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

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

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

4. A. IgE formation 1. Antigen meets B cell Ag

5. A. IgE formation 1.Antigen meets B cell 2.B cell packages & presents Ag to helper T cell

6. A. IgE formation 1.Antigen meets B cell 2.B cell packages & presents Ag to helper T cell 3.B cell proliferates

7. A. IgE formation 1.Antigen meets B cell 2.B cell packages & presents Ag to helper T cell 3.B cell proliferates 4.A switch to IgE

8. A. IgE production 1.Antigen meets B cell 2.B cell packages & presents Ag to helper T cell 3.B cell proliferates 4.A switch to IgE IL4 CD40L “class switch recombination”

9. A. IgE production 1.Antigen meets B cell 2.B cell packages & presents Ag to helper T cell 3.B cell proliferates 4.Plasma cells & memory cells Memory cell

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

11. B. Mast Cell IgE binds to the mast cell HOW? Fc  RI

12. B. Mast Cell Fc  RI High affinity 200 000/cell 10% occupancy works fully!

13. B. Mast Cell Ag Degranulation

14. B. Mast Cell Degranulation Ag

15. B. Mast Cell Ag Degranulation

16. B. Mast Cell Ag PI3 kinase

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

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

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

20. C. Control Massively complex Th1 versus Th2 Genetic factors The dendritic cell Fc  RII Innate Immunity!

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

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

23. C. Control Why Th2? Genetics Allergens The basophil Histamine! Innate immunity! Polymorphic Toll-like receptors Fc  RII (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 Fc  RI to Fc  RII

25. The End