Humoral Ir mediated by B cells

1. Chapter 12 Humoral Ir mediated by B cells

2. Major content Concept Response to TD-Ag Characteristics of primary and secondary Ir Response to TI-Ag Effect of B cell response

3. 体液免疫应答(humoral immunity) B cells encounter specific Ag, activate ,proliferate and differentiate to plasma cells，produce Abs, eliminate Ags. Ab exist in blood, important effector.

4. Classification • B cells Respond to TD-Ag（protein) • B cells Respond to TI-Ag (Glucose and Glylipid）

5. B cells response to TD-Ag

6. B cell antigen receptor complex

7. BCR direct recognize B cell epitope

8. B cell and Th cell recognize different epitope on the same Ag 载体效应

9. BCR recognize Ag and activation of B cell 信号1 * B细胞特异性结合抗原，向B细胞传递抗原刺激信号； * 通过BCR摄取抗原，并将抗原降解为肽段，形成抗原肽-MHC-II类分子复 合物，供抗原特异性Th细胞识别；

10. B cells response to TD-Ag * B cells recognition to TD Ag * B cells activation, proliferation and differentiation * Primary and secondary response * Effect of B cell response

11. B cell activation （一）active siganl 1 (Ag) * BCR specific bind epitope on B cell； *co-receptor：CD21/CD19/CD81 bind C3d linked with Ag； * Igα/Igβ：signal transduct； （二） active siganl2 (co-stimulatory molecule) *activation of naive Th：APC（DC) present double siganls and CK to naive CD4+T. develop to effective Th； * B cell present Ag：B cell take in Ag via BCR，process it，formation of peptide-MHC complex，present to Th； *Effective Th combines with B cell specifically：TCR recognize Ag presented by B； *Co-stimulatory sgnal：CD40L(on active T) bind CD40(on B cell)； （三）CKs IL-1/APC、 IL-4/Th promote activation of B cell.

12. BCR and co-receptor complex

14. Th细胞和B 细胞间相互作用 Interaction of T and B cells

16. Th help B cell activating, proliferating and differentiating

17. Cytokines promoting B cell activation, proliferation and differentiation

18. B cells proliferation and differentiation Active B cell express many CKR  receive stimuli of CK from Th  IL-2,IL-4,IL-5 promote B cell proliferation， IL-4,IL-6,IFN-g promote B cell differentiation.

19. B cell mature in germial center * Somatic hyper-mutation and Ig affinity maturation *Antigenic receptor editing： Ig gene rearrangement occur in auto-reactive B cell, edited BCR point at none-self Ag. *Ab class switch：V region does not change，only C region of H chain change.。

20. Cytokines and antibody isotype switch Flash

21. B cell mature in germial center * Somatic hypermutation and Ig affinity maturation *Antigenic receptor editing： Ig gene rearrangement occur in autoreactive B cell, edited BCR point at none-self Ag. *Ab class switch：V region does not change，only C region of H chain change.。

22. PC （late）IgG B cell primary response toTD-Ag TD Ag APC take in,process and present Ag B7-CD28 IL-1 TCR recognize peptide/MHCII B/Th interaction CD40/CD40L binding BCR recognize B cell epitope Th develop Signal 2 Signal1 secretIL-2、IL-4、IL-5、IL-6 B cell develop Mature in germinal center （early）IgM PC （die after 2 Wk） Memory B （enter lymphocyte re-cycle） （in bone marorw）

23. Primary and secondary response

24. 初次免疫应答 （Primary immune response） • Ir induced by pathogen first invaded human body. • Properties： - longer lag phase； - Most class of Ab is IgM ； - Level of Ab is low； - Affinity of Ab is low.

25. Four phases 潜伏期 对数生长期 平台期 下降期

26. 再次免疫应答 （secondary immune response） • The same Ag reenter body, stimulate memory cells to elicit prompt, efficacy and specific response. • Properties： - APC (memory B) interact with memory T； - Low amount of Ag for simulation； - Lag phase shorter； - Ab Level higher, Ab duration longer； - Most class of Ab is IgG ，affinity higher。

27. Primary and secondary humoral immune responses

28. Memory B cells present antigen to T cell

29. Raising Ab production and affinity after repetitive immunization

30. Primary and Secondary Immune Response Ab concentration Total amount of Ab IgG Lag phase Lag phase IgM 10 3 First stimuli of Ag Repetitive stimuli of the same Ag Days

31. Features Primary secondary Ag stimulation Lag phase 2-5 days 5-10 days Ab peak lower higher longer shorter duration IgM IgG、IgA Ig Class low high affinity Difference of primary and secondary response first second

32. Effect of B cell response

33. Neutralization By Antiviral Antibodies

34. Effector mechanisms against extracellular pathogens (2) OPSONISATION Bacteria in extracellular space + Ab Fc receptor binding Phagocytosis OPSONISATION

35. Action of phygosytosis

36. (3) Complement activation

37. Bacteria in plasma + Ab & COMPLEMENT Opsonisation Complement & Fc receptor Phagocytosis binding Effector mechanisms against extracellular pathogens COMPLEMENT Activation Lysis

38. FcgR and Complement Receptors Cooperate To Induce Greater Phagocytosis

39. (4) .Effector cells of ADCC

40. (4)

41. (5) IgA against adhesins

42. (6) Immune damage IgE Antibody Binds To Mast Cells & Basophils To Arm Them For Mediator Release

43. B cell response to TI Ag

44. TI-1Ag activate B cell - At high concentration,TI-1Ag induce activation of many B cells (polyclonal activation) - At low concentration, TI-1Ag induce activation of specific B cell. * TI-2 Ag direct activate mature B1 cell - Repetitive epitopes bind BCR→BCR cross-linkage→produce IgM Do not require Th，without immune memory，occur earlier.

46. Mechanism for TI-Ag activate B cell （A）： TI-1 Ag （B）： TI-2Ag

47. TI-1 TI-2 SmIg epitope mitogen R SmIg High Repeatitive epitopes ① ② Activate Activate B B2 capsule of pneumococcus LPS mitogen Signal Signal B cell activation induced by TI antigen

49. Effect of B cell mediated Ir * Neutralization：Neutralize toxin、virus *Opsonization：Ag coated with IgG and IgA，promote phygocytosis * Activation of complement：（IgG/IgM）IC，activate classical pathway - CDC - Opsonization * ADCC：NK、M、NC、EC * Mucous defense of secretary IgA * Immune damage: - hypersensitivity and AID - Graft rejection reaction：preformed Ab cause hyper acut reaction - promote tumor growth ：blocking factor，interrupt CTL reorganization to tumor Ag