1. Chapter 15 B cell mediated immune response

2. B Cells Lymphocytes that react directly with antigens Require stimulation from Helper T Cells Offspring become –Plasma cells –Memory B cells Humoral Immunity:is immunity provided by antibodies

3. Plasma Cells Plasma cells are antibody factories Are also called Antibody Forming Cells Produce huge numbers of antibodies –2000/second

4. B cells mediated immune response Humoral immunity (HI) or antibody mediated immunity: The total immunological reaction that B cells recognize antigen, then activate, proliferate, differentiate into plasma cells and produce Ab. B2 cells mediated immune response to TD-Ag B1 cells mediated immune response to TI-Ag

5. Contents  Part Ⅰ Immune response of B2 cell to TD-Ag  Part Ⅱ Rules of humoral immunity  Part Ⅲ Immune response of B1 cell to TI-Ag

6. Part Ⅰ Immune response of B2 cell to TD-Ag Characteristics of TD-Ag: Most are native antigen proteins, large molecules Possess T cell epitope and B cell epitope Both CMI and HI Need Th cells participation Produce several types of antibodies: IgG Produce immune memory

7. Part Ⅰ Immune response of B2 cell to TD-Ag B2 cells recognize TD-Ag activate, proliferate, differentiate plasma cells produce Ab Ag

8. B cells can recognise native antigens directly Y Y Y Y Y Y Y B Proliferation and antibody production Cross-linking of surface membrane Ig Y B Y B Y B Y B Y B Y B Y B Y Y B Th

9. 1. B cells recognize antigen BCRs directly recognize the epitope on the surface of Ag No APC, no MHC restriction Capture Ag by BCR, present Ag-MHC to T cells Specificity

10. 2. B cells activation, proliferation and differentiation (1) B cell activation: dual signals First signal: antigen signal BCR-- determinant on the surface of Ag Igα/Igβtransduct the first signal CD19/CD21/CD81 (co-receptor) binds to C3dg on Ag Second signal: co-stimulatory signal The CD40 on B cells binds to CD40L on activated Th cells

11. BCR complex Ag ITAM Ag （ BCR ） ITAM

12. g B cell

13. Activation of Th cells: DCs present peptide-class Ⅱ MHC complex and provide B7 for T cells, Th cells are activated and express CD40L. Th cells provide co-stimulatory signal for B cells: TCRs on activated Th cells recognize antigen peptide-class Ⅱ MHC complex presented on B cells, and CD40L on T cells bind to CD40 on B cells which provide co-stimulatory signal for B cells. Second signal: --the help of Th cells to B cells

16. Dendritic cell

18. Interaction between Th cells and B cells B cells act on Th cells: B cells present Ag-class II MHC molecules to Th cells----first signal for Th activation. B cells provide B7 for Th cells----second signal for Th activation. Th cells act on B cells: Activated Th cells provide co-stimulatory molecule for B cells: CD40L- CD40. Activated Th cells secrete Cks （ IL-4 、 IL-5 、 IL-6 、 IL-10 、 IL-13 ） which help B cells proliferate and differentiate.

19. ① ②

21. (2) B cells proliferation and differentiation ------help of Th cells Activated B cells express receptors of cytokines such as IL-4R, IL-5R. Activated Th2 cells secrete cytokines such as IL- 4, IL-5 to enhance proliferation and differentiation of B cells. B cells differentiate into plasma cells (antibody forming cells)----produce Ab, partial into memory B cells.

22. 免疫记忆

24. Differentiation of B cells in germinal Center During proliferation and differentiation, Somatic hypermutation of B cells induces affinity maturation of Ab. Some B cells differentiate to the plasma cells which produce IgM. Some B cells have an isotype switching to produce other types of Ig. Production of memory B cells.

25. Affinity maturationAffinity maturation refers to the increase in the affinity for the specific antigen of the antibodies produced during the course of a humoral immune response with the help of Th cells. Affinity maturation is the result of somatic hypermutation of Ig genes. Result in Ig with high affinity

26. Plasma cells are antibody factories; Also called antibody forming cells; Produce huge numbers of antibodies:2000/second

29. isotype switching or class switchingThe first antibodies produced in a humoral immune response are IgM, but activated B cells subsequently undergo isotype switching or class switching to secrete antibodies of different isotypes: IgG, IgA, and IgE. Isotype switching does not affect antibody specificity significantly. Occurred when Ag-activated B encounter helper T cell signals(CD40L and CKs) Result in the change of Ig Fc

33. 3. Stage of effect----the functions of Ab Neutralization Activate complement system ADCC — NK, macrophage, neutrophil Opsonization — macrophage Type Ⅰ hypersensitivity

34. NeutralizationOpsonizationActivate complement system

35. ADCC

36. Part Ⅱ Rules of humoral immunity 1. Primary response: B cells first encounter antigens 2. Secondary response : B cells encounter the same antigen secondary

38. Characteristic of primary Ir and secondary Ir lag phase affinity type maintaining time primary Ir longer low IgM shorter secondary Ir shorter high IgG longer

39. Mechanisms? Bm/Tm

41. Significance: On diagnosis: IgM is a marker for early diagnosis of infectious disease On vaccination: To obtain secondary response by more times of vaccination

42. Part Ⅲ Immune response of B1 cell to TI-Ag Characteristics of TI-Ag: Repeat B cell epitope No T cells participation Only humoral immunity Only produce IgM No immune memory

43. Part Ⅲ Immune response of B1 cell to TI-Ag B1 cells recognize TI-1 Ag: TI-1 Ag usually called B cell mitogen. High TI-1 Ag can induce polyclonal B cells proliferation and differentiation. Low TI-1 Ag only stimulate B cell clone with specific BCR. Response of B1 cell to TI-1 Ag earlier than that of B2 cell to TD-Ag. No Ig isotype swicthing, affinity maturation, and memory B cells.

44. M

46. Part Ⅲ Immune response of B1 cell to TI-Ag B1 cells recognize TI-2 Ag : Most TI-2 Ags belong to cell wall of bacteria and capsule polysaccharide with high repeat structure. Density of epitope is key to TI-2 Ag activating B cells. Only stimulate mature B1 cells. Help macrophage phagocyte and digest extracellular bacteria under antibody of capsule polysaccharide.

48. Part Ⅲ Immune response of B1 cell to TI-Ag Significance: Play important role inPlay important role in defense against extracellular microbe infection. Play an important role inPlay an important role in defense against bacteria with capsule polysaccharide.