khng nguyn 3 LFA-3 Immu
to mu v kt hp chc noglobulin
khng to nng bch cu
mu (LFA-3), lin
kt vi CD2,
phn t kt dnh
CD59 Cc t bo 19 Lin kt vi cc Protectin, Ly - 6
to mu v thnh phn b cht c
khng to th C 8 v C9 ch Mac
mu ngn cn s kt
hp ca phc h
tn cng mng
CD60a Disialyl gan- Cu trc
glioside D3 carbohy
(GD3) drate
CD60b 9- O-acetyl- Cu trc
GD3 carbohy
drate
CD60c 7- O-acetyl- Cu trc
GD3 carbohy
drate
CD61 Tiu cu, t 110 Di n v P3 integrin
bo nhn integrin, kt hp
khng l, i vi CD41
Ihc bo (GPIIb/IIIa)
hoc CD51 (th
th vitronectin)
246

CD62K Ni m 140 Phn t kt dnh 1ELAM- Lectin

bch cu ni m 1, E- dng c,
(LAMh lin !electin ECiF, v
kt vi sialyl- CCP
Lewis', lm
trung gian cho
s tng tc ln
ca cc bch
cu trung tnh
trn ni m.
CD62L Cc t bo B, 150 Phn t kt dnh LAM -i, Lectin
cc t bo T, bch cu E- dang c,
bch cu dn (LAM), lin kt selectin, EOF, v
nhn, t bo vi CD34, Gly- LECAM- CCP
NK CAM, lm trung 1

gian cho s
tng tc ln vi
ni m.
CD62P Tiu cu, t 140 Phn t kt p- Lectin
bo nhn dnh, lin kt vi selectin, dng c,
khng l, ni CD 162 (PSGL- PADGE EGF, v
m 1 ), lm trung M CCP
gian cho tng
tc ca tiu cu
vi cc t bo
ni m, bch
cu n nhn,
v bch cu ln
trn ni m
CD63 Tiu cu hot 53 Cha r, l pro Khng Protein
ho, bch tein mng ly- nguyn xuyn qua
cu n sosom chuyn hot ho mng 4 ln
nhn, i ti b mt t bo tiu cu
thc bo sau khi hoat ho
CD64 Bch cu n 72
nhn, i
thc bo
CD65 Cc t bo Thnh phn oli-
dng tuv gosacarit
ca ceramide
dodecasacarit
Cl Wt;i Bach C.III 160 - ISO Cha r, l Glyco Immu
tiling t]111) thnh vin ca protein- 1 noglobulin
h khng mt
nguyn phi ung \(lk P -1 )
l th (CHA)
Cl )6 6 h Bach can ht 95 - 1 0 0 ; Cha r. thnh CD67 1 Immu-
i vin ca ho trc (v noulohu
C. 11l
khng nguyn
phi uns th
(CEA)
Cl )6 6 c Bach cu ! 90 Cha r, thnhKhng Immu-
trmiiZ tnh, vin ca nguyn ;1 noglohulin
h
uim th hiu khng phan nd
nguyn
m rut kt phi ung tlur cho
(CEA) khng
dc hiu
(NCA)
CDll Bach call 30 Cha r, thnh Immu
trung tnh vin ca h noglobulin
khng nguyn
phi ung th
(CHA)
CD6 6 0 Biu m rut 180 - 2 0 0 Cha r, thnh Khng Immu
kt ngi vin ca h nguyn noglobulin
trng thnh, khng nguyn phi ung
ung tlur biu phi ung ih th
m rut kt (CEA) (CEA)
CD6 6 f Cha r Cha r, thnh Glyco Immu
vin ca h protein noglobulin
khng nguyn dc hiu
phi ung th thai
(CEA)
CD 6 8 Idl Gll clol 110 Cha r Macro- Mucin
Iilm ciai tilt: bn, sialin
hriiGuiingtihh
, h d i cu it\
kxm GC t ho
Kmixilt
CD69 Cc t bo B 28, 32 Cha r, khng Phn t Lectin
v T hot homodim nguyn hot ho cm ng dng c
ho, cc t er giai on du s hot
bo N K v ho
248

h o a tho
CD70 Cc t bo B 75, 95.
Cu tir gn cho Ki-24 TNF
v T hot 170
CD27, c th c
ho, v cc vai tr ng
i thc bo kch thch cc t
bo B v T
CD71 Tt c cc t 95 Th th transfer T9
bo ang homodim rin
nhn i, er
bch cu
hoat ho
CD72 Cc t bo B 42 Cha r Lyb-2 Lectin
(khng phi homodim dng c
cc t bo er
plasma)
CD73 lp hp con 69 Ecto-5-
t ho B. tp nucleotidaza,
hp con t dephotphoryl
bo T ho cc nucleo-
tit cho php thu
nhn nucleozit
CD74 Cc t bo B, 33, 35, Chui khng i li, ly
i thc bo, 41,43 kt hp vi
bch cu n (s khi MHC lp II
nhn, cc t' u v
bo kt hp phn ct
vi MHC lp lun
II phin)
CD75 Tp hp con Lactosamin, cu
cc t bo B, t gn cho
cc t bo T CD22, trung ho
trng thnh s kt dnh t
bo B-t bo B
CD75s Lactosamin sia Cu trc
lyl ho a - 2 . 6 cacbohy-
drate
CD77 Cc t bo 13 (lycosphmgol- Nhm
gia thi ipit trung tnh mu Pk
k phi thai (G a la l-* Glo-
4G alpl-> botriao-
4GalcP 1 -> ce- cyl- ce
ramide) lin kt ramic!
vi dc t Shiga, (C.b3)
 249

vi c to Shiga,
lin kt cho
cm ng ci
cht c chng
trnh
0)79 Cc t bo B a: 40 -45 Thnh phn ca Iga, Ig3 Immu
u. : 37 th th khng noglobulin
nguyn t bo B
tng ng vi
CD3, cn thit
cho s biu hin
b mt t bo v
s truyn tn
hiu
CD80 Tp hp con 60 L cht dng B7 (ngy Immu
t bo B kch thch, cu nay: noglobulin
t gn cho CD28 B7.1),
vCTLA-4 BB1
CD81 Cc t bo 26 Kt hp vi ch ca Protein
lympho CD 19, CD21 cc xuyn
to thnh ng khng mng 4
th th t bo B th
khng li
s nhn
i
(TAPA-
1)
CD82 Bch cu 50 -53 Cha r R2 Protein
xuyn
mng 4
CD83 Cc t ho tua, 43 Cha r HB15 Immu
cc t bo B, noglobulin
cc l' bo
l^angerhans
CDw84 Bch cu n 73 Cha r GR16 Immu
nhn, tiu noglobulin
cu, cc t
bo B tun
hon

CD85 Cc t bo Ho ILT/LIR GR4 Siu h

tua Immu
noglobulin
250

CD86 Bch cu dn 80 Cu t gn cho B7.2 Immu

nhn, t bo CD28 v noglobulin
B hot ho, CTLA4
cc t bo
tua
CD87 Bch cu ht, 35 - 59 Th th cho cht uPAR Ly-6
bch cu n hot ho
nhn. di urokinaza plas
thc bo, cc minogen
t bo T, NK,
mt lot cc
dng t bo
khng to
mu
CD88 Bch cu 43 Th th cho C5aR Th th
nhiu dng thnh phn b cp i
nhn, i th C5a vi pro
thc bo, t tein Cl
bo Mast
CD89 Bch cu n 50-70 Th th IgA FcaR Immu
nhn, di noglobulin
thc bo,
bch cu ht,
bch cu
trung tnh,
tp hp con
t' bo B, tp
hp con t
bT
CD90 Tin t bo 18 Cha r Thy-1 Immu
tuyn c noglobulin
CD344
(ngi), t
bo tuyn c,
t bo T
(chut)
CD91 Bch cu n 515,85 Th the a2 Thu Ih
nhn, nhiu macroglobulin EOF, LDL
t bo khng
tao mu
CD92 Bch cu 70 Cha r GR9
trung tnh,
bach
-----1 cu dn
______________
, _
nhn, tiu
can, ni m
Cl )()3 Hch cu 120 Cha r GR 11
trung tnh,
hch cu n
nhn, ni m
am Tp hp con 43 Cha r KP43 Lectin
t bo T. t dng c
bo NK
CD95 Mt loi 45 Lin kt vi cu Apo-1, Thu th
1dng t ho, t gn Fas ging Fas TNF
phn b in TNF, gy ra ci
vivo cha r cht c chng
rng trnh
CD% Cc t bo T 160 Cha r Biu hin Immu
hoat ho, t mun noglobulin
bo NK tng hot
ho t
bo T
(TACTIL
E)
CD97 Cc t bo B 75 - 85 Lin kt vi GR1 EGF, th
v T hot CD55 th cp
ho, bch i vi
cu n protein G
nhn, bch
cu ..hat
*

CD98 Cc t bo 80, 45 C th l cht 4F2,

BX t bo het- vn chuyn axit FRP-1
git t nhin, erodimer amin
bch cu ht,
tt c cc dng
t bo ngi
CD99 Cc t bo 32 Cha r MIC2,
lympho mu E2
ngoi vi, t
bo tuyn c
CD 100 Cc t bo 150 Cha r C.R3 Sema
to mu homodim phor in
er
CD 101 Bch cu n 120 Cha r BPC#4 Immu
nhn, bch homodim noglobulin
cu hat, t ... _J?r
252

bo tua, t
bo T hot
ho
CD 102 Cc t bo 55 - 65 Lin kt vi ICAM-2 Immu
lympho nghi, CD1 a/CDIS noglobulin
bch cu n (LFA-1), nhng
nhn, cc t khng lin kt
bo ni m vi
c mch CD11/CD18
(mnh nht) (Mac-1)
CD 103 Cc t bo 150, 25 Integrin aE HML-1, Integrin a
lympho ni integrin
biu m, 2- a6, aE
6% cc t
bo lympho
mu ngoi vi
CD 104 T bo tuyn 220 Integrin P4 kt In- IntegrinP
c CD4, CD8, hp vi CD49f, tegrinfM
cc t bo thn lin kt vi cc
kinh, biu m, laminin
v mt s t
bo ni m,
cc t bo
Schwann,
nguyn bo
dinh dng.
CD 105 Q c t bo 90 Lin kt vi Endoglin
ni m, cc homodim TGF-P
bch cu n er
nhn v i
thc bo hot
ho , tp hp
con cc t
bo tu
xng
CD 106 Cc t bo 100-110 VCAM-1 Immu
ni m Phn t kt noglobulin
dnh, cu t gn
cho VLA-4 (in-
tegrin a 4p.)
CD 107 Tiu cu hot 110 Cha r, l pro Protein
a ho, cc t tein mng ly- mng 1
bo T hoat sosom chuyn lin kt
 253

ho, bch ti b mt t bo 1lysosom

cu trung sau khi hot ho 1:LAMP-
tnh hot 1)
lio, ni m
hoat ho
CD 07 Tiu cu hot 120 Cha r, l pro LAMP-2
b ho, cc t tein mng ly-
bo T hot sosom chuyn
ho, bch ti b mt t bo
cu trung sau khi hot ho
tnh hot
ho, ni m
hoat ho
CD 108 Hng cu, 80 Cha r GR2,
cc t bo Khng
lympho tun nguvn
hon, nguvn nhm
ho lympho mu John
Millon-
Hagen
CD 109 Cc t bo T 170 Cha r Nhn t
hot ho, tiu hot ho
cu hot ho, tiu cu,
ni m mach GR56
CD 110 Tiu cu MPL, TPO R
CD111 Cc t bo PPRl/Nectinl
dng tu
CD112 Cc t bo PRR2
dngtu
GDI 14 Bch cu hat, 150 Th th yu t Immu
bch cu dn kch thch dng noglobulin,
nhn bach cu ht (Ci- fibronectin
CSF) dng III
CD 115 Bch cu dn 150 Th th yu t M-CSFR, Immu
nhn, i kch thch dng c-fms noglobulin,
thc bo dai thc bo (M- tyrozin
CSF) kinaza
GDI 16 Bch cu dn 70-85 Chui a th th GM- Thu the cy
nhn, bch yu t kch thch CSFRa tokine, fi-
cu trung dng bch cu bronectin
tnh, bch hat - ai thc dng III
cu a axit, bo (GM-CSF)
ni m
254

CDI17 T tin t 145 Th th yu t t C -K it Immu

bo to mu bo ngun noglobulin.
(SCF) tyrozin
kinaza
CD118 Biu hin t Th th inter INF-
bo rng feron a,p a.R
CD119 i thc bo, 90-100 Th th inter lNF-yR Fibronectin
bch cu n feron- Y dng III
nhn, t bo
B, ni m
CD 120 Cc t bo 50-60 Th th TNF, TNFR-I Thu the
a to mu v lin kt vi c TNF
khng to TNF-CX v TNF-
mu, cao p
nht cc t
bo biu m
CD 120 Cc t bo 75-85 Th th TNF, TNFR-II Thu the
b to mu v lin kt vi c TNF
khng to TNF-a v TNF-
mu, cao p
nht cc t
bo dng tu
CD Cc t bo 80 Th th inter IL-1R Immu
121a tuyn c, t leukin-1 dng I, dng I noglobulin
bo T lin kt vi IL-
la v IL-13
CDw Cc t bo B, 60-70 Th th inter- IL-1R Immu
121b di thc bo, leukin-1 dng II, dng II noglobulin
bch cu n lin kt vi IL-
nhn la v IL-ip
CD 122 Cc t bo 75 Chui p thu th IL-2RP Th th cy
NK, tp hp IL-2 tokine, fi-
con t bo T bronectin
ngh, mt s' dng in
dng t bo
B
CD 123 Cc t bo 70 Chui a thu th IL-3Ra Th th cy
ngun tu IL-3 tokine, fi-
xng, bch bronectin
cu ht, bch dng III
cu n nhn,
t bo nhn
khng l
(1)124 Cc t bo B 130-150 Th th IL-4 IL-4K Th the cy
v T trng tokine, fi-
thnh, cc t bronectin
ho tin to dng III
mu
Cl)125 Bch cu a 55-60 Th th IL-5 IL-5R Th th cy
axit, hch tokine, fi-
cu a kim, bronectin
cc t ho 13 dng III
hoat ho
CD 126 Cc t bo B 80 Di n v a IL-6Ra Immu
hot ho v th th II.-6 noglobu
cc t bo lin,th th
plasma cytokine,
(mnh), phn fibronectin
ln bch cu dng III
(yu)
CD 127 Tin lympho 68-79 Th th IL-7 IL-7R Fibronectin
tu xng, t c kh dng III
bo tin B, t nng to
bo T trng homoim
thnh, bch er
cu n nhn

CDw Bch cu 58-67 Th th IL-8 IL-8R Th th

128 trung tnh, cp i vi
1 bch cu a protein G
kim, tp hp
con t bo T
CD 129 Vn cha
c xc
nh
CD 130 Phn ln cc 130 Di dn v IL-6RP, Immu
dng t bo, chung ca IL-6, IL- noglobulin,
mnh trn IL-11, on- HRp, th th cy
cc t bo B costatin-M OSMR, tokine,
hot ho v (OSM) v cc LIFR, fibronectin
cc t bo th th yu t c dng III
IFR
plasma ch bnh bch
cu (LIF)
256

CDw T tin t 140 Di n v p IL-3RP, Th th cy

131 bo tu, bch chung ca IL-3, IL-5R3, tokine, fi-
cu ht IL-5, v cc th GM- bronectin
th GM-CSF CSFR dng III
CD 132 Cc t bo B, 64 Chui y th th Th th cy
cc t bo T, IL-2, di n tokine
t bo NK, t vi chung ca cc
bo Mast, th th IL-2, IL-
bch cu 4, IL-7, IL-9, v
trung tnh IL-15
CD133 Cc t bo AC133
ngun/ t
tin
CD 134 Cc t bo T 50 C th hot 0X40 Thu th
hot ho ng nh mt TNF
cht ng kch
thch phn t kt
dnh
CD 135 Tin thn t 130,155 Th th yu t FLK2, Immu
bo a nng, sinh trng STK-I noglobulin,
t tin t bo tyrozin
B v bch kinaza
cu n nhn
dng tu
CDw Bch cu n 180 Ho hng MSP-R, Tyrozin
136 nhn, t bo ng, s thc RON kinaza
biu m, h bo, sinh trng
thn kinh t bo, v bit
trung ng ho
v ngoi vi
CDw T bo lym- Cht ng kch ILA Thu the
137 pho B v T, thch s nhn (c TNF
bch cu n i t bo T cm ng
nhn, mt s bi s
t bo biu hot ho
m t bo
lympho),
4-1BB
CD 138 T bo B Cc ln kt Synde-
hepran sulphate can-1
proteoglvcan,
collagen dng 1
Cl) 139 T bo B 209, 2281 Cha r
CD 140 T bo m, a: 180 Chui a v [}
a.b mt s t bo h: 180 th th yu t
ni m sinh trng
ngun gc tiu
cau (PDGI )
GDI 41 Cc t bo 105 Cht chng Thrombo Lectin
ni m c dng, lin kt modulin dang c,
mch vi thrombin, feto- EOF
phc h sau modulin
hoai ho protein
c
CD 142 T bo kera 45 - 47 Nhn t khi Yen to Fibronectin
tin biu m, u chnh ca mo, dng III
cc t bo hin tng ng throm
biu m khc cc. Lin kt vi boplastin
nhau, t bo yu t Vila,
dng sao, t phc h ny
bo hot ho cc yu
Schwann. t VII, IX, v X
Khng c
cc t bo
lin h trc
tip vi bo
1 tng,tr khi
dc to ra
bi cc cht
! trung gian
phn ng
vim.
CD 143 Cc t bo 170 - ISO Peptidaza kim enzym
ni I, loi Zn dipepti- chuyen
ngoi tr cc yl peptidaza hoa an
mch mu , phan ct angio giotensin
1 ln v thn, tensin 1 v bra- (ACE)
cc t bo dykinin t cc
biu m ca (lang tin thn
mp thn v
258

rut non, t
bo thn
kinh, di
thc bo hot
ho v mt
s t bo T.
Dng ho tan
trong bo
tng
CD 144 Cc t bo 130 Thit lp ch Cad- Cadherin
ni m ni kt dnh herin-5,
cc t bo ni VE-
m cadherin
CD 145 Cc t bo 25, 90, Cha r
ni m, mt 110
s t bo
m
CD 146 Ni m 130 Phn t c kh MCAM, Immu
nng kt dnh, MUC18, noglobulin
nh v ch ni S-ENDO
t bo - t bo.
CD 147 Bch cu, 55-65 Phn t c kh M6 , neu- Immu
hng cu, nng kt dnh rothelin, noglobulin
tiu cu, t EMMPR
bo ni m IN,
basigin,
OX-47
CD 148 Bch cu ht, 240 - 260 c ch lin h s HPTPt Fibronectin
bch cu n sinh trng ca dng III,
nhn, t bo t bo protein ty-
tua, t bo T, rozin phot-
nguyn bo phataza
si, t bo
thn kinh
CD 150 Cc t bo 75 - 95 Cha r SLAM Immu
tuyn c, cc noglobulin
t bo lym-
pho hot ho
CD151 Tiu cu, t 32 Kt hp vi in- PETA-3, Protein
bo nhn tegrin l SFA-I xuyn
khng l, t mng 4
bo biu m,
t bo ni m
CD 152 Cc t bo T 33 Thu th cho CTLA-4 Immu
hot ho B7. (CD80), noglobulin
B7.2 (CD 8 6 );
cht diu ho
m tnh s hot
1 ho t bo T
CD 153 Cc t ba I 38 - 40 Cu t gn cho CD30L TNF
hot ho, i CD30, c th
thc bo hot dng kch thch
ho, hch cc t bo T
cu trung
tnh, t bo B
CD 154 Cc t bo T- 30 dng Cu t gn cho CD40L, Thu th
CD4 hot trimer CD40, cht cm TRAP, TNF
ho ng ca s hot T-BAM,
ho v nhn i gp39
t bo B
CD 155 Bch cu dn 80-90 Chc nng Th th Immu
nhn, i thng thng polio- noglobulin
thc bo, t cha r, th th virut
bo tuyn c, cho poliovirut
cc noron
CNS
CD 156 Bch cu 69 Cha r, c th MS2,
a trung tnh, lin quan n s ADAM 8
bch cu n trn dch bch (mt pro-
nhn cu integrin (in- teaza kim
tegrin leukocyte loi v
extravasation) khng
phi in-
tegrin)
CD TACE/ADAM1
156b 7: cu trc kt
dnh
CD 157 Bch cu ht, 42 - 45 ADP-ribosyl cy- BST-1
bch cu dn (50 claza, ADP
nhn, t bo bch cu vng-riboz hy-
m tu n dolaza
xng, t bo nhn)
ni m c
mch, t bo
tua nang
260

CD 158 T bo NK Ho KIR
CD 158 Tp hp con 50 hoc c ch tnh c p50.1, Immu
a t bo NK 58 ' t bo NK trn p58.1 noglobulin
cc phn t
MHC ip I lin
kt

CD 158 Tp hp con 50 hoc c ch tnh c p50.2, Immu

b t b o N K 58 ' t bo NK trn p58.2 noglobulin
HLA-CW3 lin
kt v cc alen
lin quan
CD 159 Cc t bo Lin kt vi NKG2A
a NK CD94 to
thnh th th
NK; c ch tnh
c t bo NK
trn cc phn t
MHC lp I lin
kt
CD 160 Cc t bo T BY55
CD161 Cc t bo NK, 44 iu ho tnh NKRP1 Lectin
cc t bo T c t bo NK dng c
CD 162 Bch cu 1 2 0 dng Cu t gn cho PSGL-1 Mucin
trung tnh, t homodim CD62P
bo lympho, er
bch cu n
nhn
CD 162 Cc t bo PEN 5
R NK
CD 163 Bch cu n 130 Cha r Ml 30
nhn, i
thc bo
CD 164 Cc t bo 80 Cha r MUC-24 Mucin
biu m, (protein
bch cu n 24 dc
nhn, cc t a glyco-
bo m tu syl ho)
xng
CD 165 T bo tuyn 37 Kt dnh gia t Gp37,
c, t bo bo tuyn c v AD2
biu m biu m tuyn
 2\\

tuyn c, cc c
noron CNS,
do luv, VO
Bowman
CD 1661 cac to bo 1 100 -105 (au t gn cho A XAM, Iinnu-
hot ho, ( 1) 6 , bao gm BEN, noglobulin
biu m s ko di (ly DM-
tuyn c, thn kinh in- GRASP,
nguyn bo tegrin SC- 1
si, cc 1 1 0 -
ron
CD 167 Cc t bo 63, 64 1 Lin kt vi co- DDR 1 , Fyrozin
a biu m binh dng lagen trkH, cak, kinaza th
thng v dimer eddrl th, dis-
bin i coidin lin
quan
CD 168 Cc t bo 5 ng Phn t kt RHAM
ung tlur v dng: dnh. Th M
58, 60, th cho s vn
64, 70, ng c trung
84 ho bi axit hya
luronic - s
dch chuyn t
bo trung gian
CD 169 Tp hp con 185 Phn t kt Siaload- Siu h
di thc bo dnh. Lin kt hesin immu
vi cacbohydrat noglobulin,
sialyl ho, c h sialoa-
th lm trung hesin
gian cho s lin
kt i thc bo
vi bch cu ht
v t bo lym-
pho
CD 170 Bch cu 67 dng Phn t kt Siglec-5. Siu h
trung tnh homodim dnh. Lectin OBBP2, immu
er ging Ig lin kt CD33L2 noglobulin,
axit sialic h siaload-
(Siglec). ui hesin
nm trong vng
t bo cht cha
motif (vng bo
th) ITIM
262

