I

M
M
U

/e
14 N
S,
O
AM

L
O

O
R

G
Y
 I 6.1 CD MARKERS High-yield Points
M
Important Surface Antigens/CDs on Cells 44 CD- 1 to 8 (except CD6) → T-cell markers.
M 44 CD 19,20,21 → B-cell markers.
U 44 Mantle cell lymphoma → CD 19,20,43 &5 and cyclin D1 are +ve
CD Found on Function/ Marker for
N (Primary Cell while CD23 is -ve.
O distribution ) 44 Burkitt's lymphoma → CD 19,20, 10 are +ve.
L 44 Malignant melanoma → CD HMB 45, S100 +ve.
CD1a Thymocyte & Langerhans
O cell
G
CD3 Pan T-cell marker T cell receptor
Y 6.2 MHC ANTIGENS & HLA
CD4 T helper-inducer Binds to MHC class II,
cells, macrophage +ve in Mycosis MHC Antigens (HLA system)
fungoides
ƒƒ MHC-I is expressed on all cells. MHC-II are present on
CD5 ---- Mantle cell lymphoma APCs
CD8 T cytotoxic Anti-viral & anti-cancer ƒƒ Gene for major as well as minor histocompatibility

/e
-suppressor cells properties, binds MHC -I antigens (MHCs or HLAs) are located on chromosome 6p
(short arm).
CD10 Immature B cells CALLA antigen, + in ALL,
follicular lymphoma, NHL

14
HLA typing is NOT required in
CD13,14 Monocytes
ƒƒ Corneal transplant
CD16, 56 NK cells Anti-viral ƒƒ Blood & platelet transfusion
CD19 Pan-B cell marker Appears early in B-cell ƒƒ Heart, lung & liver transplant (In these conditions size&
maturation shape of the donor organ is more important).
S,
CD20/21/22 B cell markers CD 21 is complement
receptor (CR2)
HLA classes & types of MHC antigens
Class-I Class-II Class-III
AM

CD25 Marker of T, B & Marker of HCL

macrophage Locus HLA- A, B, C, HLA-D Complements
E,F,G loci on (DP, DQ,DR)
CD30 Marker for LP -ve
chromosome 6
Hodgkin's
Found All nucleated APCs Complement
CD33,13 Most sensitive
on cells & platelets (monocyte/ (C2, C4 TNFa &b
O

myeloid cell marker

(so not on RBCs) macrophages, HSP-70)
CD34 Hematopoietic "Stem Cell" marker, & B cells)
progenitor cells Fibroma
R

Peptide a1 a2 a1 b1
CD38 Plasma cells Multiple myeloma clefts b/w
marker (also CD-33) Funcn Endogenous ExogenousAg Encode for
CD45 Leukocyte common Pan leukocyte marker, (viral/tumour) to TH cells enzyme 21
antigen Used for screening of Ag to Tc cells (CD4 cells), hydroxylase
leukemia, (CD8 cells) , GVHD
for malignant lymphoma Graft rejection response
& cell mediated
CD45RO Memory T-cells Subset of T cortical cytolysis
thymocytes
CD56 NK cell Innate immunity
High-yield Points
CD117 Most specific Marker for myeloid
myeloid cell marker lineage in AML,CML, 44 MHC-I allele presents the antigen to T-cells through proximal
blast crisis, granulocytic portion of alpha- chain.
sarcoma from left 44 CD8 T-cells, kill in context of MHC-1 while CD4 cells kill in context
ventricle, in GIST of MHC-2 [ Rule of 8; 1x8 =8 or 2x4 =8].
258 44 Best APCs are → Dendritic cells (most imp) and Langerhan cells.
44 NK cells are MHC unrestricted.
N Important negative points: Important Autoantigens & Autontibodies
I
ŽŽ MHC-1 is NOT found in → RE cells. M
Autoantigen Autoantibody D/s
ŽŽ Opsonization is NOT a function of CD4 cells. M
ŽŽ CD135 is NOT a B-cell marker. Actin Anti SM, Chronic active U
anti mitochondrial hepatitis, PBC
N
SOME IMP. HLA ASSOCIATIONS Desmin Crohn's d/s O
L
F-actin ANA ( type1), Autoimmune
HLA Seen in Anti-LKM (Type 2) hepatitis, O
A1 Hodgkin's d/s Anti-SLA (Type 3) G
Y
A3 Idiopathic hemochromatosis Thyroglobulin Autoimmune
thyroiditis
B5 Behcet's syndrome, UC, PCOD
Th.peroxidase Hashimoto
B8 Myasthenia gravis, Grave's d/s (TPO) thyroiditis

B27 Psoriasis, Thyrotropin LATS Grave's d/s

receptor

/e
Ankylosing spondylitis,
Acute anterior uveitis,
Reiter's d/s, Reactive arthritis Anti-parietal cell Ab Chronic atrophic
gastritis

14
B47 Congenital adrenal hyperplasia
Intrinsic ---- Pernicious anemia
B51 Behcet's syndrome factor-1

CW 6 Psoriasis Synaptogranin LAMES

DR2 Narcolepsy, Multiple sclerosis, Good pasture SOX-1 Vitiligo

S,
synd

DR2, DR3 SLE

6.3 ORGAN TRANSPLANTATION
AM

DR3 RHD, Grave's d/s

CAH (chronic active hepatitis), 10 biliary
cirrhosis
Sjogren's syndrome, ORGAN TRANSPLANTATION & GRAFTS
Adrenal insufficiency,
Celiac d/s, Dermatitis herpetiformis ƒƒ First organ transplantation performer
O

ƒƒ Heart → Christian Bernard.

