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Medical Immunology

Medical Immunology. Cytokines ， CKs 陈建忠 浙江大学免疫学研究所. Cytokines. Concept Characteristics Classification Cytokine receptor Biologic activity. Introduction to cytokines. Cytokines (CKs)

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Medical Immunology

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  1. Medical Immunology Cytokines，CKs 陈建忠 浙江大学免疫学研究所

  2. Cytokines • Concept • Characteristics • Classification • Cytokine receptor • Biologic activity

  3. Introduction to cytokines • Cytokines (CKs) Cytokines are small proteins that are secreted by cells and exert their biological activity through specific cell surface receptors.

  4. Introduction to cytokine • Nomenclature • Old：monokine,lymphokine, • New：colony stimulating factor, interleukin, interferon, tumor necrosis factor,growth factor, chemokine

  5. Introduction to CKs • General properties of CKs 1.Small proteins (MW:approx. 15-30 KD); 2.Extremely potent, acting at pM or fM 3.The production is transient and tightly regulated; 4.Autocrine , paracrine or endocrine; 5.Non-specific and non-MHC restriction；

  6. Introduction to CKs • Cytokine Actions • Pleiotropy:Act on more than one cell type (IFN-α / β) • Redundancy:More than one cytokine have the same action (IFN- α / β and IFN- γ)

  7. Introduction to CKs • Cytokine Actions • Synergy:Two or more CKs cooperate to produce an effect that is different or greater than the combined effect of the two cytokines when functioning separately (IL-12 and IL-18) • Antagonism:Two or more cytokines work against each other (IL-4 and IL-12)

  8. Introduction to cytokine • The CKs network It has been shown above that there are many CKs with multiple functions and apparent redundancy of action forming a complex communication network.

  9. Cytokines network

  10. Categories of CKs • Interleukin (IL) • Interferon (IFN) • Tumor necrosis factor (TNF) • Colony stimulating factor (CSF) • Chemokine • Growth factor(GF)

  11. interleukin, IL • IL 1～33 IL-2（T cell growth factor） IL-4（ B cell growth factor ,Th2 type） IL-6（ Th2 type ） IL-8（belongs to chemokine） IL-10（Th2 type） IL-11（stimulator of platelet） IL-12（Th2 type）

  12. IL-2

  13. interferon, IFN • IFNs mediate the early innate immune response; • groups type I IFN: IFN-α and IFN-β. The major source is leukocyte, fibroblasts and virus infected cells； type II IFN : IFN-γ . IFN-γ is mainly produced by activated T cells and NK cells.

  14. 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

  15. Tumor necrosis factor, TNF • TNF: cause the necrosis of tumors • TNF-αand TNF-β. • TNF-α was produced by LPS-stimulated mononuclear phagocytes and activted T cells； • TNF-β：also termed as lymphotoxin ( LT），and the major source is activated T cells.

  16. Colony-stimulating factor, CSF • Stimulating the differentiation and expansion of bone marrow progenitor; be assayed by their ability to stimulate the formation of cell clonies in culture. • Including IL-3, CSF(G-CSF, M-CSF, GM-CSF), SCF, EPO, TPO, etc .

  17. Chemokine • Chemokines are a large family of structurally homologous CKs that stimulate movement and regulate the migration of leukocytes from the blood to tissues, including about 50 different chemokines. • subfamiles: CXC, CC, C, CX3C, based on structural characteristic (cysteine residues).

  18. Chemokine • IL-8 CXC neutrophils • MCP-1 CC monocyte • Lymphotactin C lymphocyte • Fractalkine CX3C lymphocyte

  19. Growth factor(GF) • Promoting the proliferation and differentiation of cells; • Including TGF-、EGF、VEGF、FGF、NGF、PDGF , etc.

  20. cytokine receptor 1.Five families • Ig superfamily receptors • Class I cytokine receptor family • Class Ⅱ cytokine receptor family • Class Ⅲ cytokine receptor family (TNF receptor family) • Chemokine receptor family

  21. CK receptor • Multi-subunit receptor one for cytokine binding another for cytokine signaling

  22. CK Receptor • Common receptor subunit There is same receptor subunit for cytokine signaling among the different cytokine receptors. e.g. IL-2Rγ

  23. CK Receptor

  24. CK Receptors • Soluble cytokine receptors Functions： ①antagonist of CKs； ②delivery tools of CKs； ③as a index of diagnosis and surveillance of diseases

  25. Biologic actions of CKs • Anti-bacteria: IL-1 , TNF, IL-6, and IL-12, • Anti-virus:type I IFN

  26. Biologic actions of CKs • Mediate and regulate adaptive immunity : Stimulating the proliferation of lymphocytes：IFN-,IL-2 ,IL-4 ,IL-5) Stimulating the development of lymphocytes: IL-12, IFN- ,IL-4. Increasing the activity of effective cells：IFN-  , IL-2 . Inhibiting immune response: TGF-,IL-10

  27. Comparative Features of the Cytokines of Innate and Adaptive Immunity Cyclosporine

  28. Biologic actions of CKs • Stimulate hematopoiesis SCF → stem cells CSF → granulocyte and monocyte IL-4 and GM-CSF →dendritic cells EPO → erythrocyte IL-11 and TPO →platelet IL-7 → formation of pro-T • Angiogenesis

  29. Biological product of cytokines or cytokines receptor analogs • rIFN-α:Intron-A, Referon-A • rIFN-β:Prokine • rEPO:Epogen • rGM-CSF:Acimmune • Human TNF McAb:HumiraTM

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