CD 171 Noron, cc t 2 0 0 - Phn t kt L I, Siu h

ho 2 2 0 , dnh, lin kt vi NCAM- immu
Schwann, cc TLPT CD9, CD24, L1 noglobulin
t bo lym- chnh CD56, cng l
pho v bch xc thay lin kt liomo-
cu n nhn i theo philic
dng tu, cc dng t
t bo B, cc ho
t bo T -
CD4 (khng
phi t bo
T-CD 8 )
CD 172 115-120 Phn t kt SIRP, Siu h
a dnh, protein SHPS1 , Immu
xuyn mng l MYD- 1 , noglobulin
c cht ca ty- SIRP-CX-
rozin kinaza th 1 , c cht

th hot ho dng
(RTKs) v lin khng thu
kt vi cc do th -
main SH2 protein
^yrozin
phot-
phataza 1
(PTPNS1 )
CD 173 Tt c cc t Nhm mu H
bo type 2 , phn
hydratcacbon
CD 174 Tt c cc t Nhm mu
bo Lewis y, phn
hydratccbon
CD 175 Tt c cc t Nhm mu Tn,
bo phn hydrat-
cacbon
CD 175 Tt c cc t Nhm mu Sia-
s bo lyl-Tn. phn hy-
dratcacbon
CD 176 Tt c cc t Nhm mu TF,
bo phn hvdrat-
cacbon -----------------------
CD 177 Cc t bo 56 - 64 NB1 l mt N B 1
dngtu khng nguyn
c hiu bach
 26,

cu trung tnh
1ln kt CiPI, chi
dc tm thy
bch cu trung
tnh c mt
ngi trng
thnh c
NBl(97r ngi
cho kho) NHI
dc hiu hin
u tin giai
on t bo tuv
ca qu trnh
bit ho dang
tu
CD 178 Cc t bo T
1 38 - 42 Cu t gn Fas, FasL Siu ho
hot ho lien kt vi Fas TNF
gy ra ci cht
c chng trnh
CD 179 Cc t bo B 16 -18 Chui immu- VpreB, Siu h
a nguyn thu noglobin kt hp JGVPB, immu
khng cng ho Igi noglobulin
tr vi CD 17%
to thnh mt
chui nh thay
th m l mt
thnh phn ca
th th tin t
bo B ng vai
tr quan trng
giai on u
bit ho t bo B
CD 179 T bo B 22 Polypeptit 1 IGLLI, Siu h
b ging immu A.50GL5) immu
noglobulin X kt noglobulin
hp khng cng g VPB.1
ho tr vi 4.
CD179a to
thnh mt chui
nh thay th
dc biu hin
mt cch chn
lc giai on
264

u ca s pht
trin t bo B.
Cc dt bin
trong gen
CDl79b dn ti
lm suy yu s
pht trin t bo
B v bnh thiu
globulin gama
huyt ngi
CD 180 T bo B 95-105 Protein mng LY64, Th th
dng 1 bao gm RP105 ging Toll
cc on lp (TRL)
giu Leucin
ngoi bo
(LRR). Kt hp
vi 1 phn t
c gi l MD-
1 v to thnh
phc h th th
b mt t' bo
RP105/MD-1 ,
hot ng phi
hp vi TLR4
diu khin s
nhn bit t bo
B v s truyn
tn hiu ca
lipopolysacarit
(LPS)
CD183 c bit trn 46 -52 Th th chtho CXCR3, Cc th th
cc t bo B vn ng c x c , th th cht ho
c tnh t lin quan n cp i vn ng,
bnh ri lon ho hng ng protein G Siu h th
nhn di ca cc t bo 9 (GPR9) th cp i
lympho mn lympho B c protein G
tnh tnh. Lin kt
vi INP10 v
MIG-
CD 184 Biu hin u 46 -52 Lin kt vi SDF- CXCR4, Cc th th
tin trn cc 1 (LESTR/fusin), NPY3R, cht ho
t bo ngun hoi dng nh LESTR, vn dng,
tao mu mt cofactor fusin. Siu ho thu
 265

('1)34' cha uloii nh.in to) \IIMX) the cap (li
I !
trim thnh cho s hop nht protein (
lion va su tip Ihn
dng t bo 1 ,
1chng dinh (hing
cua HIV - 1
c m 95 Cc te ho
tien daim 111V
40 Thu the cho cht CMKBK Cc th the
lOi vn (lng X CCR5, hon vn
c. r

lana c c Lin t'KR-5. dng. Sic 11

kt vi M lP-la, c c - ho th the
MIP-1(5 va CKR-5. cp cli
RANTES. C CKR5 protein (
the clne vai tr
dieu khin s
nhn di v bit
ho dng bch
cu ht. Hot
dng nhu mt
(lng th th vi
1
CD4 c lp
hng kch thch
i thc bo s
cp ca HIV- 1
CDw Cc te ho 46 -52 Th th cho cht CCR7, Cc th th
197 Ivin pho B v hoa vn dng EBIK cht ho
T hot ho, MIP-3p. C the gcnl vn ng,
diu ho dng vai trl c cm Siu h thu
mnh ln t yu t trung ng bi th cp di
bo B b gian ca nhng virut Ep- protein G
nhim EBV anh hng HBV stein-
v t bo T b ln cc t bo Barr),
nhim HHV 6 lyinpho B hay CMKBR
hay7 cc hot dng 7, BLR2.
ca t bo lym-
pho bnh
thng.
CD200 Cc dng t 41 (t bo Khng nguyn, MOX-2, Siu h
bo B v no tuyn c diRtc nhn bit bi MOX - 1 Immu
hnh thng chut), MoAb MRC noglobulin
4 7 (no 0X2. Cc phn t
chut) khng cng dng
(nonlineage).
i Oirc Ing cha r
266

CD201 Cc t bo 49 Th th b mt EPCR H phc h

ni m t bo ni m ph hp td
(EPCR) c kh chc ch
nng lin kt i yu GDI
lc cao protein
c v protein c
hot ho. N
c iu ho
gim xung nh
tip xc ni m
vi yu t hoi
t ung th
CD202 Cc t bo 140 Tyrozin kinaza VMCM, Siu h
b ni m th th, lin kt TEK (ty- immu
vi angiopoi- rozin noglobu
etin- 1 , quan kinaza, lin, tyro-
trng trong vic ni m), zin kinaza
hnh thnh inach TIE2 (ty-
mu. c bit rozin
cho hnh thnh kinaza c
h thng mch cc do
trong cc t bo main
ni m. Nhng lng
khuyt tt ng Ig
TEK i km vi v EGF),
nhng c th d VMCM1
tt tnh mch di
truyn, con
ng truyn tn
hiu TEK quan
trng cho s lin
lc t bo ni
m-t bo c
trn trong qu
trnh to hnh
tnh mach
CD203 Cc t bo 101 Thuc mt lot NPP3, Cc
c dng tu( t enzym ngoi B1 0 , protein
cung, bch bo lin quan PDNP3, xuyn
cu a kim, n s thu PD-ip, mng
v cc t bo phn cc nu- gpl 30RB dng II,
mast) cleotit ngoi 13-6 h pyro-
bo. Chng xc phot-
 tc cho s phn phata/a/p
ct cc lin kt hotphodi-
phosphodieste csteraza
v lin kt phot- nucleotit
phosunphat ca ngoai bo
cc phn tr bao (E-
gm ieoxynu- NPP)
cleotit, NAD v
cc gc ng
ca nucleotit
0 ) 2 0 4 Cc t bo 220 Lm trung gian Yu t H th
dng tuV cho s lin kt, thu dn th n xc
s tip thu (n xc thi (thu
(nut), v x l thi) i dn),
mt lot cc i thc bo ging co-
phn t tch din R lagen
m. Lin quan (MSRl)
den s lng
dng bnh hc
ca cholesterol
cc thnh
ng mch
trong qu trnh
hnh thnh bnh
x va ng
mach
CD205 Cc t bo 205 Khng nguyn LY75, Protein
tua t bo lympho DEC- xuyn
75, th th bt 205, mng
gi khng GP200- dng I
nguyn gi nh MR 6
trn cc t bo
tua
CD206 i thc bo, 175-190 Glycoprotein Th th Siu h
t bo ni m mng dng I, v mannoza lectin
d bit duy i thc dng c
nht v lectin bo
dng c cha (MMR),
nhiu CRD dng MRC1
c (cc domain
nhn bit cacbo-
hydrat), n lin
kt vi cc cu
268

trc mannoza cao

trn b mt ca
cc virut, vi khun
v nm c kh
nng gy bnh.
CD207 Cc t bo 40 Protein xuyn Langerin Siu h
Langerhans mng mng lectin
dng 11 , lectin dng c
dng c c hiu
t bo Langer-
hans; cht cm
ng hiu qu
p buc v ii
ko manh m
mng dn n s
to thnh cc ht
birbeck - BG.
CD208 Cc t bo 7 0-90 Tng ng vi Protein H phc
tua an vo CD 6 8 DC mng kt h ph
nhau trong LAMP l mt hp vi hp t
cc bo quan protein lysosom D ly- chc ch
lympho lin quan n sosom, yu
vic t chc li DC-
cc khoang x LAMP
l khng nguyn
chuyn ho v
trong trnh din
khng nguyn
gii hn MHC
lp II, iu ho
mnh ln cc
DC trng thnh
c cm ng
bi CD40L,
TNF-a v LPS
CD209 Cc t bo 44 Lectin dng C; DC- Siu h
tua lin kt vi v SIGN lectin
ngoi ICAM3 v (Phi in- dng c
HIV - 1 glycopro- tegrin bt
tein g p l 2 0 cho gi
php rng buc ICAM3
th th t bo T c hiu
bng cch lm t ho
 2(9

I1 nh vng ua)
lin h !)C-t
ho '\\ kch thch
s nhiem hiu
qua cc t ho
trans m biu
hin cc th the
CD4 v th th
cht ho hng
(lng; protein
xuyn mng
1 (lng II
CD Cc t bo B, 90-1 10 1Th th inter IL-IORa H th
VV210 cc t bo T leukin 1 0 a v p IL- th cyto
b tr, v cc 1 0 RA, kine lp II
t bo ca HIL-
dng hch 10R, IL-
cu n 1 0 R,
nhn/i thc IL-10RB,
bo CRF2-4,
CRFB4
CD212 Cc t bo 130 Chui p th th IL-12R Siu h
CD4, CD 8 , IL- 1 2 , protein IL-12RB th th
v NK hot xuyn mng cytokine
ho dng I lin quan to mu
n s truyn tn
hiu IL-12
C D 213 Cc t bo B, 60 - 70 Th th lin kt IL- Siu h
a1 bch cu n i lc thp vi 1 3 R a lf th th
nhn, nguycn 1L 13, cng vi NR4, IL- cytokine
bo si, t L-4Ra c th 13Ra to mu
1
bo ni m. to thnh mt
th th chc
nng cho II.-13,
cng c coi
nh l mt pro
tein phu tr thay
i di vi
chui gamma
th th cytokine
chung cho qu
trnh truycn tn
hiu IL-4 ...........................1
270

CD213 Cc t bo B, Th th IL-13 nh IL-13Ra Siu h

a2 bch cu n mt monomer lin 2, IL- th the
nhn, nguyn k i lc cao vi in 13BP cytokine
bo si, cc terleukin-13 to mu
t bo ni m ( IL-13), nhung
khng lin k vi
IL-4: cc t bo
ngi biu hin IL-
13RA2 cho thy
lin kt IL-13 c
hiu Mi i lc cao
CDw Cc t bo T 120 Homodimer th I1-17R, Cc th
217 ghi nh hot th interleukin CTLA-8 th cyto
ho 17 kine/ cht
ho
hng
ng
CD239 Cc t bo 78 Protein mng B-CAM Siu h
hng cu dng I. Khng (Phn t immu
nguyn F8/G253 kt dnh noglobulin
ngi, t bo B),
B-CAM, l mt LU,
glycoprotein b nhm
mt t bo c mu Luj
biu hin vi mt ther
kiu phn b' hn
ch trong cc m
trng thnh v
bo thai bnh
thng v c
iu ho mnh
ln sau s bin
i c tnh trong
mt s' dng t
bo. Cu trc
ton th ca n
ging vi cu
trc ca du hiu
ung th ngi
MUC18 v phn
t kt dnh thn
kinh g SCI
 2 71

CD240 Cc t ho 45,5 Nhn mu Rliesus, RHCE, Ho Rh

CH hng cu khuig ngiiwn GcBe. RH30A,
C th l mt phn RHPI,
ca phc h digome Rh4
o chc nng knh
hay vn chuyn ing
mng hng cn N
rthhknccaovd
gi su trong \p kp
lpL
CD240 Cc t bo 45,5 Nhm mu RhD, H oR h
D hng cu Rhesus, khng Rh4,
nguyn D. C RhPI,
th l mt phn Rhll,
ca phc h oli- Rh30D
gome c chc
nng knh hay
vn chuyn
trong mng
hng cu.
Khng c mt
kiu hnh khng
c RHD ngi
da trng
CD241 Cc t bo 50 Glycoprotein kt RhAg, H Rh
hng cu hp nhm mu RH50A
Rhesus RH50,
thnh phn ca
phc h nhiu
di n v
khng nguyn
RH, cn thit
cho s vn
chuyn v s kt
hp phc h
mng Rh vi b
mt t bo hng
cu, c tnh
tng ng cao
vi RH, cc
thnh phn
30kD. Cc
9 79

khuyt tt
RhAg l nguyn
nhn ca bnh
thiu mu kinh
nin di km vi
stomatocytosis
v spherocyto
sis, lm gim
tnh thm lc, v
tng tnh thm
cation.
CD242 Cc t bo 42 Phn t kt dnh ICAM-4, Siu h
hng cu ni bo 4, nhm LVV immu
mu Land- noglobu
Steiner-Wiener. lin, phn
Cc phn t LVV t kt
c th gy ra tc dnh ni
mch kt hp bo
vi au cp tnh (ICams)
bnh hng cu
hnh li lim
CD243 Cc t bo 170 Protein 1 MDR-1, Siu h
ngun /t khng a thuc p-170 ABC ca
tin (Glycoprotein cc pro
P-gp s dng tein vn
ATP bm cc chuyn
thuc k nc ra lin kt
khi t bo, v ATP
vy nng ni
bo v tnh dc
ca chng tng
ln. Gen MDR1
c nhn trong
cc dng t bo
khng a thuc.
CD244 Cc t bo 66 2B4 l mt gly Cu t Siu h
NK coprotein b mt gn cm immu
t bo c quan ng s noglobulin
h vi CD2 v hoat ho
trong iu ho 2B4, t
chc nng t bo bo NK
git t nhin v (NAIL)
t bo lympho
 27:*

....... J

1
T. Chc nng s
cp ca 2B4 l
ciu chinh tng
tc th th-cu
t gn khc d
tng cng hot
ho bach cu.
CD245 Cc t ho I 220 - 240 Protein tng tc NPAT
cyclinE/ Cdk2
p220. NPAT lin
quan n s kin
pha s cha kho
v lin kt hot
tnh kinaza cy-
clinE/ Cdk2 tun
hon vi qu
trinh phin m
gen histon ph
thuc sao chp.
Gen NPAT can
thit cho s duy
tr t bo v c
th l thnh vin
ca cc gen
thng trc
(housekeeping
gene)
0 ) 2 4 6 c biu 177 kDa; Kinaza lympho ALK H th
hin rut sau khi ghp (t bo ln th insu
non, tinh dng CD30*), ng vai lin ca
hon v no ha to tr quan trng protein ty-
nhng khng mt gly trong s pht trin rozin
biu hin coprotein no, lin quan n kinaza
cc t bo trng cc bnh Hodgkin
lympho bnh thnh hay fi lympho
thng 2 0 0 kDa khng phi
I odgkin nt ghp
vi s hon vi
t(2;5)(p23 q35)
hay inv2(23,q35).
S pht sinh ung
th nh chc nng
kinaza c hoat
274

ho bi s oli
gomer ho ca
NPM1-ALK c
lm trung gian bi
phn NPM1
CD247 Cc t bo T, 16 Th th t bo Chui , Siu h
NK T, c vai tr CD3Z immu
trong tp hp v noglobulin
biu hin phc
h TCR cng
nh truyn tn
hiu nh vo s
khi dng khng
nguyn. TCR,
cng vi
TCRap v het
erodimer y5 v
CD3-y ,-S, v -e
tao thnh phc
h TCR-CD3.
Chui ng
mt vai tr quan
trng trong vic
nhn bit khng
nguyn cp i
vi mt vi con
ng truyn tn
hiu ni bo.
Biu hin thp
ca khng
nguyn dn ti
p ng min
dch sai hng.
CD273 Bch cu tua 25 c ch s hot Siu h Ig
mono v i ho t bo T
thc bo
CD279 T bo T v 55-60 iu ho hot
B d hoat ho ho t bo
CD314 42 Hot ho NK v H
CTL C-lectin
 275

Ph lc II. Gii ngha danh t min dch.

ABO: Cc khng nguyn ca h thng nhm mu ABO c

bc l trn b mt mng hng cu ,chng c s dng phn
loi cc nhm mu cho truyn mu. Nhng c th khng biu
hin cc khng nguyn A v B t bo hng cu s hnh thnh
cc khng th chng li chng.
A ccessory effecto r cells: C mt trong min dch tip thu
hoc min dch thch ng l nhng t bo tr th trong p ng
min dch nhng khng c kh nng nhn bit khng nguyn
c hiu. Chng bao gm cc t bo thc bo (phagocytes), t bo
Mast, v t bo NK.
AIDS: Hi chng suy gim min dch mc phi (Acquired im
mune deficiency syndrome), l mt bnh do nhim virus
HIV(Human immunodeficiency virus).
A cute L y m p h o b lastic leukenia: l mt bnh ung th mu
c tnh ca dng lympho khng bit ho bt ngun t nhng t
bo tu xng, c th lan truyn i vi c hai dng dng t bo
B v T. Hu nh tt c nhng bnh ung th bch cu ny u
biu hin ch yu dng t bo B c bit ho mt phn (k
hiu B-ALL) trong khi mt t l nh ca ung th c biu hin c
tnh ca dng t bo T (k hiu T-ALL).
A cq u ired im m u n e response: p ng min dch tip thu
hoc p ng min dch thch ng. Vic tim chng vi mt loi
Vacxin hoc mt khng nguyn no c gi l gy min dch
ch ng, c th phn bit vi vic truyn mt khng th vo mt
c th cha gy min dch. Cch lm gi l gy min dch th
ng.
A cu te-p h ase P ro tein s: l nhng protein c tm thy
trong mu ca mt c th b ly nhim vi khun xut hin trong
giai on sm ca bnh. Nhng protein ny tham gia bo v cho
276

vt ch chng li tc nhn nhim trng giai on u. V d

mt dng Lectin lin kt vi Mannose.
A d a p to r P ro tein s: L nhng protein thch ng quan trng
to s lin kt gia cc th th (receptor) v cc thnh vin ca
mu trn con ng truyn tn hiu.
A denoids: l nhng m Lympho lin kt vi th nhy, nm
khoang nhy mi.
A d h esio n m olecules: Cc phn t kt dnh lm nhim v kt
dnh gia t bo ny vi t bo khc trong qu trnh hp tc t
bo. Chng bao gm cc Integrins, Selectins, cc thnh vin ca
mt h gen ln Globulin min dch,...Chng tham gia hp tc
trong p ng min dch.
Adjuvant: T cht l mt cht bt k no c kh nng lm
tng cng p ng min dch vi mt khng nguyn c
gy min dch. Ngi ta thng trn t cht vi khng nguyn
gy min dch c hiu qu.
A doptive im m unity: L tnh min dch chp nhn c dc
nhng c th nhn cha bit p ng min dch hoc b chiu x.
c tnh min dch ny c to ra bng cch truyn cc t bo
Lympho ca nhng c th cho gy min dch
A fferent ly m p h a tic vessels: Mch dn lympho tr li ca
mt hch bch huyt. Cc i thc bo v cc t bo c tua t
nhng v tr nhim ca cc b phn c th c th tr v hch
bch huyt theo ng dn ny.
Affinity: i lc, kh nng hp dn v lin kt ca phn t ny
i vi phn t khc mt v tr nht nh trn phn t. V d
s lin kt ca mnh Fab ca phn t khng th vi mt khng
nguyn (xem thm thut ng Avidity).
A ffinity ch ro m a to g ra p h y : sc k i lc, mt kiu sc k
tinh ch mt cht da vo i lc ho hc ca n di vi mt cht
khc c lm bt ng trn mt gi th rn. V d mt khng
nguyn c th c tinh ch bng sc k i lc trn mt ct c
cha mt cht gi th gn vi cc phn t khng th c hiu vi
n.
A gam m aglobulinem ia: Bnh thiu ht gammaglobulin
trong huyt thanh. Bnh ny l do nguyn nhn ri lon di
truyn trong dng t bo B ch pht trin giai on tin B
(pre-B), khng pht trin thnh B trng thnh. Bnh ny l do
thiu ht v gen m ho cho mt Protein Tyrosin Kinase htk.
 A g g l u t i n a t i o n : S n g n g kt hin tng th n g xy ra khi c
(c p h n t k l n ^ t h lin kt v] cc p h n t k h n g n g u y n (j
tn*n l) m t c u a cc h t r c tiu tl hoc t bo s t c n h n h a u .
Vi (lu r c p h n t li l(c t i n khi lin kt VI mt s p h n t ( il ycopm-
t CMII t r n m n g h o n g c u c t h {\y gii^ kt h n g cu.
A g o n i s t p e p t i d e s : L nhng khng nguyn )()ti(!<* gv hot
ho nhng t bo T dc hiu tit ra evtokinee v sinh sn cn ^1
l car poptido ng vn. Tri li. Antagonist peptides l nhng
peptides di khng, gy tc dng ngc li.
Alleles: Alen l dng biu hin khc ca mt locus gen.
A llergens: L nhng khng nguyn gy ra hin tng qu
man hoc cc phn ng d ng. C th gi l khng nguyn gv
d ng. hay cn gi l d nguyn.
A llergic reaction : Phn ng d ng p ng li vi cc tc
nhan khng c ca mi trng hoc cc khng nguyn gy d
ng. Phan ng ny l do nhng khng th hoc do cc t bo T
khi thu tn ti t trc. C nhiu c ch min iich khc
nhau cua phn ng d ng nhng biu hin chung nht l s lin
kt ca Allergens vi khng th IgE nm trn t bo Mast gv ra
hin tng hen suyn, st, nn ma, ngt mi, sc phn v v c
th t vong (qu mn typ 1).
Allergy: Hi chng d ng i vi khng nguyn khng c
ca mi trng.
A lloantigens: D khng nguyn, c th nh ngha nh l
hiu hin a hnh mc cc locus MHC. Chng kch thch s
thi b m ghp d gen mnh m.
A llograft: Ghp m t bo d gen
Allotypes: Kiu a hnh alen c th c pht hin bng cch
s dng khng th c hiu di vi cc sn phm gen a hnh.
Trong min dch hc, nhng s khc nhau allotypes cc phn
t immunoglobulin rt quan trng i vi s giai m di truyn
ca cc khng th.
A lte re d p ep tid e ligand: Cu t gn peptide bin i, c th
l mt cht c cu trc ging mt phn cht ng vn Agonist ,
hoc mt peptide thng lin quan cht ch vi cht ng vn v
trnh t axit amin. iu ch gy ra s p ng mt phn ca
t bo T (li vi peptide ng vn.
A lte rn a tiv e pathw ay : Con ng hot ho b th bn cnh
khc con ng hot ho c in (classical pathway). Con ng
ny c khi du t protein b th C31) lin kt vi b mt ca
2 78

tc nhn gy bnh. Do , con ng hot ho b th ny c c

im min dch bm sinh(innate immunity).
A n a p h y la c tic shock: Sc phn v (lin quan n bnh qu
mn typ I c s tham gia ca IgE).
A n ap h y la to x in s : L cc mnh peptit nh ca cc protein b
th b phn hu v c gii phng ra trong qu trnh hot ho
b th (c th c gi l cht phn v). Cc mnh peptit ny
c th th (receptor) c hiu nhn bit v c tc dng lm
huy ng cc t bo gy vim tp trung n v tr c mt cc cht
phn v ny. Cc mnh C5a, Coa. v C4a u l nhng anaphy-
latoxin.
A n c h o r residu es: Cc gc r 1 0 neo l gc cc axt amin ca
mnh peptit khng nguyn ( c ch bin v c lin kt vi
rnh lin kt peptit (groove) c< phn t MHC lp I c hiu.
Anergy: S mt ng, l mt :rng thi khng c phn ng i
vi mt khng nguyn. Ngi c> trng thi mt ng l nhng c
th khng th c cc phn n{ qu mn mun i vi nhng
thch thc ca cc khng nguy n. Tng t, cc t bo T, B c
trng thi mt ng khi chng khng th p ng li i vi
nhng khng nguyn c hiu c ia chng di nhng iu kin
kch thch ti u.
A n ta g o n ist p ep tid es: Peptit ii khng, l nhng peptit
thng c quan h rt cht ch v rnh t sp xp cc axit amin
i vi cc peptit ng vn (agonist oeptides).
A ntibody: Khng th, l mt lco globulin min dch c bn
cht glycoprotein kin kt c hiu ' 5i khng nguyn.
A ntib od y co m b in in g site: L v tr lin kt vi khng
nguyn nm trn b mt phn t khi ng th.
A n tib o dy re p e rto ire : Kho d tr khng th bao gm tng
th cc khng th trong c th ca m . khng th.
A ntibody - dependent cell - m ediated cytotoxicity
(ADCC): Kh nng gy c t bo q la trung gian t bo ph
thuc vo khng th, y l qu trnh ..nt cc t bo ch gn vi
khng th c thc hin bi cc t bo git t nhin (NK) thng
qua s nhn bit ca th th Fc. Hu nh tt c cc ADCC u
c thc hin bi cc t bo NK thng qua th th Fc gamma
RIII hoc CD16.
A ntigen: Khng nguyn, l nhng phn t bt k c kh nng
lin kt c hiu vi khng th hoc vi th th khng nguyn.
 279