DR4 RA, Pemphigus vulgaris
ƒƒ Liver → Starzl.
DR2,3,4, DQ8 T1 DM ƒƒ Lung & 1 st autologous renal transplantan → by Hardy.
R

DQ1 Pemphigus vulgaris ƒƒ 1st succesful cornea transplantan → Edward Jig.

ƒƒ Types of grafts
DQw1 LL (lepromatous leprosy)
1. Autograft : From one part of body to another e.g. most
DQ2 Coeliac Sprue of the skin grafts.
DQ7 Bullous pemphigoid 2. Isograft (Syngenic graft) : Graft b/w identical twins.
3. Allograft : B/w 2 individuals of same species who are
not identical twin.
High-yield Points 4. Xenograft : B/w 2 different species. Chances of graft
44 NIDDM is NOT a/w HLA. rejection are maximum.
44 DM type 1 is a/w HLA DR2,3,4 & DQ8. ƒƒ Best donor for allograft → Identical twin.
44 MG & Grave's are a/w both HLA B8 & DR3.
44 Juvenile pauciarticular arthritis (JRA) is a/w HLA DR5 & DR8.

259
 Graft Rejection, Types Skin cancers esp SqCC are m/c type. Other cancers are-
I
BCC, malignant melanoma, NHL, ca cervix.
M Hyperacute Acute Chronic ƒƒ
M Occurs Min-hrs Wks - 6 mo Years ƒƒ Transplanted (donor) kidney is usually put in on the right
U within side of groin/pelvic area.
N Nature Irreversible Reversible Irreversible ƒƒ Organ specific features of Graft rejection
O Mech Cellular Humoral 1. Kidney → Glomerulosclerosis and tubular atrophy
L (M/c type)
2. Pancreas → Acinar loss & islet destruction
O HS reacn Type II Type IV Type II Type IV
3. Heart → Accelerated coronary artery diseases.
G ( + II in
some 4. Liver → Vanishing bile duct syndrome
Y (bile ductopenia, paucity of ducts)
books)
Due to Preformed CD4, CD8 Ab, Incompati- 5. Lungs → Obliterative bronchiolitis.
(mediator) antibodies T cells immune bility
(Intravascular comple­ of minor
thrombosis.) xes MHC Ag High-yield Points
E.g. Most Resistant- 44 M/c indication for liver transplantation → Chronic liver failure,
susceptible - liver

/e
biliary atresia (in children).
kidney 44 M/c GN in transplanted kidney → MPGN type-II.
Renal
44 Type of transplant with the best graft survival → Autograft
Resistant- allograft
44 Commonest tissue transplant with best overall survival →

14
liver & heart may
develop Corneal transplant because of avascularity.
glomeru- 44 Factors that improve graft survival → ABO compatibility, absence
lonephritis. of anti-HLA antibodies, HLA compatibility b/n D-loci.
Biopsy Vasculitis, Tubulitis Vasculitis, Interstitial 44 All types of allograft are susceptible to chronic rejection & it is
finding fibrinoid (Inflamma­ fibrinoid fibrosis & the major cause of allograft failure. Both MHC class I & II (Class
S,
necrosis & tion of necrosis tubular II>I) have role in allograft rejection.
thrombosis peritubular & throm- atrophy
capillaries) bosis N Organ of the cadaver which can NOT be used for transplant
AM

Response Irreversible Avoidable No Irreversible, → Bladder

to by HLA- No
immuno- matching Stem cell transplantation
supression
ƒƒ Based on the source, stem cells can be broadly classified
ƒƒ HLA matching can match the major antigens (MHC Ag) into two types as
not the minor antigens, so immunosupression is required
O

°° Embryonic stem cells (ESCs) and

even after HLA matching.
°° Adult stem cells (ASCs).
ƒƒ HLA involved in graft rejection : HLA I & II. Class I ƒƒ The ESC are capable of forming the cells of all three germ
R

molecules promote direct alloreactivity. Class II MHC is layers and they are termed as pluripotent stem cells.
most crucial in BM transplantation. ƒƒ 1990 Nobel prize was awarded to Dr. E. Donnall Thomas
ƒƒ Major impact in graft loss comes from the effects of for hemopoietic stem cell transplantation.
HLA-B and -DR antigens ƒƒ D/s commonly treated with stem cell transplantation:-
°° The effects of HLA-DR mismatches are the most
important in the first 6 months after transplantation. Malignant conditions Non-malignant conditions
°° The HLA-B effect emerges in the first 2 years. Auto- AML, HD, NHL, Autoimmune diseases
logous neuroblastoma,
°° HLA-A mismatches have a deleterious effect on long-
Ewing's
term graft survival.
ƒƒ A cadeveric donor (someone who has recently died), is Allo- AML, ALL, CML, NHL, Aplastic & Fanconi’s anemia
genic myelodysplastic PNH , Dyskeratosis congenita,
usually required for kidney transplantation. syndrome, Thalassemia, sickle cell d/s
ƒƒ Order of immunogenicity myeloproliferative d/s Glanzmann thrombasthenia,
BM > skin > kidney > liver > Heart. (i.e. BM transplantation SCID, Wiscott’s Aldrich synd
require maximum HLA matching). Chronic granulomatous d/s
ƒƒ Triple therapy immunosupression for post renal- transplant Cong. neutropenia,
congenital
260 patients include → Cyclosporine + Aza + pred [ CAP]
a megakaryocytosis, IEMs
ƒƒ After transplantation there is↑ed risk of malignancy.
ƒƒ Hemopoietic stem cell gene therapy has been used to treat 3. Allogenic BM (& liver ) transplants are most commonly
severe combined immunodeficiency (SCID), using viral I
a/w GVHD. GVHD is not seen with /rare with renal (&
vectors & neurodegenerative d/s (lysosomal enzymes M
lung)transplant.
deficiency). M
ƒƒ T1DM (type 1 diabetes) can be treated by → Adipose U
tissue derived mesenchymal stem cells implantation into N
6.4 HYPERSENSITIVITY O
liver.
ƒƒ Pancreatic islet (langerhans cells or b cells) auto- ƒƒ Grave's d/s belongs to Type II hypersensitivity. L
transplantation is performed following total ƒƒ Complements are used in type III hypersensitivity. O
pancreatectomy. The surgeon first removes the pancreas G
and then extracts and purifies islets from the pancreas Y
High-yield Points
which are infused through a catheter into the patient's liver.
44 An example of type 5 HS rxn is Myasthenia gravis & Grave's d/s.
Graft versus Host D/s (GVHD) 44 Farmer's lung is type IV > III HS rxn.
44 Complement mediated HS rxn are → Type 2 and 3
1. Animal GVHD is also k/as Runt d/s.
44 TOC for anaphylaxis → Adrenaline.
2. I f GVHD occurs <3 months then it's called acute GVHD,
44 DOC for type II, III & IV HS → Steroids.

