Transcript IgE - Anaesthetist

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!
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
CD40L
IL4
“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
B. Mast Cell
Degranulation
•
•
•
•
•
Serotonin
Pg, leukotrienes
Proteases
Chemokines
Cytokines
Histamine
(H1, H2, H3)
B. Mast Cell
Target organs
•
•
•
•
Lungs
Heart
Vasculature
Cutaneous
ANAPHYLAXIS
Cardiovascular
collapse
Urticaria
Bronchospasm
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
Th1
pattern
in
CD4+
phenotype
helper cells…
Gamma
interferon
production!
IL12
IL4
C. Control
Th2 phenotype
• A particular
pattern of cytokine
production in
CD4+ helper
cells…
ATOPY
IL4
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