The biology of IGE and the basis of allergic disease.
Allergic individuals exposed to minute quantities of allergen experience an immediate response. Immediate hypersensitivity reflects the permanent sensitization of mucosal mast cells by allergen-specific IgE antibodies bound to their high-affinity receptors (FcepsilonRI). A combination of factors contributes to such long-lasting sensitization of the mast cells. They include the homing of mast cells to mucosal tissues, the local synthesis of IgE, the induction of FcepsilonRI expression on mast cells by IgE, the consequent downregulation of FcgammaR (through an insufficiency of the common gamma-chains), and the exceptionally slow dissociation of IgE from FcepsilonRI. To understand the mechanism of the immediate hypersensitivity phenomenon, we need explanations of why IgE antibodies are synthesized in preference to IgG in mucosal tissues and why the IgE is so tenaciously retained on mast cell-surface receptors. There is now compelling evidence that the microenvironment of mucosal tissues of allergic disease favors class switching to IgE; and the exceptionally high affinity of IgE for FcepsilonRI can now be interpreted in terms of the recently determined crystal structures of IgE-FcepsilonRI and IgG-FcgammaR complexes. The rate of local IgE synthesis can easily compensate for the rate of the antibody dissociation from its receptors on mucosal mast cells. Effective mechanisms ensure that allergic reactions are confined to mucosal tissues, thereby minimizing the risk of systemic anaphylaxis.
Gould
Hannah J
HJ
The Randall Centre, King's College London, United Kingdom. hannah.gould@kcl.ac.uk
Sutton
Brian J
BJ
Beavil
Andrew J
AJ
Beavil
Rebecca L
RL
McCloskey
Natalie
N
Coker
Heather A
HA
Fear
David
D
Smurthwaite
Lyn
L
D000485:Allergens; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009000:Monocytes / Q000276:immunology; D019906:Nuclear Magnetic Resonance, Biomolecular; D017455:Receptors, IgE / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000737:chemistry / Q000378:metabolism; D012552:Schistosomiasis / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000485:Allergens; D017455:Receptors, IgE; D017452:Receptors, IgG; D007073:Immunoglobulin E