Studies with murine models demonstrate 2 pathways of systemic
anaphylaxis: one mediated by
IgE, Fc epsilonRI, mast cells,
histamine, and
platelet-activating factor (PAF), and the other mediated by
IgG, Fc gammaRIII, macrophages, and PAF. The former pathway requires much less antibody and
antigen than the latter. As a result,
IgG antibody can block
IgE-mediated
anaphylaxis induced by small quantities of
antigen without mediating Fc gammaRIII-dependent
anaphylaxis. The
IgE pathway is most likely responsible for most human
anaphylaxis, which generally involves small amounts of antibody and
antigen; similarities in the murine and human immune systems suggest that the
IgG pathway might mediate disease in persons repeatedly exposed to large quantities of
antigen. Mice, like human subjects, can experience
IgE/Fc epsilonRI/mast cell-mediated gastrointestinal and systemic
anaphylaxis in response to ingested
antigen. Gastrointestinal symptoms depend on
serotonin and PAF; mediator dependence of systemic symptoms has not been determined. Both local and systemic
anaphylaxis induced by ingested
antigens might be blocked by
IgA and
IgG antibodies.
IL-4 and
IL-13 signaling through the
IL-4 receptor alpha chain, in addition to promoting the
mastocytosis and
IgE antibody production that mediate most human
anaphylaxis, exacerbates the effector phase of
anaphylaxis by increasing target cell responsiveness to vasoactive mediators. As a result,
IL-4 receptor alpha chain antagonists might be particularly effective suppressors of
anaphylaxis.