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B CELL DEVELOPMENT: Part II

B CELL DEVELOPMENT: Part II. October 27, 2008. Deborah A. Lebman, PhD dlebman@vcu.edu Goodwin Research Lab Rm 290. Reading: Janeway Immunobiology, Chapter 9. B CELL ACTIVATION REQUIRES TWO SIGNALS. Interaction with antigen initiates the antibody response

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B CELL DEVELOPMENT: Part II

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  1. B CELL DEVELOPMENT: Part II October 27, 2008 Deborah A. Lebman, PhD dlebman@vcu.edu Goodwin Research Lab Rm 290 Reading: Janeway Immunobiology, Chapter 9

  2. B CELL ACTIVATION REQUIRES TWO SIGNALS • Interaction with antigen initiates the antibody response • The second signal can be provided by an “armed” helper T cell • Some microbial antigens can provide both signal and are T cell independent or TI antigens

  3. T INDEPENDENT ANTIGENS I (TI-1) ARE MITOGENS

  4. TI-2 ANTIGENS HAVE REPETIVE EPITOPES Cytokines (possibly from dendritic cells can induce isotype switching

  5. PROPERTIES OF DIFFERENT TYPES OF ANTIGEN

  6. T CELLS STIMULATE BOTH PROLIFERATION AND DIFFERENTIATION The key T cell derived players: CD40L and cytokines

  7. T CELL HELP REQUIRES A COGNATE INTERACTION B cell binds an epitope, internalizes the antigen for processing and presentation of peptide on MHC Class II The TCR recognizes a peptide derived from the pathogen and is activated to help Cognate interaction: T cell and B cell recognize the same antigen, but not the same epitope

  8. IN A COGNATE INTERACTION B CELLS “POLARIZE” T CELLS • T-B Contact: • T cells “face” B cell • Contact prevents IL-4 from • assisting irrelevant B cells TH2 derived IL-4 stimulates proliferation Other cytokines (IL-5 and IL-6) stimulate differentiation

  9. THE INITIAL COGNATE INTERACTION OCCURS IN THE T CELL ZONE B cells bind antigen in blood or lymph node Trapping is mediated by activation of adhesion molecules (LFA1) and chemokine receptors(CCR7) Some B cells become plasmablasts during this initial encounter

  10. PLASMA CELLS VS B CELLS

  11. FATE OF B CELLS IN THE PRIMARY FOCUS • B cells have two fates: • Plasma cells • Enter follicle

  12. THE GERMINAL CENTER REACTION Intense proliferation: centroblasts have reduced mIg Reduced proliferation: centrocytes increase the level of mIg Somatic Mutation and Isotype Switching

  13. INCREASED AFFINITY PERMITS RESCUE OF THE B CELL

  14. TARGETING OF CLASS SWITCHING Transcriptional activation of CH targets them for recombination

  15. CYTOKINES DIRECT ISOTYPE SWITCHING

  16. HEAVY CHAINS CONFER FUNCTIONALITY TO Ig

  17. ISOTYPES HAVE TISSUE PREFERENCES

  18. POLYMERIC ISOTYPES ARE TRANSCYTOSED

  19. HIGH AFFINITY IgG AND IgA NEUTRALIZE TOXINS

  20. HIGH AFFINITY IgG AND IgA INHIBIT VIRAL ENTRY

  21. High affinity IgG and IgA block bacterial colonization

  22. IgM and IgG Activate Complement

  23. IgG (with complement) Opsonizes Pathogens

  24. IgG Mediates ADCC

  25. IgE Mediates Mast Cell Degranulation

  26. THE HUMORAL IMMUNE RESPONSE

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