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15 Cytokines and Their Receptors

15 Cytokines and Their Receptors. Master the concept and classification of the cytokines; Master the main properties and Biological effects of the cytokines; Master the main properties and function of IFN,TNF,IL and CSF; Understand the cytokine receptors.

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15 Cytokines and Their Receptors

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  1. 15 Cytokines and Their Receptors

  2. Master the concept and classification of the cytokines; Master the main properties and Biological effects of the cytokines; Master the main properties and function of IFN,TNF,IL and CSF; Understand the cytokine receptors.

  3. 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

  4. Cytokine Mj Cytockines are low-molecular-weight regulatory proteinsor glycoproteins secreted by white blood cells and various cells (vascular endothelial cell, epidermic cell and fibroblast ) in body in response to a number of stimuli. Activated Th1 cell macrophage IL-2 a A B’ D C P56 B C58 IL-1 COOH NH2

  5. Inducing stimulus Cytokine-producing cell Cytokine gene Cytokine Receptor signal Gene activation Overview of the induction and function of Cytokine Biological effects

  6. 15-1 General Characteristics of Cytokines Mechanisms of function

  7. (1) Binding to specific receptors and performance

  8. Circulation (2) Action manners 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 Binding to target cells in distant parts of the body. endocrine

  9. 2 Complexity of actions (1) Pleiotropism 多效（重叠性) Activation proliferation differentiation B IL-4 proliferation Thymus cell proliferation Mast cell

  10. (2) Redundancy 丰裕兴 Stimulating the proliferation of the B cells B IL-2，IL-4，IL-5 (3) Synergy 协同性 More effectively inducing the exchange of IgE B IL-4 + IL-5 (4) Antagonism 拮抗性 _ IL-4 interdicts the action that IFN-  induces Ig exchanges IL-4 B + IFN-

  11. 3 Rapidity On stimulation, rapid synthesis , release , action and degradation.

  12. 15-2 Classification and function of cytokines 1. interleukin, IL 2. colony stimulating factor,CSF 3. interferon,IFN 4. tumor necrosis factor,TNF 5. chemokine CK 6. growth factor,GF

  13. 1 Interleukin, IL Interleukins are secreted by some leukocytes and act upon other leukocytes, IL-1~IL-35 have been identified. IL-4 IL-2 IL-13

  14. 2 Interferon,IFN The cytokines that resist viral infection, and interfere viral replication, including IFN, IFN ( type I ); IFN ( type II ) virus infection cell IFN IFN IFN-, IFN-

  15. The anti-virus mechanism of IFN- a virus viral replication Inhibition of viral replication IFN-induced protein stimulating Signal-transduction nuclear nuclear IFN-a

  16. 3 Tumor necrosis factor,TNF The cytokines that induce directly apoptosis of tumor cells, including TNF, TNF (Lymphotoxin, LT）, FASL, CD70L, CD30L, CD40L, OX40L, TRAIL (TNF related apoptosis-inducing ligand) TNF-a

  17. Biological activities of TNF-. A cancerous tumor in a mouse injected with endotoxin (left) shows hemorrhagic necrosis, unlike a tumor in an untreated mouse (right). Endotoxin induces the production of TNF-, which then acts to destroy the tumor.

  18. Transgenic mouse (top) bearing a TNF- transgene becomes anorectic and severely wasted. Normal mouse is shown on the bottom.

