Summary

In 1902, Richet and Portier tried to immunize a dog with a toxic sea anemone (Actinia) extract. However, to their surprise, the dog died 25 minutes after the second injection. They named the harmful effect anaphylaxis (from Greek, lack of protection) (1). Awarded with the Nobel Prize in 1913, Richet explained that the two necessary and sufficient features for anaphylaxis to develop are an incubation time in between injections and two injections of the same “poison.” Thereafter, the often-life-threatening phenomenon of systemic anaphylaxis (or anaphylactic shock) was found to be caused rapidly after exposure to several environmental antigens (allergens) that enter the circulation and are usually derived from certain foods, drugs, insect venoms, latex, and immunotherapy injections. Similar to all allergic reactions, anaphylaxis is induced by rapid, immunoglobulin E (IgE) antibody–mediated release of immune mediators, such as histamine and platelet-activating factor (PAF) from tissue-resident mast cells (MCs) and presumably from peripheral blood basophils (2, 3). However, in contrast with other forms of allergy such as asthma, allergic rhinitis, and atopic dermatitis, anaphylaxis is systemic and life-threatening owing to cardiovascular and respiratory symptoms (2). Allergic and anaphylactic reactions imply that allergens from the circulation cross epithelial and/or endothelial (the vascular lining) barriers to interact with IgE bound to MCs. However, the mechanisms were unknown. On page 656 of this issue, Choi et al. (4) elegantly demonstrate that such allergens are trapped by dendritic cells (DCs) that produce microvesicles (MVs) to interact with MC-IgE in the skin.