Cytokines

1. Cytokines Concept Characteristics Classification Biologic activity Cytokine receptor

2. Concept cytokines are low-molecular-weight proteins secreted by activated immunocytes and various other cells, which act on their target cellsby binding to their receptors.

3. Cytokines have a numerous biological functions, such as inducing growth, differentiation, chemotaxis, activation, enhanced cytoxicity and /or regulation of immunity. Naming

4. Characteristics 1. Most cytokines are low molecule weight proteins or glycoproteins 2. Cytokines come from many kinds of cells----activated immune cells, matrix cells and some tumor cells. one cell may secrete many kinds of cytokines, different cells may secrete the same cytokines.

5. 3. Cytokines act by binding to corresponding receptors on the target cell

6. 4. Cytokines act on target cells by the way of paracrine, autocrine or endocrine.

7. autocrine action Acting on cells that produced them paracrine action Acting on cells close by endocrine action Acting on cells at a distance 细 胞 因 子 发 挥 作 用 的 三 种 方 式 作用于分泌细胞自身 自分泌 autocrine 作用于比邻细胞 旁分泌 paracrine 血液循环 内分泌 endocrine 远距离作用

8. 5. The biologic effects of cytokines are highly efficient, multiple, overlapped, antagonistic and synergic, which act in a network.

9. Cytokines can have effect in spite of very low concentration. One picogram (10-12 g) of IFN-αwas able to protect one million cells from 10 million virus particles in a tissue culture experimentsOne kind of cytokine may have multiple effects.Several kinds of cytokines may have the same or similar effect.One kind of cytokine may inhibit activities of other kinds of cytokines.One kind of cytokine may enhance activities of other kinds of cytokines.

11. Th1 和 Th2 细 胞 的 分 化 Th0 +IL-2 +IL-4 Th1 Th2 IL-2 IFN-g 抑制 IL-4 IL-10 细胞免疫 体液免疫

12. 骨髓基质细胞 下 丘 脑 造血干细胞 IL-1 IL-6 TNF-a IL-1 IL-6 IL-7 SCF IL-1 IL-6 IL-11 TNF-a GM-CSF G-CMF M-CSF 内皮细胞 IL- 4 M-CSF GM-CSF IL-1 TNF-a 单核细胞 IL- 4 M-CSF GM-CSF Mj IL-1 TNF-a 纤维母细胞 IL-1 TNF-a TGF-b PDGF FGF 中性粒细胞 IL-1 IL-8 TNF-a IL-12 IL-10 IL- 4 G-CMF IFN-g GM-CSF IL-10 IL-13 IL-4 TGF-b IL-2 IFN-g IL-2 NK 细胞 IL-2 IL-12 IL- 4 IL-6 TH1 TH2 Tc B IFN-g 嗜酸性粒细胞 IL-10 IL-13 IL-4 IL-4 IL-2 IL- 4 IL-4 IL-5 IL-6 IL-13 IL-10 TGF-b IL-2 IFN-g IL-4 IL-4 IL-4 IL- 6 内皮细胞 NK1+T

13. Classification 1. Interleukin (IL) 2. Interferon (IFN) 3. Colony stimulating factor (CSF) 4. Tumor necrosis factor (TNF) 5. Growth-factor (GF) 6. Chemokine be grouped by their functions and structures

14. 1. Interleukin The term was used to describe cytokines produced by leukocytes. In fact, they can be produced by other cell populations. IL-1---IL-35.

15. 2. Interferon Interferon are involved in defense against viral infection and in activation and modulation of immunity. Type I interferon IFN-α , IFN-β: Anti-virus and anti-tumor Type II interferon IFN-γ: Immunoregulation and anti-tumor

16. IFN-a 的 抗 病 毒 作 用 病毒 抑制病 毒复制 病毒复制 IFN-诱导蛋白 诱导刺激 信号转导 胞核 胞核 IFN-a

17. 3. Colony stimulating factor Colony stimulating factors (CSFs) drive the development, differentiation and expansion of cells of the myeloid series. IL-3GM-CSF (granulocyte macrophage colony- stimulating factor)M-CSF (monocyte colony stimulating factor)G-CSF (granulocyte colony- stimulating factor)SCF (stem cell factor)EPO (erythropoietin )

19. 4. Tumor necrosis factor Tumor necrosis factor (TNF) which can induce tumor necrosis is produced by a variety of cells including activated macrophage and T cell . It has other important biologic effects. TNF-α , TNF-β:Proinflammatory

20. 5. Growth-factor Growth-factor are cytokines which drive the growth of their target cells.Transforming growth factorsTGF- α , TGF- βTGF- β : immunosuppressive

21. 6. Chemokine Chemokines are cytokines which direct cell migration and /or activate cells.CXC CC C CX3C CCR5----HIV

22. Biologic activity 1. Take part in innate immunity 2. Take part in adaptive immunity 3. Mediate inflammation 4. Stimulate hematopoiesis

23. Biologic activity 1. Take part in innate immunity IFNs have three types,IFNα,IFNβ and IFNγ. IFNα and IFNβ are produced in response to viral infection by the infected cells and act on their target cells to inhibit viral replication.

24. Biologic activity 2.Take part in adaptive immunity cytokines have effects on activation, proliferation and differentiation of lymphocytes.

25. Biologic activity 2. Take part in adaptive immunity Cytokines have an important role in generation of antibody class diversity.

27. Biologic activity 3. Mediate inflammation Chemokine . 4.Stimulate hematopoiesis These cytokines act on hematopoietic stem cells resulting to generation of blood cells.

29. Cytokine receptors 1.Membrane-binding cytokine receptors The receptor consists of extracellular region, transmembrane region and cytoplastic region.

30. Grouped by structure:(1) Immunoglobulin family(2) Type I cytokine receptor family(3) Type II cytokine receptor family(4) TNF receptor superfamily(5) Chemokine receptor family

31. -S-S- -S-S- -S-S- 细胞因子受体分类 免疫球蛋白超家族受体 I类细胞因子受体 II类细胞因子受体 TNF-R 趋化因子受体 C1C3C2 C1C3C2 C1C3C2 CC C C C1C3C2 G 蛋白 IL-2 IL-3 IL-4 IL-5 IL-6 IL-7 IL-9 IL-11 IL-12 IL-13 IL-15 OSM GM-CSF G-CSF LIF CNTF 生长激素催乳素 IFN-a IFN-b IFN-g TNF-a TNF-bCD40 神经生长因子（NGF） FAS IL-8 RANTES MIP-1 PF4 MCAF NAP-2 IL-1 M-CSF C-kit

33. Some cytokines use a common chain for signal transduction g -链 参 与 组 成 的 细 胞 因 子 受 体 IL-2R IL-4R IL-7R IL-9R IL-15R 共用的 g 链

34. 2. Soluble cytokine receptors These receptors can compete with memebrane-binding receptors for binding to the cytokines, resulting to inhibition of the effects of the cytokines.