anafilaksis.pdf - Mechanisms of allergic diseases The...

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Mechanisms of allergic diseases The pathophysiology of anaphylaxis Laurent L. Reber, PhD, a,b,c,e Joseph D. Hernandez, MD, PhD, d and Stephen J. Galli, MD c,e,f Paris, France, and Stanford, Calif Anaphylaxis is a severe systemic hypersensitivity reaction that is rapid in onset; characterized by life-threatening airway, breathing, and/or circulatory problems; and usually associated with skin and mucosal changes. Because it can be triggered in some persons by minute amounts of antigen (eg, certain foods or single insect stings), anaphylaxis can be considered the most aberrant example of an imbalance between the cost and benefit of an immune response. This review will describe current understanding of the immunopathogenesis and pathophysiology of anaphylaxis, focusing on the roles of IgE and IgG antibodies, immune effector cells, and mediators thought to contribute to examples of the disorder. Evidence from studies of anaphylaxis in human subjects will be discussed, as well as insights gained from analyses of animal models, including mice genetically deficient in the antibodies, antibody receptors, effector cells, or mediators implicated in anaphylaxis and mice that have been ‘‘humanized’’ for some of these elements. We also review possible host factors that might influence the occurrence or severity of anaphylaxis. Finally, we will speculate about anaphylaxis from an evolutionary perspective and argue that, in the context of severe envenomation by arthropods or reptiles, anaphylaxis might even provide a survival advantage. (J Allergy Clin Immunol 2017;140:335-48.) Key words: Anaphylaxis, basophils, cysteinyl leukotrienes, epinephrine, food allergy, histamine, IgE, mast cells, platelet- activating factor, urticaria The recent International Consensus on Anaphylaxis described anaphylaxis as ‘‘a serious, generalized or systemic, allergic or hypersensitivity reaction that can be life-threatening or fatal.’’ 1 This definition is intentionally ‘‘generic’’ in that it does not mention any of the specific immune elements that might be involved in particular instances of the disorder because these can vary depending on individual circumstances. In this review we will describe the key immune elements, such as antibody isotypes, effector cells, and biological mediators, that can contribute to the development and pathophysiologic manifesta- tions of anaphylaxis. In particular, we will note the extent of evidence implicating these immune components in anaphylaxis in human subjects versus that induced in mouse models of the disorder, focusing especially on forms of anaphylaxis induced by reactions of allergens with antigen-specific antibodies. We will not extensively review forms of anaphylaxis induced by the antibody-independent activation of effector cells, such as mast cells and basophils, topics that have been reviewed elsewhere.
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  • Fall '19
  • The Land, Histamine, Mast cell, Allergy

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