/e
& in > 3mo it's chronic GVHD. 44 Type 1 DM is type 4 HS & type 2 DM is type 2 HS
3. Characterised by jaundice, GI lesions, skin rashes. 44 Type 1 Lepra rxn is type 4 HS & type 2 is Lepra rxn type 3.
ƒƒ Details given in table

TYPES (Mech)
TYPE I
IgE Ab
Pathogenesis
Localised
(ATOPY) 14 Seen in
Allergic - conjunctivitis/ - rhinitis/- asthma/- dermatitis/-fever
(Hay fever), Allergy to food,
S,
↓ (Run in families, have genetic PK (Prausnitz Kustner) rxn,
Mast cells degranulan predisposin) Theobald Smith phenomena,
↓ Casoni test
Release of mediators
AM

Systemic Anaphylaxis
TYPE II Kill the Complement MAC (C5-C9) mediated → lysis of target cell
Antibody target cells Mismatch BT, AIHA, Granulocytopenia,
mediated Thrombocytopenia
↓ Pernicious anemia,
Antigen is FIXED on cell Pemphigus vulgaris,
O

membrane/ connective tissue Good pasture's synd, Rheumatic fever

Cells with Fc receptor (NK/macro/neutro) mediate

R

→ ADCC (Antibody dependent cytotoxicity)

Auto-Ab vs target cells MG, Grave's d/s

TYPE III Antigen is Local

Immune complex which settles SOLUBLE Arthus reaction
down in organs (skin,vessel, [ NOT fix] (Farmer's lung, Acute PSGN, Reactive arthritis,
LN,kidney, joints,spleen) GN-Syphllitic /membranous)
↓ Systemic
Thrombi formation Serum sickness, SLE, PAN,RA, drug induced AIHA

TYPE IV CD4 T cells Immune granulomas

↓ (TB,leprosy, LGV, Syphilis, Sarcoidosis, Montenegro test for
T Classic Leishmaniasis)
cell mediated Delayed HS Rheumatoid arthritis,
Multiple sclerosis,
Type 1 DM,
CD8 T cells GBS, Patch test for contact dermatitis/poison ivy dermatitis,
↓ John Mote cutaneous basophil reacn 261
Cellular cytotoxicity Direct cell mediated cytotoxicity
Graft rejection, tumour cell lysis, virus infected cell lysis
 I
N Important negative points: HYPERSENSITIVITY RXNS ANTIGENS
M ŽŽ NOT an immune complex mediated disease → Good
pasture syndrome. Haptens
M
U ŽŽ NOT seen in serum sickness → Anaphylaxis. ƒƒ Small molecules that are antigenic but not immunogenic
N (Unable to induce immune response).
O ƒƒ Haptens have immunological reactivity but no
L 6.5 ANTIBODIES/ IMMUNOGLOBULINS immunogenicity.
ƒƒ They are able to react with preformed antibodies but are
O
ANTIBODIES unable to stimulate their production independently.
G
ƒƒ They require carrier for it to become immunogenic (
Y ƒƒ All antibodies are immunoglobulins (Ig) . production of antibody).
ƒƒ All immunoglobulins are glycoproteins consisting of 2 ƒƒ E.g. Quinine, Penicillin, Hydralazine , Halothane
light chain and 2 heavy chain. Chromosome for light chain
is at chr. 2 ( κ locus ) 22 ( l locus ) & locus for heavy chain Epitope (Antigenic determinant)
is at chr 14.
ƒƒ Part of antigen that is recognized by the immune system,
ƒƒ Immunoglobulin subtypes (i.e., G, M, A, D, E) are
specifically by antibodies, B cells, or T cells.

/e
determined by the type of heavy chain present.
ƒƒ Epitope is the smallest unit of antigenicity.
ƒƒ Heavy chains are structurally and antigenically distinct for
°° Paratope is the combining area of antibody
each class while L chains are similar (either κ or λ).
corresponding to epitope.

