2. Immune response and regulation 免疫应答 (immune response, Ir) Body receive stimulation from Ag ， Specific lymphocytes recognize Ag ， they activate, proliferate and differentiate or become a state of anergy and apoptosis ， exert biological effect.

3. Immunological functions Functions Normal abnormal Defense c lear pathogen ↑hypersensitivity 、 (anti-infection ） ↓immune deficiency （ chronic infection ） homeostasis tolerant to auto-tissue ↑Autoimmune disease （ clear damaged and aged cells ） surveillance clear mutate cell ↓ ontogenesis （ Anti-tumor ） (persistent viral infection )

4. Classification Innate immunity （ non-specific ） Acquired immunity （ specific ） - Humoral immunity - Cellular immunity

5. Physiological IR （ Immune protection ） Non-self  reject Self  tolerant Pathological IR （ Immune damage ） IR too high  hypersensitivity IR too weak  Immune defect Tolerance terminate  Autoimmune disease Classification

6. Classification of specific immunity （一）体液免疫（ humoral immunity ） –To exogenous Ag or soluble Ag outside of cell （二）细胞免疫 (cell-mediated immunity) –To endogenous pathogen ， cellular Ag （ tumor Ag 、 grafted Ag ）.

7. Place of Ir Peripheral immune organ (lymph node 、 spleen and so on).

8. Process of Ir 3 stages ： Presenting and recognizing Ag ： Activation 、 proliferation and differentiation Effect

9. Basic process of Ir

10. Cellular immune response

11. lT recognize Ag and activation lEffect of T cell mediated IR and mechanism lBiological effect of cellular immunity

12. 3 stages ： ③ Production of effector cells ① Recognition phase ② Activation ， proliferation ， differentiation

13. APC presenting Ag to T cell Ag +APC peptide-MH Complex T cell

14. Interaction between APC and T cell TCR peptide-MHC LFA-1 change conformational structure CD4 MHC CD8 MHC Co-stimulatory molecule

15. 一、 Requirement for T recognizing Ag and activation （一） T cell recognize Ag * MHC restriction TCRαβchainre cognize Peptide on APC (Epitope of T cell ) MHC on APC surface (MHC restriction)

17. TCR 的 MHC 限制性识别示意图

18. Molecules involved in T cell recognition

19. Recognition phase 1. Take in Ag ： 2. Process and present Ag: 3. Interaction between APC and T cell Recognition of Ag ： Double recognition: TCR-peptide ， TCR-MHC Co-receptor:CD4-MHCII, CD8-MHCI Binding of co-stimulatory molecules on APC and T cells ： B7-CD28

20. Depend on 2 signals and CK 第二节 Activation ， proliferation ， differentiation

21. T cell activation for signal requirement 1 、 2 signals for Th activation （ 1 ） Active signal 1 (Ag) TCR specifically recognize peptide /MHC （ 2 ） Active signal 2 (binding of co- stimulatory molecule) B7-CD28 Adhesion molecules-their ligands 2 、 CK(IL-2 、 4 、 12…)

22. Signal 1 （ Ag ）： TCR recognize peptide-MHC Signal 2 （ Co-stimulator ）： binding of ADs

23. CD4 + T activation T cell activate signal 1 （ Ag recognition signal ） T cell activate signal 2 （ co-stimulator signal ） Flash

24. * T acquire signal ， but lack signal 2 ， anergy and apoptosis occur. * Block or enhance active signal 2, can reduce or increase Ir 。

25. The first signal for T cell activation TCR MHC-peptide Specifically recognize

26. Second signal for T cell activation AD on APC + co-stimulatory signal AD on T cell CD28/B7 ： involve in T cell activation CTLA4/B7 ： suppress T cell activation

27. CK ： Promote T cell activation

28. Proliferation and differentiation of T cell Th effector T CTL Active T memory T

29. 2. Proliferation and differentiation of CD4 + T Active T Express variety of CKs and receptors T cell grow Th0 Th1 Th2 IL-12,IFN-  IL-4 IL-2+IL-2R

30. Th divide into Th1 and Th2

31. Proliferation and differentiation of CD8 + T Th independent （ direct activation ） Th independent （ indirect activation ）

32. IL-2

35. go to effector T ； go to memory T ； go to apoptosis. Where will Active T go?

