Anaphylaxis: Etiology, Clinical Manifestations, Diagnosis and Management

Abstract

Anaphylaxis: Etiology, Clinical Manifestations, Diagnosis and Management 169 Animal modelsStudies with murine models demonstrate 2 pathways of systemic anaphylaxis: one mediated by IgE, FcεRI, mast cells, histamine, and platelet-activating factor (PAF), and the other mediated by IgG, FcγRIII, 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 FcγRIII-dependent anaphylaxis (Finkelman et al., 2005). 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. Antigen cross-linking of antigen specific IgE bound to mast cell FcεRI stimulates mast cell degranulation, with the rapid release of histamine and serotonin and the synthesis and secretion of platelet activation factor (PAF) and leukotrienes. These mediators act on target cells to increase vascular permeability which cause depletion of intravascular volume. The resulting decrease in vital organ perfusion is the primary cause of the symptoms that characterize murine anaphylaxis (Finkelman et al., 2005). The other pathway in mouse is Ig-E independent pathway. As contrary of clasical pathway, at first immunized and antigen challenged mice had anaphylaxis despite the absence of mast cells, FcεRI and IgE. This pathway is also complement independent but requires IgG antibody, macrophages, Fc RIII and PAF. Regardless which pathway takes place, mouse anaphylaxis occurs in very short time and displays similar symptoms. Potentially important differences between mouse and human anaphylaxis are proposed as follows: 1. Mouse IgG has some ability to activate mast cells, an effect that is not shared by any human IgG isotype, 2. IgE binds weakly to murine, but not human low-affinity Fc Rs, 3. Human but not mouse macrophages, Langerhans cells and dendritic cells can express FcεRI, and 4. Human platelets, B cells and natural killer cells, and neutrophils express low affinity IgG receptor (Fc RIIA, Fc RIIC, and Fc RIIIB, respectively) that are not expressed in mouse (Finkelman et al., 2005). Less antibody and antigen are required to trigger IgE dependent anaphylaxis then IgG mediated anaphylaxis. IgG and IgA blocking antibodies inhibit the ability of small quantities of antigen to induce IgE dependent anaphylaxis by neutralizing antigen before it can cross link mast cell associated IgE. IgG antibodies also inhibit IgE-dependent anaphylaxis by mediating an interaction between FcεRI and Fc RIIb on mast cells. In mice the predominant determinants that influence whether IgE dependent anaphylaxis is induced appear to be the quantity of antigen specific IgG antibody produced and the quantity of antigen used to challenge immunized mice. This suggests that IgG antibodies, in addition to me...