14
ƒƒ Ag combining site is at amino terminus composed of both
°° Idiotopes are the specific antigenic determinents
H & L chains.
present on paratope.
ƒƒ Light chain consists of 1 variable and 1 constant region
ƒƒ Types:-
while H chain has 1 variable and >3 constant regions.
°° Linear/sequential type (T-cells related),
Variable regions are responsible for antigen binding and
S,
°° Confirmational types (B-cells related).
constant region are responsible for biologic function.
ƒƒ The tendency of an antibody to bind a specific epitope →
ƒƒ Fab fragment consists of both H and L chain while Fc
Antibody affinity.
fragment has only H chain. J chains is for polymeric Abs.
AM

ƒƒ Isotype switching is a gene rearrangement process whereby

the µ and δ CH gene segments are spliced out and replaced
with either g e or α CH gene segments.
ƒƒ Hypermutation is a process whereby a high rate of mutations
occur in the variable segments of both the heavy chain
O
High-yield Points
44 Complete antigen has both immunogenicity + immuno-reactivity.
44 Immunoreactivity (Immunological reactivity) is ability to
produce specific and observable rxn with Ab).

(VH) and the light chan (V or Vl). Somatic hypermutation 44 Immunogenicity is ability to produce an immune response.
is a molecular phenomena responsible in immunoglobulin
genes for affinity mutation of Ab response.
Forssmann antigen
R

Heterogenetic or heterophile glycolipid protein

High-yield Points found in different biological species & classes. E.g.
44 If a child is suffering from recurrent infections caused by bacteria dogs,horses,cats,turtles, sheeps,Guinea pig kidney cells &
having polysaccharide capsule, assay of IgG2 will be helpful in enteric organism, pneumococci etc, Cold agglutinin test in
evaluation. mycoplasma.
44 IgG is most potent (+++) in opsonizing.
44 IgM is most potent (+++) in fixing complement. Antigen- antibody reaction curve
44 IgA > IgM> IgG are present in milk.
ƒƒ Prozone phenomena is d/to → Antibody excess.
44 Most common immunoglobulin deficiency is IgA.
ƒƒ Equivalence zone is d/to → Antigen- antibody complex
44 IgG gives strong precipitation reaction and complement fixation
test while IgM gives strong agglutination reaction.
precipitation.
44 Anamnestic reaction is augmented antibody production on ƒƒ Post-zone phenomena is d/to → Antigen excess.
subsequent exposure. It is seen in persons who have had past
typhoid/ enteric fever or who have had immunization against Reagin- antibody
typhoid. ƒƒ In syphilis is → IgG.
262 ƒƒ In atopy is → IgE.
ƒƒ In false +ve VDRL is → IgM
IMMUNOGLOBULINS (IG) I
M
IgG IgA IgM IgD IgE
M
•• Heavy chain g a m d e U
•• Structure/size Monomer, Smallest Dimer Pentamer(Largest Ig ), Monomer Monomer N
K/a millionaire molecule O
•• Valency 2 4 10 L
O
•• Amount in 75% (Major Ig of Minute Minute Least
serum serum) (65% is IgG1
G
type) Y
•• Concentrated Equally distributed in Body secretions Present on Sub-mucosa
in blood & tissue fluid (provides local / human
mucosal immunity) B-lymphocytes
•• Half life Longest t1/2 Short lived, disappear early Shortest t1/2
from blood (2-3d)

/e
•• Transplacental + (Only Ab which - Synthesis start by fetus at - -
passage crosses placenta) 20 wks (before birth)
•• Heat stability + + + + - (i.e. Heat labile)

14
•• Complement ++ + +++ (strongest activator of X
fixation via classical pathway via alternate classical pathway) Does NOT fix
pathway (only Ig) complement
•• Agglutination viral agglutination, Agglutinating/lytic Ab
S,
Toxin neutralization
•• Opsonization Opsonizing Ab Indirectly acts by Mediates
(directly acting Ab) producing C3b (opsonin) ie Immediate HS
phagocytosis (TYPE-1 HS)
AM

•• Properties Precipitating Ab Local/secretory/ Antigen receptors on B-cell Atopic or reaginic

mucosal Ab , found +nt Ab
in payer's patches
•• Other points Produced in 20 P
 revents Indicates acute /recent
immune response attachment of infection. Produced in
O

bacteria / viruses to primary immune response

mucous membranes to an antigen.
R

Heterocytotropic Def. of Ig A is Presence is an indicator of Homocyto­

Ab detected by PC often a/w with cong. infection (eg. syphilis) tropism,
anaphylaxis, overproduction of P-K reaction
IgG are antibodies of IgE Ab (so↑ risk of demonstrates IgE
2o immune response anaphylaxis)
Acts as blocking Ab Susceptible to
during desensitization mercaptoethanol
in T/t of atopy
•• Importance ↑ excretion in multiple ↓in - kwashiorkor, ↑ excretion in Waldenstrom ↑ in parasitic
myeloma (light chains) GIT/ resp. disease macroglobulinemia infections

263
 T cell dependent and Independent immune
I High-yield Points
M response
44 Covalent interactions are NOT seen in → antigen -antibody
M Immune T-cell dependent B-cell independent
complex formation.
U 44 Compliment activation by classical pathway is performed mainly response
N by IgM, f/b IgG by means of their Fc fragments. Nature of Mainly proteins, RBCs Polysaccharides
O 44 Compliment activation is by alternative pathway is done by IgG antigens (Complex structure) Flagellin (simple)
L and Ig A.
Induces both T & B cell Only B-cell mediated
O 44 Compliment activation is NOT done by → IgG4, IgG5, IgD. stimulation
G 44 Most potent antibody in opsonization (antibody mediated lysis)
Y Age group Infants of >6 weeks Infants of >2 yr are
→ IgM > IgG.
are capable of this capable of this response
response
Superantigen Effect Results in higher titres Results in low titres
of IgG, mainly of IgM,
ƒƒ A class of antigens (protein molecules) which does not
Long lasting Short lasting
require antigenic processing & not specific for a T cell
receptors. Booster + No (because no