  19. 4 Colony stimulating factor, CSF The cytokines that stimulate hemopoietic cells to form cell colony, Participate hemopoietic function are called CSF, for example GM-CSF,G-CSF,M-CSF, Epo (erythropoietin),Tpo (thrombopoietin). G-CSF GM-CSF

  20. The functions of CSF

  21. 5 Growth factor The cytokines that promote growth of various cells, epidermal growth factor，insulin-like growth factor，vascular endothelial growth factor vascular endothelial growth factor (VEGF)

  22. Growth factors applied to angiogenesis

  23. VEGF promotes Tumor Angiogenesis

  24. VEGF promotes Tumor Angiogenesis

  25. 6 Chemokine chemokines, a group of low-molecular-weight cytokinws including interleuki 8, that affect chemotaxis and other aspects of leukocyte behavior. Solution Structure Of The Cx3C Chemokine Domain Of Fractalkine Stromal Derived Factor-1 a

  26. Cytokines possessing chemotaxis cytokine（IL-8) C5a

  27. Chemokine make the shapes of cells changed

  28. Cytokine receptor member receptors Secrete receptor

  29. 15-10Cytokines in the Clinic Cytokines and immunological disorders Tumor Transplantation rejection Immunodeficiency Hypersensitivity Autoimmune diseases

  30. Cytokine and tumor

  31. The role of IL-8 signaling in the tumor microenvironment. Tumor-derived IL-8 has the capacity to exert profound effects on the tumor microenvironment. For example, secretion of IL-8 from cancer cells can enhance the proliferation and survival of cancer cells through autocrine signaling pathways. In addition, tumor-derived IL-8 will activate endothelial cells in the tumor vasculature to promote angiogenesis and induce a hemotactic infiltration of neutrophils into the tumor site. Although IL-8 can promote cell invasion and migration, the capacity of IL-8 to induce tumor-associated macrophages to secrete additional growth factors will further increase the rate of cell proliferation and cancer cell invasion at the tumor site.

  32. Immunodeficiency X-linked SCID, (XSCID)

  33. Mutations in the  c ( common  chain) chain of the receptors for interleukins IL-2, -4,-7,-9 and -15 **Signal transduction , **lymphocyte differentiation, proliferation and maturation

  34. IL-2R IL-4R IL-7R IL-9R IL-15R common  chain

  35. "bubble boy" disease, In the 1990s, late   researchers tested a gene therapy treatment that would restore the function of a crucial gene, gamma c, to cells of the immune system. This treatment appeared very successful, restoring immune function to most of the children who received it.

  36. 银屑病中CXCR1及CXCR2表达增高

  37. 白细胞介素-8受体1型和2型在强直性脊柱炎中均高表达白细胞介素-8受体1型和2型在强直性脊柱炎中均高表达

  38. Overexpression of cytokines The animal model for high dose of INF resulting the cachexia of mouce.

  39. Cytokines and application Supply and addition Blockage and antagonist

  40. Engineering cytokines on the market cytokine indication IFNα Leukemia, hepatitis, cancer, AIDS chronic granuloma, Allergic dermatitis, infectious diseases, rheumatoid arthritis IFNγ G-CSF Autograph , hemotocytopenia, AIDS, leukemia , aplastic anemia Autograph , hemotocytopenia, AIDS, leukemia , aplastic anemia GM-CSF Epo Anemia IL-2 Cancer, immunodificience, vaccine adjuvant IFNβ multiple sclerosis IL-11 thrombocytopenia SCF Stem cell transplantation combined with G-CSF EGF Burn, ulcer bFGF Burn, peripheroneuritis

  41. Engineering cytokines used in the clinical experiment cytokine indication company Immunex，Schering-Plough IL-10 Dermatitis, infectious diseases, rheumatoid arthritis IL-12 Cancer, AIDS GI Tpo Thrombocytopenia GI， TNF mutant Cancer Many company Immunex Flt3/flk3 Ligand(FL) Cancer Tumor chemotherapy HGS MPIF-1 Chronic ulcer of skin, multiple sclerosis Genzyme TGF- MIP-1mutant Tumor chemotherapy British Biotech OPG（osteoprotegerin） Osteoporosis Amgen Mulitkine Tumor CEL-SCI Immunodeficiency HGS BlyS

  42. 二、细胞工程抗体和基因工程抗体 抗体技术的发展经历了三个阶段 第一代：多克隆抗血清 第二代：细胞工程抗体 第三代：基因工程抗体

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