Nhn (hung, cc khng nguyn khi xm nhp vo c th u c

kh nng lm sn sinh khng th. Tuy nhin, mt s khng
nguyn ch c c tnh lin kt vi khng th nhng khng lm
sn sinh khng th. Cc khng nguyn ny thng c phn t
r t n h c gi l H a p te n cn p hi lin k t VI m t loi p ro te in
mang (carrier protein) tr thnh mt immunogen c kh nng
sn sinh khng th.
A n tig en - c a p tu re assay: Xt nghim bt gi khng nguyn,
l mt k thut to ra s lin kt ca mt khng nguyn vi mt
khng th c hiu. Phc h ny c lin kt vi mt khng th
th hai c nh du enzyme hoc phng x sau thc hin
phn ng enzyme to mu c trng tip theo o mu hoc o
phng x pht hin khng nguyn. Xt nghim ny c thc
hin nh k thut ELISA hoc k thut RIA.
A n tig en ic d e te rm in a n t: Quyt nh khng nguyn, cn c
gi l epitop, l mt phn ca phn t khng nguyn lin kt c
hiu VI mt phn t khng th hoc vi th th khng nguyn.
Epitop ca mt phn t protein.
A n tig e n recep to rs: Cc th th ca khng nguyn. l
nhng phn t protein nm trn b mt mng t bo T v t bo
B c kh nng nhn bit c hiu s trnh din khng nguyn.
M t qu trnh bc l mt peptit khng nguyn c ch bin
lin kt vi mt phc h ph hp m ch yu (MHC: Major
Histocompetibility) trn b mt mt t bo trnh din khng
nguyn (APC: Antigen pregenting Cell).
A n tig en P r e g e n tin g Cell: T bo trnh din khng nguyn
(APC) l nhng t bo ca h min dch bao gm ch yu l cc
t bo thc bo n nhn (Mononuclear phagocytes), cc i thc
bo (Marcophages), cc t bo c tua (dendritic cells v folicule
dendritic cells) t bo Langerhan ca da, v t bo B.
A n tig en processing: S ch bin khng nguyn. Qu trnh
tiu ho cc prtin khng nguyn ngoi sinh bng cc protease
ca lyzosom v bng mng ca t bo sau khi nut khng
nguyn. Qu trnh ny cng c thc hin vi cc khng
nguyn virus nhim ni bo hoc i vi cc khng nguyn ca
bn thn (autoantigen) nh tc dng ca mt c quan c bit l
proteasome ca t bo ch. Peptit khng nguyn sau khi c
ch bin s trnh din cho cc t bo T.CD4* hoc T.CD84*.
280

A n ti-im m u n o g lo b u lin antibody: Khng th khng li vng

khng bin i ca immunoglobulin (lng p h t hin cc phn
t khng th lin kt vi chng trong xt nghim min dch.
A n tis e ru m (an tisera): Khng huyt thanh (hoc cc khng
huyt thanh) l huyt thanh ca ng vt c gy min dch
khng li mt khng nguyn no . Trong huyt thanh c mt
tp hp bao gm nhiu khng th a dng (polyclonal antibod
ies), trong mi mt khng th lin kt vi mt epitop nht
nh ca mt khng nguyn. V vy mi mt khng th trong
khng huyt thanh u c mt cu trc ring b i t .
A p lastic anem ia: S thiu mu do khng pht trin dng t
bo ngun tu xng. Thiu mu do b hu hoi tu xng. C
th iu tr bnh ny bng cy ghp tu xng
A poptosis. Cht theo chng trnh l mt hnh thc cht ca
t bo theo mt chng trnh c kch hot ni ti. c im
ca apoptosis l s phn hu nhn t bo v ngng t nhn
trong cc mnh nhn c bao bc bi cc bng mng cha c
t bo cht, sau c cc i thc bo tiu ho. Cc t bo
trong qu trnh tng sinh lun lun chu apoptosis l mt qui
lut t nhin ca s pht trin v cng din ra trong qu trnh
p ng min dch. Tri li, ci cht hoi t (necrosis) xy ra do
t bo b u c, b nhim c hoc thiu oxy. Hoi t d li
mt s lng rt ln cc mnh v t bo.
A ppendix: Trong gii phu gi l rut tha, l mt m
lympho lin kt vi rut r gy ra hin tng vim rut tha.
A r th u s reactio n : Phn ng min dch do arthus tim ra. Phn
ng xy ra do khi tim mt khng nguyn l vo lp biu b. Khi
k h n g n g u y n l s phn n g VI k h n g th ngoi bo g y ra
hot ho cc b th, t bo thc bo v hin tng dp ng vim
ti ch.
A rtefact: Vt lm gi, m hnh lm gi nhm minh ho mt
iu g .
A topic allergy, atopy: C a, mt tnh trng nhy cm tng
ln i vi s qu mn tc th, qua trung gian khng th IgE
A tte n u a te d : Lm yu i mt tc nhn gy bnh, chng hn vi
khun gy bnh, virus bnh c lm yu tc dng gy bnh khi
dc da vo c th vt ch gy ra p ng min dch nhng
khng gy bnh lm sng nghim trng.
A u to an tib o d ies: Cc t khng th l nhng khng th c
hiu chng li khng nguyn ca bn thn c th (autoantigen).
 281

A utograft: T ghp, s cy ghp ln mt khng th bng

chnh m t bo ca bn thn.
A u to im m u n e diseascs: cc bnh t min, l nhng bnh
pht sinh do h min dch chng li ban thn.
A u to im m u n e hem olytic anem ia: Bnh thiu mu do tan
mu t min, do t khng th lin kt vi khng nguyn trn b
mt hng cu to ch ph hu hng cu
A u to im m u n e response: p ng min dch, s p ng
min dch chng li cc khng nguyn ca bn thn, cng gi l
tnh t min (Autoimmunity).
A u to im m u n e th ro b o c v to p e n ic p u rp u ra : Bnh xut hyt
t min do thiu ht tiu cu Cc t khng th pht sinh trong
bnh ny lin kt vi cc tiu cu to ch ph hu tiu cu, lm
gim s lng tiu cu.
Avidity: Ho tnh, l tng cc lc lin kt i lc ho hc gia
hai phn t hoc gia cc t bo VI cc t bo khc c nhiu v
tr lin kt.
A zath io p rin e: Mt loi thuc km hm min dch mnh c
kh nng dit cc t bo tng sinh nhanh. Cc t bo ny gm
cc t bo lympho gy ra p ng thi b m t bo cy ghp.
p sheet: L gp p, mt dng cu trc bc 2 c bn ca phn t
protein.
B acteria: Vi khun, mt dng vi sinh vt nhn s (procariote)
bao gm nhiu loi v nhiu chng khc nhau. Vi khun c th
sng trn b mt t bo khong khng bn ngoi mt t bo vt
ch, trong cc bng mng (vesicles) hoc trong cht dch t bo
(cytosol). Rt nhiu loi vi khun gy ra cc bnh truyn
nhim khc nhau.
B are ly m p h o cy te syndrom e: Hi chng thiu ht nghim
trng dng t bo lympho, trong MHC lp II khng c biu
h in trn b m t t bo do th iu h t m t s gen diu ho khc
nhau. Bnh nhn mc bnh ny b thiu ht min dch c tnh
,ch c mt s" t t bo TCD4+
Basophils: L dng t bo bch cu (Leucocyte) cha cc ht
nhum mu vi thuc nhum base, c chc nng gn ging t
bo Mast. l t bo a kim.
B-cell a n tig e n re c e p to r hoc B - cell R ece p to r (BCR): Th
th ca t bo B l mt phn t immunoglobin xuyn qua mng
282

(IgM v IgD hoc IgG) lin kt khng cng ho tr VI cc chui

ga(CD79a) v IgP(CD79b).
P-cell corona: Vnh t bo B nm trong l lch (spleen) l
mt vng tht c mu trng kt hp s b vi cc t bo B.
p-cell m itogens: Cht kch thch s phn chia t bo B, lm
tng sinh t bo B.
Blool g ro u p an tig en s: Cc khng nguyn nhm mu.
Bone m arrow : Tu xng, l mt c quan lympho trung ng
c chc nng to mu, sinh ra cc t bo mu khc nhau bao
gm hng cu, tiu cu, t bo mono, cc t bo bch cu nhn
a hnh (polymorphonuclear leucocytes), cc t bo lympho (lym
phocytes). Tu xng cng l ni pht sinh v pht trin t bo
B ng vy c v v cng cha ng cc t bo ngun (stem
cells) sinh ra cc dng t bo T khi tu. V vy, s cy ghp tu
xng c th sa cha c tt c thnh phn c bn ca t bo
mu, cn thit cho p ng min dch.
B o o ster im m u nizatio n : Gy min dch nhc li. Tim khng
nguyn gy min dch nhc li sau khi tim ln u lm tng
trng thi min dch
B ro n c h ia l-a sso c ia te d lym pho tisues: Hoc BALT. Nhng
m lympho lin kt vi ph qun. Nhng m ny rt quan trng
i vi s p ng min dch vi cc khng nguyn b ht vo v
i vi nhim trng h hp.
B u rs a o f F ab riciu s: Ti Fabricius, mt c quan min dch
ca lp chim, l ni.cn thit cho s pht trin ca t bo B cu
lp chim. Nu c quan ny b ct i chim non th s gy ra s
mt i cc t bo B chim trng thnh. Ngi ta khng tm
thy c quan tng ng ny ngi.
C l in h ib ito r: (Cl-INH), cht km hm Cl, l mt protein c
ch s hot ho b th Cl, lm mt hot tnh enzyme ca phc
h Clr: Cls. Thiu ht Cl-INH l nguyn nhn ca bnh ph
mch di truyn.
C3/ C5 co n v ertase: Enzyme lm bin i C3/ C5. S to ra
enzyme ny trn b mt tc nhn gy bnh hay trn t bo dch
cn ph hu l mt giai on quan trng ca con dng hot ho
b th. C3/ C5 convertase sau xc tc cho s loi b mt s ln
cc phn t C3 trn b mt tc nhn gy bnh gip cho s
opsonin ho v to ra mt dy phn ng gy tn thng mng t
bo tc nhn gy bnh (vi khun).
 2f t : *

C5a recep to r: Tim the (a b the 05a, l mt th th c by

vng xoan xuyn qua mng lin kt vi protein G heterotrime.
C alcin eu rin : L mt pholphataza serin/ threonin ca t bo
cht ng vai tr quan trng nhng cha c xc nh r trong
vic truyn tn hiu qua th th TCR Cc thuc km ch min
dch nh cyclosporin A v FK 506 to ra cc phc h vi cc pro
tein ca t bo gi l mmunophilin c tc dng lin kt v gy
bt hot calcineunn s lm km ch p ng min dch ca t
bo T.
C alnexin: L mt protein 88kDa c tm thy li ni cht
(ER: Endoplasmic Reticulum) c kh nng lin kt vi cc thnh
vin protein dc gp np mt phn thuc siu h globulin min
dch v gi cho cc protein ny li trong li ni cht cho n
khi chng c gp np hon ton, cn gi l protein bo mu.
C a p tu re assay: Xt nghim bt gi min dch.
C arrier: Cht mang c bn cht protein l, lin kt vi mt
khng nguyn phn t nh khng c kh nng p ng min
dch (khng sinh min dch). Dng khng nguyn ny c g 1 l
hapten. In vivo, cc protein ca bn thn c th cng c th c
dng lm cht mang nu chng c ci bin ng bng mt
hapten. iu ny quan trng trong hin tng d ng VI thuc.
C aseatio n Necrosis: Hoi t trong li, mt dng hoi t c
thy gia cc khi u ht trong bnh lao phi. Ngi ta thy
xut hin cc vng trng nh phomat gia m hoi t.
CD: Cm bit ho (Cluster of Differentiation).
CD45: L mt cm bit ho khng nguyn chung cho cc bch
cu c bn cht l mt tyrozin photphataza bc l nhng dng
ng phn khc nhau trn b mt cc lympho T khc nhau. Cc
dng ng phn ny ni chung biu th mt chc nng nh CD
45R do m t exon m ho c m t k iu lin k t n h t n h VI m t
khng th c hiu.
CDR: Vng xc nh b sung (Complementarity determining
regions).
CDR1, CDR2, CDR3: L ba vng xc nh tnh b sung ti
v tr tn cng ca khu vc bin i (V.Domain) trn cc phn
t khng th hoc trn cc TCR. Ba vng ny to nn cc thng
lng (loop) tip xc trc tip vi khng nguyn hoc peptit.
284

Cell a d h e n tio n molecules: Cc phn t kt dnh t bo. gi

tt l CAM. l nhng protein b mt t bo, to ra s lin kt
gia cc t bo vi nhau trong cc m.
C ell-m ed iated im m u n ity hoc C ell-m ediated im m une
response: Tnh min dch trung gian qua t bo hoc s p
ng min dch qua trung gian t bo. M t s p ng min
dch thch ng trong khng nguyn c hiu vi t bo T ng
vai tr ch yu. p ng min dch ny bao gm tt c tnh min
dch thch ng nhng khng bao gm qu trnh tit khng th.
C ell-surface Im m unoglobulin: Globulin min dch trn b
mt t bo. l th th t bo B (BCR).
Cellular Immunology: Mn hc min dch chuyn nghin
cu tnh min dch trn c s t bo.
C e n tra l ly m p h oid organs: Cc c quan lympho trung ng
l nhng v tr p h t trin ca cc t bo lympho ngi, tuyn
c, (thymus) l nhng c quan lympho tru n g ng.
C e n tra l to leran ce: S dung np mc trung ng. S
dung np c thit lp trong qu trnh pht trin ca cc t bo
lympho cc c quan lympho trung ng khc vi dung np
mc ngoi vi (peripheral tolerance).
C en tro b lasts: Nguyn bo trung tm. l nhng t bo c
kch thc ln ang phn chia nhanh, c tm thy cc trung
tm mm, cng l nhng t bo t bin soma mc cao.
Cc t bo B ghi nh v cc t bo tit khng th u bt ngun
t cc t bo ny.
C entrocy te: T bo trung tm. L cc t bo nh khng chia
trung tm mm bt ngun t nguyn bo trung tm. Chng c
th chn (trng thnh) thnh cc t bo plasma tit khng th
hoc tr th n h t bo ghi nh, hoc c th cht theo chng trnh
(apoptosis). iu ny ph thuc vo s tng tc gia th th
ca chng vi k hng nguyn.
C h ed iak - H igashi Syndrom e: L mt hi chng thiu ht
chc nng ca t bo thc bo, cha r nguyn nhn. nhng
t bo ny, lysosome mt kh nng dung hp vi cc th th n
bo(phagosome) v kh nng git vi khun ca nhng t bo
thc bo ny b suy gim.
C hem okines: L cc xitokin c phn t nh gip cho s di
ng v hot ho t bo, c bit l cc thc bo v cc t bo
lympho. Chng c vai tr quan trng trong p ng vim.
 285

C h ro n ic g r a n u lo m a to u s disease: Bnh u ht mn (u ht
mn tnh). l bnh thiu ht min dch, trong d c nhiu u
ht hnh thnh (lo vic loi tr khng dy ca cc t bo thc
bo. Bnh do thiu ht h thng enzyme NADP-H oxidase dng
to ra gc superoxit tham gia dit vi khun.
ClassII - associaed in v a ria n t chain, CLIP: Poptit lin kt
vi phc h ph hp m ch yu lp II ti rnh lin kt ca
M H C lp II s a u khi b "ct gt b n g cc pro tea se. P e p tit ny
sau d c ly khi rnh lin kt nh protein H,A - DM trong
c ch lin kt vi mnh peptit, khng nguyn s c trnh din
cho ly m p h o TCD4.
Class switching: Xem isotype switching.
Class: Xem isotype.
Classical pathw ay: Con dng hot ho b th kinh in
c b t u nh k h n g th lin k t vi k h n g n g u y n , tip theo
cc thnh phn b th Cl, 04. C2 c bin i to C3/ C5
c o n v e r t a s e (xem t h m a l t e r n a ti v e path w a y ).
Clonal deletion: S loi b dng, s loi b nc t bo lym-
pho cha chn bng cch lin kt VI cc t khng nguyn(auto
antigen). Loi b dng l mt c ch ch yu ca s dung np
trung ng v cng xy ra s dung np ngoi vi.
Clonal expansion: S lan truyn dng. l s tng sinh
ca dng t bo lympho c hiu vi mt khng nguyn kch
thch. Qu trnh trn xy ra trc khi c s bit ha thnh t bo
hiu qu. l giai on c bn ca p ng min dch thch
ng cho php cc qu trnh c hiu khng nguyn tng slng
chin u c hiu qu vi tc nhn gy bnh.
Clonal selection theory: L thuyt la chn dng. L l
thuyt trung tm ca min dch thch ng trong d s p ng
min dch thch ng bt ngun t cc t bo lympho ring bit
c hiu khng nguyn. Nhng t bo ny tng sinh p ng li
khng nguyn v bit ho thnh cc t bo hiu qu c hiu
khng nguyn loi b tc nhn gy bnh v to ra cc t bo
ghi nh (memory cells) lm bn vng tnh min dch. L thuyt
ny c Niels Jerne v David Talmage nu ra u tin, sau
c Macfarlane Burnet hon thin.
Clone: Mt qun th t bo bt ngun t mt t bo t tin.
Cloned T- cell line: To mt dng t bo T hay clon mt dng
T. Nui cy tip tc dng t bo T bt ngun t mt t bo t
286

tin. Dng t bo T clon cn phi c kch thch thng

xuyn bng mt khng nguyn duy tr s tng trng ca
chng. Dng T clon s c dng trong nghin cu tnh c
hiu, s tng trng v cc chc nng gy hiu qu ca chng.
Clontypic: Mt kiu clon, ni ln c im duy nht ca mt
dng t bo ring bit. V vy, mt khng th n dng (mono
clonal antibody) phn ng vi mt th th b m t dng T ny
l khng th nhn bit c hiu kiu clon T.
C lu sters of D iffentiation (CD): Cm bit ho khng
nguyn. L nhng phn t bc l trn b mt t bo, c nhn
bit bi nhng khng th n dng c hiu vi chng. S" lng
CD h i n n a y c a cc t bo h m i n dch c tm r a ln
n hng trm loi (CD1-CD247).
Co-dominant: ng tri. Mt gen c biu hin khi c hai
alen ca mt locus u c biu hin nh nhau trong cc d hp
t. Hu nh tt c cc gen c c tnh ny bao gm cc gen c
tnh a hnh cao ca phc h ph hp m ch yu (MHC).
Coding joint: on ni m, ch ni m c to thnh bng
cch ni khng chnh xc ca mnh gen V vi mt mnh gen J
(hoc D) trong phn t globulin min dch (Immuno globin) hoc
ca cc gen m ho cho th th ca t bo T.
Co-isogenic: Xem congenie.
Collectins: L mt h cc lectin lin kt vi ng ph thuc
canxi, hoc l nhng lectin cha cc trnh t ging collagen. Cc
protein lin kt vi mannose cng l cc collectin.
Com binatorial diversity: S a dng do t hp. Cc th th
min dch biu hin hai kiu a dng do t hp c phn bit vi
nhau. S a dng do t hp sinh ral do s kt hp cc n v
thng tin di truyn tch bit. Cc mnh gen ca th th ni vi
nhau theo nhiu cch t hp khc nhau to nn cc chui th th
khc nhau, sau hai chui th th (chui nng v chui nh
ca Ig, chui X v p hoc Yv 5 ca TCR) s kt hp vi nhau to
ra v tr nhn bit khng nguyn.
Com m on lyphoid progenitors: cc t tin chung ca t bo
lympho. l cc t bo ngun sinh ra tt c cc t bo lympho.
 287

Chng bt du t cc t bo lifiuon to mu da nng (pluripotent

hematopoietic stem cells).
C om m on variable Imm unodeficiency: S thiu ht min
dch bin dng chung. l s thiu ht chung trong vic sn
xut cc khng th, trong nguyn nhn pht sinh bnh cha
r. C s lin quan rt mnh m vi s xc lp bn gen ca
phc h MHC.
C om petitive b in d in g assays: Cc xt nghim lin kt cnh
tranh, l nhng xt nghim huyt thanh hc trong nhng
khng nguyn cha bit s c pht hin v nh lng nh
kh nng km hm s lin kt ca chng i vi mt cu t gn
(ligand) nh du bit vi mt khng th c hiu vi chng.
Complement: B th. L nhng protein huyt tng phn
ng vi nhau nhm tn cng cc dng tc nhn gy bnh ngoi
bo. B th c th c hot ho t pht i vi mt s tc nhn
gy bnh (con ng hot ho bn cnh bt u t C3b) hoc do
khng th lin kt vi tc nhn gy bnh (con ng hot ho
kinh in bt u t Cl). Hiu qu ca cc con ng hot ho
b th l to ra phc h tn cng mng (MAC) v opsonin ho tc
nhn gy bnh to iu kin d dng cho cc thc bo tiu dit
tc nhn gy bnh.
C o m p lem en t Receptors (CR): Cc th th ca b th. L
nhng protein trn b mt mng t bo lin kt vi cc b th
gn vi cc tc nhn gy bnh. Cc th th ca b th cc thc
bo (phagocytes) cho php chng nhn bit tc nhn gy bnh v
ph hu chng.
C o m p le m e n ta rity d e te r m in in g regions (CDRs): Cc vng
xc nh b sung. L mt phn phn t th th tip xc vi cu
t (ligand) c hiu v xc nh tnh c hiu ca chng. CDRs
l phn d bin i nht ca protein t th, to cho cc th th
tnh a dng cu trc. Vng ny bao gm su vng thng lng
(loops) u tn cng xa ca cc khu vc (domain) d bin i
ca th th, ba vng thng lng t hai domain ca th th.
Conform ational epitopes, d iscontinuous epitopes: Cc
quy nh khng nguyn khng gian hoc gin on. Cc epitopes
n y c h n h th n h t m t s v n g tch b it trong trnh t cu
trc bc nht ca mt phn t protein khng nguyn gp li
trong khng gian. Cc phn t khng th ch lin kt vi nhng
288

epitopes khng gian cc khng nguyn t nhin khng b bin

tnh.
C ongenic strains: Cc chng chut nht ging nhau v di
truyn tt c cc locus nhng ch khc nhau mt locus. Mi
chng ny c to ra bng lai cho lp li gia cc chut mang
c im mong mun tp trung vo mt ni chut cung cp c
s di truyn cho mt b SU tp cc ni congenic.
C o n s ta n t regions: Cc vng khng bin i, vng hng dnh.
C o n ta c t hypersensitivity: Qu mn tip xc. L mt dng
qu mn mun, trong cc t bo T p ng li cc khng
nguyn gy di ng khi tip xc vi da. V d: Mt cht c pen-
tad eca-catecol l cy leo Ivy (cy thng xun) khi tip xc vi
da s gy hin tng qu mn tip xc.
C ontinuous epiopes hoc linear epitopes: Cc quyt nh
khng nguyn lin tc hoc cc quyt nh khng nguyn thng
bao gm trnh t lin tip cc gc acid- amin ca mt epitopes.
Convertase: Hot tnh enzyme lm bin i protein b th
thnh dng c hot tnh. Vic to ra C3/ C5 convertase l mt s
kin quan trng nht trong hot ho b th.
Coomb test: Xt nghim coomb. L xt nghim khng th lin
kt vi t bo hng cu. Hng cu khi c bao bc bng cc
khng th, s b ngng kt nu chng bc l i vi mt khng
th khng li Ig. Xt nghim coomb kh quan trng pht hin
cc khng th khng ngng kt chng li cc t bo hng cu c
sn xut c mt khng nguyn RH khng ph hp trong khi c
thai.
c - Reactive protein: Protein phn ng c, mt dng protein
ca pha cp tnh lin kt vi phthorylcholin, trong phot-
phorylcholin l thnh phn c - polysaccharide ca vi khun
Streptococcus pneumoniea. Nhiu loi vi khun cng c phot-
phorylcholin trn b mt t bo c th kt hp vi protein phn
ng c. V vy c - reactive protein c th lin kt vi nhiu loi vi
khun to iu kin opsonin ho hp n cc thc bo. Protein
khng th lin kt vi cc m ca ng vt c v.
Cross - m atching: mt xt nghim phn loi nhm mu v
xt nghim tnh ph hp m c dng trong truyn mu v
trong cy ghp m t bo.
Cross - reaction: Phn ng cho. Phn ng lin kt gia mt
khng th v mt khng nguyn khng gy p ng tng hp
 2H9

khng the . I)o , nu mt khng th khng li khng nguyn

A, cng lien kt vi khng nguyn B, ngi ta ni rng khng
t h ny p h n n g cho VI k h n g nguvn B.
C u ta n e o u s lym phoid antigen: Khng nguyn lympho (CLA)
(a da l mt phn t tham gia vo dn dt t bo lympho quay
tr li da ca ngi.
C u ta n e o u s T- Cell lymphoma: u lympho ca t bo T da,
s sinh trng c tnh ca cc t bo T da.
C yclophospham ide: Thuc km hm min dch c bn cht
l tc n hn alkyl ho c tc dng dit nhanh chng cc t bo
ang phn chia, bao gm c cc t bo lympho tng sinh p ng
V I k h n g n g u y n .

