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:
• Limfosit limfokin• Monosit monokin• Sitosin yg aktif dlm khemotaktik
khemokin• Sebagai media antar leukosit 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 autokrin• Berefek thdp sel didekatnya parakrin• Berefek pada sel yg sama tp berjauhan endokrin
• Produser sitokin paling banyak adalah: sel –Th dan makrofag
Efek sitokin
• 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, ILInterferon , IFNTumor necrosis factor, TNFColony stimulating factor, CSFChemokine 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-
_____________________________________ Types Produced cells Main functions
____________________________________ IFN- leukocyte anti-virus,immune regulation IFN- fibroblast anti-tumor IFN---Type II Th1,NK ------- weaker anti-virus effect stronger immune regulation effect anti-tumor
_____________________________________
Type I
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
High affinity IL-2R
Low affinity IL-2R Moderate affinity IL-2R
IL-2
IL-2 receptor
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
Part Cytokine and diseaseⅤ• Cytokines and diagnosis: IL-3, CSF• Cytokines and treatment: Th1 and Th2• Cytokines and disease prevention: CSF, IL-2• Cytokine assay
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