5_b_cell.ppt
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5_b_cell.ppt Presentation Transcript

  • 1. POP QUIZ: Avg = 63%, + 5% curve
  • 2.
    • Returns a year later with pneumonia;
    • Severe back pain.
    • Electrophoresis of serum:
    • 1: Normal serum
    • 2. Mrs. Smith
    • 3. Normal serum Western Blot w kappa light
    • 4. Mrs. Smith w kappa light
    • 5. Mrs. Smith w lambda light.
    • What does this tell you?
    • Found plasmacytoma [tumor of plasma cell] extruding from vertebra
    • X ray of skull:
    • Treatments?
    • Prognosis?
    • IN WRITING; ON MOODLE. KEEP IT SHORT.
    • PLASMACYTOMA,
    • OR MULTIPLE MYELOMA
  • 3. Questions:
    • What evidence that Mrs. Smith’s tumor is “monoclonal”? Would there be a way to further confirm this?
    • Why did Mrs. Smith become anemic?
    • Mrs. Smith became more susceptible to infection, even though she had so much IgG. Why?
    • Treatment;
    • Prognosis?
  • 4. W, M: 7-8:15, Theater: Please remind your friends and in Kaplan. Ch 5 quiz opens W; due F.
  • 5. Differentiation Phase
    • Most B cells never stimulated by antigen; only 1/100,000 naïve B cells encounter; others die by apoptosis.
  • 6. Somatic Hypermutation; Affinity Maturation
    • Mutagenesis targeted to only the V regions; no other genes!
    • 10 -3 /bp; about 10 -8 /bp in other genes.
    • Occurs upon antigen stimulation w T cell help.
    • Successful mutations tend to cluster around CDRs; others disrupt Fab structure and are selected against.
    • Mutation occurs even in cells with nonproductively rearranged Ig genes; does affinity maturation?
  • 7. T-independent antigens
    • Can activate without T cell help
    • Usually because of repeated epitope that strongly cross-links BCR.
    • Repeated protein, polysaccharide antigens.
    • Extensive cross linking sends strong stimulatory signal.
    • Rapid response, but no isotype switching or somatic hypermutation.
    • No memory cells.
  • 8. T-dependent B cells
    • Cross linking of BCR can initiate activation, but cannot induce differentiation and antibody production unless also receives T cell help.
    • CD40( R) on B cell receives signal from CD40L on effector Th.
    • T cell help induces class switching, somatic hypermutation, differentation into plasma, memory cells.
  • 9. Properties of Td antigens
    • Must be able to get T cell help, so must have peptides.
    • Must be perceived as “non-self”. Why?
    • Must be large and complex enough to be able to cross-link BCR, and to contain both B and T cell epitopes.
    • Dosage
    • Route of entry
      • Ingested tends to produce active IgA response in mucosa, but inhibits IgG production in lymph.
  • 10. Three signal model of B cell activation Signal 1: Conveyed into cytopolasm by Ig alpha, beta Upregulates MHC II, CD40, cytokine receptors. If second signal not received, apoptoses or becomes “anergic”.
  • 11. Linked Recognition Signal 2: T cell epitope must be linked to B cell epitope! So can you activate a B cell against, say, DNA? How? Signal 3: Th cell reorients cytoplasm; releases cytokines only on side of cell making contact. Division; differentiation into plasma cells or memory cells.
  • 12. Lymph node follicles
    • Most interaction between B cells, antigen and Th occurs in “follicles” in lymph nodes and spleen.
    • Follicular Dendritic Cells coated with antigen
  • 13. Switch between membrane bound vs secreted via RNA Processing/Differential Splicing
  • 14. Class [isotype] switching: After antigen stimulation w T cell help Hyper-IgM syndromes: No isotype switching or somatic hypermutation.
  • 15. Plasma cells
    • If dividing follicular B cell receives sustained Bcl-6 signaling, becomes a memory cell.
    • If Bcl-6 drops off, plasma cell.
    • Expanded rER, Golgi
    • Little or no CD40, MHC II, BCR
    • Migrate to lymph nodes, spleen, bone marrow, and continue secreting antibodies, for several months.
    • Up to 40% of total protein synthesis is antibodies.
  • 16. DIVERSITY: SUMMARY
  • 17. NK, eosinophils cytotoxic.
  • 18. Ch 5 Self-test questions you should be able to answer:
    • A.I-II: #2, 4
    • A.III-V: ALL
    • B.I: 1,2, 4-7
    • B.II: 2-4
    • B.IV: 2,3,5
    • B.V-VII: 2-4
    • C.I-IV: ALL
    • D.I-VI: 1-6,8