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, IL Interferon , IFN Tumor necrosis factor, TNF Colony stimulating factor, CSF Chemokine  Transforming growth factor

Ⅰ. Interleukin (IL) IL-1~IL-29 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

Moderate affinity IL-2R IL-2 receptor High affinity IL-2R g b a Low affinity IL-2R Moderate affinity IL-2R IL-2

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 Cytokines and diagnosis: IL-3, CSF Cytokines and treatment: Th1 and Th2 Cytokines and disease prevention: CSF, IL-2 Cytokine assay