/e
effect with immunological
ƒƒ They are called superantigens as they generate massive
repeated memory)
immune response by activating upto 20% of T cells exposure
& massive release of cytokines like TNFa , IL-1

14
{ NMemory response is NOT seen in seen carbohydrate
(Conventional antigens activate only 0.001% T cells). antigen}
ƒƒ There is no processing of the toxin by APCs.
ƒƒ They bind to invariant region (a-chain of MHC II) with Monoclonal Antibodies (Mab)
β-chain of T-cell receptor.
ƒƒ Steps to produce mab: fusion, selection, and screening.
S,
ƒƒ Examples of superantigen are:
ƒƒ In hybridoma technique sensitized lymphocytes of mice
°° Staphylococcal enterotoxins (F) in Kawasaki d/s
°° Pyrogenic exotoxins C spleen (HPRT+ cells) and myeloma cells (HPRT-) are
°° Toxic shock syndrome toxin (TSST-1) produced by. fused and grown over HAT medium.
AM

Staph. aureus, ƒƒ B-cell hybridomas produces the same antibody as the

°° Group A streptococcal pyro/erythrogenic exotoxin A. parental B cell.
ƒƒ Trastuzumab (Herceptin) is a humanized monoclonal
antibody to HER2/neu developed to specifically target
O

tumor cells and, it is hoped, spare normal cells. In clinical

trials, the combination of Trastuzumab with chemotherapy
improved response in patients with carcinomas
R

overexpressing HER2/neu.
ƒƒ Nomenclature of Monoclonal antibodies: Parts of
the antibody can be replaced with human amino acid
sequences, or pure human antibodies can be engineered:

Antibody is Substem used

termed as
If the constant region of Mab Chimeric -xi-
is replaced with the human
form
Part of the variable regions Humanized -zu-
may also be substituted
Partially chimeric and partially -xizu-
humanized

264
 6.6 IMMUNE CELLS T - Cell B - cell I
•• Surface marker Ag - receptors. Surface lg, M
ƒƒ Cells of immune system are broadly divided into:- Fc receptor,
M
°° T-cells complement
receptor. U
°° B-cells
N
°° Null cells/NK cells •• Marker CD- 3 (Pan - T cell CD-19 ( Pan-B cells
marker marker) O
°° Phagocytic cells
present on all T-cells) (+nt on all B cells) L
Surface smooth Surface Rough with O
T CELLS & B- CELLS projections G
•• Multiplication T-cells undergo blast B-cell undergo Y
ƒƒ T and B cells also called T and B lymphocytes are transformation transformation
morphologically indistinguishable but can be identified (evidenced by ↑ with
by markers on their cell membranes and their molecular DNA bacterial
receptors. synthesis) on endotoxins.
ƒƒ T-cells differentiate into:- treating with
mitogens ex-
°° Memory T-cells phytohemagglutinin

/e
°° Cytotoxic T cells (CD8 ) or concanavalin A
°° Helper T cells (CD4+).
ƒƒ B-cells differentiate into:-

14
°° Plasma cells High-yield Points
°° Memory B-cells 44 Intestinal epithelium is rich in T-cells
44 Most potent activator of T cells → Mature dendritic cells
Differentiation of T and B lymphocytes 44 Master regulator of immune system → CD4+ Helper T-cells.
Histiocytes are present in sinuses (in LN) and in cords of Billroths
S,
(in spleen).
B Cells T-cells 44 Paracortical LN hyperplasia is seen in → T-cells hyperplasia,
phenytoin therapy, small pox vaccination, viral infections.
AM

44 Necrotizing lymphadenitis is seen in → Kikuchi Fujimoto d/s.

Memory Plasma Memory Cytotoxic Helper
B-cells cells T-cells T-cells T-cells
CD 4 Cells
ƒƒ Formation of memory helper T cells
Effector B cells, Fights viruses, CD4 + CD8 +
ƒƒ Activation of cytotoxic T cells (CD4 TH1)
O

produce protective cancer cells

antibodies ƒƒ Activation of B cells to produce antibodies (CD4 TH2)
- Null Cells
R

Difference between T - Cell and B - cell ƒƒ Constitute 5-10% of circulating lymphocytes.

T - Cell B - cell ƒƒ These are large granular lymphocytes (LGL) that is
developed inside of bone marrow. They contain azurophilic
•• Old name Small lymphocyte Large lymphocyte
granules.
•• % in blood. 70% 20%
ƒƒ Called "Null" cells as they do not have any surface markers
•• In Bone marrow. rare or –nt Numerous i.e. No T cell receptors (TCR) but antigens present CD16
In LN 85% 15%
& CD56.
In Spleen. 15% 35%
In Thymus. 90% 10% ƒƒ Term null cell is no longer commonly used, they are often
•• Rosettes E - rosettes or EAC - rosette
referred to as natural killer cells (NK cells) or killer cells.
(sheep ƒƒ Examples (subsets) are -
RBC (SRBC) rosette) °° Antigen dependent cytotoxic cells (ADCC),
•• Location °° Lymphokine activated killer cells ( LAK cells ) are NK
In Lymph Node Paracortical Germinal follicles, cells activated with IL-2. Used for t/t of RCC.
medullary cords. ƒƒ Activation of NK cells is regulated by IFN g . Proliferation
In spleen Peri-arteriolar Mantle zone (red of NK cells is done by IL-2 and IL-15.
(White pulp) pulp) 265
In Payer's
patches Peri-follicular Central follicles.
 I
M
M
U
N
O
L
O
G
Y

