Immediate Hypersensitivity: A Defense against Arthropods?

IMMEDIATE HYPERSENSITIVITY: A DEFENSE AGAINST ARTHROPODS? JAMES H. STEBBINGS, JR.* It is known, but not widely recognized, that many reactions to insect bites are immediate hypersensitivity reactions [1, p. 146; 2]; that these reactions are far more common than hay fever, asthma, and other immediate hypersensitivity reactions of clinical importance is indisputable . I propose the hypothesis that a major function of the immediate hypersensitivity reactions has been the protection of terrestrial vertebrates from the bites of, or invasion by, arthropods. Beyond the obvious notion that the most common agent inducing a biological response may be a clue as to the function of that response, two observations induced me to pursue the line of thought presented in this paper. Since the time of Osier [3] hay fever has been considered a product of modern culture; Burnet has commented on its apparent increase in recent decades [4, p. 142]. A concurrent decrease in frequency of insect bites, and presumably of the immediate hypersensitivity reactions which often follow, has not been quantified but is scarcely deniable. Second, a frequent, readily observable, and presumably beneficial function of the immediate hypersensitivity reaction to insect bites in man is the inducement of avoidance behavior. The natural functions of reagirne antibodies, or immunoglobulin E, have remained obscure despite their clinical importance as mediators of atopic diseases [5; 6, p. 31]. Elevated serum IgE levels have been found in individuals currently or previously infested with parasitic worms [7, 8], but it is not known whether this affects the course of parasitic disease [8]. The phenomenon of "self-cure," an expurgation of parasitic worms with considerable peristalsis and diarrhea due to noncytotoxic mediated histamine release in animals such as sheep and goats (and the rat [9]), appears to be mediated by IgE antibodies [10]. Although common viral and bacterial infections do not seem to influence IgE levels [7], IgE might play a role in protection against upper respiratory tract infections, at least in highly allergic subjects [5]. ?Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis , Minnesota 55455. Perspectives in Biology and Medicine · Winter 1974 | 233 Thé magnitude of the challenge posed by biting arthropods is, upon reflection, evident to anyone who has spent much time out of doors in humid climates; data on the number of insect bites to be expected under various natural conditions, however, seem scarce. Widespread plagues of black flies so severe as to cause significant mortality in both wild and domestic animals are known, and one plague of mosquitoes led to the deaths of 173 head of livestock in Florida [11, p. 334]. In the extreme, the number of bites is limited by the penetrable surface area of the host [12, p. 145]; the attack rate of arctic mosquitoes on a single exposed forearm may reach 280 bites per minute [13]. In studies ofdiurnal biting cycles of tropical mosquitoes (potential disease vectors), bites per hour are measured in the tens to hundreds [14, p. 28]; biting rates for midges as high as 2,000 per hour have been reported [15, p. 148]. Outbreaks of mosquitoes, midges, and black flies frequently assume such proportions that outdoor work has to be abandoned [11, p. 334] and normal community life is impossible [15, p. 152]. That the skin of early man was severely stressed by the environment, through insect bites and trauma, and thus a more common target in the past of autoimmune disease, has been suggested [16]. In brief, arthropod saliva is a major source of antigens with which birds and mammals must periodically cope. Of antigens of parasite origin, no others would seem to enter the body more rapidly, and few in such quantity. The normal sequence of development of immunologic responses to insect salivary antigens has been well studied [2]. Subjects previously unexposed to a specific insect, or a related species, show no reactions whatsoever; in time, delayed reactions occur in response to a bite. Later immediate reactions will appear, but the delayed reactions still occur. In a yet later stage only the immediate reaction occurs, although the delayed reactions may recur if the subject is bitten by a large number of insects. After prolonged and intense exposure such as may occur...