Allergic host defences

Abstract

A review of allergic host defences argues that allergic immunity has an important role in host defence against noxious environmental substances. Have we got it wrong about allergy? Allergic reactions tend to be seen as the result of a misfire from an immune system that evolved to repel invasive parasites. In a Perspective this week, Noah Palm, Rachel Rosenstein and Ruslan Medzhitov see things differently. They discuss competing hypotheses about the origin and potentially beneficial aspects of TH2 cytokine-dependent allergic immune responses, with emphasis on the possibility that allergic reactions are excessive or exaggerated responses of a system that serves a necessary function, protecting the body from environmental toxins such as noxious substances, venoms and xenobiotics. The authors propose a model in which type 2 inflammatory responses are heterogeneous depending on the stimulus, and speculate that diverse evolutionary pressures may have selected for this class of immune responses. Allergies are generally thought to be a detrimental outcome of a mistargeted immune response that evolved to provide immunity to macroparasites. Here we present arguments to suggest that allergic immunity has an important role in host defence against noxious environmental substances, including venoms, haematophagous fluids, environmental xenobiotics and irritants. We argue that appropriately targeted allergic reactions are beneficial, although they can become detrimental when excessive. Furthermore, we suggest that allergic hypersensitivity evolved to elicit anticipatory responses and to promote avoidance of suboptimal environments.