/e
14
S,
AM

Fig.: Dendritic cells & effect

O
R

   
Fig.: Epitope Fig.: Superantigen

266 Fig.: T-Cell mediated CMI

 I
M
M
U
N
O
L
O
G
Y

/e
14
©VDA

Fig.: Activation of Th1 & Th2 cells & their role in immunity

S,
AM
O
R

©VDA

Fig.: Competence signaling & B-cell proliferation mechanism

267
 ƒƒ Role:- Immune privilege sites
I
°° Part of innate immune response. ƒƒ Are able to tolerate the introduction of antigens without
M
°° 1st line of defense against virus infected cells & cancer
M eliciting an inflammatory immune response.
cells → osmotic lysis or trigger apoptosis. Lyse the cell
U without prior sensitization (cytotoxicity is not MHC
ƒƒ E.g. Brain, eyes, placenta, fetus, seminiferous tubules in
N restricted). testicles.
O
ƒƒ No prior sensitization required for NK cells to act.
L
No immunological memory (Non immune mediated).
O 6.7 COMPLEMENTS
No antibody induced action.
G
Y Phagocytic Cells ƒƒ Complements are acute phase proteins.
ƒƒ Macrophages ƒƒ Liver synthesize central components . Spleen, macrophages,
ƒƒ Microphages and intestinal mucosa can also synthesize.
°° Neutrophils ƒƒ Classical pathway is activated by → IgM (most potent),
°° Eosinophils IgG (requires 2 molecules), and immune complexes (eg.
°° Basophils in SLE)

/e
ƒƒ Antigen presenting cells (APCs) ƒƒ In alternate C3 works on C3 convertase.
°° Dendritic cells ƒƒ C3 convertase splits C3 into → C3a (Anaphylotoxin) +
°° B cells

14
C3b ( cell bound).
°° Langerhans cells
ƒƒ Alternate pathway is activated by → Bacterial endotoxin
Macrophages (most potent) and zymogen, lgA & lgG4, cobra venom
ƒƒ Major role in phagocytosis. ƒƒ C3 is first common point b/w classical and alternate
ƒƒ They down regulate the inflammatory response once pathway. C3 is involved in both classical and alternate
S,
initial bacterial replication is controlled. pathway.
ƒƒ Critical role in nonspecific defense like innate immunity.
ƒƒ Macrophages also help in initiating specific defense
AM

mechanisms (adoptive immunity) by recruiting other

immune cells such as lymphocytes. For example, they are
important as → antigen presenters to T cells.
Monocyte - Macrophage Lineage Derivatives
O

These cells form part of RES & are concerned with

phagocytosis
ƒƒ Kupffer cells of liver
R

ƒƒ Microglial cells of CNS

ƒƒ Langerhans cells of skin
ƒƒ Dendritic cells in lymphoid tissues
ƒƒ Epithelioid cells & Multinucleated giant cells
ƒƒ Histiocytes of connective t/s.

High-yield Points
44 Tumour giant cells (as in HCC, soft tissue sarcomas) are not
derived from macrophages but are formed from dividing nuclei
of neoplastic cells.
44 Antigen presenting cells (APCs) are → macrophage
subpopulation (Dendritic cells in lymphoid tissues, Langerhan's Fig.: Complement synthesis pathway
cells in epidermis, NK-cell, B-cells).

268
ƒƒ Functions: Basic functions of complements are INTERLEUKINS I
opsonization, chemotaxis, lysis of foreign cells, and
M
clumping of antigen bearing cells. Role in innate immune
IL Source Function M
response.
{ N NOT a function of complement → B- cell transformation.} IL-1 Macrophage Pyrogenic, APR U
proliferan & differentian of T,B cells N
 ost important opsonizing
M C3b, Ig G O
IL-2 T H1 Activates B and TH cells , cytotoxicity of
complement (Major serum opsonin)
T & NK cells L
Most important chemotactin C5a O
IL-3 T-cells Stimulates hematopoiesis precursors/
G
Anaphylotoxin C5a (most potent) pluripotent stem cell
C3a , C4a Y
IL-4 T H2 Proliferation of B-cell & TC cells, ↑IgE
MAC (Membrane attack complex) C5b - C9
IL-5 TH2 B-cell differentiation, ↑IgA & IgM
↑Vascular permeability LTC4, LTD4, LTE4 production, Eo differentiation
SRS-A (Slow reacting substances LTC4, LTD4, LTE4 IL-6 TH1, B-cell differentiation, ↑IgA production
of anaphylaxis) macrophage

/e
Leukotriene which is chemotactic LT-B4
IL-7 Spleen,BM, B &T cells growth factor
(Promotes leucocyte adhesion)
stromal cells
Vasodilatation PGD2, PGE2, PGI2 PGF2α

14
IL-8 Induces chemotactic response

Complement deficiencies & their importance

Deficiency or ↓ level of
DAF (Decay accelerating factor)
C1 esterase inhibitor
C2
AM
Pro & Anti-inflammatory cytokines
A/w ƒƒ Proinflammatory cytokines that are present with
PNH dominance of CMI → IL1 ,IL6 IFNγ ,TNFα.
S,
Hereditary angioneurotic ƒƒ Anti-inflammatory cytokines that are present with
edema dominance of humoral immunity → IL4 ,IL6 ,IL10 ,IL13,
M/c hereditary complement TGF-b, IFNa.

