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