IgE atopy

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IgEatopyanaphylaxis
Pathogenesis

• J van Schalkwyk
• Perioperative Physician
• Auckland City Hospital

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Major Players

• Mast Cell
• Basophil
• IgE
• B cell
• Plasma cell
• T cell
• Dendritic cell

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A complex drama!

1. How IgE forms
2. Mast cell and basophil
3. Control

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A. IgE formation

• 1. Antigen meets B cell

Ag
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A. IgE formation

1. Antigen meets B cell
2. B cell packages presents Ag to helper T cell

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A. IgE formation

1. Antigen meets B cell
2. B cell packages presents Ag to helper T cell
3. B cell proliferates

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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

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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

CD40L
IL4
class switch recombination
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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
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B. Basophil Mast cell

• IgE binds to the mast cell

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B. Mast Cell

• IgE binds to the mast cell
• HOW?
• FceRI

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B. Mast Cell

• FceRI
• High affinity
• 200 000/cell
• 10 occupancy works fully!

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B. Mast Cell
Degranulation
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B. Mast Cell
Ag
Degranulation
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B. Mast Cell
Ag
Degranulation
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B. Mast Cell
PI3 kinase
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B. Mast Cell

• Degranulation
• Serotonin
• Pg, leukotrienes
• Proteases
• Chemokines
• Cytokines

Histamine (H1, H2, H3)
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B. Mast Cell

• Target organs
• Lungs
• Heart
• Vasculature
• Cutaneous

Cardiovascular collapse Urticaria Bronchospasm
ANAPHYLAXIS
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B. The Basophil

• Role still unclear!
• lt 1 of white cells
• No tryptase
• Lots of histamine
• Rich in FceRI

Late phase?
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C. Control

• Massively complex
• Th1 versus Th2
• Genetic factors
• The dendritic cell
• FceRII
• Innate Immunity!

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C. Control

• Th2 phenotype
• A particular pattern in CD4 helper cells

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C. Control

• Th2 phenotype
• A particular pattern of cytokine production in
  CD4 helper cells

ATOPY
IL4
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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
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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

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The End