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The latest buzz on the evolution of allergies

BEELike a vestigial sting from our evolutionary past, an allergic reaction is a jab to the system. Its most extreme form, anaphylaxis, causes a rapid drop in blood pressure, itchy hives and breathing problems, and can result in death.

But the same immune response to bee stings that can lead to anaphylaxis may have originated as a defense mechanism, according to research led by Stanford pathologist Stephen Galli, MD. In a study published today in the journal Immunity, Galli and his team showed that mice injected with a small dose of honeybee venom were later protected from a higher dose of the same venom. This protection depended on “allergic-type” immune reactions. The findings provide the first experimental evidence in support of the toxin hypothesis of allergy.

From our news release:

The study builds on earlier work by the researchers, characterizing the innate immune response to snake venom and honeybee venom. Innate immune responses occur in subjects exposed to a foreign substance, such as a pathogen or a toxic material like venom, for the first time. Immune cells called mast cells, which reside in most of the body’s tissues, are poised to unleash signals that turn on defense responses when a pathogen or toxin intrudes. In a previous study, the researchers found that mast cells produce enzymes that can detoxify components of snake venom, and that mast cells can also enhance innate resistance to honeybee venom.

Such innate immune responses do not require prior immunization or the development of specific antibodies. By contrast, during an adaptive immune response, the immune system generates antibodies that recognize the invading pathogen or toxin; this process makes it possible to vaccinate against infectious diseases. Adaptive immunity is usually a faster, more specific and more effective form of defense than innate immunity.

In allergic reactions, a type of antibody called IgE binds to the surface of mast cells and prompts them to initiate an adaptive immune response when exposed to the antigen recognized by that IgE. “The functions of IgE and mast cells are mostly known in the context of allergies,” said Thomas Marichal, DVM, PhD, a postdoctoral scholar and co-lead author of the study.

To find out whether IgE antibodies were also involved in adaptive defense responses to venom, Marichal, along with Philipp Starkl, PhD, the other lead author, compared responses of mice pre-immunized with bee venom to those of control mice injected with a salt solution. The immunized mice had more venom-activated immune cells and more venom-specific IgE antibodies. They were also three times more likely to survive a potentially lethal dose of venom. Three types of mutant mice - mice without IgE antibodies, without IgE receptors on their mast cells, or without mast cells - were not protected from the lethal dose of venom by pre-immunization. This showed the defense response was dependent on IgE antibodies and mast cells. Similar experiments using snake venom from the Russell’s viper demonstrated that the response could be generalized to different types of toxic venom.

Galli explains the implications of the research for understanding the origins of allergies:

Our findings support the hypothesis that this kind of venom-specific, IgE-associated, adaptive immune response developed, at least in evolutionary terms, to protect the host against potentially toxic amounts of venom, such as would happen if the animal encountered a whole nest of bees, or in the event of a snakebite. Anaphylaxis probably represents the extreme end of a spectrum of IgE-associated reactivity, which in some unfortunate individuals is either poorly regulated or excessively robust, so the reaction itself can become dangerous to them.

Future work will examine why IgE responses reach such a harmful level in some individuals.

Previously: Mast cells not required for wound healing, according to Stanford study, Researchers find mechanism for destruction of key allergy-inducing complexes, and Synthetic antibodies may be able to mimic the real thing
Photo by ndboy

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