36. 二、 Effect and mechanism of T cell mediated IR ( 一 ) CD4 + Th1 mediate effect (inflammation) ( 二 ) CD8 + T C mediate effect (lyses of cell)

37. Cytotoxicity of CD8 + CTL(T C ) MHC restriction recognition of Tc * TCR recognize peptide/MHC-I on target cell ; requirement for Tc activation Active signal 1: TCR recognize Ag; Active signal 2: Co-stimulatory molecule bind its ligand CK: APC→ active Th →CKs （ IL-2 ， IL-6… ）

38. A ： lack active signal 1 ， T C leave target cell B ： T C recognize infected cell ， With signal 1 and 2 ， T C grow ， kill target cell and leave A B Double signals for T C activation

39. The killing mechanism for Tc cell The specific recognizing and binding phase The killing phase （ 1 ） active CTL de-granule release perforin →lysis of target cells release granzyme→ apoptosis of target cells （ 2 ） Fas-FasL pathway → apoptosis of target cells （ 3 ） Release cytotoxic CKs （ IFN-γ ， TNFα/β ）

40. CTL release perforin and granzyme to cause necrosis and apoptosis of target cell

41. CTL release perforin and form a channel in target cell membrene （ G=T 细胞颗粒， Go= 高尔基体， M= 线粒体， N= 核）

42. T C express FasL to induce apoptosis of target cell Actuve T C express FasL AAAAAA Interaction of Fas- FasL to induce apoptosis of target cell FasL Viral infected targeted cell

44. The process for T C killing target cell

46. CTL killing possess high Ag-specificity and MHC restriction

47. CTL kill one more target cells Property ： Specificity 、 MHC restriction 、 high efficacy

48. CD8 + T C mediated Ir T/Target cell TCR recognize peptide-MHC-I Interaction of ADs CD4 + Th activate Secret CKs Resting Tc transform to active Tc Release perforin and granzyme Fas 、 FasL Death of target cell signal 2 1

50. The effect caused by CD4 + Th1 Release many kinds of lymphokines ， lead to inflammation 1 、 Function on M  —secret CK –Activate M  : IFN-γ 、 CD40L –Induce and attract M  : IL-3 、 GM-CSF 、 TNF 、 MCP-1

51. 迟发型超敏反应 (delayed type hypersensitivity, DTH) ： caused by lymphocytes 、 lymphocytes and monocytes are main cells found in inflammation site. Activation 、 proliferation 、 differentiation and migration of immune cells take too long time, inflammation occur too late and maintain longer, referred to DTH.

52. Active M  activated by Th1

53. Gathering of lymphocytes and monocytes/M 

54. 2 、 to T cells promote proliferation of Th1 、 CTL ， enlarge immune effect 3 、 to B cells promote the production of Ab 4 、 To neutrophill activate

56. CD4 + T DTH mediated cellular Ir TDAg APC take in 、 process 、 present Ag Active signal 1 CD4 + Th1 recognize peptide-MHC-II complex Th1 activation proliferation Active signal 2 Th1 contact APC CKs Activated M  Resting M  Secret inflammatory Cks DTH CKs

57. Effect of active T ( 一 ) CD8 + CTL mediate cytotoxicity ( 二 ) CD4 + Th1 mediate DTH ( 三 )CD4 + Th2 assist B to produce Ab

58. The process of Immune response

59. 三、 Biological effect of cellular immunity ( 一 ) Killing endogenous microorganism → anti- infection immunity; ( 二 ) Killing tumor cell → anti-tumor immunity; ( 三 ) Immune damage killing grafted cells → graft rejection reaction killing auto cells and tissue → AID 。 DTH

61. Review Questions Describe the process of IR mediated by CD8 + T. 简述 CD8 + T 细胞介导的免疫应答过 程。 Describe the process of CD4 + T activation 简 述 CD4 + T 细胞的活化过程。 Describe the interaction of APC and Th 简 述 APC-Th 细胞是如何相互作用的。