The Biology of IgE and the Basis of Allergic Disease

Abstract

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.

Inefficient processing of mRNA for the membraneform of IgE is a genetic mechanism to limit recruitment of IgE‐secreting cells

“…In agreement with the murine data, *100-fold more transcripts for se than for me were detected in stimulated human PBMC. In contrast, measurement of the ratio of expression of mRNA for the secreted and membrane form of c 4 , the human homologue of mouse c 1 , showed about equal amounts of mRNA for sc 4 and mc 4 (Fig. 5b).…”

“…In these days, IgE is best known for its strong, unwanted effector functions, in the form of allergic reactions [4]. These can range from annoying, local symptoms like hay fever, to life-threatening, systemic reactions like anaphylactic shock.…”

IgE expression pattern in lung: Relation to systemic IgE and asthma phenotypes

“…As IgG easily diffuses in tissue, tissue IgG concentrations may be comparable to serum concentrations. Thus, unless local/tissue IgE concentrations are several orders higher than normally seen in serum, the disparity between IgG and IgE concentrations in tissue may result in relatively low IgE binding to mast cells even when accounting for the difference in affinity of respective receptors, perhaps explaining the lack of positive staining for IgE on parenchymal mast cells 20,22 . Whether this leads to differences in regulation of local versus systemic reactions remains to be evaluated, but will be difficult to study in humans 23 .…”

Eosinophils and Trichinella infection: toxic for the parasite and the host?

“…It has been suggested that the immunoglobulins IgG and IgA (including secretory IgA) are able to trigger eosinophil degranulation [31]. However, the presence of IgE receptors on eosinophils remains controversial [31][32][33]. Recently, T cells have also been shown to have a role in eosinophil degranulation.…”