Cyclosporin A: Thuc km hm min dch mnh, km hm s

truyn tn hiu t cc TCR, ngn cn hot ho t bo T v chc
nng gy hiu qu. Thuc ny tc dng VI Cyclophilin to ra
phc h gy bt hot phosphotase serin/ treonin calcineurin.
Cytokinees: Protein tit ca cc t bo gy tc ng vo cc
t bo khc. Xitokin c t bo lympho tit ra c gi l lym-
hokin hoc interleukin (vit tt l IL). Xitokin tc ng ln cc
th th c hiu vi xitokin c mt t bo m chng nhm ch.
Cytokine recep tors: Cc th th nhn bit xitokin. S lin
k t gia th th v xitokin to ra cc hot ng mi trong t bo
nh; tng trng , bit ho, hoc cht.
Cytotoxic T cells: Cc t bo T gy c. L nhng t bo dit
cc t bo khc. Tt c cc t bo T gy c u l cc T- CD8 ch
nhn bit MHC - lp I, nhng t bo TCD4 cng c th dit cc
t bo khc mt s trng hp. Cc t bo T gy c c vai tr
quan trng trong vic bo v vt ch chVig li cc c nhn gy
c ni bo.
Cytotoxins: Cc cht c i vi t bo, l nhng protein do
t bo T c tit ra ph hu t bo ch (nhim trng hoc
bin dng bt thng). Perforin, granzyme hoc pramentin t
nhng c t t bo dc xc nh.
Defective e n d o g e n o u s retroviruses: L nhng phn genom
ca retrovirus ci v genom ca t bo vt ch v hot ng nh
cc gen ca vt ch. C rt nhiu nhng b phn gen ca retro
virus c ci trong genom ca chut nht.
Delayed - type hypersensitivity: Qu mn mun. L mt
dng min dch qua trung gian t bo do mt khng nguyn l
tip xc vi da, lm huy ng cc t bo T- CD4 gy ra hin
290

tng vim. c gi l qu mn mun l do phn ng din bin

t hng gi n hng ngy sau khi tim khng nguyn di da.
phn bit vi cc qu mn tc th (immediate hypersensitivity)
trong phn ng di da tnh theo pht ngay sau khi tim
khng nguyn di da.
D e n d ritic cells: T bo c tua, cng c gi l cc t bo li
x thu (interdigitating reticular cells), l tm thy trong khu
vc t bo T ca cc m lympho. Chng l nhng t bo c tim
nng kch thch mnh nht cc p ng min dch ca t bo T.
Cc m khng phi lympho cng cha cc t bo dendritic nhng
dng nh khng c kh nng kch thch p ng t bo T trc
khi chng c hot ho v di chuyn n cc m lympho. T bo
c tua bt ngun t t bo tin thn tu xng. Cn phn bit
vi t bo nang c tua (follicular dendritic cell) l loi c chc
nng trnh din khng nguyn cho t bo B.
D e n d ritic e p id e r m a l cells (dEC): T bo tua biu b. L
mt lp t bo chuyn bit ca t bo Ty, , tm thy da ca
chut nht v mt s loi ng vt khc, khng c ngi. Tt c
cc dEC u c th th T dng Y, (y TCR).
D esensitization: Lm mt tnh nhy cm. Mt phng php
hay to cho cc th hay b d ng biu hin liu lng cht gy di
ng tng ln hy vng km hm phn ng d ng ca chng.
iu ny c th cho vic chuyn i cc kiu t boT-CD4 v do
l bin i tng hp khng th IgG thay cho IgE.
D. gene segm ents, diversity gene segm ents: Cc mnh
gen to a dng. L cc trnh t ngn ADN ni cc mnh gen V
v J trong cc gen chui nng ca Ig v cc gen chui p v ca
TCR trong qu trnh pht sinh soma ca mt exon vng bin i
Diacylglycerol (DAG): Diaxylglyxerol l mt sn phm phn
hu ca lipit c gii phng ph bin t phospholipit inositol
nh tc ng ca phospholipase C-y. Vic sn xut DAG do phn
ng tip nhn ni ghp ca nhiu th th kch thch to ra. Cc
DAG tip theo s hot ho protein kinase c trong t bo v s
truyn tn hiu xa hn.
Diapedesis: S di chuyn ca cc t bo mu, c bit l bch
cu t thnh mch mu n cc m t bo.
D ifferential S ignalin g Hypothesis: Gi thuyt truyn tn
hiu bit ho. Gii thch con ng khc bit gia cc qu trnh
la chn m tnh v dng tnh (negative, positive selection)
trong qu trnh chn ca t bo T tuyn thymus.
 291

D ifferential antigens: Cc khng ngu yn bit ho, c pht

hin mt s t bo nh re khng th dc hiu. Nhiu khng
nguyn bit ho c vai tr quan trng c trng cho cc phenotyp
bit ho c a t bo m ch n g bc l, c h n g h n n h cc Ig b
mt ca t bo B.
DiGeorge Syntrom e: Hi chng DiGeorge, mt bnh thiu
ht di truyn theo gen ln, dng nh biu hin s thiu ht
pht trin cc chm t bo thn kinh quan trng. Hu qu bnh
cn l s thiu ht truyn hoocmon parathyroid dn n mt
kh nng pht trin biu m tuyn thymus.
Dir 'ect coom bs test: Xt nghim (test) coomb trc tip, s
dng anti-Ig to ngng kt cc t bo hng cu nhm pht hin
c c t k h n g t h b a o q u a n h t b o h n g c u t r o n g b n h t m i n

hoc p ng min dch khng thai nhi ngi m (xem indirect

coombs test).
D iscontino us epitopes: Cc quyt nh khng nguyn gin
on (xem comformational epitopes).
ADN - d e p e n d e n t p ro tein kinase: Protein kinase ph thuc
ADN, c mt tiu n v xc tc (c hot tnh enzyme) ng vai
tr quan trng trong ti t hp cc mnh gen VDJ. t bin lm
thiu yu t ny s a n phenotyp thiu ht min dch t hp
c tnh hoc bnh Seid (Severere Combined Immunodeficiency).
Double - neg ativ e thymocytes: Cc t bo c m tnh kp,
l nhng t bo T cha chn (cha trng thnh) bn trong tuyn
c khng biu hin c hai loi ng th th CD4 v CD8. Vic
bc l chn lc chng din ra song song vi s pht trin ca t
bo T. C 4 qun th t bo T ch yu bn trong tuyn c l:
qun th m tnh kp, qun th dng tnh kp, qun th ch
cha mt loi CD4 v qun th ch cha mt loi CD8.
Double positive thymocytes: Cc t bo c dng tnh kp.
L qun th t bo T nm trong tuyn c u bc l c hai loi cm
bit ho l CD4 v CD8. v sau s cht theo chng trnh (apoptosis).
Early in d u c e d responses or early non a d a p tiv e r e
sponses: Cc p ng c to ra sm, l mt lot phn ng bo
v ca vt ch trong giai on u ca nhim trng. Chng
phn bit vi min dch bm sinh (innate immunity) v c c pha
cm ng v phn bit vi min dch thch ng (adaptive immu
nity) v khng xy ra theo c ch chn lc dng cc t bo lym-
pho c hiu vi khng nguyn.
Early P ro B cell: xem Protein-B-cell.
292

Effector cells: Cc t bo hiu qu, l cc t bo lympho c

the to qu trnh ho gii trung gian loi b tc nhn gy
bnh ra khi c th. Cc t bo ny khng cn bit ho xa hn,
trong khi nhng t bo ghi nh cn phi c bit ho v phn
chia trc khi tr thnh cc t bo hiu qu. Cc t bo lympho
hiu qu cn dc gi l cc t bo hiu qu c v trang.
Effector m echanism : C c h h i u qu, c s d n g loi
b cc tc nhn gy bnh thc hin trong p ng min dch bm
sinh v p ng thch ng.
E ffe re n t ly m p h atic vessel: Mch bch huyt i ra, ng ra
ca cc t bo lympho ri khi hch bch huyt i vo h tun
hon.
ELISA: xt nghim hp ph min dch lin kt enzym (xem
enzyme-liked Immuno Sorbent Aassay).
ELISPOT assay: Xt nghim ELISA ci bin, trong cc t
bo c t ln trn cc khng th hoc khng nguyn gn
ln b mt ca mt gi th nha cm by pht hin cc sn
phm chn lc ca t bo. Cc sn phm by c sau pht
hin bng mt khng th gn vi mt enzym c th phn hu
mt c cht to mu to ra vt c mu khi thm c ch't ca en
zyme.
E m b rio n ic S tem Cells (ES cells): Cc t bo phi gc, cc t
bo phi ngun. l nhng t bo ang pht trin lin tc c
kh nng bit ho thnh tt c cc dng t bo khc. Cc t bo
ES c th c s dng trong thao tc di truyn, nui cy m,
sau c ci t thnh cc bng phi nguyn bo (blastocysts)
dng d to cc dng t bin chut nht. Cc gen trong t bo
ES c loi b bng k thut ti t hp cng ngun ( hoc ti t
hp gen tng ng: homologous recombination), sau t bo
ES c dng to ra dng chut c gen knock-out.
E n c a p s u la te d b acteria: Vi khun c v bao bng mt lp o
cacbohydrat dy nhm bo v cho chng khi b thc bo. Vi
khun c v bao ny c th gy ra nhim trng ngoi bo. N ch
b thc bo v b ph hy bng cc i thc bo khi lp v ny
c lin kt vi khng th v b th c to ra c th b
nhim.
E n d o g e n o u s pyrogens: Cht gy st ni sinh l nhng cyto
kine c kh nng lm tng nhit c th. N c phn bit vi
cc cht endotoxin ngoi lai ca cc vi khun gram m cng gy
 293

ra hin t n g st. Chnh n h n g e n o to x in vi k h u n n y c n g

khi dng cc pyrogon n 1 sin l.
Endotoxin: L cc ni (lc t vi khun ch c gii phng ra
k h i t b o v i k h u n b c h t t r o n g c t h b n h i m b n h , t r i V I

ngoi c t (exotoxin) dc vi k h u n ti t ra khi c h n g cn sng.

Mt ni c t q u a n trng n h t c a vi k h u n g r a m m l
lipopolysaccharide (LPS) c tc dng rt mnh gy tng hp cy-
tokine v gy r a h i n tng sc ni c t.
E n h a n c e rs: L nhn^ trnh t c hiu nm trong ADN go-
nom c tc dng hot ha s phin m (transcription).
ELISA: Xt nghim min dch hp ph lin kt enzym, l k
thut c s dng rng ri trong sinh hc, y hc cng nh min
dch hc.
Eosinophils: L nhng t bo bch cu a axit c tc dng
bo v chng li nhim bnh k sinh trng. Cc t bo ny c
hot ha bng cc t bo lympho trong p ng min dch thch
ng. Bnh thng mt t bo a axit trong mu rt thp
nhng s c tng ln rt cao trong trng hp b d ng hoc b
nhim trng.
E otax in 1, E o tax in 2: l cc chemokin, cc cht tit c bn
cht ha hc tc ng c hiu ln bch cu a axit.
Epitope: Quyt nh khng nguyn, l mt trnh t cu trc
nm trn phn t khng nguyn c nhn bit bi cc khng
th hoc cc th th ca khng nguyn. Mt Epitope ca t bo
T l mt trnh t peptit ngn t mt khng nguyn c bn ch't
protein c lin kt vi phn t MHC v dc nhn bit bi mt
t bo T ring bit. Cc epitope ca t bo B l nhng quyt nh
khng nguyn c cc t bo B nhn bit. Cc epitope ny c
cu trc gin on, in hnh ngha l c cu trc khng gian
nht nh.
E pitope sp read in g : S lan ta epitope c m t mt thc
t l cc p ng min dch di vi cc t khng nguyn (Autoan-
tigen) c khuynh hng da dng hn v dai dng hn.
E p s te in - B a r r virus (EBV): L nhng herpesvirus gy
nhim chn lc ln cc t bo B ca ngi bng cch lin kt vi
cc th th ca b th (CR2 hoc cn gi l CD21). EBV thng
lin quan cht ch vi bnh ung th vm hng.
E q u ilib riu m dialysis: S thm tch cn bng, l mt k
thut trong cc khng th trong ti thm tch c bc l ty
theo s lng thay i ca cc phn t khng nguyn c th
294

khuch tn qua mng thm tch. S lng ca khng nguyn

bn trong v bn ngoi ca ti ti thi im trng thi khuch
tn cn bng s c xc nh theo s lung v i lc ca khng
th.
E-rosettes: Phn ng to hoa hng ca t bo hng cu cu.
Phn ng ny xy ra khi cc t bo T ca ngi c x l vi
cc t bo h n g c u cu. P h n n g to hoa h n g vi hng c u cu
thng dng tch t bo lympho T ca ngi.
Erp57: L phn t bo mu tham gia vo qu trnh gn mnh
peptit khng nguyn ln trn phn t MHC lp I li ni cht.
E ry th ro b la s to s is fetalis: Bnh tan mu nguyn bo hng
cu c tnh, l mt dng bnh tan mu c tnh do Rh trong
khng th khng Rh ca ngi m xm nhp vo thai nhi lm
tan mu di dng nguyn bo hng cu (Erythroblast) c th
thai nhi.
E-selectin: Xem selectin
E xperim ental allergic enceph alom yelitis (EAE): Bnh
vim h thng thn kinh trung ng thc nghim, c to ra
sau khi chut nht c gy min dch vi cc khng nguyn
thn kinh cng vi t cht mnh.
E x tra v a s a tio n : L s di ng ca cc t bo hoc th dch t
cc mao mch mu n nhng m xung quanh.
F a b fragm ent: Mnh ct ca phn khng th lin kt VI
khng nguyn, c to ra bng cch x l khng th vi papain.
F (ab )2: Mnh khng th lin kt vi khng nguyn khi x l
khng th vi tripxin.
Fc fragm ent: Mnh khng th vng khng bin i khi x
l khng th bng papain.
Factor B, factor D, factor H, factor I, factor P: L nhng
thnh phn ca con ng hot ha b th bn cnh (alternative
pathway). Factor B c vai tr rt ging vi vai tr ca C2b trong
hot ha c in. Factor D l mt protease serin gy ra phn hy
factor B. Factor H l mt protein c ch c vai tr ging vi yu
t thc y phn r. Factor I l mt protease lm phn hy cc
thnh phn khc nhau ca con ng hot ha bn cnh. Factor
p gi l properdin l mt thnh phn iu ha dng tnh ca
con ng hot ha bn cnh, lm n nh C3 convertase trn b
mt t bo vi khun ca con ng hot ha bn.
Farmers lung: L mt bnh qu mn ca phi do s tng tc ca
cc khng th IgG vi mt s lng ln cc d nguyn (allergen) xm
 295

n h p vo n g h h p v i vo t h n h ca phi gy vim phi

v lm bien i t r a o i kh.
F a s : Mt t h n h vin ca h t h th tip n h n T N F ( T u m o r
Necrosis Factor). N c bc l t r n mt s t bo to cho cc
t bo c n h y c a m i vi n h n g t bo bc* l cu t F as tiu
dit chng.
Fc receptor: Cc th th i vi mnh Fc ca khng th- Cc th th
ny bao gm FcyR, FceR Cc FcyR bao gm FcyRI* RII, Rin l nhng
t h t h b m t lin kt vi p h n Fe c a cc p h n t IgG. Cc t h
th Fcy c bc l t r n b m t t bo th c bo ly m p h o B, t bo
NK v cc t bo nang c tua. Chng ng vai tr quan trng
tr o n g p n g m i n dch th dch.
FACS: My phn hng t bo bng tia,hunh quang hot ha
(Fluorescence-activated cell sorter). My dng o kch thc
t bo, tnh cht c ht v pht quang khi cc t bo ny lin
kt vi khng th nh du hunh quang c nhn dng khi
ngi ta cho 1 t bo i qua mt my pht hin quang hc c
chm tia chiu qua. Vic phn tch mt t bo theo cch ny
c gi l o dng chy t bo (flow cytometry) v my ny c
gi l flow cytometers hoc goi l cell sorters.
Follicular cen ter cell lymphoma: Bnh u lympho dng B
nang lympho hoc cc m lympho.
F r a m e w o r k regions: Cc vng gi khng bin i nm
xen gia cc khu vc bin i ca phn t Ig v cc th th t
bo T. Vng ny gip cho phn t protein tng i n nh cc
khu vc siu bin c th tip xc vi khng nguyn.
G protein: L mt dng protein nm bn trong mng t bo
lin kt vi GTP v lm bin i GTP thnh GDP trong qu
trnh truyn tn hiu t bo. C 2 kiu protein G, kiu 1 hetero-
trime (vi 3 tiu n v l a,p, y), kiu 2 l protein G nh hn v
d nh protein G Ras v Raf, n tc dng xui chiu VI nhiu s
kin truyn tn hiu xuyn qua mng.
GALT: Cc m lympho lin kt vi rut.
GEF: Guanine nucleotide exchange factor: Yu t trao i nu-
cleotit Guanin.
Gene conversion: S bin i gen, xy ra chim v th to
ra tnh a dng ca cc th th nhn bit immunoglobulin. S
bin i gen thng xy ra vng V.
296

Gene knockout: L mt bit ng ch r s ph b mt gen

bng phng php ti t hp ging nhau.
Gene th e ra p y : Liu php gen, phng php cha bnh bng
cch lm bin i gen hoc a mt gen mi vo thay th cho gen
gy bnh.
G enetic im m unization: G y m i n dch di tr u y n , l m t k
thut vi to ra s p ng min dch thch ng.
G e rm in a l centers: Cc trung tm mm, l nhng v tr
cc t bo B tng sinh (phn chia mnh m), c chn lc dng,
c chn trng thnh v xy ra apoptosis (cht theo chng
trnh).
G erm lin e diversity: Tnh a dng dng mm, thng ni v
s a dng ca cc th th nhn bit khng nguyn l nh s
tha k ca nhiu mnh gen m ha cho cc khu vc V. Kiu a
dng ny khc vi kiu a dng do s sp xp li ca gen hoc do
s biu hin t bin soma ca gen.
G o o d p a s tu r e s syndrome: L mt bnh t min trong cc
t khng th (autoantibodies) pht sinh chng li lp mng c
bn hoc cc collagen kiu IV gy ra bnh ph hy mch mu.
B ny nhanh chng chuyn sang c tnh.
G ra ft rejection: S thi b mnh ghp.
G ranulocyte: Cc bch cu nhn a hnh cha nhiu ht.
G ranulocyte - m acrophage colony - stim ulating factor
(GM - CSF) : L mt cytokine tham gia vo qu trnh sinh
trng v bit ha ca cc t bo dng bch cu v dng mono
cng tham gia vo bit ha v sinh trng cc t bo c tua
(dendritic cells), i thc bo v bch cu dng ht.
G ra v e s disease: L mt bnh t min trong xut hin cc
khng th chng li th th nhn hocmon kch thch thyroid, t
gy ra s sn xut qu mc hocmon thyroid v gy bnh
cng nng tuyn gip (hyperthyroidism).
H an tig en , h is to c o m p atib ility antigen: Khng nguyn ph
hp t chc (khng nguyn ph hp m). V d MHC (Major his
tocompatibility complex) l khng nguyn ph hp m ch yu
c vai tr quan trng nht trong p ng min dch. MHC ca
chut c gi l H-2.
Haplotype: Kiu n bi.
Haptens: L nhng phn t nh c tnh khng nguyn nhng
khng gy ra p ng min dch. Hapten cn c lin kt vi
 297

m t p r o t e in m a n g ( p r o t e in c a r r ie r ) s t o t h n h m t k h n g

n ^ u v n (Im m u n o g e n ) gy ra (lp n min (lch sinh k h n g th

h o r p n g m i n dch tl^ t ho T.
H ash im o to s th yroiditis L mt bnh t min pht trin
(lai (lng cc k h n g th chng li cc k h n ^ n g u y n dc hiu t h y
roid. C h n h n h n g k li n ^ the ny s h u y ng t bo NK xm
nhp vo cc m v lm ton thng m hoc gy vim.
H alp er CD4 T cells L n l ng t bo T CI)4 b tr (TH) gip
cho cac t bo B sn xut khng th trong p ng min dch th
dch. Cc lympho TH bao gm THl v TH2 trong TH2 sn
xut cytokine IL-4 v II,-5.
H em agglutinin: Cht gy ngng kt, v d cc lectin.
Hematopolesis: L qu trnh to ra cc yu t t bo ca
mu bao gm hng cu, bch cu v tiu cu. Tt c nhng t
bo m u u c b t ngun t cc t bo n g u n to m u a
nng (plunpotent hematopoietic stem cells).
Hemolytic disease of the newborn: L mt bnh tan mu
ca tr s sinh. Bnh ny xy ra do bt ng khng nguyn
nhin mu Rh gia c th m v tr s sinh.
H e r e d ita r y a n g io n e u ro tic edema: Bnh ph mch thn
kinh di truyn, do thiu ht gen ca cht c ch Cl (Cl inh)
trong h thng hot ha b th.
Heterozygous: D hp t biu hin nhng c th mang 2
alen khc nhau ca cng 1 gon.
H e y m a n n s nephritis: L bnh vim thn c to ra cho
ng vt khi tim vo chng cc t bo biu m ng.
High e n d o th e lia n vemeles: Mao mch ni m. L nhng
mao mch dc bit c tim thy cc m lympho. Cc t bo
lympho di chuyn t mch mng i vo cc m lympho bng cch
lin kt v di ng di qua cc t bo ni m theo nhng ng
mao mch ny.
High - zone tolerance: S dung np liu khng nguyn cao.
( S dung np khi tim khng nguyn c th cc liu thp v
cao).
Hinge region: Vng khp ni ca phn t khng th, c th
dc gi l vng bn l, gip cho phn t khng th mm deo
inh ng cho php cc "cnh tay" Fab dang ra gc rng hp
khc nhau lin kt vi cc epitop khng nguyn.
298

