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Topics. Humoral Immune Response Part I Antibody effector functions Thymus dependent and independent antigens Linked recognition B cell Activation, proliferation and differentiation Isotype switching, Affinity maturation Distribution and function of Ab Accessory cells.

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  1. Topics • Humoral Immune Response Part I • Antibody effector functions • Thymus dependent and independent antigens • Linked recognition • B cell Activation, proliferation and differentiation • Isotype switching, Affinity maturation • Distribution and function of Ab • Accessory cells MICR 415 / 515 / 682

  2. Extracellular Bacteria • Destruction of extracellular bacteria • Neutralize the toxins • Prevents the spread of intracellular infections MICR 415 / 515 / 682

  3. Th CD4+ APC APC Cytokines Th 2 B Cell Antibody Production Humoral Immune Response Bacteria Ag MICR 415 / 515 / 682

  4. Bacteria Th2 CD4+ B Cell B Cell Cytokines B Cell B Cell B Cell Plasma Cell B Cell B Cell Humoral Immune Response Bacteria Ag Epitope recognition Internalization of Ag Processing and presentation Stimulation by armed Th2 cell B cell proliferation Differentiation Production of Ab MICR 415 / 515 / 682

  5. MICR 415 / 515 / 682

  6. Antibody effector functions MICR 415 / 515 / 682

  7. Thymus dependent antigens Proteins Require T cell help MICR 415 / 515 / 682

  8. Thymus independent antigens Bacterial Lipopolysaccharides (LPS) Do not require T cell MICR 415 / 515 / 682

  9. Linked recognition Fig 9.3 MICR 415 / 515 / 682

  10. MICR 415 / 515 / 682

  11. Adhesion molecules interaction • Stimulation via TCR • CD40 /CD40 ligand stimulation (Accessory signal) MICR 415 / 515 / 682

  12. MICR 415 / 515 / 682

  13. Secretion of cytokines (IL4) by the Th2 cell MICR 415 / 515 / 682

  14. IL4, CD40 lead to B cell proliferation IL5 and IL6 lead to B cell differentiation into plasma cells B cell proliferation and differentiation MICR 415 / 515 / 682

  15. A variable region can be associated with the constant region of any isotype mRNA splicing IgM IgD IgA IgG IgG1, IgG2a, IgG2b, IgG3 IgE Isotype switching MICR 415 / 515 / 682

  16. MICR 415 / 515 / 682

  17. Cytokines determine Isotype MICR 415 / 515 / 682

  18. B cell is activated Migrate to primary follicles of spleen and lymph nodes Proliferates and forms germinal center (follicular dendritic cells) Proliferating B cells are called centroblasts (random somatic Hypermutation of V region) Produce centrocytes (positive selection by FDC) Differentiation into memory cells and Ab producing plasma cells (Th cells) MICR 415 / 515 / 682

  19. MICR 415 / 515 / 682

  20. MICR 415 / 515 / 682

  21. MICR 415 / 515 / 682

  22. Affinity maturation Caused by: • somatic hypermutation • Selection cells with high affinity receptors MICR 415 / 515 / 682

  23. MICR 415 / 515 / 682

  24. Yes Interaction with T cells Differentiation No Apoptosis Centrocyte selection at the germinal center Take up foreign Ag from FDC? MICR 415 / 515 / 682

  25. MICR 415 / 515 / 682

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  27. MICR 415 / 515 / 682

  28. Distribution and function of Ab • Pathogens are can grow in all the body • Ab need to be available in all the body • Route of entry of pathogens: • Epithelial barries: • Mucosa of the respiratory, digestive, urogenital tract, damaged skin • Directly to the blood • Insects, wounds, needles MICR 415 / 515 / 682

  29. IgM First to be produced Low affinity Forms pentameres (high avidity) Large, confined to the blood Activates complement MICR 415 / 515 / 682

  30. IgG Monomeric IgG is the most important in the blood IgG Opsonization, Complement activation, neutralization Transported through placenta IgA forms dimers IgA is most important in secretions (epithelium of intestine and respiratory tract) Neutralizing antibodies Present in mother’s milk MICR 415 / 515 / 682

  31. IgA MICR 415 / 515 / 682

  32. IgE • Monomeric • Binds receptor in mast cells beneath skin and mucosa • Acts as a receptor • Binding causes degranulation of mast cells MICR 415 / 515 / 682

  33. MICR 415 / 515 / 682

  34. Distribution of Igs • IgG, IgM: Plasma • IgG, IgA (monomeric): Extracellular fluid • IgG Fetus • IgA (dimeric): Secretions, cross epithelia • IgE Mast cells beneath epithelia MICR 415 / 515 / 682

  35. MICR 415 / 515 / 682

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