Influence of Stressors on Immune Functioning

Stressful events provoke alterations of several aspect of immune functioning, as reflected by alterations of T and B cell proliferation, natural killer cell activity, trafficking of immune cells. Analysis of the mechanisms underlying the stressor-provoked immunological alterations is complicated by the numerous factors that influence the neuroendocrine and behavioral effects of stressors. In addition, the nature of the stressor itself may have important ramifications, as psychogenic (of psychological origin), neurogenic (physical) and systemic stressors (e.g., immune challenge) do not invariably lead to identical outcomes, and may actually activate different neural circuits. It is our contention that acute stressful events initially give rise to a cascade of neuroendocrine and neurotransmitter alterations that initially promote immune activation (after all, it may be adaptive to mount an immune response in the face of environmental threats). This is followed by a second wave of changes that limit immune functioning. The precise nature of the changes observed may vary with the characteristics of the stressor, as well as numerous experiential factors (e.g., stressor history).

Our neurochemical studies revealed that subchronic (repeated, predictable) stressors promote compensatory changes culminating in increased neurochemical functioning. However, if the stressor is sufficiently protracted and unpredictable (even if the stressors are relatively mild), the wear and tear on the organism (allostatic load) ultimately favors neurochemical dysfunction and may increase vulnerability to illness. In addition to evaluating the effects of stressors we evaluate the effects of pharmacological treatments in attenuating the effects of stressors (e.g., antidepressant agents, compounds that specifically affect different neuropeptide receptors, various cytokine receptor antagonists, as well as monoamine acting agents).

Supported by NSERC.

Last Modified November 7, 2009