The Function of Allergy: Immunological Defense Against Toxins

Abstract

This paper proposes that the mammalian immune response known as "allergy" evolved as a last line of defense against the extensive array of toxic substances that exist in the environment in the form of secondary plant compounds and venoms. Whereas nonimmunological defenses typically can target only classes of toxins, the immune system is uniquely capable of the fine-tuning required to target selectively the specific molecular configurations of individual toxins. Toxic substances are commonly allergenic. The pharmacological chemicals released by the body's mast cells during an IgE antibody-mediated allergic response typically cause vomiting diarrhea, coughing, tearing, sneezing, or scratching, which help to expel from the body the toxic substance that triggered the response; individuals frequently develop aversions to substances that have triggered such responses. A strong allergic response often includes a decrease in blood pressure, which slows the rate at which toxins circulate to target organs. The immune system identifies as toxic the following kinds of substances: (1) those low-molecular-weight substances that bind covalently to serum proteins (e.g., many plant toxins); (2) nontoxic proteins that act as carriers of toxins with low molecular weights (e.g., plant proteins associated with plant toxins); (3) specific substances of high molecular weight that harmed individuals in ancestral mammalian populations for a span of time that was significant from the standpoint of natural selection (e.g., the toxic proteins of bee venom. Substances that bind covalently to serum proteins generally are acutely toxic, and because many of these substances also bind covalently to the DNA of target cells, they are potentially mutagenic and carcinogenic as well. Thus, by protecting against acute toxicity, allergy may also defend against mutagens and carcinogens. The toxic hypothesis explains the main phenomena of allergy; why IgE-mediated allergies usually occur within minutes of exposure to an allergen and why they are often so severe; why the manifestations of allergy include vomiting, diarrhea, coughing, sneezing, scratching, tearing, and a drop in blood pressure; why covalent binding of low-molecular-weight substances to serum proteins frequently causes allergy; why allergies occur to many foods, pollens, venoms, metals, and drugs; why allergic cross-reactivity occurs to foods and pollen from unrelated botanical families; why allergy appears to be so capricious and variable; and why allergy is more prevalent in industrial societies than it is in foraging societies. This hypothesis also has implications for the diagnosis, prevention, and treatment of allergy.

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).…”

A Clinical Perspective in Evolutionary Medicine: What We Wish We Had Learned in Medical School

“…Allergic symptoms provide such a dilemma. While there is some support for the view that allergy provides an anti-toxin benefit (Profet 1991), severe allergy (anaphylaxis) is deadly, requiring immediate life-saving medical treatment. The paradox of deadly hypersensitivity reactions to innocuous triggers, such as peanuts and pollen, has led some researchers to speculate that a changed modern environment causes the immune system to misfire in allergic and related diseases (Strachan 1989;Bach 2002).…”

Human Organisms from an Evolutionary Perspective: Its Significance for Medicine

“…There are many types of allergies. They can be partially categorized as follows: (1) injected allergies (drugs, venom), (2) ingested allergies (foods), (3) inhaled allergies (pollen and animal dander), and (4) skin allergies (plants) (Profet 1991 andBarnes et. al.…”