Histamin: L mt dng amin dn ximt ca histiin e tit

ra cc ht ca t bt Mast. Khi khng nguyn (thng l aller
gen) lin kt vi IgE trn t bo Mast s lm gii phng histamin
cc t bo ny, gy ra hin tng gin mach v co c trn, to ra
hin tng q u m n p h n v (qu m n typ 1).
HIV: Virus gy bnh suy gim min dch (Human Immunode
ficiency Virus), bnh do virus gy ra l hi chng suy gim min
dch mc phi (AIDS).
HLA: (Human Leulcocyte Antigen): Khng nguyn t bo bch
cu ca ngi; cn c ngha l MHC (Major Histocompatibility
Complex) ca ngi. Cc ch ci t sau HLA, v d HLA-A l
ch r cc locus ring cho c th, cn cc s l ch r alen, v d
HLA-A 0201.
HLA-DM: L mt phn t tham gia vo qu trnh loi b
chui bo mu li v t mnh peptit khng nguyn vo rnh ca
phn t MHC lp II trong c ch trnh din khng nguyn ca
MHC II cho lympho T-CD4.
chut nht protein tng ng l H-2M.
H odgkin's disease: Bnh Hodgkim, l bnh ung th ca h
min dch c c im l dng t bo B b t bin to ra cc t
bo to ln, gi l t vo Reed - Steinberg. C t nht hai dng t
bo rt khc nhau, l u lympho Hodgkim v hch u s
(nodular sclerosis).
Homeostasis: Trng thi sinh l bnh thng, trng thi
ny, cc t bo lympho ngi khng b nhim khun lun lun
c s lng bnh thng v n nh.
Homologous reco m b in atio n : S ti t hp tng ng cc
gen ca t bo c th b ri lon hoc b ph hy bng k thut
ti t hp tng ng vi cc bn sao c a vo trong c
cc trnh t c lm sai lch. Khi a cc gen c trnh t sai
lch vo t bo, chng s ti l hp chn lc vi cc gen ca t
bo qua cc vng cn li ca trnh t tng ng, thay th gen
chc nng bng mt bn sao khng c chc nng.
Host - v e rs u s - graft disease (HVGD): Bnh ca phn ng
thi b mnh ghp d gen khi mnh ghp chng li vt ch.
Thut ng c dng ch yu trong cy ghp ty xng b tht
bi.
H um an ization : To ra c tnh ca ngi thut ng ch ra
kh nng ca cng ngh gen s dng gen ca chut nht m ha
 2 99

cho vng siu bin ca khng th n cng c chn trong th

vin biu hin trn phage dc ci vo cc vng khung ca cc
gen Ig ca ngi. Khng th ti t hp ny c tnh c hiu mong
mun nhng khng gy ra p ng min dch khi a vo c th
ca ngi c cha bnh.
H u m o ral Im m unity: Min dch th dch, c to ra c hiu
qua trung gian khng th. Tnh min dch th dch c th c
chuyn cho cc c th nhn khng gy min dch bng cch dng
huvt thanh min dch c khng th c hiu.
Hybridomas: Th lai, c to ra sn xut khng th n
dng (Monoclonal anti body). Chng l dng t bo lai nh s
d u n g hp gia cc t bo B s n x u t k h n g th c h i u VI cc
t bo n tu nyelom "sng bt t. Nh vy th loi c hai u
im l cc kh nng sinh sn cao v lin tcsn xut ra khng
th n dng c hiu theo mun.
H y p e r a c u te graft reaction: S thi b mnh ghp cp tc
do khng th t nhin hnh thnh t c th nhn chng li
khng nguyn ca mnh ghp.
H ypereosinophilia: Trng thi bt bnh thng v s lng
qu cao ca cc bch cu a axit trong mu.
H y p e rim m u n izatio n : Gy min dch lp li t trng thi
min dch mc cao hn.
H ypersensitivity: S qu mn cm, qu mn. Cc phn ng
qu mn c phn loi thnh 4 kiu: Qu mn typ I c s tham
gia ca IgE lm khi ng cc t bo Mast tit histamin gy
phn ng co mch v co c trn, qu mn typ II c s tham gia
ca IgG chng li cc khng nguyn ca b mt t bo hoc
khng nguyn trung gian, qu mn typ III c s tham gia ca
phc h khng nguyn-khng th v qu mn typ IV l qu mn
c s tham gia ca cc lympho T.
H u p e r v a r ia b le regions: Cc vng siu bin, nm phn b'
thnh ba vng nh khu vc bin i (variable domain) ca
phn t khng th to ra s tip xc vi khng nguyn.
iC3b: Mnh b th bt hot c to ra t s phn hy c3b.
ICAMS (I n te r cellular a d h e s io n molecule): Cc phn t
kt dnh lin kt gia cc t bo, l nhng cu t gn (ligands)
i vi cc cht integrin ca t bo bch cu, c vai tr rt quan
trng trong s lin kt gia cc t bo lympho v cc t bo bch
cu khc vi mt s t bo trong c cc t bo trnh din
300

khng nguyn (APC) v cc t bo ni m cc 1CAM l thnh

vin c a m t h ln cc Ig.
ICAM1: L mt cu t gn quan trng nht d vi cc in-
tegrin CD lla, CD18 hoc LFA-1. N nhanh chng to cm ng
trn cc t bo ni m b nhim v c vai tr quan trng trong
p ng vim.
ICAM2: Lin tc bc l mc thp ni m.
ICAM3: Ch bc l cc t vo bch cu v c vai tr quan
trng trong s kt dnh gia cc t bo T v cc APC, c bit vi
t bo c tua.
Im m unoglobulin: Cc globulin min dch.
Iccosomes: L cc mnh nh ca mng c bao bc bng cc
phc h min dch, trong phn b cc qu trnh tin trin ca
cc t bo nang c tua ca cc nang lympho.
ICOS: L mt protein c quan h vi CD28. C mt cc t
bo T hot ha c th gip tng cng p ng min dch qua
trung gian t bo T. Protein ny lin kt vi mt cu t gn khc
l LICOS phn vit vi cc phn t B7.
Idiotopes: c coi l mt epitop ca mt dng khng th
ring bit. Mi phn t Ig u c kh nng lin kt vi hng hot
khng th hng ti nhng c im duy nht v c gi l cc
idiotype (mt typ khng th ring bit, idio: c tnh c bit). Mt
idiotyp c to ra t hng lot cc idiotope.
Idiotypic n etw ork: Mng li idiotyp, l tp hp cc th th
nhn bit khng nguyn ca cc t bo lympho hoc ca khng
th c hnh thnh do s tng tc nhn bit min dch ln
nhau gia chng.
Iga, IgP: Th th ca t bo B hoc CD79a, CD79b.
IL: Interleukins.
I m m a tu r e B Cells: Cc t bo B cha chn l nhng t bo
ch mi sp xp li cc gen chui nng, chui nh v vng V v
mi ch bc l IgM b mt (mlgM cha bc l y mlgD).
Im m e d ia te h y p e rs e n s itiv ity reactions: Cc phn ng qu
mn tc th, l nhng phn ng qu mn xy ra tnh theo pht
p ng li khng nguyn l.
Im m u n e clearance: S "khai quang" min dch l hin tng
loi b nhanh chng khng nguyn l xm nhp nh kh nng
tng hp nhanh khng th hnh thnh phc h khng nguyn
- khng th.
 301

Im m u n e complex: Phc h min dch.

Im m une deviation: S phn k min dch, xy ra s p ng
min (lch di vi mt khng nguyn c u th do cc t bo Tj| 1
hoc T||2 m nhim.
Im m un e m odulation: S iu bin min dch, bao gm
nhng bin i khc nhau trong p ng min dch, Immune re
sponse genes (Ir genes). Cc gen p ng min dch, biu hin
tnh da hnh v di truyn trong kim sot cng p ng min
dch i VI mt khng nguyn ring bit. Thc t, tt. c cc
phenotup (biu hin kiu hnh) ca gen Ir l do s lin kt khc
bit ca cc mnh peptit khng nguyn i vi cc phn t MHC
c bit l MHC-II. S thiu ht ca cc gen Ir (Ir gene defect)
thng xy ra nhng khng phi lun lun nh vy, l do mt
kh nng lin kt VI mt peptit khng nguyn n mc khng
thy xut hin p ng min dch ca cc t bo T.
Im m u n e surveillance: S gim st min dch, y l mt
qu trnh c coi l tn ti trong c th pht hin v loi tr
cc khi ung th c thc hin qua trung gian cc t bo lvm-
pho c hiu.
Im m u n e system: H min dch, c m t v cc m, cc t
bo v cc phn t tham gia p ng min dch v i khi c
coi l tng th ca c ch bo v vt ch.
Im m nity: Tnh min dch, l kh nng khng li s nhim
bnh.
Im m u nization : Gy min dch, mt phng php ch ng
to ra p ng min dch thch ng bng cch a mt khng
nguyn l vo c th, phng php ny th hin 2 kiu: gy min
dch ch ng (active) gay min dch th dng (passive immuni
zation) nh a mt lng khng th hoc huyt thanh min
dch vo c th non di v min dch.
Im m u nob lo tting : Chuyn thm min dch. y l k thut
bao gm cc protein dc tch bng din di trn gel poly acryla-
mide (PAGE), sau dc chuyn thm ln mt mng nitrocellu
lose v c pht hin bng s lin kt ca chng vi cc khng
th c hiu c nh du (v d khng th nh du phng x,
cht hunh quang hoc khng th cng hp to phn ng enzym
pht mu c trng).
Im m u n o d eficien cy diseases: Cc bnh thiu ht min dch.
Cc bnh ny c th do di truyn (inherited) hoc c th tip thu
302

c (acquired) trong i sng c th. Cc bnh biu hin mt

kh nng t bo v min dch.
Im m unodiffusion: S khuych tn min dch, l hin tng
khuych tn ca khng th v khng nguyn khi gp nhau s
to ra cung kt ta, nu khng th v khng nguyn c tnh c
hiu tng tc vi nhau. Hin tng ny c ng dng nhn
dng khng th hoc khng nguyn trong k thut Ouchterlong.
Im m u n o e le c tro p h o re sis: in di min dch, l mt k t h u t
trong , cc khng nguyn c phn tn bng in di, sau
c pht hin bng khng th c hiu nh kh nng khuych
tn ca chng.
Im m uno fluo rescence: Min dch hunh quang l mt k
thut pht hin phn t khng nguyn nh s dng cc khng
th nh du bng cht mu hunh quang.
Im m u n o g en etics: Di truyn min dch, l mt kha cnh
nghin cu phn tch di truyn cc khng th khng li cc phn
t a hnh v di truyn nh cc khng nguyn nhm mu, hoc
cc phn t protein ca MHC. Mn hc ny cng dnh cho vic
phn tch di truyn hoc s dng k thut di truyn bt k no
phn tch cc phn t quan trng trong min dch hc.
I m m u n o g lo b u lin domains: Cc khu vc Ig l c tnh
chung cho cc protein thuc h ln cc Ig min dch bao gm cc
khng th, cc th th t bo T, cc phn t MHC v nhiu phn
t tng t ca h min dch cc khu vc min dch bao gm hai
l gp p c duy tr bng mt cu disulfit, cn c gi l np
gp Ig (Immunoglobulin fold). C hai kiu domain Ig ch yu l
cc domain c ( vng khng bin i) vi mt l gp 3 nhnh v
mt l gp 4 nhnh v cc domain V (vng bin i), mi domain
cha thm mt nhnh ngoi.
Im m u n o h isto c h e m istry : Ho m min dch, mt k thut
min dch nhm pht hin cc khng nguyn m t bo bng
cch s dng khng th cng hp enzym c hiu khng nguyn
pht hin di knh hin vi quang hc, knh hin vi hunh
quang hoc knh hin vi in t.
Im m u noligical Ignorance: S yn lng min dch, mt hin
tng t dung np trong , cc t bo lympho phn ng v
khng nguyn ch ca chng u c pht hin trong mt c
th nhng khng Ihy s tn cng ca bnh t min.
Tt c cc bnh t min xy ra khi s yn lng min dch b
ph v.
 303

Im m uno lo gical memory: S ghi nh min ch. l dc

im quan trng ca tnh bo v min dch, khi a mt khng
nguvn vo c th. s p ng min dch tip thu v thch ng s
dc th hin v c ghi nh li trong cc t bo v phn t ca
h min dch. S ghi nh min dch c tnh c hiu cao v c i
sng lu di.
Im m unologically privileged sites: Cc v tr c quyn
min dch. Mt s m t bo mt s v tr trong t bo nh no,
khng gy hin tng thai b mnh ghp. l cc v tr dc
quyn min dch v do hiu qu ca hng ro vt l i vi s di
ng t bo v khng nguyn v do c sn cc cht ha gii ha
tan nh xitokin c kh nng km hm min dch.
Im m un oph ilins: L nhng protein c hot tnh enzym pepti-
dyl - prolyl cis - trans isomerase to lin kt gia cc thuc km
hm min dch cyclosporin A, FK 506 v rapamicin.
I m m u n o p r c ip ita tio n analysis: Phn tch kt ta min
dch l phng php s dng khng th c hiu pht hin cc
protein khng nguyn ho tan hoc protein mng tan trong cht
ty ra (detergent) dc nh du, sau d s dng tip k
thut in di SDS - PAGE pht hin bng phng x t ghi
(autoradiography).
I m m u n o r e c e p to r tyrosine - b ased a c tiv a tio n motifs
(ITAMS): Cc hnh thc hot ha th th min dch da vo ty-
rozin. Cc th th ca t bo T v t bo B lun lin kt vi cc
loi phn t xuyn qua mng c hot tnh Tyrosinekinase. Mi
mt hnh thc ITAM bao gm mt cp YXXL to ra mt khong
trng nh khong 10 axit amin. Chng l cc v tr phot
phoryl ha tyrozin v lm kt hp tysosine kinase vi cc phn
lin kt phot photirozin khc, tham gia vo qu trnh truyn tn
hiu ca th th.
Im m u n o reg u latio n : S diu ha min dch.
I m m u n o su p p re s s iv e drugs: Cc thuc km hm min dch,
c dng hn ch s thi b mnh ghp v cha bnh t
min c tnh.
Im m unotoxin: c t' min dch.
Mt dng khng th c kt hp v ha hc (cng hdp) vi cc
phn t cht c c ngun gc thc vt hoc vi sinh vt c kh
nng nhn bit v lin kt vi khng nguyn dc hiu ca t bo
ung th dit khi u, cng c th di dng thuc km hm
min dch.
304

I n d ir e c t Coombs test: Xt nghim Coomb gin tip, mt

kiu xt nghim trong mt dng huyt thanh cha bit r
khng th c xt nghim bng cch trn vi cc t bo hng
cu bnh thng. Sau ra t bo hng cu v li trn tip theo
vi mt khng th khng Ig. Nu khng th trong huyt thanh
cha bit r lin kt c vi hng cu th s ngng kt do khng
th khng Ig s c xy ra. Trong khi xt nghim Coomb
trc tip s dng khng th khng Ig gy ngng kt cc t bo
hng cu pht hin c hay khng mt dng khng th bao ly
hng cu in vivo trong bnh t min hoc trong p ng min
dch do bt ng khng nguyn nhm mu gia c th m v thai
nhi.
Infectious mononucleosis: Mt bnh gy st do nhim
trng virut Epsteim Barr c km theo ni hch lympho v mt
mi.
In lam m m atio n : Vin sng ty, thut ng ch hin tng tch
ly cht dch, protein huyt tng, cc t bo bch cu b khi
pht bng s tn thng c th, b nhim hoc p ng min
dch ti ch. Hin tng ny c gi l p ng vim (in lam-
matory response), khi cc t bo c chc nng min dch xm
nhp vo m b vim c gi l s thm nhim vim (in-
flammtory infiltrate).
Influenza: Bnh thng hn.
I n n a te im m unity: Tnh min dch bm sinh, l tnh min
dch c sn ngay sau khi mt c th ra i, c mt mi thi im
v khng c kh nng p ng p hn bit c hiu.
Inositol t r i p h o s p h a te (IP3): L sn phm phn hy ca
inositol phospholipid di tc dng ca phospholipase C7. IP3
lm gii phng ion canxi t ni d tr bn trong t bo li ni
cht (endoplasmic reticulum).
Integrin: L nhng protein heterodime trn b mt t bo
tham gia vo s tng tc t bo, t bo v t bo - cht nn gian
bo. Chng c vai tr quan trng trong tng tc kt dnh gia
cc t bo lympho v cc t bo trnh din khng nguyn (APC),
cng nh vai tr di ng cc t bo lympho v t bo bch cu
vo m. Pi - integrin cn gi l khng nguyn rt chm (very late
antigen - VLA) l mt h cc integrin c cc chui Pi, v a to ra
kt dnh gia cc t bo khc v vi cc protein gian bo.
I n te r d i g ita tin g r e ti c u la r Cells: Tng t dendritic Cells.
 305

I n t e r f e r o n s : La n lu in ^ xitokin (cvtokinees) to cho cc t ho

kim h m s n h n ln cua virus.
I n te rf e ro n a: (IFN-a) v interferon \\ (IFN-) tng ng c
bch cu v nguyn bo si (fibroblast) cng nh cc loi t bo
khc, sn xut ra trong khi interferon! 7 (IFN-y) l sn phm ca
cc t bo TCD4* (hl), TCI)8+ v cc t bo NK. IFN-y c tc
dng hot ha khi pht i vi di thc bo (macrophage).
I n te r l e u k in (IL): L thut ng chung cho cc xitokin dc
bch cu sn xut ra trong interleukin-2 (IL-2) l mt xitokin
quan trng nht i vi s pht trien ca p ng min dch
thch ng.
I n tr a c e llu l a r cytokinee staining: Nhum xitokin ni bo l
k thut a thm vo trong t bo mt khng th khng xitokin
c nh du hunh quang.
I n tr a c u t a n e o u s injection: Tim vo da, subcutaneus injec
tion l tim vo di da, intramuscular injection l tim vo
mch mu.
I n v a r i a n t ch ain (Ii): L mt chui peptit khng bin i
tham gia vo vic hng dn v bo v s lin kt ca phn t
MHC lp II vi mnh peptit khng nguyn s c trnh din.
Chui peptit li c COI l phn t bo mu (chaperon) cho qu
trnh lin kt MHC-II peptit khng nguyn.
ISCOMS: L cc phc h kch thch min dch ca khng
nguyn c gi trong cht nn lipit. Cht nn lipit ny ng vai
tr nh mt t cht v cho php khn^ nguyn i vo t bo
cht. Sau khi dung hp lipit VI mng sinh cht t bo.
Isoelectric focusing: in di hi t ng in, din di phn
vng ng in, l k thut in di trong cc phn t protein
di chuyn trong mt gradient pH c to ra bng mt dung dich
cc ampholit. Khi mi mt protein t n mt v tr nht nh
mt pH no trng vi pH im ng in ca protein th n s
khng tch in, khng di chuyn, s hi t ti im ang in
ca chng.
Isotypes: Cc bin dng phn t Immunoglobulin thuc v
cc lp khc nhau bao gm: IgM, IgG, IgA, IgA, IgE, mi chng
c mt chui nng phn bit nhau do cc gen vng c quy nh.
Mt Isotype ca khng th xc nh c ch hiu qu lin kt vi
khng nguyn. Cc chui nng c cc khu vc c khc nhau c
m ha t cc exon 3 ni vi cc v tr V (D) J dc sp xp li.
T cho php mt phn t khng th c mt khu vc V bin i
306

ca chui nng lin kt vi cc Isotype cha vng c khc nhau

to ra s ti t hp soma.
Isotype switching: Khi ng tng hp cc dng Isotype. Mt
khng th u tin c sn xut trong p ng min dch th
dch l IgM. Tuy nhin t bo B c hot ha tip theo s
khi ng tng hp cc khng th Isotype khc nhau nh IgG,
IgA, IgE v.v. Vic khi ng tng hp cc Isotype khng tc ng
vo tnh c hiu ca khng th nhng lm bin i chc nng
gy hiu qu ca khng th v kh nng ny l do s ti t hp
trong qu trnh sp xp li cc vng gen V v cc exon vng c
ca chui nng.
Isotypic exclusion: S loi tr Isotype. M t vic s dng
ch mt chui nh K hoc trong phn t khng th do t bo B
tng hp ra.
J gene segment: Mnh gen ni c tm thy mt s
khong cch 5 ca cc gen c trong Ig v trong locus ca th th
t bo T. Chng hn cc chui TCR v TCR cn c mt mnh
gen D (diversity gene: gen to tnh a dng) c sp xp cung
vi mnh gen J hnh thnh mt exon y vng V.
J a n u s k in a s e s (JAKs): L mt tyrosine kinase c hot ha
bng s kt hp vi cc th th xitokin. Cc kinase ny phot-
phorin ha cc protein nh bit l: cht truyn dn tn hiu
v cc cht hot ha phin m (Signal Transducers and Activa
tors of Transcription - STATs). Cc STAT ny bnh thng c
tm thy trong cytosol nhng s di ng vo nhn t bo khi c
photphorin ha v s hot ha hng lot gen.
Ju n ction al diversity: S a dng cc mnh gen ni (xem
mc gen J)
Killer activatory receptors (KARs): L th th b mt t
bo ca cc t bo NK hoc cc t bo T gy c. Chng l nhng
th th hot ha cc qu trnh dit t bo.
Killer T cell' Danh t chung ch cc t bo gy c
K inin system: Mt dy phn ng enzim ca cc protein bo
tng c to ra do s tn thng t bo, gy nn mt s hin
tng vim, cng bao gm c qu trnh hot mch peptit bra-
dykinin.
C-Kit: Ni v' th th C-Kit c mt trong qu trnh pht trin
cc t bo B v nhng t bo bch cu khc lin quan n mt
yu t t bo ngun nm cc t bo ty xng. Kit c hot ng
protein kyrosine kinase.
 307

Kit: B sinh phm thng c dng trong xt nghim ha

sinh v min dch.
Kupffer cells: L cc thc ho nm gan c chc nng thu
dn rc thi v t bo cht t mu nhng cha r c hot ng
khi ng p ng min dch.
L a n g e r h a n s cells: L nhng thc bo c tua (phagocytic
dendritic cells) c tm thy lp biu b. Chng c th di ng
t biu b n cc hch bch huyt khu vc, chng c bit
ha thnh cc t bo c tua.
Large pre-B cells: Cc t bo tin B kch thc ln thng c
th th tin B v sau ny s mt i khi chuyn dng thnh cc t
bo tin B nh.
LAT: Xem Linker of activatnn in T cells.
Latency: S yn lng. Mt sc> virus khi xm nhp vo t bo
khng nhn ln hoc ti bn v trng thi yn lng. Khi virus
dc ti hot ha v nhn bn chng s gy ra bnh tt.
L ate-phase reaction: Phn ng pha chm: l nhng phn
ng qu mn qua trung gian typ I din r a dai dng v thng di
khng VI thuc antihistamine.
Lentiviruses: L mt nhm cc retrovirus (virus cha ge-
nome ARN) bao gm HIV gy bnh AIDS ngi. Chng c thi
gian bnh lu di.
Leprosy: Bnh phong (hi) do vi khun Mycchacterium leprae
gy ra nhiu dng bnh phong. C 2 dng phong khc nhau l:
le p ro m a to u s leprosy biu hin kh nng nhn ln rt cao ca
vi khun gy bnh v sn xut rt nhiu khng th m khng
gy p ng min dch qua trung gian t bo. Dng th 2 l
tu b e rc u lo id leprosy trong bnh nhn hu nh khng c
khng th hoc rt t khng th nhng m tn thng v c
biu hin mnh tnh min dch qua trung gian t bo.
Leukemia: Ung th bch cu, mt dng ung th c tnh tru
hin s lng rt cao cc t bo c tnh trong mu. Bnh c th
biu hin cc t bo lympho, cc t bo ty myelocytic hoc
monocytic.
Leukocvte: Thut ng ch cc t bo bch cu ni chung bao
gm lymphocyte, polymorphonuclear leukocytes v monocytes.
Leukocyte com m on antigen: Cm bit ha CD45 chung cho
bch cu
308

Leuko cy te fu n ctio n al a n tig e n s hoc LFAs: L nhng phn

t kt dnh. Chng hn LFA1 l mt 2 integrin; LFA2 l mt
thnh vin ca h ln Immunoglobulin; LFA3 l CD58. LFA1 c
vai tr quan trng lm kt dnh t bo T vi cc t bo ni m v
cc t bo trnh din khng nguvn.
Leukocytosis: Bnh biu hin tng s lng t bo bch cu
trong mu. Bnh ny ni chung xy ra trong trng hdp nhim
trng c tnh.
L eu k otrien: L nhng cht ha gii c bn cht lipit gy
vim. Cc cht ny bt ngun t axit arachidonic. Chng c
cc i thc bo v nhng t bo khc sn xut ra.
LICOS: L mt cu t gn (ligand) ca ICOS, mt protein c
lin quan n CD28 do cc t bo T hot ha c kh nng gy
tng hp chng nhng t bo c tua hot ha hoc cc t bo
B.
L ight zone: Xem germinal centers.
L in e a r epitope: Xem continuous epitope.
Link age disequiliriu m : S khng cn bng trong lin kt,
ni v cc len nhng locus ca phc h MHC c di truyn
lin kt vi nhau nhiu hn so vi d bo theo tn s lin kt ca
mi c th.
L in k ed recognition: S nhn bit lin kt, cc epitop c t
bo B v t bo T b tr cng c nhn bit lin kt vi nhau
hot ha t bo B.
L in k e r o f a c tiv a tio n in T cells (LAT): L mt dng protein
thch ng nm trong t bo cht c cha mt s gc tyrosine. Cc
gc ny c th c photphorin ha bng tyrosine kinase ZAP-70.
Protein ny lin kt vi tp hp lipid mng v iu ha h thp
cc s kin truyn tn hiu trong s hot ha t bo T.
Low-zone tolerance: S dung np vng thp (xem High-zone
tolerance).
LP S -binding p ro te in (LPB): Protein lin kt vi LPS
(Lipopolysaccharide-ni c t thnh t bo vi khun), LPS trc
khi tng tc vi CD14 ca i thc bo, n cn lin kt vi LPB.
L-selectin: L mt phn t kt dnh thuc h selectin dc
tm thy trong cc t bo Lympho. L-selectin lin kt vi CD34
v GlyCAM-1 nm trn cc mao mch xen k cc t bo ni m
gip khi ng s di chuyn ca cc t bo Lympho s khai (na-
 309

V(* l y m p h o c y t e s ) (i v o inn l ympl o. 1,-S(*l(*rtin c n g (lc ^1 l

* " D 62 L .

