History for the research of the cytokines

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1 History for the research of the cytokines
 In 1957，Interferon （IFN ） was found  In 1969， termed lymphokine  In1974，denominated cytokine  cytokinology；  international cytokine society 《 Cytokine 》  Companies for developing cytokines in many countries

2 Definition定义 由免疫细胞及组织细胞分泌的在细胞间发挥相互调控作用的一类小分子可溶性多肽蛋白，通过结合相应受体调节细胞生长分化和效应，调控免疫应答. 半衰期短，具有高效性。

3 properties of the cytokines
action manners作用方式: 自分泌、旁分泌、内分泌 1 Bind to receptors on the membrane of the same cell that secreted it autocrine Binding to receptors on a target cell in close proximity to the producer cells paracrine Circulation Binding to target cells in distant parts of the body. endocrine

4 Pleiotropy (多效性) IL-4 Activation proliferation differentiation B
1 一种CK可以对不同细胞发挥不同作用 Activation proliferation differentiation 活化 增殖 分化 B IL-4 proliferation 增殖 Thymus cell proliferation 增殖 Mast cell

5 Redundancy(重叠性) synergy(协同性) Antagonism(拮抗性) _ +
1 B Stimulating the proliferation of the B cells IL-2、 IL-4、 IL-5 不同CK作用类似 synergy(协同性) 1 More effectively inducing the exchange of IgE B IL IL-5 IL-5促进IL-4诱导B细胞类别转换（IgE） B cell Antagonism(拮抗性) 1 _ IL-4 interdicts the action that IFN-  induces Ig exchanges IL-4 B IFN- + 不同CK相互抑制

6 Non-specificity(非特异性)
rapidity (迅速性) 1 On stimulation, rapid synthesis , release , action and degradation. high potency (高效性) 1 Infinitesimal cytokines perform remarkable biological effects（pM,10-12 M). Non-specificity(非特异性) 1 perform in the non-specific manner, and not restricted by MHC

7 成纤维细胞 TC 网络性 BC 内皮细胞 IL-3、IL-5、IL-4、IL-6、 GM-CSF 1 IL-1、 IFN
IL-1 IL-6 GM-CSF G-CSF M-GSF IFN TNF TGF IL-1 IFN TNFIL-1 TGF IFN IL2 IL-4 IL-5 IL-6 IFNIL2 IL-4 TNF IL-1 IFN IL-5 GM-CSF G-CSF M-GSF TNF IFN IL-1 TGF TNF TNF IL-1 TGF IL-1 IL-6 GM-CSF G-CSF M-GSF BC IL-1 IL-6 内皮细胞

8 Classes of cytokines 1. interleukin,IL
2. colony stimulating factor,CSF 3. interferon,IFN 4. tumor necrosis factor,TNF 5. growth factor,GF 6. chemokine

9 i 白细胞介素Interleukin, IL interleukins are secreted by some leukocytes and act upon other leukocytes, IL-1~IL-38 have been identified.

10 Interleuukin-2 , IL-2 Activated Th1 cell 133 amino acids, MW 15KDa 1 a
P56 B C58 B’ C NH2 COOH 105 133 amino acids, MW 15KDa

11 IL-2 的功能 IL-2 activated Th1 cell NK cell B cell Macrophage
Activated T cell NK cell Promoting proliferation and production of cytokines Promoting proliferation and differentiation of cells, and synthesis of Ig Activated （LAK） Inhibition of cytotoxicity, promoting secretion of IL-1

12 i 干扰素Interferon,IFN the cytokines that can inhibit the development of tumor cells, interfere viral replication, and participate immune response, and so on. including IFN, IFN( type I); IFN( type II ).

13 Who secrete IFN ? Type I interferon ：IFN-, IFN- anti-virus
Virus-infected cells Type I interferon ：IFN-, IFN- anti-virus Type II interferon : IFN-γ, immune regulation CD8+T cell, CD4 + T cell, NK cell

14 IFN- 的作用 Activated Th1 cell NK cell IFN- B cell macrophage T cell
Virus infected cell NK cell Promoting Activation killed Promoting production of IgG3 and IgG2a Inhibiting expression of CD23 and production of IgE Promoting expression of MHC-II and Fc, antimicroorganism and antitumor, synthesis of TNF-， promoting IL-2 production IL-2R expression Enhancing IV hypersensitivity Plantation rejection cytotoxicity Inhibiting Viral replication, proliferation

15 肿瘤坏死因子Tumor necrosis factor,TNF
Cytokines that induce directly apoptosis of tumor cells, including TNF, TNF (Lymphotoxin, T） , FASL, CD70L, CD30L, D40L, OX40L, TRAIL(TNF related apoptosis-inducing ligand ),and so on.

16 Who secrete TNF ? TNF-a TNF-b ( lymphotoxin- a, LT- a) Two types:
Activated macrophage Activated T cell TNF-a 157 aa TNF-b = LTa 171 aa Homology 28% Same receptors Same bioactivities

17 TNF-a 的作用 Bone marrow T cell B cell
Up-regulation of the cytokine production(IL-2, IL-4, g –IFN,CSF) and expression of IL-2 receptor T cell B cell Inducing differentiation up-regulation of antibody production IL-2 IL-4 g -IFN TNF-a Mj macrophage neutrophil Bone marrow Up-regulation of production of prostaglandin前列腺素 and cytokines (IL-1, IL-6,IL-8,GM-CSF) Chemotaxis and activation of neutrophil Stimulating production of CSF Up-regulation of hemopoiesis

18 大剂量TNF注射造成恶液质的小鼠模型

19 集落刺激因子Colony stimulating factor, CSF
cytokines that stimulate hemopoietic cells to form cell colony, Participate hemopoietic function are called CSF, for example GM-CSF, G-CSF, M-CSF, Epo, Tpo, etc.

20 The funtion of CSF i

21 i 生长因子Growth factor,GF the cytokines that promote growth of various cells, Including epidermal growth factor表皮生长因子，insulin-like growth factor胰岛素样生长因子，vascular endothelial growth factor血管内皮生长因子，神经生长因子、血小板生长因子等.

22 i Chemokine趋化因子 chemokines, a group of low-molecular-weight cytokines, including interleukin-8, that affect chemotaxis and other aspects of leukocyte behavior. 含有2对或1对保守的半胱氨酸残基（C）形成的分子内二硫键。包括：C亚家族， CC亚家族，CXC亚家族，CX3C亚家族

23 趋化作用 cytokine（IL-8) C5a

24 WSXWS:Trp-Ser-X-Trp-Ser
细胞因子受体 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 -S-S- C1C3C2 -S-S- C1C3C2 保守的半胱氨酸 CC C -S-S- C1C3C2 WSXWS 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 IL-1 M-CSF C-kit IL-18 IFN-a IFN-b IFN-g IL-10 TNF-a TNF-b CD 神经生长因子（NGF） FasL IL-8 RANTES MIP-1 PF4 MCAF NAP-2 WSXWS:Trp-Ser-X-Trp-Ser

25 细胞因子的功能 1.调控免疫细胞的发育、分化和活化 2. 抗感染免疫 3. 抗肿瘤 4. 诱导细胞凋亡 5. 促进造血 6. 促进损伤修复

26 谢谢您的聆听！