Rous-Whipple Award Lecture
The Mast Cell-IgE Paradox: From Homeostasis to Anaphylaxis

https://doi.org/10.1016/j.ajpath.2015.07.025Get rights and content
Under an Elsevier user license
open archive

Mast cells and IgE are so inextricably linked to the pathology of allergic disorders, including fatal anaphylaxis, that it can be difficult to think of them in other contexts. Surely, we do not have mast cells and IgE so that we can eat a peanut and die! It is thought that mast cells and IgE and basophils (circulating granulocytes, whose functions partially overlap with those of mast cells) can contribute to host defense as components of adaptive T helper cell type 2 immune responses to helminths, ticks, and certain other parasites. Accordingly, it was suggested that allergies are misdirected type 2 immune responses in which IgE antibodies are produced against any of a broad variety of apparently harmless antigens. However, components of animal venoms also can sensitize individuals to develop severe IgE-associated allergic reactions, including fatal anaphylaxis, on subsequent venom exposure. Here, I describe evidence that mast cells can enhance innate host resistance to reptile or arthropod venoms during responses to an initial exposure to such venoms and that acquired type 2 immune responses, IgE antibodies, the high-affinity IgE receptor FcεRI, and mast cells can contribute toward acquired resistance in mice to the lethal effects of honeybee or Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against noxious substances.

Cited by (0)

Supported by the NIH grants R37 AI23990, R01 CA072074, R01 AR067145, and U19 AI104209; the National Science Foundation (United States-Israel Binational Science Foundation Grant 2013263); the Sean N. Parker Center for Allergy Research; and the Department of Pathology, Stanford University School of Medicine.

Disclosures: None declared.

The Rous-Whipple Award is given by the American Society for Investigative Pathology to a senior pathologist with a distinguished career in experimental pathology research and continued productivity at the time of the award. Stephen J. Galli, M.D., recipient of the 2014 ASIP Rous-Whipple Award, delivered a lecture entitled The Mast Cell-IgE Paradox: From Homeostasis to Anaphylaxis, on April 27, 2014, at the annual meeting of the American Society for Investigative Pathology in San Diego, CA.