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IgE

atopy
&
anaphylaxis
J van Schalkwyk
Perioperative Physician
Auckland City Hospital
Pathogenesis
Major Players
• Mast Cell
• Basophil
• IgE

• B cell
• Plasma cell
• T cell
• Dendritic cell

A complex drama!

A. How IgE forms

B. Mast cell and
basophil

C. Control
A. IgE formation
1. Antigen meets
B cell
Ag
A. IgE formation
1. Antigen meets
B cell
2. B cell packages
& presents Ag
to helper T cell
A. IgE formation
1. Antigen meets
B cell
2. B cell packages
& presents Ag
to helper T cell
3. B cell
proliferates
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
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”
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
B. Basophil & Mast
cell
IgE binds to the
mast cell


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

HOW?

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

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

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

B. Mast Cell

Histamine
(H1, H2, H3)
Target organs

• Lungs
• Heart
• Vasculature
• Cutaneous

B. Mast Cell


Cardiovascular
collapse
Urticaria
Bronchospasm
ANAPHYLAXIS
B. The Basophil
Role still unclear!

• < 1% of white cells
• No tryptase
• Lots of histamine
• Rich in FceRI
Late phase?
C. Control
Massively complex

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


C. Control
Th2 phenotype
• A particular
pattern in CD4+
helper cells…

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

IL4
ATOPY
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

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
The End