Histofisiologi Organ Limfoid &

Pengantar Imunologi
dr. Wahyunia Likhayati S, M.Biomed
 Organ Limfoid
Organ Limfoid Primer
(Timus dan Sumsum tulang)

Organ Limfoid Sekunder

(limfonodus, limpa, jaringan limfoid difus yang terdapat pada mukosa sistem
pencernaan seperti tonsil, plakat peyer dan appendiks)
 Functions of the Lymphatic System
1. Monitor body surfaces and fluid compartments
(e.g. epidermis, mucosae*, interstitium)
2. React to the presence of potentially harmful
antigens recognized as “non-self”
3. Autoimmune diseases (rheumatoid arthritis, type I diabetes, etc.)

Lymphatic System consists of:

A. Cells
1. Lymphocytes (B,T, natural killer)
2. Antigen-presenting cells (dendritic cells, Langerhans’ cells & macrophages)
B. Lymphatic “tissue” –diffuse and nodular
C. Lymphatic “organs” (lymph nodes, spleen, thymus)
D. Lymphatic vessels that carry the cells and fluid

*Mucosae refers to lining tissue of the body cavities, e.g. GI

tract, respiratory tract, genitourinary tract
 Lymphoid organs are classified as:

Primary lymphoid organs

• Thymus
• Bone marrow
• Lymphatic nodules of the distal intestinal
tract (e.g. ileum and appendix)

Secondary (effector) lymphoid

organs/tissue
• Spleen & lymph nodes (organs)
• Mucosal associated lymphoid tissue
(MALT), e.g. lymphocytes and
lymphatic nodules in the lamina
propria

Ross, Fig. 14.1

 Antigen/imunogen
• Suatu molekul atau sel yang mampu
merangasang respon imun.
• Karakteristik suatu bahan berfungsi sbg
antigen:
– Harus besar, kompleks & asing bagi penjamu
– Jumlahnya memadai
– Biasanya mrpk protein dg berat molekul >10.000 dalton
– Epitopnya (determinasi antigen) harus mudah di akses
 benda asing
= antigen

⎛ sistem
imun
Respons
imun

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 Sistem limfoid (imun)
• Mempertahankan tbh dr agen penginvasi melalui
pemanfaatan dua respon imunitas humoral dan seluler
• Organ limfoid primer adl sumsum tlg tempat
perkembangan sel B dituntaskan dan timus tempat
perkembangan sel T dituntaskan
• Jaringan limfoid skunder; kel. Getah bening, tonsil, limpa,
jar mukosa di kulit, sal nafas, sal cerna dan saluran
perkemihan
 IMUNITA
S
Mekanisme pertahanan tubuh
terhadap benda asing

• Mikroorganisme & produknya

• Makanan
• Bahan kimia
• Obat
• Dll

16
 benda asing
= antigen

⎛ sistem
imun
Respons imun

▪ nonspesifik
(innate)
▪ spesifik
(adaptive)

selular homural 17
 Sifat sistem imun
Kemampuan membedakan
self dan nonself.

Berdasarkan
kemampuan suatu molekul protein
yaitu reseptor antigen: surface Ig & TCR
untuk mengenali molekul lainnya: antigen
secara spesifik
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 IMUNITA
S
INNATE ADAPTIVE
Sinonim Natural Acquired
Nonspesifik Spesifik
Sifat Antigen nonspesifik Antigen spesifik
Respons cepat Respons lambat
Tidak ada memori Ada memori
Komponen Barrier alami Limfosit
(kulit, mukosa) Ag-recognition mol:
Fagosit B cell dan T cell
Mediator solubel: receptors
mis.:komplemen Molekul yg disekresi:
Pattern-recognition mis.:antibodi
molecules 19
IMUNITA
S

20
 IMUNITAS
INNATE

Semua unsur yang berperan dalam

proteksi tubuh terhadap benda asing,
yang sudah tersedia sejak lahir
dan bekerja segera setelah terjadi paparan.

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 IMUNITAS
ACQUIRED
Bekerja-sama dengan innate immunity.
Diperoleh setelah ada paparan antigen
→ acquired.

Spesifik untuk antigen terpapar.

Bekerja relatif lebih lambat dari innate
immunity.

