Chapter 15 B cell mediated immune response

1. Chapter 15 B cell mediated immune response

2. Chapter 15 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

3. Contents • PartⅠ Immune response of B2 cell to TD-Ag • PartⅡ Rules of humoral immunity • PartⅢ Immune response of B1 cell to TI-Ag • PartⅣ Signal transduction of T and B cells

4. PartⅠ Immune response of B2 cell to TD-Ag Characteristics of TD-Ag: • Most native Ag • Protein, 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

5. PartⅠ Immune response of B2 cell to TD-Ag • B2 cells recognize TD-Ag activate, proliferate, differentiate plasma cells produce Ab Ag

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

7. 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 signal to T cells

8. 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

9. Ag Ag （BCR） BCR complex ITAM ITAM

10. g B cell

11. 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

14. Dendritic cell

16. Interaction between Th cells and B cells B cells act on Th cells: • B cells present Ag to Th cells. • B cells provide B7 for Th cells. 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.

17. ① ②

19. (2) B cells proliferation and differentiation------help of Thcells • 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.

20. 免疫记忆 免疫记忆

22. 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 switch to produce other types of Ig. • Production of memory B cells.

23. Affinity 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.

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

27. The 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.

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

32. Neutralization Opsonization Activate complement system

33. ADCC

34. PartⅡ Rules of humoral immunity 1.Primary response 2. Secondary response

36. Characteristic of primary Ir and secondary Ir lagphaseaffinitytypemaintaining time primary Irlonger lowIgM shorter secondary Irshorter highIgG longer

37. Mechanisms? Bm/Tm

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

40. PartⅢ 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

41. PartⅢ 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 swicth, affinity maturation, and memory B cells.

42. M

44. PartⅢ 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.

46. PartⅢ Immune response of B1 cell to TI-Ag Significance: • Play important role in defense against extracellular microbe infection. • Play an important role in defense against bacteria with capsule polysaccharide.

47. PartⅣ signal transduction of T and B cell activation TCR recognition and linkage Activation of PTK( p56lck, p59fyn, ZAP-70) Signal transduction in the cell Activation of transcription factor

48. APC