Micro 204 Flipped Classroom Session Antibodies IgE and IgA Chris Allen Tony DeFranco
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Micro 204
Flipped Classroom Session
Antibodies
IgE and IgA
Chris Allen Tony DeFranco
IgE Antibody Function
mast cell or basophil
FcεRI
IgE including histamine chemokines cytokines
mediators
inflammation
Parasitic worm
Normal Functions of Antibodies Neutralization
toxins
viruses
Mast cell
Parasitic worm
inflammation
bacteria Complement activation
Macrophage bacteria
Opsonization
Toxic granules Foreign/ infected
cell
Antibody-dependent cytotoxicity
IgG
IgE
IgM
IgA
IgG
IgG
Differences in Fc Receptors
Macrophage
bacteria
FcγR
Mast Cell FcεRI
IgE IgG
Changes in Antibodies n Class switch recombination
• Membrane vs secreted
mutation, selection
Low affinity
High affinity
• Affinity maturation
IgE Constant region (function)
Variable region (antigen-binding)
Transmembrane & Intracellular
Domains
B cell Plasma cell
IgG
IgE IgM IgD
IgA AID
B Cell Differentiation Pathways
Germinal Center
Activated B Cell
Short-Lived Plasma Cell
Affinity Maturation Hypermutation, Selection
Long-Lived Plasma Cell
Memory B Cell
Germinal Center Selection
Plasma Cell
Memory B Cell
Antigen
highest affinity
BCR signal
T cell T cell help GC
B Cells
Differentiation
highest affinity
Proliferation
Apoptosis
Helminth parasite model: Nippostrongylus brasiliensis infection
Differences in Kinetics of Antibody Responses Infection N. brasiliensis L3 larvae
Erazo A. et al. Immunity 2007, 26:191-203.
Cheng L.E. et al. J Immunol 2010, 185:5040-5047.
Differences in IgG1 vs IgE Germinal Center B Cell Responses
N. brasiliensis infection
Talay O. et al. Nat Immunol 2012, 13:396-404.
Yang Z. et al. Immunity 2012, 36:857-872.
He J.S. et al. J Exp Med 2013, 210:2755-2771. Similar data in:
IgG1+ Germinal Center B Cells IgE+ Germinal Center B Cells
Questions
n Why do IgE+ B cells disappear from the germinal center?
n What are the implications for the IgE antibody response?
Why IgE B cell lifespan and affinity may be limited
Neutralization
toxins
viruses
Mast cell
Parasitic worm
inflammation
IgG IgE IgA
Systemic IgE
activation
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