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Medical Immunology

Explore the concepts, characteristics, and classification of cytokines, the network of CKs, and their actions in immune responses. Learn about interleukins, interferons, growth factors, and more in the context of immune system regulation.

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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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