deficiency
C3 Alternate pathway activation,
severe recurrent pyogenic High-yield Points
infectns
44 IL-1, IL-6 & estrogens are involved in osteoporosis.
C3, C4 Classsical pathway activation 44 IL-12 is produced by macrophage & dendritic cells . It is critical
O

C1, C2, C4 SLE, Collagen vascular d/s for induction of TH1 response.
C6- C9 Nisseria ( Bacteremia) 44 Interferron g converts macrophage into epithelioid cells.
44 Most potent stimulator of Naive T-cells is --- mature dendritic
R

cells

6.8 CHEMOKINES
INTERFERONS
CHEMOKINES Interferon Source Role
ƒƒ Chemokines receptors : CXCR4 are found mostly on IFN a Leukocytes -
T cells.,while CCR5 on macrophages. Anti HIV drug IFN b Fibroblasts, Anti-viral activity
Maraviroc is an CCR5 antagonist.
IFN g T cells Anti-viral activity, macrophage
Category Type Examples activation, MHC class-I & II expre­
ssion on cells, Activates NK cells.
C-X-C a chemokines IL-8
C-C b chemokines MCP-1,
MIP-a, RANTES, Eotaxin
C g chemokines Lymphotactin
269
CX3C Fractalkine
 I 6.9 IMMUNODEFICIENCY DISEASES
M
M PRIMARY IMMUNODEFICIENCY SYNDROMES
U
N
O
L
O Disorders of specific defect Disease of complement Disease of phagocytosis → CGD, CHS
G
Y

Humoral/ B-Cell Defects
ƒƒ X-linked agammaglobulinemia
ƒƒ Common variable
Immunodeficiency
Cellular /T-Cell Deficiency Combined T& B cell Deficiency
ƒƒ Di George's syndrome ƒƒ Nezelof syndrome
(Thymic hypoplasia)
ƒƒ Chronic mucocutaneous candidiasis ƒƒ Ataxia-telangiectasia

/e
ƒƒ Transcobalamin deficiency ƒƒ PNP def. ƒƒ Wiskott-Aldrich syndrome
ƒƒ Immunodeficiency with hyper ƒƒ Swiss-type
IgM

14
agammaglobulinemia
ƒƒ Acquired ƒƒ Severe combined
hypogammaglobulinemia Immunodeficiency
ƒƒ Transient
ƒƒ ADA deficiency
hypogammaglobulinemia of
infancy
S,

ƒƒ A/w thymic hypoplasia, recurrent sino - pulmonary

AM

IMPORTANT PRIMARY IMMUNODEFICIENCY

SYNDROMES infections, premature aging, endocrine disorders
(e.g.IDDM) high incidence of lymphomas, HD, leukemias
(T-cells type).
Bruton's Agammaglobulinemia
ƒƒ Deficits in cerebellar functions → nystagmus may be seen.
ƒƒ X-linked d/s c/by defective opsonization d/to deficiency
O

of tyrosine kinase required for B- cell maturation & Chronic granulomatous d/s of childhood [CGD]
opsonizing antibodies/immunoglobulins.
ƒƒ Inheritance is XR (in boys) >AR (girls).
ƒƒ Recurrent infections with encapsulated organisms are
R

ƒƒ D/to deficiency of NADPH oxidase leading to loss of

common.
peroxidase activity → inability to bleach (defective killing),
ƒƒ CMI normal.
even though the MPO are present in phagolysosomes.
ƒƒ Screening test → NBT test (Nitroblue-tetrazolium
Common Variable Deficiency
chloride)
ƒƒ Abnormal B-cell function, but serum level is normal. ƒƒ DHR (Dihydrorhodamine) test & immunoblot test for
Humoral immunity (NOT cellular) affected. NADPH oxidase is also used.
ƒƒ Deficiency of T-cell may be seen. ƒƒ Specific inability to kill catalase +ve bacteria (staph.
ƒƒ M/c associated with giardiasis. Also a/w lymphoid aureus, coliforms) can lead to sepsis → death.
malignancies, recurrent bacterial infections, herpes d/to ƒƒ Persistent CMI & humoral response.
antibody deficiency. ƒƒ A/w seborrheic dermatitis, eosinophilia, granulomas of the
intestine causing obstruction.
Ataxia Telangiectasia
ƒƒ AR disorder c/by triad of cerebellar ataxia + oculocutaneous Job’s syndrome
telangiectasia, and immunodeficiency. ƒƒ Hyper IgE syndrome d/to defective phagocytosis.
270 ƒƒ ↓ lgE & absent lgA. ƒƒ Recurrent infections are common.
Chediak - Higashi syndrome (CHS)
NK- → JAK-3 SCID (XL SCID-ve) I
ƒƒ AR disorder a/w mutation in LYST gene. M
+
ƒƒ Impaired phagolysosome formation d/to defective B
M
NK+ → IL-7 deficiency
fusion of phagosome +lysosome [giant lysosomes] →giant U
primary granules are seen in neutrophils. T- N
ƒƒ D/to defective phagocytosis → abnormal killing NK- → Fatal O
ƒƒ There is defect in microtubule polymerization & so - L
B
leucocyte motility is impaired → defective chemotaxis NK → ADA deficiency SCID
+ O
ƒƒ A/w G
1. Defect in platelet aggregation → Bleeding tendencies Y
2. Defective nerve conduction in brain High-yield Points
3. O culocutaneous albinism as melanin synthesis require 44 NBT test is used to detect --- defect in phagocytosis
lysosomal enzyme. 44 Enzyme responsible for respiratory burst of phagocytic cells ---
4. NK cell dysfunction, neutropenia, photophobia & NADPH Oxidase
nystagmus

