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.