1. 1 Immunoregulation

2. 2 The immune response is subject to a variety of control mechanisms which serve to restore the immune system to a resting state when the response to a given antigen is no long required.

3. 3 抗体浓度对抗体产生的调节 家兔经抗原免疫后产生特异性抗体，用血清交换人为降低抗体浓度后，可引起抗体产生量 的反馈性升高, 并在到达一定强度后逐渐下降。说明机体可感知自身抗体浓度的变化，并 自行启动调节机制

4. 4 Immunoregulation:homostasis Normal anti-infection anti-tumour Abnormal Auto-immune disease Tumour Persisitent infection Allergy

5. 5 Regulation of innate immunity Immunoregulation mediated by Inhibitory Receptor Regulation by Treg Idiotype network Immunoregulation by other mechanism Immunoregulation

6. 6 A. Regulation of innate immunity 1.Feedback Regulation of secretion of inflammatory factor

7. 7 固有免疫中针对 TLR 信号转导的负向调节 TIR: Toll/IL-1 receptor; ASK1: 凋亡信号调节激酶 1; IRAK: IL-1 受体相关激酶 ; MAPK: 丝裂原激活 蛋白激酶 ; MyD88: 髓样分化因子 88; NF-  B: 核因子  B; PI 3K: 磷酸肌醇 3 激酶 ; PIP2 ： 2 磷酸磷脂 酰肌醇 ; PIP3: 3 磷酸磷脂酰肌醇； PKB: 蛋白激酶 B; Rac: 小 G 蛋白 ; SIGIRR: 单一 Ig IL-1R 相关分子 ; TIRAP: TIR (Toll/IL-1 受体 ) 相关蛋白 ; TRAF6: TNF 受体相关因子 6 。 炎症细胞因子基因转录 TLR4CD14ST2SIGIRR MD2 MyD88 TIRAP TRAF6 SOCS1 IRAK1 IRAK4 NF-  B MAPK PKB PI 3K MyD88s IRAK-M 受体 衔接蛋白 信号分子 激酶 转录因子 抑制因子 基因转录 激活 抑制 Rac1 PIP 2 PIP 3 ASK1 TIR

8. 8 A. Regulation of innate immunity 1.Regulation by SOCS (suppressor of cytokine signaling)

9. 9 SOCS 蛋白以负向反馈环路阻抑细胞因子的信号转导

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11. 11 免疫细胞激活性受体和抑制性受体及其作用特点 基因转录 激活 抑制 Zap-70, SykSHP-1, SHP-2 ITAMITIM Src PTK PTKPTP 磷酸化 激活性 受体 抑制性 受体 磷酸化脱磷酸化

12. 12 T 细胞激活及相关免疫反应中的共信号分子及其受体 家族 配体 受体 ITAM/ITIM Ig-SF B7-1 CD28 ITAM B7-2 CTLA-4 ITIM B7-H1 PD-1 ITIM B7-DC ? B7-H2 ICOS B7-H3 ? HVEM BTLA ITIM TNF CD40L CD40 OX40L OX40 4-1BBL 4-1BB T T APC

13. 13 24 h B7 CD28 Ag TCR B7 CTLA-4 Activation I T I MI T I M I TAM inhibition T cells Negative regulation of T cell activation by CTLA-4

14. 14 Negative regulation of Ab production by Inhibitory receptor Fc  RII-B Interfere B cell signaling BCR (mIgM) 抗 BCR 抗体 Ag-Ab complex Fc  RII-B ITIM

15. 15 Receptors of human NK cells Inhibitory receptor Activation receptor Ig super family C-Lectin SF

16. 16 allo- cell tumor cell normal cell virus- Infected cell NK + + + + – kill no kill NK’s cytotoxic activity depends on activation of the signaling initiated by the ligation of inhibitory receptor with its ligand activation receptor inhibitory receptor

17. 17 T Cell B cell  T cell Mast cell NK cell TCR-CD3 BCR-Ig  /Ig  V  9V  2 TCR Fc  RI KIR-S + DAP12 CD94/NKG2C + DAP12 NKG2D + DAP10 NCR +  /Fc  R1  CD16 +  /Fc  R1  CTLA-4, PDL-1, BTLA Fc  RII-B, CD22 CD94/NKG2A Fc  RII-B KIR-L CD94/NKG2A ILT2 Cell Activating receptor Inhibitory receptor Activating receptor and Inhibitory receptor of Immune cells

18. C. Regulation T Cells(Treg) Suppressor T cells (Ts) (1970s) Regulatory T lymphocytes (Treg) are a subset of CD4+ T cells whose function is to suppress immune responses and maintain self-tolerance 18

19. Treg ： Marker 19

20. Treg Humans IPEX (immune dysregulation, polyendocrinopathy,enteropathy, X-linked syndrome) is also associated with deficiency of Treg and is now known to be caused by mutations in the FOXP3 gene. 20

21. Treg ： Generation and Maintenance 21

22. 22 Treg:subsets characteristicNature Tregadaptive Treg Induction locationThymus (periphery),periphery Foxp3++++ IL-2 dependence++ CD25+++-/+ Antigen specificityAuto-antigenTissue-specific Ag and exogenous Ag mechanismCell-contact, CK independence Cell-contact, CK dependence FunctionInhibit ART mediated Response Inhibit pathological response ExampleCD4+CD25+TCD4+ Tr1,Th3 Naturally Treg and adaptive Treg

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27. 27 Counter action of Th1 and Th2 subsets

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30. 30 IFN-  induced Th1 to activate intracellular killing Macrophages TB in Lysosomes

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32. 32 D. Regulation by idiotypes and anti-idiotypic antibodies Antibodies formed against Ag-binding sites of an Ab are called anti-idiotypic antibodies, and are capable of influencing the outcome of an immune response. Id and AId interactions may enhance or suppress Ab responses.

33. 33 Network Theory （ 1974 ） Jerne explains how the specific immune response is regulated. The immune response is regulated by a complicated network consisting of antibodies and anti-ab. The principles of the network theory are beginning to be exploited in prevention, diagnosis and treatment of disease. Network Theory （ 1974 ） Jerne explains how the specific immune response is regulated. The immune response is regulated by a complicated network consisting of antibodies and anti-ab. The principles of the network theory are beginning to be exploited in prevention, diagnosis and treatment of disease. Niels K. Jerne 1911-1994,UK 1984 Nobel Prize Niels K. Jerne 1911-1994,UK 1984 Nobel Prize

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36. 36 Idiotype network and antigen internal image Ag Ag Ab1 (Id) Ab2 (AId) Ab3 Ab   epitope

37. 37 利用独特型网络进行免疫干预的两种主要途径 Ag Ab2  Enhance Ab1 Ab1 Ab2 B A Ab3 / Ab1 Ab1 Ab2  Ab2  Impair Ab1

38. 38 E. Regulation by apoptosis 1. Activation-induced cell death (AICD)

40. 40 F. Regulation by neuroendocrine system Lymphocytes express receptors for many hormones, neurotransmitters and neuropeptides.

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43. 43 G. Genetic control of immune response 1.Control of immune response by MHC Immune response genes (Ir) control all immune responses Most of the polymorphic residues in MHC molecules reside in the peptide-binding groove MHC restriction APC-Th, Th-B MHC II CTL-Target MHC I 2. Non-MHC-linked genes affect immune response :TCR ， BCR ， C

44. 44 Question The inhibitory receptors of immune system and its biological significanceThe inhibitory receptors of immune system and its biological significance Difference between nature Treg and inducible TregDifference between nature Treg and inducible Treg