Lyme disease: Bnh nlim trng mn tnh xon khun Bor-

relia burgdorferi, xoan khun ny c th trn thot s p ng
Tiin dch.
Lymph: Dch ngoi bo c tch ly trong cc m v c
vn chuyn theo mch lympho tr v h thng bch huyt i qua
ng ngc vo mu.
Lym ph nodes: Hch bch huyt, c quan lympho th cp
hoc ngoi vi.
L y m p h a tic system: H tlg lympho, bao gm cc knh
lympho v m t bo gm cc hch lvmpho, m Pcyer v nhng
thnh phn lvmpho c t chc trong lch.
L y m p h a tic vessels hoc lymphatics: Cc mao mch lym
pho cha dch lympho vn chuyn vo h thng lympho.
Lym phoblast: Mt dng t bo lympho kch thc ln c qu
trnh tng hp ARN v protein mnh m.
Lym phocytes: Cc t bo lympho bt ngun t ty xng v
c bit ha thanh 2 dng lympho B v lympho T.
L ym p hocyte function-associated antigens: Xem Leuko
cyte functional antigens.
L ym ph ocy te r e c e p to r rep erto ire: Kho d tr th th ca
t bo lympho, l tng th tt c cc th th khng nguyn nm
trn t bo B v T ca c th.
L ym phocytic ch o rio m en in g itis virus (LCMV): L mt
dng virus gy bnh vim mng no chut v i khi xy ra
ngi. Vi khun ny c dng trong nghin cu thc nghim.
L ym p hoid d e n d r it ic cells: Nhng t bo bch cu c tua bt
ngun t cc m lympho, khi bt ngun t cc t bo myeloid th
dc gi l t bo tua dng tu myeloid d e n d r itic cells.
L ym ph oid organs: Cc c quan lympho.
Lym phokine: L nhng xitokin c sn xut t cc t bo
lympho.
Lym phom as: Cc khi u (ung th) ca cc t bo lympho,
nm trong cc m lympho hoc trong cc m t bo khc nhng
khng i vo mu. C rt nhiu kiu lymphomas biu hin s
bin dng cc giai on phat trin khc nhau ca cc dng t bo
lympho B v T.
310

Lymphopoiesis: S bit ha cc t bo bt ngun t mt t

tin chung ca dng lympho.
L y m p h o to x in (LT): c t lympho, chng hn yu t hoi t
ung th TNF-P (P-tumor necrosis factor), mt xitokin do cc t
bo TCD4 vim tit ra nhm gy c trc tip i vi mt s bin
dng t bo.
Lyn: Xem tyrosine kinase.
Lysosomes: Cc bo quan c tnh axit cha rt nhiu enzim
thy phn. Cc khng nguyn l khi b thc bo c bao bc
trong bc mng endosome s dung hp vi cc th Iysosome v b
tiu ha.
Lytic granules: Cc ht phn gii cha perforin v granzyme
c c tnh quan trng ca nhng t bo T gy c.
M cells: Nhng t bo c np gp lin kt vi cc m lympho
ca rut (gut-associated lymphoid tissue-GALT) tip nhn cc
khng nguyn v tc nhn gy bnh. Chng cng c th l con
ng ly nhim HIV.
Mac 1: Cht kt dnh integrin CD1 lb : CD18 hoc CR2
Macroglobulin: Nhng globulin c trng lng phn t ln,
thng l cc protein bo tng bao gm IgM v a2-
macroglobulin.
M a c ro p h a s e activation: S hot ha i thc bo, ng vai
tr quan trng trong vic kim sot nhim trng v cng gy ra
s tn thng cc m xung quanh.
M a c ro p h a s e m a n n o se recep to r: Th th nhn bit mari
nse ca i thc bo.
M acropinocytosis: S ung bo mc cao, c thc hin
bi cc t bo c tua (dendritic cells).
MadCAM-1: Mt dng phn t kt dnh ca cc t bo nim
mc cn gi l mucosal adhesine, c nhn bit bi cc protein
b mt ca t bo lympho
Major basic protein: Mt dng protein base ch yu c cc
bch cu a axit (Eosinophils) tit ra nhm khi ng cc t bo
mast, gy v cc ht trong t bo ny gii phng ra histamin.
M ajor h isto c o m p atib ility com plex (MHC): Phc h ph
hp m ch yu, ngi c gi l HLA (Human Leukocyte An
tigen).
O riginal an tig e n ic sin: S vi phm khng nguyn gc, m t
kh nng p ng min dch khng th ca ngi i vi nhng
 311

quyt nh khng nguyn (epitope) b sai lch gia chng virus

nguyn gc v cc virus c mi quan h trong khi b qua epitope
(' tnh sinh min dch cao.
Panning: gn lc, cc di qun th t bo lympho c th c
phn lp bng cch gn lc trn cc a petri ph cc khng th
n dng chng li cc du hiu (du n-marker) b mt ca mi
loi t bo t c th tm ra nhng qun th lympho ring
bit lin kt c hiu.
P a r a c o r tic a l a r e a hoc P aracortex: L mt vng cha t
bo T ca hch bch huyt nm ngay bn di phn nang ca v
m y ch yu bo gm t bo B, vng cn v.
P arasites: Th k sinh
P aro x y sm al n o c tu r n a l h e m o g lo b in u ria (PNH): L bnh
thiu ht cc protein iu hpa b th vi phm vo con ng
hot ha dn n hin tng tan mu tc thi.
P a r tia l a g o n ist peptide: Xem altered peptide ligands: Cc
peptit ng vn mt phn
Passive h e m a g g lu tin a ti 3n: S ngng kt hng cu th ng
l k thut pht hin khng th trong hng cu c bao
ph khng nguyn v cc khng th c pht hin s gy
ngng kt cc t bo hng ru ph khng nguyn.
Passive im m unizatio n. Gy min dch th ng, bng cch
tim khng th hoc khng huyt thanh vo c th tip nhn
cha h bit p ng min dch (i lp VI gy min dch ch
ng c thc hin cc c th bit p ng min dch).
P a th o g e n ic m ic ro o rg a n is m hoc pathogens: Cc vi sinh
vt gy bnh.
Pathology: Mn bnh, l hc l mt khoa hc nghin cu bnh
P a t t e r n r e c o g n itio n re c e p to rs (PRRs): Cc th th nhn
dng mu, thut ng ing ch cc th th lin kt vi cc
mu phn t c quan h vi vi sinh vt gy bnh.
P a t t e r n re c o g n itio n molecules: L cc phn t th th ca
h min dch bm sinh dng nhn bit b mt khng nguyn
ca vi sinh vt gy bnh.
PECAM (CD31). Mt phn t kt dnh t bo c tm thy
cc t bo lympho v khp ni ca cc t bo biu m. S tng
tc gia cc CD31 gip cho cc t bo bch cu ri khi mao
mch mu v i vo m.
312

P e n ta d ecacatech o l: L mt cht ha hc trong l cy

Thng xun (Dichroa febrfuga) c c t, cht ny gy ra hin
tng qu mn do nhim cht c ca cy thng xun.
P e n tra x in s : Mt dng lectin c bn cht protein bao gm 5
tiu n v giYig nhau. V d protein phn ng c v mt s pro
tein huyt thanh amyloid cng l nhng pentraxin.
Perforin: L mt protein to ra l thng ca mng khi c
polyme ha, c ngha quan trng trong c cht dit t ho vi
khun. Perforin c cc t ba T gy c v NK tit ra khi cc
t bo ny tip xc vi cc t bo ch c hiu.
P e r l a r t e r i o l a r lym phoid s h e a th (PALs): Phn bn trong
ca vng li l lch cha ch yu t bo T.
P e r ip h e r i a l blood m o n o n u c le a r cells (PBMN): Cc t bo
n nhn ca mu ngoi vi bao gm cc lympho v cc mono i
vo mu ngoi vi.
P e r i p h e r a l or sec o n d a ry lym phoid organ: Cc c quan
lympho ngoi vi hoc th cp: hch bch huyt, lch, cc m lym-
pho, nim mc.
P e r i p h e r a l tolerance: Dung np ngoi vi, mt qu trnh tip
nhn cc t bo lympho trng thnh m ngoi vi tri vi dung
np trung ng (central tolerance) l qu trnh tip nhn cc t
bo lympho cha chn trong qu trnh pht trien ca chng.
P e y e r s patches: m Peyer, l tp hp cc t bo lympho
dc theo rut non
P h a g e d isplay library: Th vin biu hin trn thc khun
th, mt k thut c s dng pht trin nhng khng th
mi c tnh c hiu bt k da vo qu trnh tch dng (cloning)
cc gen m ha cho vng V ca Immunoglobulin c biu hin
trn cc phage.
Phagocytosis: S n bo, m t qu trnh nut cc vt th l
ca cc t bo thc bo. V d i thc bo, bch cu trung tnh.
Cc vt th khi c nut vo nhng t bo ny c th dc bc
li bng cc bc mng (vesicle) c g1 l phagosome. Tip theo
cc phagosome ny s dung hp vi mt hoc nhiu lisosome
hnh thnh mt th gi l phagolisome. Trong th ny cc tc
nhn gy bnh hoc vt th l s b tiu ha, b ph hy bng cc
enzim ca lisosome.
 313

P h o sp h alid y lin o sito l b isp h o sp h ate ( P P 2). L mt phot-

)hol ipi d l i n kt m n g , hi p h n h y b a n g p h o s p h o l i p a s e C-y t o
*a cc phana t t.n hiu (liacyl^lycerol v Inositol trisphosphato.
P h o s p h o l i p a s e C-y: La mt enzim (uan trng truyn tn
hiu. N (lc hot ha hxni protoi tyrosine kinase. V phn
mnh tyrosine kinase li (lc hot ha bng s kt hp gia
khng nguyn v th th ca t bo.
Plasma: L mt cht dch ca mu cn gi l huyt tng.
P la sm a cells: T bo plasma l dng bit ha cui cng ca t
bo B ch yu c chc nng tit khng th. Cc t bo plasma
dc tm thy trong phn ty ca hch lympho. trong phn li
mu d ca lch v c ty xng.
Plasm ablast: Mt dng t bo B nm trong hch lympho c
nhiu c im ca t bo plasma.
P la te le t a c tiv a tin g factor (PAF): Yu t hot ha tiu cu,
l cht ha gii lipid tham gia vo dy chuyn ng mu.
Platelets: L cc tiu cu c vai tr quan trng trong ng
mu c hnh thnh t cc t bo c nhn khng l (megakar
yocytes), cn c tn l thrombocyte.
P-nucleotide: L trnh t nucleotide c tm thy cc vng
ni gia cc mnh gen ca cc gen vng V m ha cho cc th
th. P-nucleotide c lp li o ngc ti vng cui ca nhng
mnh gen ln cn to ra nhng dng cp tc gip cho qu trnh
ti t hp. Chng c th hnh thnh nhng trnh t palindromic
nn gi l P-nucleotide.
Poison Ivy: Cy Thng xun c l cha cht c pentadeca-
catechol (tn khoa hc: Dichroa febrifuca Lour).
Polyclonal activation: S hot ha a dng, l qu trnh
hot ha li ko theo nhiu dng (nhiu clone) t bo khc nhau.
Cht mitogen (cht kch thch phn bo) gy ra hin tng hot
ha nhiu dng t bo c gi l polyclonal mitogens.
Polygenic: Ni v h thng gen m ha cho MHC cha dng
mt s locus gen. Nhng MHC ny u c chc nng ging nhau
v mang tnh a hnh v c nhiu alen trn mi mt locus.
Poly-ig recep to r: Th th lin kt vi cc Ig polyme c bit
l IgA. Th th ny nm mng t bo lp biu m.
P o ly m erase c h a i n reactio n (PCR): Phn ng trng hp
chui dng nhn mt on gen hoc phn t ADN.
314

P olym orphism : Tnh a hnh, s tn ti nhiu dng khc

nhau ca mt vt. Tnh a hnh di truyn l s bin dng ca
mt locus gen trong cc bin dng pht sinh tn s ln hdn
1%. Phc h MHC l mt n gen a hnh nht ngi.
P o ly m o r p h o n u c le a r leulcocytes: Cc bch cu nhn a
hnh, bch cu nhn nhiu thy v c ht.
Polyspecificity: Tnh a c hiu, mt s khng th c kh
nng lin kt vi nhiu khng nguyn khc nhau, c tnh a c
hiu hoc tnh a phn ng.
Posotive selection: S chn lc dng tnh ni v qu trnh
chn dng t bo T tuyn c. Ch cc t bo T c th th nhn
bit cc khng nguyn c trnh din bi chnh cc MHC ca
bn thn mi c th chn trng thnh Thymus (tuyn c)
Pre-B.Cell r e c e p t o r hoc Pre-B.Cell r e c e p t o r complex:
Th th hoc phc h th th ca t bo tin B. l s biu
hin (bc l) ca t nht 5 loi protein lm cho t bo tin B i
vo chu trnh t bo, lm ng li cc gen RAG, v phn hy
cc protein ca gen ARG (Recombination Activating Genes: cc
gen hot ha ti t hp).
P r e c ip i n reaction: Phn ng kt ta, mt k thut nh
lng s sn xut khng th. S lng khng th c xc
nh theo s lng cc kt ta nhn c vi s lng khng
nguyn c nh. Phn ng kt ta cng c th c dng
nh r ha tr khng nguyn v cc vng d tha khng th
hoc khng nguyn trong cc hn hp khng nguyn v khng
th.
P red n iso n e: L mt steroid tng hp c hot ng khng
vim v km hm min dch, dng cha bnh t min bnh
ung th bch cu v x l thi ghp c tnh trong cy ghp m.
Pre-T-Cell receptor: Th th t bo tin T, thng l chui a
ca t bo tin T, cc c bo - Thymocyte thay th cho cc chui
p trong giai on u ca s pht trin ca t bo T tp hp li
thnh th th t bo tin T.
P r im a r y focus: S hi t s khai, hi t s cp, ni v qu
trnh hot ha t bo B c hnh thnh vng bao quanh gia
cc vng cha t bo T v t bo B ca m lympho. y c s
tng tc gia cc t bo T v t bo T t t bo B c th
bit ha thnh t bo plasma tit khng th.
 315

P r i m a r y follicle: Nang S cp cha cc t bo B lu tr, l v

tr s hnh thnh cc trung tam mm v cc nang th cp.
P r im a r y im m m u n e response: p ng mi (lch s cp,
c th hin khi gy min (lch s cp i vi mt khng
nguyn.
P r im a r y interactio n : S tng tc s cp, l s lin kt ca
cc phn t k h n g th vi khng nguycn, phn vit vi s tng
tc th cp (secondary interaction) trong c hin tng kt
ta ca cc k h n g nguyn ha tan hoc s ngng kt ca cc ht
khng nguyn.
P r im a r y lym pho id organ: C quan lympho s cp, xem c
quan lympho trun g ng (central lymphoid organ).
Priming: Lm mi, to mi, s to mi cho cc t bo lympho
s khai cha h tip xc vi khng nguyn s xy ra khi khng
nguyn c trnh din cho chng dng to ra p ng min
dch. Cc t bo c khi ng nh vy s bit ha thnh dng
t bo hiu qu (effector cells) hoc es bo ghi nh (memory cells)
c kh nng to p ng min dch th cp v p ng tip theo.
Pro-B-Cells: Cc t bo khi thy B, biu hin cc protein
ch th b mt, nhng cha c s sp xp li cc gen chui nng.
P r o d u c tiv e r e a r r a n g e m e n ts : S sp xp li sn phm, mt
chui th th bt k ca t bo lympho c sp xp li theo hai
cch khc nhau: sp xp li sn phm v sp xp li khng to
ra sn phm, sp xp li sn phm l to ra khung c chnh
xc di vi mt th th theo yu cu.
P ro g enitor: Nhng t bo khi thy, l nhng t bo
bit ha hn t t bo ngun ty xng (stem cells) thnh tng
qun th cc t bo mu chn v mt i kh nng t bin i
tr li ging nh t bo ngun ty xng.
Programme! cell death: Cht theo chng trnh, xem apop-
tosis.
Proferdin: Xem yu t p, mt yu t' tham gia vo qu trnh
hot ha b th theo con ng bn cnh (alternative pathway).
P ro sta g la n d in : L mt sn phm bin i ca lipit bt ngun
t axit arachidonic, c nhiu hiu qu di vi hng lot m t
bo, bao gm cc hot ng gy vim.
P roteasom e: Mt vi th bao gm nhiu tiu dn v cha cc
protease tham gia phn hy cc protein ni bo. Cc peptit ni
sinh b phn hy trong proteasome s c lin kt vi MHC-I
316

trnh din khng nguyn. Hai tiu n v ca protea-some c

cm ng vi interferon (IFN) c m ha trong cc dm gen ca
MHC.
P ro tectin: (CD59) l mt protein b mt t bo, gip cho t
bo vt ch bo v khi tc dng gy tn thng ca b th. N
ngn cn vic hnh thnh phc h tn cng mng (MAC) bng
cch km hm s lin kt ca C8 v C9 vo phc h C5b, C6, C7.
P ro te c tiv e Im m unity: Trnh min dch, l s khng
chng li nhim trng c hiu, gy nhim trng hoc tim
chng.
P r o te i n A: Mt loi protin ca thnh t bo t cu vng
(Staphylococcus aureus), lin kt c hiu VI Fe ca IgG, gip
cho vi khun khi tc ng opsonin ha ca IgG v ngn cn con
ng hot ha b th.
P r o te i n k in a se C: (PKC) l mt h enzym serine/ thereonine
kinase c hot ha bng diacylglycerol v ion canxi. Qu trnh
hot ha ny l kt qu ca s truyn tn hiu nh nhiu th th
khc nhau.
P r o te i n tiro sin e kinase: L enzym lm kt hp nhm pht
pht vo cc gc tyrosine, c vai tr quan trng trong qu trnh
truyn tn hiu v iu ha s sinh trng t bo. Hot ng ca
protein tyrosine kinase li c iu ha bng protein tyrosine
phosphatase.
P ro to oncogene: Gen tin ung th, l cc gen kim sot v
iu ha qu trnh sinh trng. Khi cc gen ny b t bin s
gy bin dng c tnh t bo, dn n ung th (xem thm onco
gene).
P ro viru s: L mt dng ADN ca retrovirus khi ci vo genom
ca vt ch, n c th gi li s bt hot phin m lu di.
P-selectin: Xem selectin.
P-Ta: xem pre - T - cell receptor.
P u lm o n a r y s u rf a c to m t A a n d D proteins: Cc protein b
mt A v D ca phi l nhng lectin h pentraxin c vai tr quan
trng trong p ng min dch pha c'p.
Purin nucleotide phosphorylase (PNP) deficiency: S
thiu ht purin nucleotit photphprylaza, s thiu ht ny gy ra
thiu ht min dch c dnh, gy ra s tch ly purin nucleotit
gy c cho s pht trin t bo T.
 31 7