/e
ƒƒ Leucocyte functions improve with vit C 200mg daily. DI-George Syndrome
ƒƒ 3rd and 4th pharyngeal pouch syndrome.
Leucocyte adhesion deficiency (LAD) ƒƒ Results from failure of developmental of 3rd and 4th

14
pharyngeal pouches.
LAD 1
ƒƒ C/by hypoplasia /absence of thymus causing pure T-cell
ƒƒ Caused by defect in CD 18 molecule → Integrin defect defect (most severe form of T-cell deficiency) and severe
ƒƒ Recurrent bacterial infection d/to defective adhesion defect in CMI → Candidal infection.
ƒƒ On CT scan there is no thymus and parathyroid glands are
S,
ƒƒ H/o delayed separation of umbilical cord.
absent (resulting in neonatal tetany, hypocalcemia) aortic
LAD 2 arch anomalies, deformed aortic knuckle, generalized
osteoporosis. CATCH 22 spectrum results in d/to deletion
AM

ƒƒ Caused by absence of Sialyl- Lewis X→ Selectin defect

of chromosome 22q.
ƒƒ C/f recurrent bacterial infection, platelet dysfunction, short
ƒƒ Facial abnormilities.
stature, Bombay blood group & mental retardation. ƒƒ Condition is reversed by implantation of thymic tissue.
Nezelof's Syndrome
High-yield Points
O

ƒƒ Results from failure of development of only 3rd pharyngeal

44 Delayed separation of umbilical cord is also seen in alloimmune
pouch.
neutropenia, Sialyl Lewis X antigen deficiency , factor XIII
ƒƒ Superior parathyroid glands are present but inferior
R

deficiency,urachal anomalies, and histiocytosis-X.

Wiskott Aldrich Syndrome
ƒƒ XLR d/s with wasp gene mutation.
ƒƒ Eczema, bleeding tendencies (bloody diarrhoea in male
newborn may be seen) d/to thrombocytopenia
ƒƒ ↑ IgA & IgE but normal IgG , ↓ IgM, thymus normal.
SCID
ƒƒ D/to lack of combined T,B,NK cells deficiency.
ƒƒ X-linked form (SCIDX1) is a/w arrest of fetal thymus &
lymphopenia,T- B+NK-
ƒƒ AR variants a/w ADA deficiency
parathyroid glands and thymus are absent. So parathyroid
functions are normal.
6.10 THYMUS
THYMUS
ƒƒ Thymic hypoplasia, aplasia or agenesis
Is seen in DiGeorge syndrome and Nezelof's syndrome.
Patients have lymphopenia, ↓ immunity and they die from
infections. Also seen in SCID ( with reticular dysgenesis),
and ataxia telangiectasia.
Acquired causes of thymic atrophy in young age are
malnutrition, ionizing radiation, prolonged steroid/
271
cytotoxic t/t.
 ƒƒ Thymic hyperplasia
I
B-cell follicles (germinal centres) are increased in number
6.11 MISCELLANEOUS POINTS
M ƒƒ Nephritic factor is - IgG seen in type-II MPGN (C3,
within the thymus. These patient develop Myasthenia
M properdin). C3 Nephritic factor (C3 NeF) is an antibody
gravis (MG) in 60-65% cases. It can also be seen in Grave's
U d/s, SLE, RA, scleroderma, cirrhosis. to the complement system comprising mostly of IgG
N ƒƒ Thymoma immunoglobulins role in pathogenesis type-II MPGN
O causes hypocomplementemia.
°° M/c primary tumour of anterior mediastinum
L ƒƒ Rheumatoid factor is - IgM antibody directed against IgG
°° A/w MG, other autoimmune conditions and
O paraneoplastic syndrome such as acquired ƒƒ M-components - IgG in 53% patients and IgA in 25%
G hypogammaglobulinemia, pure red cell aplasia, Grave's patients
Y disease, PA, dermatomyositis, cushing syndrome. ƒƒ Paraproteins - In multiple myeloma there is increase
synthesis. P~ are abnormal immunoglobulins circulating in
plasma and excreted in urine. Most common para protein
High-yield Points is IgG (in 2/3 cases of MM), IgA (M component is also a
44 Removal of thymoma (thymectomy), improves neuromuscular paraprotein)
disorder (MG) ƒƒ Cryoglobulins are - Proteins which are coagulated when
44 Thymic hyperplasia in a young female is a good prognostic plasma or serum is cooled / chilled to a very low temperature

/e
predictor. (2oC-4oC). Most commonly they are monoclonal IgG or
IgM. (↑in urine in RA, SLE, MM, Lymphocytic leukemia).

14
Prognosis after thymectomy is better if--- ƒƒ Bence John protein are → light chain proteins composed
ƒƒ Patient is young (< 40 year) of k & l (Kappa and Lambda) mainly (in 80%)
ƒƒ Females benefit more Their excretion in urine is increased in MM.
ƒƒ Duration of d/s is shorter/ early stage of thymoma. ƒƒ Tamm- Horsfall protein - It is a urinary glycoprotein
ƒƒ Absence of thymoma secreted by mucous glands of renal tubular cells in thick
S,
ƒƒ A/w MG or thymic hyperplasia ascending limb of loop of Henle and distal tubule as
eosinophilic hyaline casts/pigmented casts in ischemic
ATN.
AM
O
R

272