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IgE atopy & anaphylaxis

Pathogenesis. IgE atopy & anaphylaxis. J van Schalkwyk Perioperative Physician Auckland City Hospital. Major Players. Mast Cell Basophil IgE B cell Plasma cell T cell Dendritic cell. A complex drama!. How IgE forms Mast cell and basophil Control. A. IgE formation.

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IgE atopy & anaphylaxis

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  1. Pathogenesis IgEatopy&anaphylaxis J van Schalkwyk Perioperative Physician Auckland City Hospital

  2. Major Players • Mast Cell • Basophil • IgE • B cell • Plasma cell • T cell • Dendritic cell

  3. A complex drama! • How IgE forms • Mast cell and basophil • Control

  4. A. IgE formation 1. Antigenmeets B cell Ag

  5. A. IgE formation • Antigen meets B cell • B cell packages & presents Ag to helper T cell

  6. A. IgE formation • Antigen meets B cell • B cell packages & presents Ag to helper T cell • B cell proliferates

  7. A. IgE formation • Antigen meets B cell • B cell packages & presents Ag to helper T cell • B cell proliferates • A switch to IgE

  8. A. IgE production • Antigen meets B cell • B cell packages & presents Ag to helper T cell • B cell proliferates • A switch to IgE CD40L IL4 “class switch recombination”

  9. A. IgE production • Antigen meets B cell • B cell packages & presents Ag to helper T cell • B cell proliferates • Plasma cells & memory cells Memory cell

  10. HOW? B. Basophil & Mast cell IgE binds to the mast cell

  11. B. Mast Cell IgE binds to the mast cell HOW? FceRI

  12. B. Mast Cell FceRI • High affinity • 200 000/cell • 10% occupancy works fully!

  13. Ag B. Mast Cell Degranulation

  14. B. Mast Cell Ag Degranulation

  15. B. Mast Cell Ag Degranulation

  16. Ag B. Mast Cell PI3 kinase

  17. B. Mast Cell Degranulation • Serotonin • Pg, leukotrienes • Proteases • Chemokines • Cytokines Histamine (H1, H2, H3)

  18. B. Mast Cell Target organs • Lungs • Heart • Vasculature • Cutaneous ANAPHYLAXIS Cardiovascular collapse Urticaria Bronchospasm

  19. B. The Basophil Role still unclear! • < 1% of white cells • No tryptase • Lots of histamine • Rich in FceRI Late phase?

  20. C. Control Massively complex • Th1 versus Th2 • Genetic factors • The dendritic cell • FceRII • Innate Immunity!

  21. Th1 phenotype IL12 Gamma interferon production! IL4 C. Control Th2 phenotype • A particular pattern in CD4+ helper cells…

  22. C. Control Th2 phenotype • A particular pattern of cytokine production in CD4+ helper cells… ATOPY IL4

  23. C. Control Why Th2? • Genetics • Allergens • The basophil • Histamine! • Innate immunity! Polymorphic Toll-like receptors FceRII (CD23) inhibits soluble CD23 promotes alternate IgE switches IgE V genes and atopy

  24. Implications Diagnostic • Tryptase • Histamine • Newer tests of basophils in anaphylaxis Therapeutic Exciting but expensive prospects for immune modulation • omalizumab • GE2 cross links FceRI to FcgRII

  25. The End

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