Pus: M, l hn hp cc mnh v t l)o v xc bch cu trung

tnh c mt cc vt th ng v vim p xe (abscesses) b n h i m
khun ngoi bo (v d cc vi khun gy m xanh Pseudomonas
aoruginosa).
Pyogenic bacteria: Cc vi khun gy m, l nhng VI khun
c v bc ln gv, kh khn cho qu trnh thc bo khi nhim vo
cc vt thng thng gy ra m. Cc vi khun ny thng gy
t vong cho tr nh v hin nay cn gy nhim trng m cho c
ngi gi.
Rulel2/23: 1jUi ny ni rng cc on gen ca khng th hay
th th t bo T c th c lin kt vi nhau ch nu mt on
c mt trnh t tn hiu nhn bit vi mt on cch gm 12 cp
base v on kia cha mt on cch gm 23 cp base.
Rac: xem cc phn t protein G nh (small G proteins)
R a d ia tio n bone marrovv chimeras: Vt ghp ty xng b
chiu x, l cc con chut b chiu x nng v sau c
ghp cc t bo tu xng ca mt dng chut khc, do d cc t
bo bch cu s khc bit v mt di truyn vi mi trng chng
pht trin. Nhng con chut ghp ny c vai tr quan trng
trong nghin cu s pht trin cc t bo lympho.
R a d io im m u n o a s sa y (RIA): Xt nghim min dch phng x.
S tng tc khng nguyn- khng th c th c nghin cu
nh xt nghim min dch phng x trong khng nguyn hay
khng th c nh du bng hot ng phng x. Mt khng
nguyn hay mt khng th khng nh du s c dnh vo mt
cht h tr cng chng hn nh b mt nha, v t l khng th
hoc khng nguyn nh du c duy tr trn b mt s
c xc nh o s lin kt.
Raf: xem cc phn t protein G nh (small G proteins).
RAG: Cc gen hot ho s ti t hp RAG-1 v RAG-2 m
ho cho protein RAG-1 v RAG-2. y l nhng protein quan
trng i vi s sp xp li cc gen th th. Chut thiu c hai
loi gen ny khng th to ra cc th th do vy khng c cc t
bo lympho.
Rapam ycin: (hoc sirolimus) L thuc c ch min dch c tc
dng loi b hot ng ca cht tit t bo.
Ras: xem cc phn t protein G nh (small G proteins).
R e a r r a n g e m e n t: S sp xp li, s biu hin cc th th
khng nguyn i hi s sp xp li cc on gen trong qu trnh
318

pht trin lympho. Trnh t vng V c biu hin l to nn t

s sp xp li cc on gen.
R e c e p to r editing: Sa i th th, s thay th ca mt chui
nh trong th th khng nguyn t phn ng trn t bo B cha
trng thnh bng mt chui nh cha qua s t phn ng c
gi l s sa i th th iu ny cng c xy ra vi chui nng.
R eceptor associated tyrosine kinase: Tyrosine kinase kt
hp th th. Cc th th k hng nguyn ca lympho lin kt VI
th th lin kt tyrosine kinase thnh phn chnh ca h Src th
th ny lin kt vi ui th th khng nguyn thng qua cc
vng SH2 ca chng.
R eceptor- m e d ia te d endocytosis: Thc bo qua trung gian
th th l s nut vo trong cc th thc bo cha cc phn t
lin kt vi cc th th b mt. Cc k hng nguyn lin kt VI
cc th th t bo B c thc bo nh qu trnh ny.
Reccessive le th al genes: Cc gen ln gy cht m ho cho
mt protein cn thit cho ngi hoc ng vt pht trien n tui
trng thnh. Khi c hai bn sao b thiu st, ngi hoc ng
vt s cht ngay trong t cung hoc ngay sau sinh.
Trong bt k trng hp m cc t bo hoc m c cy ghp,
chng s n t th cho v c cy vo trong t h n h n
(recepient) hay vt ch.
R ecom bination activating genes: Cc gen hot ho s ti
t hp: xem RAG-1 v RAG-2.
R eco m b in a tio n signal sequences_ RSSs: Cc trnh t tn
hiu ti t hp l cc on ADN ngn nm bn cnh cc on
gen c ti sp xp sn sinh mt exon vng V. Chng
lun cha mt on by hoc on mi bo th phn bit nhau
nh 12 hoc 23 cp base. Cc on gen ch c t hp vi nhau
nu mt on nm cnh mt RSS cha on cch gm 12 cp
base cn on kia nm cnh mt RSS cha on cch gm 23 cp
base_ quy tc 12/23 ca s ni ghp cc on gen.
Red pulp: Phn ty l vng khng lympho trong l lch
cha cc t bo hng cu b ph hu c gi l phn tu .
Reed- S t e r n b e r g cells: Cc t bo Reed- Sternberg l cc t
bo B ln c tnh xut hin trong bnh ung th Hodgkin.
R e g u la to r o r s u p p re s s o r T cells: Cc t bo T iu ho hay
p ch l cc t bo c th c ch p ng t bo T.
R e s p ir a to r y burst: S bng n h hp. Vic cc t bo bch
cu trung tnh hoc i thc bo thu nht dc cc phn dc
 319

opsonin ho s kch thch bin i chuyn ho trong t bo gi l

bng n h hp. Diu ny s (lan ti s san xuat hng lot cc
cht trung gian.
R e s p ir a to r y syncytial virus (RSV): Virus hp bo h hp l
mt tc nhn gy bnh ngi. N l mt nguyn nhn gy bnh
ph bin trong nhim vng ngc trm trng tr em nh, thng
di km vi kh th, v c cc bnh nhn suy yu min dch v
bnh nhn AIDS.
Rev P ro te in l sn phm gen rev ca virus gy suy gim
min dch ngi (human immunodeficiency virus HIV). Protein
Rev ny s thc y s truyn ARN virus t nhn ra t bo cht
trong qu trnh nhn ln ca virus.
Reverse tra n s c rip ta s e : Enzyme p h in m ngc l mt
thnh phn cn thit ca retrovirus v n chuyn h gen ARN
thnh ADN trc khi tch hp vo ADN ca t bo ch. Enzyme
sao chp ngc cng cho php cc trnh t ARN c chuyn
thnh ADN b sung (complementary DNA cDNA), bi vy n
dc tch dng v tr thnh mt tc nhn quan trng i vi
sinh hc phn t.
R everse tra n s c r ip ta s e - polym erase c h a in re a c tio n (RT-
PCR): Phn ng chui trng hp- enzyme phin m ngc c
s dng khuych i cc trnh t ARN. Enzyme phin m
ngc c s dng chuyn cc trnh t ARN thnh cc trnh
t ADN b sung (cDNA), n lt n s c khuych i nh
PCR.
R hesus/Rh blood gro up antigen: Khng nguyn nhm mu
Rhesus l mt khng nguyn mng t bo hng cu c th thy
trn b mt t bo hng cu ca kh Rhesus. Cc khng nguyn
chng li Rh khng lm ngng kt cc t bo hng cu ngi,
do khng th chng li Rh c th pht hin nh s dng mt
php th Coombs.
R h e u m a tic fever: St thp khp gy ra do cc khng th
c kch thch bi s nhim vi mt s loi Streptococcus. Cc
khng th ny s khng cho vi cc khng nguyn ca thn,
khp v tim.
R h e u m a to id arth ritis: Chng vim khp dng thp l mt
bnh sng khp thng gp c th do mt phn ng t min.
Bnh ny lin quan n s sn xut cc nhn t thp khp, mt
320

khng th IgM chng IgG m c th c to ra trong cc phn

ng min dch bnh thng.
S a n d w ic h ELISA: K thut bnh kp ELISA s dng khng
th lin kt vi b mt bt gi protein bng cch lin kt vi
epitope ca n. Protein c bt gi ny sau s c pht hin
nh mt khng th lin kt enzyme c hiu cho mt epitope
khc trn b mt phn t protein. iu ny to ra mt php
kim tra c tnh c hiu cao.
S c a t c h a r d analysis: Phn tch Scatchard l mt phn tch
ton hc s lin kt cn bng cho php i lc v ho tr ca s
tng tc cht gn - th th c th c xc nh.
S c a v e n g e r receptors: Cc th th thu dn khng nguyn c
trn trn b mt cc i thc bo v cc t bo khc lin kt vi
hng lot cht gn thi b (khng nguyn) v loi b chng ra
khi dng mu. Cc t bo Kuffer trong gan c bit c nhiu cc
th th ny.
SCID, seid: xem severe combined immunodeficiency.
SDS- PAGE l tn vit tt thng gp ca in di trn gel
polyacrylamide (polyacrylamide gel electrophoresis_ PAGE) i
vi cc protein c ho tan trong cht ty natri dodecyl sulfate
(sodium dodecyl sulfate_ SDS). K thut ny c s dng rng
ri m t protein c bit l sau khi nh du v ngng kt
min dch.
S e c o n d a ry a n tib o d y response: Cc phn ng khng th
th cp l phn ng khng th c cm ng do s tim ln th
hai hay tim tng cng khng nguyn tc l gy min dch th
cp (secondary immunization). Phn ng min dch bc hai s
khi ng nhanh chng hn sau khi tim khng nguyn, t
c mc cao hn, c i lc cao hn phn ng bc nht v ch
yu l gm cc khng th IgG. Bi vy, phn ng i vi mi ln
gy min dch li tng ln v cng , v cc p ng ln th
hai , th ba v nhng ln tip sau l c mc tng dn.
S econd se t rejection: Thi b b th cp. Khi th nhn ca
m hay c quan u tin loi b phn cy ghp th m ghp
th hai t cng mt th cho y s b loi b nhanh chng hn v
vi mt cng mnh hn nhiu. Hin tng ny c gi l s
thi b b th cp.
Co - s tim u la to r y signal: Tn hiu ng kch thch cn thit
cho s hot ho lympho thng c gi l mt tn hiu cp hai,
vi tn hiu th nht bt ngun t s lin kt khng nguyn vi
 :V2\

mt th th klng nguyn, c hai tn hiu ny du cn thit cho

s hot ho ca hu ht cc lyrnpho.
S e c o n d a ry in teraction s: Tng tc th c) (xem tng tc
s cp- primary interactions).
S e c re to ry com ponent: Thnh phn tit c lin kt vi cc
khng th IgA trong qu trnh tit ca c th l mt on cn li
ca th th poly- Ig lin kt vi IgA sau khi vn chuyn qua t
bo biu b.
Selected: Mt t bo coi l c chn lc bi khng nguyn
khi cc th th ca n lin kt v khng nguyn d. Nu kt qu
l t bo bt u tng sinh, th iu ny c g 1 l chn lc
dng, v t bo ny s to nn mt dng; nu kt qu ca vic
lin kt khng nguyn l t bo b cht th iu ny c gi l
chn lc dng m tnh hay loi b dng.
Selectin: L mt dng lectin thuc h cc phn t lin kt b
mt t bo ca cc t bo bch cu v cc t bo ni m m lin
kt vi cc phn ng trn phn t glycoprotein c cc c tnh
ging mucin.
Self antigens: Cc t khng nguyn (autoantigen). Cc
khng nguyn trong c th mi c th thng dc gi l t
khng nguyn. Cc t bo lympho c phn ng VI cc t
khng nguyn trong sut giai on cha trng thnh ca
chng, v nhng t bao no thc s phn ng vi cc t khng
nguyn b cht theo chng trnh (apoptosis).
Self tolerance: S dung np bn thn mt c th l s mt
ng i vi mt khng nguyn khi khng nguyn ny c to ra
bi chnh cc m ca n. S dung np ny c gi l s t dung
np. Xem thm s dung np (tolerance).
Sensitization: To ra nhy cm. Cc phn ng d ng i hi
s gy min dch trc hay l s to ra nhy cm vi cc
cht gy d ng kch thch cc phn ng nhy bn. Cc phn ng
d ng ch xy ra cc c th c nhy cm (sensitized).
Sepsis: S nhim trng l s ly nhim vo dng mu. Hin
tng ny rt nghim trng v thng gy cht, s ly nhim
vo dng mu ca cc vi khun Gram m s khi ng shock
nhim trng do s gii phng cht tit t bo TNF- a .
S e q u en ce motif: Mt mu trnh t l mt kiu cc nucleotide
hay cc axit amin nm trong cc gen hoc cc protein khc nhau
m thng c nhng chc nng lin quan. Cc mu trnh t
quan st thy trong cc peptide lin kt vi mt glycoprotein
322

MHC c bit l ph thuc vo yu cu i vi cc axit amin c

bit t c s lin kt vi phn t MHC .
S eroconversion: S chuyn i huyt t h a n h l mt pha ca
s ly nhim khi cc khng th chng li tc nhn gy nhim ln
u tin c pht hin ra trong mu.
Serology: Huyt thanh hc s s dng khng th kim tra
v o c khng nguyn bng cch dng cc php th huyt
thanh (serological assays) c gi nh vy bi v cc php th
ny ban u c tin hnh vi huyt thanh, phn dch cn li
mu ng, t cc c th c gy min dch.
S erotonin: Cht ha gii trung gian. Cc t bo ph chut
nht cha cht ha gii trung gian tan, kch thc nh trong cc
ht ca chng.
Serotype: Typ huyt thanh. Cc dng vi khun khc nhau
cng nh cc tc nhn gy bnh khc i khi c th c phn
bit nh cc typ huyt thanh ca chng tc l kh nng mt
huyt thanh min dch lm ngng kt hay ph hu mt s' chng
vi khun ny ch khng phi l chng khc.
Serpin: l mt h ln cc cht c ch proteaza kiu serin.
Serum: Huyt thanh l phn dch cn li ca mu ng.
S e r u m sickness: m huyt thanh, hin tng xy ra khi
huyt thanh hoc protein huyt thanh ngoi lai c tim vo
mt ngi no . Hin tng ny l do s hnh thnh cc phc
h min dch gia protein c tim vo v cc khng th c
hnh thnh chng li n. iu ny c m t qua st,
bnh than v vim thn.
Severe co m b in ed im m u n e deficiency (SCID): Suy gim
min dch kt hp nghim trng l mt bnh suy gim min dch
trong c khng th ln p ng t bo T u khng c. iu
ny thng l kt qu ca s thiu ht t bo T. t bin scid
cng to nn bnh ny chut nht.
SH2 domains: Vng SH2 xem cc tyrosine kinase h Src.
Khp tn hiu (signal joint) c to ra nh s ni kt chnh xc
ca cc trnh t tn hiu nhn bit trong qu trnh ti t hp
sinh dng lm sn sinh cc th th t bo T v cc gen khng
th.
Signal transducers and activators o f transcriptions
(STATs): Cht cm ng tn hiu v hot ho sao m (xem kinase
Janus)
 Signal t r a n s d u c t i o n S dn truyn tn hiu m t qu trnh
chung trong d cc t bo nhn dc s bin i trong mi
trng ca chng. Ti cc t bo lympho, nhng s bin di quan
trng nht l nhng bin i xy ra trong qu trnh lay nhim
lm sn sinh khng nguyn kch thch cc t bo ca h thng
min dch to ra p ng min dch thu c.
Single c h a in Fv fragment: on n chui Fv 0 cha mt
vng V ca chui nng c lin kt bng mt on peptide tng
hp ko di vi vng V ca mt chui nh c th dc to ra bng
k thut di truyn.
Single- positive thymocytes: Cc t bo tuyn c dng
tnh n. Trong qu trnh trng thnh ca t bo T tuyn c,
cc t bo T trng thnh c nhn bit bng s biu hin ca
c CD4 v ng th th CD8, do vy chng c gi l cc t
bo tu y n c d n g tn h n
Sirolimus: L mt tn thuc c chp nhn i vi cht ho
hc rapamycin; c hai tn ny u c th c dng hon i cho
nhau trong cc vn bn.
SLC: Cht tit ho hc c tn SLC c sn xut bi mch
bch huyt, c tc dng thu ht cc t bo tua.
Small G proteins: Cc p ro te in G nh l cc protein n
phn chng hn nh Ras, chng hot ng nh nhng phn t
tn hiu ni bo dc theo rt nhiu s kin tn hiu xuyn mng.
Smallpox: Bnh u ma l mt bnh ly nhim gy ra bi
virus u ma (virus variola), n tng git cht ti 10% ngi
mc bnh. Ngy nay n b loi b hon ton nh tim chng.
S om atic d iv e rs ific a tio n theory: Thuyt s a dng ho th
sinh dng (th soma). Khi cc nh min dch hc pht hin ra
khng th l bin i, h lun bn nhiu gi thuyt khc
nhau trong c th uyt s a dng ho sinh dng cho rng
cc gen m ha cho cc phn t khng th l khng thay i
nhng chng dc a dng ho trong cc t bo sinh dng. iu
ny ng mt phn v hin nay cc siu t bin trong t bo
sinh dr.g c nghin cu r. Tuy nhin cc gi thuyt khc
cng cn c! c gii thch cc c tnh khc ca s a dng
khng th, bao gm s sp xp li cc gen v s chuyn i cc
dng tng dng.
Som atic gene th e ra p y : Liu php gen sinh dng (xom liu
php gen).
324

S o m atic h y p e r m u t a t i o n : Siu t bin sinh dng. Trong

p ng t bo B i vi khng th, cc trnh t ADN vng V tri
qua qu trnh si u t b i n s in h dng, kt qu l to ra th
h cc khng th bin i, mt s trong s lin kt vi i lc
cao i vi khng nguyn. iu ny cho php i lc ca khng
th tng ln. Cc t bin ny ch tc ng ln t bo sinh dng
v khng c di truyn qua t bo sinh dc.
S o m atic r e c o m b in a tio n : Ti t hp sinh dng. Trong qu
trnh pht trin ca lympho, cc on gen th th tri qua qu
trnh t i t h p s in h d n g to ra cc exon vng V nguyn vn
m ho cho vng V ca mi phn t khng th v cc chui th
th t bo T. Nhng s kin ny ch xy ra cc t bo sinh
dng v nhng bin i ny l khng di truyn.
Spacer: on cch: xem lut 12-13.
Specificity: T n h c h i u ca mt phn t khng th quyt
nh kh nng phn bit i vi cht sinh min dch ca n vi
cc khng nguyn khc.
S p e c tra ty p in g : Ngi ta s dng k t h u t n h k i u p h
xc nh cc kiu on gen ADN nht nh cho ra mt s cch
qung lp li ca 3 nucleotide hay mt codon.
Spleen: L lch, l mt c quan nm pha trn bn tri ca
khoang mng bng cha mt tu lin quan n vic loi b
cc t bo mu gi ci v mt tu trng lin quan n cc t bo
lympho p ng i vi cc khng nguyn c vn chuyn ti l
lch bng ng mu.
Src- fam ily tyrosin e kinases: Cc tyrosine kinase h Src
l cc protein tyosine kinase lin kt vi th th. Chng c mt
s vng c gi l vng tng ng- Src 1, 2, 3. Vng SH1 cha
v tr hot ng ca kinase, vng SH2 c th lin kt vi gc
phosphotyrosine, v vng SH3 lin quan n nhng tng tc
vi cc vng giu proline trong cc phn t protein khc.

S ta p h y lo co ccal e n t e r o to x in s (SEs): Ni c t c a
S taphy llo coccu s, gy nn ng c thc n v cng kch thch
cc t bo T lin kt vi cc phn t ca MHC lp II v vng vp
ca nhng th th t bo T nht nh, chnh v vy cc ni c t
Staphyllococcus l cc siu khng nguyn.
STATs: xem cc kinase Janus.
 Stem- cell factor (SCF): N h n t t bo gc l mt protein
xuyn mng trn t ho nn tu xng lin kt vi C-Kit, mt
th th tn h i u c tc cntf ln s p h t tri n t ho B v cc t
bo )ch cu khc.
S tro m a l cells: T bo nn s pht trin ca cc t bo lympho
H v cc t bo lympho rr din ra di s tng tc vi cc t bo
nn c vai tr cung cp cc tn hiu khc nhau c tnh cht tan
v lin kt t bo i vi s p h t trin t bo lympho.
S u b c u t n n e o u s layer: Cc khng nguyn c th c tim
vo bn trong t n g di da cm ng mt p ng min dch
thu c (Xem intracutaneos).
S u p e ra n tig e n s : Cc siu k h n g n g u y n l cc phn t
kch thch mt tp con cc t bo T b n g cch lin kt vi cc
phn t MHC lp II v vng vp ca nhng th th t bo T qua
kch thch s hot ho cc t bo T c biu hin cc on gen
vp c bit. Cc ni c t" Staphyllococcus l mt trong cc
ngun siu khng nguyn .
S u p p r e s s o r T cells: Cc t bo T p ch. (Xem cc t bo T
iu ho- regulator T cells).
S u rface im m u n o g lo b u lin (slg): Cc khng th b mt. Cc
phn t khng th lin kt vi mng m hot ng nh th th
khng nguyn trn cc t bo B thng dc gi l cc p h n t
khng th b mt.
S u r r o g a te light chain: C hui n h i d i n dc to nn t
hai phn t c tn l Vpre-B v X5 . Cng lc, chui ny cng c
th bt cp vi mt chui nng cu trc, chng s di chuyn ln
b mt t bo v bo tn hiu cho s pht trin ca t bo pre-B.
S w itch reg io n of DNA: Vng ADN c h u y n i, khi s
chuyn i cc isotype xy ra, exon hot ng vng V ca chui
nng tri qua s ti t hp sinh dng vi mt gen vng c nh
3 ca mt v n g ADN c h u y n i; s lin kt ADN ny khng
nht thit phi xy ra cc v tr chnh xc bi v chng xut
hin trong vng ADN intron, do tt c cc s ti t hp
chuyn i ny u c to ra.
Syk: Xem tyrosine kinase.
S y m p a th e tic o p h th a m ia : Khi mt mt b tn thng th
thng c mt c phn ng t min lm ph hu mt kia y l
hi chng c gi l bnh ng cm nhn cu.
326

S y n g eneic graft: Cy g h p ng gen l s cy ghp gia

hai c th hon ton ging nhau v mt di truyn. S cy ghp
ny c chp nhn nh cy ghp chnh n.
S ystem ic an ap hylaxis: P h n v h t h n g l dng nguy
him nht ca phn ng qu mn tc thi. N lin quan n vic
khng nguyn trong dng mu kch thch cc t bo ph trong
ton b c th. S hot ho cc t bo ph ny s gy nn s gin
mch, tch lu dch m, lm sng thanh qun v thng gy
cht.
S ystem ic lupus erythm atosus (SLE): Bnh Luput ban
h t h n g l m t b n h t m i n tr o n g cc t k h n g t h ch n g
li ADN v protein lin kt vi axit nucleic s to nn cc phc
h min dch lm ph hu cc mch mu nh c bit l cc
mch mu ca thn.
T lym phocytes: Cc t bo T hay lympho T l mt tp con
ca cc t bo lympho m c im ca chng l s pht trin
din ra tuyn c v mang cc th th lng d phn t c
lin kt vi cc phn t protein ca phc h CD Hu ht cc t .

bo T cha th th lng d phn t a: nhng cc t bo T .

li cha th th lng d phn t . .
Transm em brane activator and CAML- interactor_ TACI:
Cht hot ho xuyn m ng v cht tng tc CAML l
thnh vin ca h th th TNF v l mt trong hai nhm th th
chnh ca BLyS. N c tm thy trn cc t bo B, cc t bo c
tua, cc t bo T v c th l mt th th quan trng nhn cc
tn hiu t BLyS.
T a c ro lim u s hay FK506: l mt dc cht polypeptit c ch
min dch. N s bt hot cc t bo T bng cch c ch s dn
truyn tn hiu t th th ca t bo T ny. Tacrolimus v
cyclosporing l nhng cht c ch min dch ph bin nh't trong
cy ghp m.
Transporters associated w ith antigen p rocessing (TAPI
and TAP2): Tc nhn vn chuyn m nh p ep tit khng
nguyn lin kt vi qu trnh ch bin khng nguyn ni
sin h l cc protein lin kt ATP lin quan n vic vn chuyn
cc loi peptit khng nguyn t t bo cht vo khoang ca li
ni cht, ti y chng s lin kt vi cc phn t MHC lp I.
TAP- a s s o c ia te d p r o te in (Tapasin): Mt dng Protein lin
kt vi TAP c vai tr quan trng trong s lp ghp peptit khng
 .327

nguvn vi cc phn tu M1C 1) 1; nu t bo thiu protein

Tapasin ny th )ln tu MliC l) I s km bn trn h m t t
bo.
A n t i g e n - b i n d i n g t a r g e t ce lls: ( c t bo ch lin k t VI
k h n g ngu y n . Chc n n g ca cc t bo T tc ng l lun lun
kim tra s thav di m chng to ra trn cc t bo ch lin
kt khng nguyn Cc t bo ny c th l cc t bo B d c
hot ho sn xut ra khng th; i thc bo c hot
ho git vi khun hoc cc te bo khi u; hay cc t bo
dc nh du m b git bi cc t bo T gy dc.
P r o te i n Tat: l sn phm gen tat ca HIV. N c to ra khi
cc t bo nhim tim n b hot ho. N s lin kt vi mt tc
nhn tng cng sao m nam trong on di lp li tn cng ca
provirus, qua d lm tng cng s sao m ca h gen tin virus.
T- cell clone: Mt dng t bo T l mt tp hp cc t bo
xut pht t mt t bo T ban u.
T-cell hybrid: Cc t bo lai T l cc t bo c hnh thnh
bng cch dung hp mt t bo T c hot ho c hiu
khng nguyn vi mt t bo T ca m u bch huyt. Cc t bo
lai ny s cho ra th th ging nh t bo T c hiu to nn
chng v li c kh nng sinh trng c trn mi trng nui
cy ging nh t bo khi u.
T-cell line: Dng t bo T l dng cc t bo nui cy T sinh
trng c do cc chu k kch thch lp li thng l nh khng
nguyn hoc cc t bo trnh cin khng nguyn. Khi tng cc t
bo T n l t nhng dng ny c nhn ln chng s to ra
mt dng t bo T v tnh.
T-cell r e c e p t o r (TCR): Th th t bo T l mt
heterodimer ca cc chui siu bin a, p lin kt vi nhau bng
lin kt disulfide c biu hin trn b mt mng t bo nh
mt phc h vi cc chui CD3 khng bin i. Cc t bo T
mang kiu th th ny thng c gi l cc cc t bo Ta:p.
Mt kiu th th khc c to nn t cc chui bin i y v
cng biu hin vi CD3 trn mt qun th t bo T. c hai loi
th th ny u c biu hin cng vi mt homodimer gm hai
chui lin kt disulfide vi nhau.
T-cell zone: V ng t bo T trong cc m bch huyt cha rt
nhiu t bo T v khc bit hn VI vng t bo B v cc nhn t'
nn.
328

