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Medical immunology

Medical immunology. Chapter 14 Immunoregulation. 教学大纲 熟悉 T 细胞亚群及其相互调节机制、独特性网络和抗原内影象概念 了解抗原、抗体、抗原抗体复合物、补体以及 ITAM/ITIM 对免疫应答的调节作用 了解免疫应答的基因调控、凋亡机制对免疫应答的调节以及整体和群体水平的免疫调节. 免疫调节（ immunoregulation):

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Medical immunology

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  1. Medical immunology Chapter 14 Immunoregulation

  2. 教学大纲 • 熟悉T细胞亚群及其相互调节机制、独特性网络和抗原内影象概念 • 了解抗原、抗体、抗原抗体复合物、补体以及ITAM/ITIM对免疫应答的调节作用 • 了解免疫应答的基因调控、凋亡机制对免疫应答的调节以及整体和群体水平的免疫调节

  3. 免疫调节（immunoregulation): the body control persistent and intensity of immune response by positive or negative regulators in order to maintain the balance of the whole body. functions： 1. enhance immunity ,eliminate foreign antigens ； 2. diminish harm to self tissues。

  4. Section 1 Discription I . Sensing of immune systemprecondition of immunoregulation II . Sensing signals by immune system & Quantitative change and qualitative alteration of immune molecule *Antigen doses *Antibody concentration *Proporation between Ag and Ab

  5. & Quantitative change of Immune cells clone & Affinity between ligand and receptor

  6. III . Mechanism of negative regulation play a major role & negative regulation is critical for maintaining self homeostasis * can maintain self tolerance * can maintain proper Ir Ⅳ . immune intervention :artificial

  7. Section 2molecule regulate immune response • I .Role ofantigen

  8. Regulation of antigen • Physicochemical properties of antigen • dosage • Inoculate ways • As the antigen concentration drops, relatively the intensity of immune response fall off.

  9. 结构相似的不同抗原之间竞争性调节

  10. Regulation of antibody & . Organism sense and adjust concentration of Ab & . Ab mediate immunoregulation * block antigen：Ab bind competitively specific Ag epitope with BCR or TCR , block soluble Ag or membrane Ag

  11. Mediate inhibitory receptor cross-link： • Receptor cross-link：BCR-Ag-Ab-FcγRIIb Fc region of Ab FcγRIIb Ag BCR

  12. Antibody dependent B cell suppression

  13. Ⅳ.Role of complement & regulation of complement activation * complement active fragment inactivate spontaneously * complement regulatory protein:negative

  14. & complement active fragment mediate immunoregulation * C3b、C4b、iC3b bind with Mφ * immune adherent facilitate to eliminate IC opsonization

  15. 6. CKs and Immunoregulation * 1.CKs regulate development and germination of immune cells * 2.Bidirectional immunoregulation of CKs

  16. lymphoid Myeloid stem cell

  17. IFN-γ、TNF-α : promote expression of MHC on APC • Positive regulation : • Negative regulation: IL-2、IL-4、IL-5、IL-6：promote T、B cell activation 、proliferation、differentiation IL-12、TNF-α：activate CTL Il-10、TGF-α：inhibit Mφ、T cell , reduce release of CKs

  18. CKs regulate differentiation of Th cell and affect type of Ir

  19. T细胞亚群与细胞因子 IL-12 IL-4

  20. Section 3 Role of cells

  21. T cell andimmunoregulation Immune regulation of Th1/Th2

  22. + – Relation between CKs and differentiation of Th0 into Th1 and Th2 subsets

  23. * Th1和Th2互为抑制细胞，从而调节机体的细胞免疫和体液免疫应答；

  24. 免 疫 偏 离 immune deviation 免疫偏离（immune deviation）:Th1或Th2细胞的优先活化而导致不同类型免疫应答及其效应呈优势的现象。

  25. Immune deviation • Th1 autoimmune disease • Th2 type – I hypersensitivity Graves disease，SLE

  26. Suppressor T cell • CD4+ CD25+ regulatory T cells • Secrete CKs to inhibit function of effect T cells • Also can affect the activation and function of innate immune cells • be used for immunotherapy of chronic inflammatory or autoimmune disease

  27. Apoptosis in immune response • CTL and NK exploit apoptosis as one mechanism for killing target cells that express Fas • AICD (activation induced cell death) Th cells express both Fas and FasL , may kill either themselves or one another lack of Fas/FasL, tumor or AID

  28. regulation of cell apoptosis negative * FasL/Fas pathway mediated AICD activated T cell clone apoptosis.

  29. activated induced lymphocyte clonal apoptosis

  30. Functions of AICD： Eliminate activated T/B cell clone，terminate immune response and keep immune tolerance。

  31. Role of regulatory receptoron the immune cell surface *co-signal molecule on T cell surface CD28 B7 co-stimulator ITAM CTLA-4 B7 co-inhibitory molecule ITIM

  32. 肿瘤逃逸 缺乏B7

  33. Role of regulatory receptor on the surface of immune cells (1) Activated receptor（positive ） ( ITAM ) (2) Inhibitory receptor（negative ） ( ITIM )

  34. 免疫细胞的激活性受体和抑制性受体 免疫细胞 激活性受体 抑制性受体 B cell BCR/Iga/b FcgRⅡB T cell TCR/CD3 CTLA-4, KIR NK CD16, DAP12 KIR,CD94/NKG2 mast cell FceRⅠ FcgRⅡB, gp49B1

  35. T/B细胞激活性受体的调节作用

  36. T/B细胞抑制性受体的调节作用

  37. role of NK cell activated receptor and inhibitory receptor

  38. Role of the idiotypic network （1）idiotype Ig, TCR, BCR V region antigenic specificity，can induce production of anti-idiotype (Ab2）。

  39. The unique V-region amino acid sequences of immunoglobulin

  40. 独特型和抗独特型抗体(抗体模型)

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