Allergy, hypersensitivity and stress

The toxin hypothesis of allergy is related to the PHM hypothesis and the stress response. As mentioned previously, the toxin hypothesis proposes that allergy is an important defense mechanism that protects the host from harmful environmental substances, e.g., toxins, irritants, and venoms[17,18].
Palm et al[18] describe how the high sensitivity of IgE-mediated responses may have evolved to allow anticipation of dangerous exposures and thus cause avoidance of noxious substances. Experiments in mice and rats sensitized to a specific food allergen produced stress/anxiety effects and avoidance behavior associated with trace amounts of that specific allergen in their cages[81–83]. The anxiety-like behavior was shown to be dependent on allergic mechanisms. Corticotropin releasing hormone and Th2 cytokine increases in the prefrontal cortex paralleled the allergen-induced anxiety in the rat experiments[82]. It seems plausible that these allergy-induced effects also occur in humans. Observational studies show stress-related neuropsychiatric disorders are associated with allergic disorders in humans[84,85]. Although the above findings were related to IgE-mediated hypersensitivity, it may be that other types of immune hypersensitivity would have a similar relationship to stress responses.
Stress effects (e.g., increased anxiety, sleep disruption, elevated heart rate, and lower heart rate variability) occur in many CIDs[2,9,86,87]. The PHM hypothesis proposes that this is largely caused by frequent stress responses from exposures to PHM antigens and other cross-reacting antigens/allergens due to PHM colonization. This underlying physiological stress from PHM colonization could lead to greater perceived stress effects from ordinary daily activities and adverse life events.
Chronic stress can have significant effects on immune function through many mechanisms [88,89], including changes in the gut microbiota[90] and reduced secretory IgA[91,92]. A microbe-driven COPD-like disorder spontaneously developed in aging mice with SIgA deficiency[93].
IgE responses may be protective against diverse pathogens. For instance, studies have provided evidence that anti-microbial IgE antibodies may play a protective role in HIV[94] and Borrelia burgdorferi [95] infections. The association of selective IgE deficiency with increased asthma, chronic rhinosinusitis, otitis media, autoimmune disease, cardiovascular disease and cancer may be relevant[96–99]. Although the significance of these associations is uncertain, they are compatible with the view that IgE antibodies help protect humans from harmful colonization/infection.
PHM colonization could signal the immune system that there is a need for an increased protective response, including allergic responses and avoidance behavior. Thus, allergic symptoms and stress responses that would increase avoidance would be appropriate.’
More research is needed, but these findings are compatible with microbial hypersensitivity contributing to the defense against many types of microbes, including PHMs.