2.soluble cytokine receptor PartⅣ Biological functions of

SITOKIN
-Sekresi protein yang menjembatani dan mengatur sistem
imun, inflamasi dan hematopoiesis
-Sitokin diproduksi sebagai respon stimulus dari proses
imunitas
-Sitokin biasanya bekerja dalam waktu yang singkat, jarak
antar sel yg dekat, dan dalam jumlah (konsentrasi) yang
sangat kecil
-Sitokin bekerja dengan melekat pada membran reseptor yg
spesifik, kemudian memberi signal pd sel melalui messenger
kedua (sering terjadi enzim tyrosinkinase merusak kejadian
tersebut)
Sekresi sitokin oleh:
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•
Limfosit
Monosit
Sitosin yg aktif dlm khemotaktik
Sebagai media antar leukosit
limfokin
monokin
khemokin
interleukin(IL)
Reseptor sitokin
Sitokin
• Tidak seperti hormon yg tersimpan dalam
kelenjar(dlm btk molekul), sitokin cepat
disintesis dan disekresikan oleh sel yg berbeda
setelah ada stimulus
Sitokin
Aktivitas sitokin
• Berefek thdp sel yg mensekresinya sendiri
• Berefek thdp sel didekatnya
• Berefek pada sel yg sama tp berjauhan
autokrin
parakrin
endokrin
• Produser sitokin paling banyak adalah: sel –Th dan makrofag
Efek sitokin
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Pleiotropism
Redunden
Sinergik
Antagonis
Membentuk network sitokin
Pleiotropism
• Kemampuan satu sitokin untuk dapat
menyebabkan multiplikasi dari tipe sel target
Redunden
• Multipel sitokin mempunyai efek yg sama atau
overlaping
Sinergik
• Dua atau lebih sitokin mempunyai efek saling
menguatkan
Antagonisme
• Kemampuan satu sitokin untuk menghambat
aksi sitokin lainnya
Klasifikasi sitokin
Interleukin, IL
Interferon , IFN
Tumor necrosis factor, TNF
Colony stimulating factor, CSF
Chemokine
Transforming growth factor
Ⅰ. Interleukin (IL)
• Sitokin yg disekresi oleh leukosit yg mampu memberi
tanda /menjembatani aktivitas leukosit lainnya
• IL-1~IL-29
Ⅱ. Interferon (IFN)
A group of glycoproteins that produced by
human or animal cells following the
infection of virus and exposure to various
inducing agents
Comparison of IFN-, IFN-, IFN-
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Types
Produced cells
Main functions
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IFN-
leukocyte
anti-virus,immune regulation
I
IFN- Type fibroblast
anti-tumor
IFN---Type II Th1,NK ------- weaker anti-virus effect
stronger immune regulation effect
anti-tumor
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Ⅲ.Tumor necrosis factor (TNF)
TNFs were originally thought of as selective
antitumour agents, but are now known to have a
multiplicity of actions.
 TNF- is produced mainly by LPS activated
monocytes and macrophages.
 TNF-(lymphotoxin, LT) is produced mainly by
activated Th0 and Th1.
Ⅳ. Colony-stimulating factors (CSF)
Cytokines that stimulate proliferation or differentiation
of pluripotent hematopoietic stem cell and different
progenitors.
 Multi-CSF (IL-3)
 Granulocyte macrophage-CSF(GM-CSF)
 Monocyte-CSF(M-CSF)
 Granulocyte-CSF(G-CSF)
 Stem cell factor(SCF)
 Erythropoietin(EPO)
Ⅴ. Chemokine
Chemokines are cytokines which recruiting
monocytes,granulocytes and lymphocytes in blood to
the sites of inflammation.
 CXC chemokines(α subgroup):IL-8
 CC chemokines(β subgroup):MCP-1
 C chemokines(γ subgroup)
 CX3C chemokines(δ subgroup)
*C: cysteine; X: any amino acid
Ⅵ. Transforming growth factor
Growth-factor are cytokines which stimulate the
growth of their target cells.
 Transforming growth factor-(TGF- )
 Epithelia growth factor(EGF)
 Vascular endothelia cell growth factor(VEGF)
 Fibroblastic growth factor(FGF)
PartⅢ CK receptor
1. Membrane-binding cytokine receptors:
The receptor consists of extra-cellular region,
trans-membrane region and cytoplastic
region.
CK receptors can be grouped into five
families according to structure and
function:
(1) Ig receptor superfamily:IL-1R,PDGFR,FGFR
(2) Type Ⅰ CK receptor superfamily: CSFR
(3) Type Ⅱ CK receptor superfamily: IFNR
(4) Type Ⅲ CK receptor superfamily: TNFR
(5) G-protein linked receptor superfamily: CCR5
IL-2 receptor
Low affinity IL-2R
Moderate affinity IL-2R
High affinity IL-2R
IL-2
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
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

Three forms of the IL-2 Receptor
(CD25)
Some cytokines use a common chain for signal transduction
2.soluble cytokine receptor
PartⅣ Biological functions of cytokines
1.Take part in nonspecific immunity
------anti-bacteria, anti-virus
2. Take part in specific immunity
3. Stimulate hematopoiesis
4. Take part in inflammatory reaction
PartⅤ Cytokine and disease
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Cytokines and diagnosis: IL-3, CSF
Cytokines and treatment: Th1 and Th2
Cytokines and disease prevention: CSF, IL-2
Cytokine assay