Allergic host defences

Abstract

Allergies are generally thought to be a detrimental outcome of a mistargeted immune response that evolved to provide immunity to macro-parasites. Here we present arguments to suggest that allergic immunity plays an important role in host defense against noxious environmental substances, including venoms, hematophagous 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.

Role of the inflammasome in defense against venoms

“…These data suggest that the immune response can enhance resistance to the noxious effects of envenomation by directly detoxifying venom components. Thus, at least some immune responses to venoms are likely to be intentional and beneficial rather than accidental and pathological (3,28). We found that caspase-1-deficient mice, like mast-cell-deficient mice, were hypersensitive to the noxious effects of envenomation as measured by venom-induced hypothermia and tissue damage.…”

“…As venoms are well known as triggers of the allergic response, immune responses to venoms are often considered to be pathological rather than beneficial (3,28). However, data obtained more than four decades ago by Higginbotham suggested that some immune responses to venoms might act to control the toxic effects of envenomation through detoxification of venom components rather than cause immunopathology (26,27).…”

“…These venoms, which consist of a complex mixture of toxic components, are usually delivered into their victims via bites or stings (2). The targeting of mammalian species by venomous animals has presumably introduced evolutionarily relevant selective pressures to either avoid or minimize the toxic effects of envenomation (3).…”

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

“…Subsequently, it was proven that one of the functions of PRRs is the sensing of tissue damage, and many DAMPs had been identified currently (1)(2)(3)19). Recently, Medzhitov et al proposed that allergic reactions are a component of the host defense system against noninfectious noxious environmental factors, including venoms, noxious xenobiotics, and irritants that can induce tissue damage (25). However, despite extensive research in recent years, our understanding of the molecular mechanisms underlying the physiological inflammatory response to trauma and pathological sterile inflammation remains incomplete.…”

AMCase is a crucial regulator of type 2 immune responses to inhaled house dust mites

“…It is well established that immune responses to inhaled allergens like house dust mite (HDM), cockroach, and animal dander provide much of the underlying basis of asthma pathogenesis such as eosinophilic inflammation of the airway, goblet cell metaplasia, and bronchial hyperreactivity (1)(2)(3)(4)(5). HDM is one of the commonest allergens, and up to 85% of asthmatics are known to be typically HDM-allergic (1).…”