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• Fgs sistem imun adl membedakan “diri sendiri”
dari “asing”
• Setiap individu /organisme harus mampu
melindungi diri dari ancaman baik dr luar (virus
dan bakteri yang terhirup dan tertelan) dan dari
dalam (neoplasma, tumor)
• Untuk melindungi diri tubuh manusia
mengembangkan reaksi pertahanan seluler yang
disebut respon imun
 RESPON IMUN HUMORAL
• Bersifat tdk lgs dan dilaksanakan oleh imunoglobulin spesifik
(antibodi) yang dihasilkan sel B aktif (sel plasma) & dibantu o/sistem
komplemen
– IgG (gama) plg banyak di tubuh, mampu menembus plasenta
melindungi tbh dr bakteri
– IgM plg besar bertanggung jawab dalam respon imun primer
– IgA tdpt dlm sekresi tbh; kolostrum, air mata, air liur, sekresi sal
nafas, GIT, sal kemih. Fgs utama mempertahankan permukaan
mukosa thd virus dan bakteri
– IgE melekat ke sel mast dan basofil, terlibat dalam reaksi
hipersensitifitas tipe I
– IgD tdpt dlm jml kcl di serum, kemungkinan mempengaruhi
defisiensi limfosit B kendati peranannya blm jelas
Fungsi Imunoglobulin
• Menyebabkan sitotoksisitas
• Memungkinkan imunisasi pasif
• Meningkatkan opsonisasi (pengendapan komplemen
pd suatu antigen shg kontak lekat dg sel fagositik mjd
lbh stabil)
• Mengaktifkan komplemen
• Dapat menyebabkan anafilaksis
Fungsi utama Komplemen
1.Menyebabkan lisis sel
komplemen berinteraksi satu sama lain membentuk
membrane attack complex (MAC) di permukaan sel sasaran
=> memasukkan molekul pembuat pori di membaran sel
imunogen => membran rusak => air dan elektrolit masuk sel
=> sel pecah dan mati
Fungsi utama Komplemen
2.Pembentukan berbagai mediator imun, berperan
dalam proses peradangan
3.Opsonisasi ; sel fagositik akan lbh mampu menelan
apabila bahan imunogen dilapisi komplemen.
=> ex; histamin, bradikinin
 RESPON IMUN SELULER
• Respon imun yang dilaksanakan oleh limfosit T
• Peran sel T ;
– Fungsi pengendali; sel T penolong /CD4 (cluster of
deferentiation 4)
– Fungsi pelaksana; sel T sitotoksik (pemusnah) / CD8
=> mampu mematikan sel terinfeksi virus, sel tumor
 Fungsi Sel CD4
• Pengendali ; mengaitkan sistem monosit-makrofag ke sistem
limfoid
• berinteraksi dg sel penyaji antigen untuk mengendalikan Ig
• Menghasilkan sitokin yang memungkin tumbuhnya sel CD4
dan CD8
• Berkembang menjadi sel pengingat
Fungsi imunitas seluler
• Sel CD8 mematikan scr langsung sel sasaran
• Sel T menyebabkan reaksi hipersensitifitas tipe lambat
• Sel T memiliki kemampuan menghasilkan sel pengingat
• Sel T sbg pengendali CD4 dan CD8 memfasilitasi dan
menekan respon imun seluler dan humoral
Sitokin
 Antigen & Antibodi
• A molecule that is recognized by cells of the adaptive
immune system is called an antigen and typically elicits a
response from these cells.
• An antibody is a glycoprotein of the immunoglobulin
family that interacts specifically with an antigenic deter-
minant. Antibodies are secreted by plasma cells that
arise by terminal differentiation of clonally proliferating
B lympho- cytes whose receptors recognize and bind
specific epitopes.
Lymphocytes
• In all secondary lymphoid tissue
the lympho- cytes are supported
by a rich reticulin fiber network of
type III collagen.
• The fibers are produced by
fibroblastic reticular cells, which
extend numerous processes along
and around the fibers.
Reticular (Reticulin) Fibers
• Form a delicate supporting
framework for highly cellular
tissues (endocrine glands, lymph
nodes, liver, bone marrow,
spleen, smooth muscle).
• Composed mainly of Type III
collagen, with a carbohydrate
moiety that reduces Ag+ to
metallic sliver = argyrophilic.
• Special stain: silver impregnation
to visualize.
• Thinner than type I collagen
(Type III fibrils are 30-40 nm diameter;
type I fibrils are ~200 nm diameter)

Source Undetermined
Reticular Fibers (type III collagen)
made by reticular cells (specialized fibroblasts)

Top left: Ross and Pawlina, Histology: A Text and Atlas. Others: Sources Undetermined
• Large aggregates of B cells called lymphoid
nodules or follicles tran- siently
characterize all secondary lymphoid
organs.
• Aggregates of uniform cell density and
staining represent primary nodules, while
those with larger, more euchromatic cells
centrally are termed secondary nodules.
Here two secondary nodules can be seen,
with germinal centers (GC) at different
stages of development.
• Rapid proliferation of activated B
lymphoblasts in the germinal center causes
smaller, naive lymphocytes to be pushed
aside and crowded together peripherally as
the follicular mantle (M).
 Organ
Limfoid