Tec-kinase: S hot ho cc th th khng nguyn t bo

bch cu c kt hp vi s hot ho PLC- Y thng qua cc
thnh vin ca h Tec-kinase thuc v cc kinase ging src. Cc
Tec kinase khc l Btk cc t bo B b t bin trong bnh
thiu ht min dch ngi, bnh agammaglobulinemia lin kt
nhim sc th X (X- linked agammaglobulinemia XLA) v ltk
bch cu T.
Term inal com plem ent com ponent: H thng b th c th
c hot ho trc tip hoc nh khng th, nhng c hai con
ng ny u dn ti s hot ho cc t h n h p h n b t h cui
c n g dn ti s hnh thnh phc h tn cng mng.
Term inal d eoxylnucleotidyl transferase (TdT): Enzyme
transferase deoxylnucleotidyl tn cng gip chn cc nucleotide
khng theo mu hay N-nucleotide trong cc v tr ni gia cc
on gene ca th th t bo T v cc gene vng V ca phn t
immunoglobulin. Cc N-nucleotide ng gp rt ln vo s a
dng lin kt ca cc vng V.
T e r t ia r y response: p n g bc ba. Khi mt khng nguyn
c tim li ln th ba, phn ng p ng s c gi l p
ng bc ba v s nhim ny qu trnh m in dch ho cp
b a (tertiary immunization).
THI cell: Cc t bo THI l mt phn nhm ca cc t bo T
CD4 phn bit nh cc cytokine m chng sn xut. Chng
lin quan ch yu n vic kch thch cc i thc bo v i khi
c gi l cc t bo T CD 4 gy vim.
TH2 cell: Cc t bo TH2 l mt phn nhm ca cc t bo
T CD4 phn bit nh cc cytokine m chng sn xut. Chng
ch yu lin quan n vic kch thch t bo B sn xut khng
th, v thng c gi l l cc t bo T CD4 tr gip.
TH3 cell: Khi nim cc t b o TH3 c s dng m
t cc t bo c nht c kh nng to ra ch yu nhn t' gy
bin dng sinh trng p trong p ng i vi khng nguyn.
Chng pht trin u th trong p ng min dch th dch i
vi cc khng nguyn c tip xc qua ng ming.
T h o ra c ic duct: Hch bch huyt t hu ht cc phn trong c
th tr phn u, c v tay phi, c tp trung vo mt mch
bch huyt ln, m c h ngc, mch ny chy song song vi ng
mch ch ti phn ngc v vo mch mu di n. Mch
 329

ngc ny do vy s dn dch bch huyt v cc t bo bch cu

lympho quay tr li vng tun hon mu.
Thymectomy: S c t b tu y n c b n g p h u th u t.
Thym ic anlage: Cc nguyn bo tu y n c l mt m t
vng nn tuyn c s pht trin trong qu trnh pht trin phi.
(Xem thymic stroma).
Thym ic cortex: V ng v tu y n c l vng ngoi ca mi
khe tuyn c trong cc t bo tuyn c s khai s sinh si, ti
sp xp li cc gene th th t bo T ca chng v tri qua mt
qu trnh chn lc tuyn c, c bit l chn lc dng tnh i
vi cc t bo biu b v tuyn c (thymic cortical epithelial
cells).
Thym ic strom a: C ht nn tu y n c cha cc cht nn t
bo cha cc t bo biu b v cc m lin kt hnh thnh nn
mt vi mi trng cn thit cho s pht trin ca t bo T.
Thymocytes: Cc t bo tu y n c l cc t bo lympho T
tm thy tuyn c. chng cha ch yu l cc t bo T ang
pht trin, rng mt s t bo tuyn c hon ton trng
thnh v mt chc nng.
Thymus: T u y n c l ni din ra s pht trin ca t bo T.
l mt c quan biu m lympho pha trn ca gia ngc,
ngay pha sau xng c.
Thym us - d ependent antigens (TD antigens). Mt s
khng nguyn s kch thch cc p ng ch cc c th c t bo
T; chng c gi l cc k h n g n g u y n p h th u c t u y n c.
Cc khng nguyn khc kch thch s sn xut khng th khi
vng mt t bo T th c gi l cc k h n g n g u y n k h n g
p h th u c tu y n c (thymus- independent antigens_ TI
antigens). C hai dng khng nguyn TI, TI- 1 c hot tnh kch
thch t bo T t bn trong v TI- 2 c l c kh nng hot ho t
bo B bng cch c nhiu epitope ging nhau lin kt cho vi
cc th th t bo B.
Cc t bo T v lympho T l cc m t ngn gn cho cc t bo
lym pho ph thuc tuyn c v qun th lympho ny s khng
th pht trin nu thiu mt tuyn c hot ng.
Time- lapse video microscopy: Ngi ta s dng knh hin
vi ghi hnh tng khong thi gian kim tra cc qu trnh sinh
hc t cc qu trnh nhanh nh s di chuyn ca t bo n cc
qu trnh chm nh s n hoa.
330

Tingible body m acro phage: Trong qu trnh hnh thnh

trung tm mm xut hin cc t bo c gi l i th c bo
th b t m u. Cc t bo thc bo ny s nut cc t bo B cht
theo chng trnh c to ra vi s lng ln trong sut qu
trnh p ng ca trung tm mm.
Tissue d e n d r i t i c cell: Tt c cc t bo c tua xut pht t
mt t bo gc to mu s di c ti rt nhiu v tr kh nhau trn
khp c th. Bi vy chng c gi l cc t to t u a m.
Tissue graft: S cy ghp cc c quan hay cy m chang hn
nh cy ghp c s dng trong y hc sa cha cc thiu
st ca c quan hay m.
Tissue specific a u to im m u n e disease: Mt s bnh t min
tn cng cc m nht nh, chng hn vo t bo p ca tu o
Langerhans trong bnh tiu ng t min; cc bnh dng ny
c gi l b n h t m in c h i u m.
Titer: P h e p c h u n khng huyt thanh l mt php o
nng ca cc khng th c hiu da trn s pha long huyt
thanh ti im cui cng chng hn mt mc bin i nht nh
trong kim tra ELISA.
Toll-like receptor: TLR1-10 (xem cc th th ging Toll).
Cc t b o ly m p ho T (T lymphocytes): Xem t bo T (T cells).
TNF: Cc cht c ca t bo lympho (lymphotoxin), tc nhn
hoi t khi u a (tumor necrosis factor- a).
TNF re c e p to r_ TNFR: C mt s cc thnh vin trong h cc
t h t h TNF Mt s dn ti s cht theo chng trnh ca t
bo biu hin chng (TNFR-I, II, Fas), trong khi nhng th th
khc li dn ti s hot ho (CD 40, 4-1 BB). Tt c nhng th
th ny chuyn tn hiu nh l cc protein bc ba.
Tolerance: D u n g n p m i n dch l s mt p ng min
dch i vi mt khng nguyn. H thng min dch l dung np
vi cc khng nguyn ca chnh n. S dung np vi khng
nguyn ca bn thn l mt c im thit yu ca h thng
min dch. Khi s dung np ny b mt i, h thng min dch c
th ph hu m ca chnh n ging nh xy ra trong bnh t
min.
Toll p a t h w a y : Con ng Toll l mt con ng tn hiu c
in kch hot nhn t phin m NF X B bng cch ph hu cht
c ch ca n I X B.
 331

Tt ca cc thnh vin ca h Toll cc th th c pht hin

cho ti nay l ging vi h Toll ca Drosophila. Chng c t
tn l cc th th ging Toll (Toll- like receptor-TLR) v nh s
ng sau, chang hn th th ging Toll 4 hay TLR-4.
P a la tin e tonsil: Amian vm ming nm c hai pha ca
hu. N tp trung mt lng ln cc t bo lympho dc sp xp
nh l mt phn ca h thng min dch kt hp vi rut hay
mng nhy.
Toxic shock syndrome: Hi chng sc c t l mt phn
ng dc t h thng gy ra do s sn xut mt lng ln cytoki-
nee ca cc t bo TCD4 b hot ho bi siu khng nguyn vi
khun, chng hn c t- 1 gy hi chng sc c t (TSST-1) do
Staphyllococcus aureus tit ra.
Cc c t b bt hot c gi l c t gim lc (toxoid)
th khng cn dc na nhng vn duy tr tnh sinh min dch do
chng c th c s dng gy min dch.
T h1: xem cc t bo T iu ho (regulatory cell).
TNF r e c e p to r-a ss o c ia te d factors -TRAFs: Cc nhn t lin
kt vi th th TNF l mt h protein bao gm t nht l su
thnh vin nhiu th th h TNF khc nhau (TNF family recep-
tors_ TNFRs). Chng chia s mt vng c gi l vng TRAF,
v ng vai tr quan trng nh l tc nhn chuyn i tn hiu
gia pha trc l cc thnh vin ca h TNFR v pha di l
cc nhn t phin m.
Transcyto sis: S vn chuyn tch cc cc phn t qua cc t
bo biu b c gi l xuyn bo. S xuyn bo ca cc phn t
IgA lin quan n s vn chuyn xuyn qua cc t bo biu m
rut trong cc nang bt ngun t b mt nn y bn v ho
nhp vi b mt nh khi tip xc vi khoang rut.
T ransfection: S ti np. S a cc mnh nh ADN vo
trong t bo c gi l s c h u y n n h i m Nu ADN ny c
biu hin m khng cn phi kt hp vi ADN ca t bo ch th
hin tng ny c gi l s chuyn nhim chuyn tip, nu
ADN ny kt hp vi ADN ca t bo ch khi n nhn ln
cng vi s nhn ln ca ADN t bo ch qua to nn s
chuyn nhim n nh.
T ransg en esis: S truyn gen. Cc gen ngoi lai c th chn
vo h gen ca t bo chut bng q u t r n h t r u y n gh p gen.
Qu trnh ny s to ra cc con chut chuyn ghp gene s dng
332

trong nghin cu chc nng ca gene dc chn vo hay gene

chuyn ghp v s iu ho gene .
T ran slo c atio n : Chuyn on nhim sc th. Mt s bnh ung
th c cc c h u y n o n n h i m sc t h trong mt con
nhim sc th c ni mt cch bt thng vi mt nhim sc
th khc.
T r a n s p la n ta tio n : S cy ghp m hay cd quan t c th ny
vo c th khc c gi l s gh p m. C q u a n cy ghp
(transplanted organ) hay m ghp c th b loi b do h thng
min dch tr khi c th nhn dung np i vi cc khng
nguyn ca m ghp hay cc thuc c ch min dch c s
dng chng li s loi b ny.
T ransporters associated w ith antigen processin g - TAP:
Xem TAPI v TAP2: Tc nhn vn chuyn lin kt VI qu
trnh ch bin khng nguyn
T u b e r c u l in test: Php th ao/tuberculin l mt php th
lm sng trong mt dn xut protein tinh ch (purified pro
tein derivative_ PPD) ca Mycobacterium tuberculosis, tc nhn
gy nn bnh lao, c tim di da. PPD kch thch mt dng
phn ng qu mn mun c th no b nhim bnh lao hay
vi cc c th c min dch vi n.
Tuberculoid leprosy: Bnh lao hi: xem bnh hi
T u m o r immunology: Min dch ung th l mn hc nghin
cu kh nng bo v ca vt ch chng li cc khi u thng s
dng phng php cy ghp khi u.
T u m o r n ecrosis factor- a : Yu t h o i t kh i u a l mt
cht tit ca t bo c sn xut bi i thc bo v cc t bo
T. N c nhiu chc nng trong p ng min dch. y l mt
thnh vin chnh thc ca h cc cht tit t bo TNF. Cht tit
ny hot ng nh l protein tit hoc protein lin kt t bo c
chc nng tng tc vi cc th th thuc h cc th th Lc
nhn hoi t khi u, cc th th ny n lt n s tng tc vi
cc phn bn trong ca t bo thng qua cc thnh phn TRAFs
(tumor necrosis factor receptor- associated factors).
T u m o r necrosis factor- : Yu t h o i t khi u ( xem
c tlympho (lymphotoxin).
Cc khi u c ghp vo trong th nhn ng gen c th sinh
trng tip tc hoc b loi b thng qua s nhn bit ca t bo
T i vi cc k h n g n g u y n cy ghp c h iu khi u (tu-
 333

mor- specific transplantation antigens TSTA) hay cc k h n g

nguyn loi b khi u (tumor rejection antigens). TSTA l cc
peptice ca t bin hoc cc protein t bo biu hin qu mc
lin kt vi cc phn t MHC lp I trn b mt t bo khi u.
TdT- d e p e n d e n t dUTP- biotin nick en d labeling: P h p
t h TUNEL nhn bit cc t bo cht theo chng trnh ti ch
nh cc on c trng trn ADN ca chng. dUTP gn vi
biotin c thm vo u 3 t do trn cc mnh ADN nh en
zyme TdT c th c nhn bit bng nhum ho hc m min
dch vi streptavidin lin kt vi enzyme.
Two- d im e n sio n a l gel electrophoresis: in di gel hai
chiu, cc protein tch nhau ra nh tp trung ng in theo
mt chiu, tip l in di SDS- PAGE trn mt bn gel dng
tm o mt gc ph hp theo chiu ban u. Phng php ny c
th tch v nhn bit mt lng ln cc protein khc bit nhau.
Type 1 h y p e rs e n s itiv ity reactions: Cc phn ng qu mn
tyt 1 c phn loi theo c ch ca chng: Cc p h n ng q u
m n typ 1 lin quan n khng th IgE kch thch cc t bo
ph; Cc p h n ng q u m n typ 2 (typ 2 hypersensitivity re
actions) lin quan m khng th IgG chng li cc khng
nguyn ni cht hay b mt t bo; Cc p h n ng q u m n
ty p 3 (type 3 hypersensitivity reactions) lin quan n phc h
khng nguyn khng th; Cc phn ng q u m n typ 4 (type
4 hypersensitivity reactions) l qua trung gian t bo T.
T yrosine kinase: Enzyme tyrosine k in a se l mt enzyme c
kh nng phosphoryl ho c hiu cc gc tyrosine trong phn t
protein. Chng rt quan trng trong vic hot ho cc t bo
lympho T v B. Cc tyrosine kinase quan trng di vi s hot h
t bo B l Blk, Fyn, Lyn v Svk. Cc tyrosine kinase quan trng
i vi hot ho t bo T l Lck, Fyn, ZAP-70.
U rticaria: Ni my ay l mt thut ng k thut gi
chng pht ban, tc l da b v nga gy nn bi phn ng d
ng.
N- te rm in a l V domain: Vng bin i trong chui polypep
tide ca mt phn t khng th hay th th ca t bo T c
to nn bi mt v n g V c u tn c n g N n l. Cc vng V
bt cp s hnh thnh nn v tr lin kt khng nguyn ca phn
t khng th v th th t bo T.
334

V gene segments: Cc mnh gen V.95 axit amin u tin ca

cc vng V trong phn t khng th hay th th t bo T dc
m ho bi cc o n gen V di truyn c C rt nhiu on
gen V khc nhau trong h gen ca dng t bo sinh dc. to
ra mt exon hon chnh m ho cho mt vng V, mt on gen V
phi c sp xp li lin kt vi mt on gen J hoc DJ
c ti sp xp.
V accination: T im c h n g l s trnh din c cn nhc to
min dch tp nhim i vi mt tc nhn gy bnh bng cch
tim vaccine l tc nhn gy bnh b lm yu hoc cht
(khng cn kh nng gy bnh).
Valence: Ho tr ca mt khng th hay mt khng nguyn l
s cc phn t khc nhau m n c th lin kt ti cng mt thi
im.
Variability: Tnh a dng ca mt phn t protein l thc
o s khc nhau gia cc trnh t axt amin ca cc dng khc
nhau ca phn t . Cc protein a dng nht c bit n l
cc khng th hay cc th th ca t bo T.
V ariab le region - V region: Vng bin i ca mt phn t
khng th hay th th t bo T c hnh thnh bi cc vng tn
cng amino ca cc chui polypeptide thnh phn. Cc vng ny
c gi l cc vng bin i (variable region - V domain) v l
cc phn bin i nhiu nht ca phn t. Chng cha cc v tr
lin kt vi khng nguyn.
V a s c u la r ad d ressin : Cht kt dnh mao mch. Cht ch nh
vng mch l cc phn t trn t bo ni m m cc phan t lin
kt bch cu s bm vo . Chng c vai tr cha kho trong
vic xc nh v tr c trng ca bch cu trong c th.
Vav: xem cc phn t protein tng thch (adaptor proteins).
V(D) J recom b in ase: Enzyme lin kt cc mnh gen ca cc
gen th th t bo B, T c gi l. N c to thnh t mt s
enzyme nhng quan trng nht l sn phm ca gen hot ho
enzyme ti t tp RAG-1 (recombinase - activating gene) v
RAG- 2 m sn phm protein ca chng, RAG- 1, RAG- 2 c
biu hin trong qu trnh pht trin ca lympho v to nn hp
phn c hiu lympho duy nht c bit ca enzyme ti t hp
V(D)J. '
V(D)J (V(D) reco m b in atio n ): Qu trnh ti t hp c tm
thy ch cc t bo lympho ca ng vt c xng sng, n cho
php s ti t hp li cc mnh gen khc nhau thnh mt trnh
 335

t m ho chui polypeptide hon chnh ca phn t khng th

hoc th th t bo T.
Very late a n tig e n s VLA: Cc khng nguyn rt mun l cc
thnh vin h i cc tc nhn hp nht lin quan n tng tc
t bo- t bo v t bo- cht nn. Mt s VLA c ngha quan
trng i VI bch cu v s di c ca lympho.
Vessicles: Cc bng mng l cc ti nm trong t bo cht,
c bao bc bi mng
Viral envelope: v bc virus. Nhiu loi virus sn sinh ra bi
cc t bo dng vt c v c bc trong lp v v i r u s ca pro
tein v lipid mng t bo ch lin kt VI li virus bng cc pro
tein v virus.
Virion: L cc tiu phn virus hon chnh m trong hnh thi
ny virus lan truyn t t bo ny sang t bo khc hoc t c
th ny sang c th khc.
Virus: L cc tc nhn gy bnh cu thnh t mt h gen axit
nucleic bc trong mt v protein. Chng ch c th nhn ln
trong mt t bo sng v chng khng c c quan trao i cht
cho mt cuc sng c lp.
Vpre B: xem th th tin t bo B (pre- B- cell receptor).
W e g e n e rs gran u lo m ato sis: bnh to ht W e g e n e rs.
Khng th chng li proteinase- ca bch cu c ht trung tnh
c hnh thnh trong q u t r n h t o u h t W eg en e r mt bnh
t min trong c cc mch hoi t trm trng. S hin din
ca cc khng nguyn khng t bo cht trung tnh (anti-
neutrophil cytoplasmic antigen_ ANCA) l mt du hiu
chun on bnh.
Weibel- Palade bodies: T h W eibel- Palade l cc ht
trong t bo ni m cha tc nhn chn lc p. S hot ho cc t
bo ni m nh cc cht trung gian nh histamin v C5a s dn
ti s di chyn nhanh chng ca tc nhn chn lc p ti b mt
t bo.
W este rn blotting: k thut thm min dch lai khng nguyn
khng th. Mt hn hp cc protein s c tch bit nhau
thng bng in di trn gel v c chuyn bng thm qua
mng nitrocellulose; khng th c nh du s c s dng
nh mt mu d kim tra cc protein c hiu.
Wheal a n d flare reaction: Khi mt lng nh cht gy d
ng c tim vo da ca mt c Lh d ng, ngi ta s quan st
336

thy p h n ng sng v N bao gm vng da cha dch v

phn ng vng ng, v lan rng.
Cc vng tit ca m lympho trong l lch c gi l tu
trng (white pulp).
Wiskott- A ldrich syndrome: Hi c h n g W iskott c m
t bi nhng thiu st trong b khung xng ca t bo do t
bin trong protein WASP. Bnh nhn b bnh ny rt nhy cm
vi vi khun to m.
Wu and Kabat plot: Khong Wu v Kabat (Wu and Kabat
plot), hay cc khong bin i, c to ra t cc trnh t axt
amin ca cc protein lin quan bng cch ch ra s bin i ca
cc trnh t so vi s cc gc axt amin. S bin i l s cc axt
amin khc nhau quan st c mt v tr c chia ra bi tn
s ca axt amin ph bin nht.
Xenogeneic: ng vt c to ra t cc loi khc nhau c
gi l n g v t d gen
Xenograft: G hp k h c loi (xenograft), ghp c quan t
nhng loi khc nhau ang c khm ph nh l mt gii php
cho s thiu ht nghim trng cc c quan ca ngi cn cho cy
ghp. Vn chnh ca vic cy ghp gen khc loi l s xut
hin cc khng th t nhin chng li cc khng nguyn ca b
phn cy ghp; nhng c gng ang c tin hnh thay i
phn ng ny bng cch to ra nhng sinh vt chuyn gen.
Xld (X-linked im munodeficency: Chut mang cc t bin
trong gen btk c s thiu ht trong vic to ra khng th, c
bit l trong nhng phn ng s cp. Nhng con chut ny c
gi l xld, thiu ht min dch lin kt vi nhim sc th X) bnh
ny tng t nh bnh thiu y globulin ngi (X- linked agam
maglobulinemia).
X 'linked agam m aglobulinem ia. XLA: Bnh thiu y
globulin lin k t n h i m sc t h X (X- linked agammaglobu-
linemia_ XLA) l mt ri lon di truyn trong s pht trin
ca t bo B b km hm giai on t bo tin B (pre- B) v
khng t bo trng thnh cng nh khng th no c to ra.
Bnh ny l do thiu st trong gen m ho cho enzyme tyrosine
kinase btk gy ra.
X- lin k ed h y p e r IgM sy n d ro m e :Hi c h n g q u m c IgM
lin k t X (X- linked hyper IgM syndrome) l bnh m c rt t
hoc khng c khng th Ig G, IgA, IgE c to ra v thm ch
 rm

c (lap ng IgM cng khng (lu nhifntf lng IgM trong huyt
hanh li thng ( mc cao. Bnh ny lion quan n thiu st
trong gen m ho cho cht gn CI.)40 v (-1)154.
X- linked lyniphoproliferative syndrom e: Hi c h n g
t n g sinh ym pho lin kt X (X- linked lymphoproliferative
syndrome) l bnh thiu ht min dch him gp nguyn nhn
do t bin trong gen c tn l vng SH2 cha gen 1A (SH2D1 A).
H trai vi s thiu ht ny trong trng hp in hnh s b bi
nhim EBV trong thi th u, i khi b ung th m bch huyt.
X- linked severe com bined im m unodeficiency_ X-
linked SCID: T h iu h t min dch kt hp t r m tr n g lin
k t vi X (X- linked severe combined immunodeficiency. X-
linked SCID) l mt bnh trong s pht trin ca t bo T b
ngn li ngay giai on sm trong tuyn c v khng c s sn
xut t bo T trng thnh hay khng th ph thuc t bo T
no xy ra. Bnh ny l do thiu st trong gen m ho ho cho
chui c, mt hp phn ca mt s th th i vi mt vi loi
cht tit t bo khc nhau (cytokinees).
ZAP- 70: Protein c gi l ZAP- 70 c tm thy cc t
bo T v l h hng ca Syk trong cc t bo B. N cha hai
vng SH2 m khi lin kt VI chui c phosphoryl ho s
dn n s hot ho hot ng kinase. C cht t bo ch yu
ca ZAP- 70 l mt protein th thch nghi kch thc ln gi l
I AT.
338

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 NH XUT ON I HC QUC GIA H NI
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C h iu tr c h n h i m x u t bn:

Gim c: PHNG Quc BO

Tng bin tp: NGUYN b t h n h

C h u tr c h n h i m ni d u n g :

Ngi nhn xt: GS. TS. NGYN n h b n g

GS. TS. TRUNG PHN

PGS. TS. NGUYN NH HIN

Bin tp: MNH CNG

Bin tp ti bn: QUC THNG
Ch bn: NG TH H
Trnh by ba: NGC ANH

MIN DCH HC
1----------- cd S
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M s: 1K-63H2008
In 1.000 cun, kh 16 X 24 cm ti Cng ty In & Vn ho phm
S' xut bn: 106 - 2008/CXB/120 - 14/HQGHN, ngy 23/1/2008
Quyt nh xut bn s: 63 KH-TN/XB
In xong v np lu chiu qu IV nm 2008.