Organ Organ
Limfoid Limfoid
Primer Sekunder

Sumsum Tonsila Limpa

Timus Limfonodus MALT BALT
tulang Palatina (Spleen)
Limfonodus
• kelenjar getah bening
(kelenjar limfe)
• Permukaan cekung
🡪 hilus
• Dibungkus kapsula
(simpai) 🡪 jar.ikat
fibrosa
• Masuk ke bagian
tengah membentuk
trabekula
HEV (High Endothelial Venules)
• Lymphocytes are intrinsically mobile, so they
can leave the blood- stream by preferential
migration across walls of specialized blood
vessels called high endothelial venules (HEVs).
• These thin-walled vessels, with diameters of
30-50 mm, are in the paracortex of a lymph
node. They are specialized for passage, by
selective diapedesis, of B and T cells from the
blood into perivascular areas.
• Endo- thelial cells in HEVs have cell adhesion
molecules that facilitate highly specific
transmigration of T and B cells.
Limfonodus
• Hilus 🡪 vasa eferen
• Cembung 🡪 vasa
aferen
• Di bawah kapsula 🡪
sinus subkapsularis atau
sinus marginalis
• Sel Retikulum
• B cells occupy lymphoid
nodules in the cortex,
and T cells are in the
paracortex, or thymus-
dependent region.
Limfonodus 🡪 Korteks
• Bangunan bulat
berisi limfosit
🡪 limfonodulus
• Sentrum
germinativum
• Korona
Limfonodus 🡪 Medulla
• Kerumunan
limfosit
memanjang
🡪 genjel
medulla
(medullary
cords)
• Sinus
medullaris
Lien Pulasan Perak
• struktur
kerangka
dasar
pembentuk
lien 🡪
jaringan ikat
reticular dan
serat
retikulin
Spleen/Lien
Blood FLow
 • In the open circulation, capillaries
• In the closed circulation,
capillaries branching from the
penicillar arterioles connect
directly to the sinusoids and the
blood is always enclosed by
endothelium.
from about half of the penicillar
arterioles are uniquely open-
ended, dumping blood into the
stroma of the splenic cords. In this
route plasma and all the formed
elements of blood must reenter
the vasculature by passing through
narrow slits between the stave
cells into the sinusoids. These
small openings present no obstacle
to platelets, to the motile
leukocytes, or to thin flexible
erythrocytes.
Lien Hewan
• Paling luar 🡪 simpai
atau kapsula fibrosa
(jaringan ikat padat
kolagen)
• Stigma Malphigi
• Pulpa putih (pulpa
alba) lebih gelap
• Pulpa merah (pulpa
rubra) 🡪 lebih
terang dan banyak
sinusoid
Lien Manusia
• Pulpa putih (pulpa
alba) 🡪 folikel 🡪
arteri folikularis /
arteri centralis
• Pulpa merah (pulpa
rubra) 🡪 Arteri
penisili, Arteri hulsen,
pembuluh kapiler
darah, sinus venosus
Tonsila Palatina
• Epitel berlapis gepeng
tanpa lapisan tanduk
• Sumur-sumur 🡪 kriptus
berisi benda liur.
• Dibentuk oleh
limfonodulus/ Nodulus
Limfatikus
• Tengahnya 🡪 terang
Sentrum Germinativum
• Tepinya 🡪 agak gelap
Korona
Timus
• While immature B lymphocytes emerge from the bone marrow, the primary
or central lymphoid organ in which T cells are produced is the thymus, a
bilobed structure in the mediastinum.
• A main function of the thymus is induction of central tolerance, which along
with regulatory T cells prevents autoimmunity. The organ originates from
the embryo’s third pair of pharyngeal pouches (endoderm), with precursor
lymphoblasts circulating from the bone marrow to invade and proliferate in
this unique thymic epithelium dur- ing its development.
• Fully formed and functional at birth, the thymus remains large and very
active in T-cell production until puberty during which it normally undergoes
involution, with decreasing lymphoid tissue mass and cellularity and reduced
T cell output
Timus
• The thymic cortex contains an
extensive population of T
lymphoblasts (or thymocytes),
some newly arrived via
venules, located among
numerous macrophages and
associ- ated with the unique
thymic epithelial cells (TECs)
that have certain features of
both epithelial and reticular
cells. These
Badan Hassal
• Their function is not well
understood, but they express the
cyto- kine thymic stromal
thymopoietin, which instructs
dendritic cells in the human
thymus to induce CD4+ regulatory
T cell develop- ment. They may
also play a role in removing
apoptotic thymocytes. Their size
and number increase in the
elderly, and they often calcify with
advancing age.
Timus
• Medulla 🡪
BadanHassal
(bulat, merah,
degenerasi hialin
(hialinisasi))
• Sel epiteloid
konsentris.
• Sel reticulum/sel
reticular 🡪 bintang
• timosit
Apendiks Vermiformis
• Epitel selapis silindris
• Lamina propria 🡪
kriptus Liberkuhn
• (Limfonodulus) 🡪
sentrum germinativum
yang besar (tunika
muskularis mukosa).
• Tunika Submukosa 🡪
banyak pembuluh
darah.
• TunikaMuskularis 🡪
lapisan sirkular dan
lapisan longitudinal
Pembuluh Limph
DAFTAR PUSTAKA
1. Hiatt JL, Gartner LP. Color Textbook of Histology. WB
Saunders Co, Philadelphia, USA. 1997.
2. Junqueira LC, Carneiro J. Basic histology text and
atlas: London: McGraw Hill; 2005.
3. Young B, Woodford P, O'Dowd G. Wheater's
functional histology: a text and colour atlas: Elsevier
Health Sciences; 2013.
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