Stress has been difficult to define because of its dual function in life. It can be a positive influence that satisfies a need for excitement (environmental enrichment) or a negative influence that interferes with homeostasis and life functions. The latter is referred to as a state of distress. Our use of stress will refer to this darker side of stress. The interaction between stress and the immune system is a conundrum because of the negative impact that stress can have on immune functions, and because active immune responses can be stressors in and of themselves. Stress can also activate or suppress immune responses depending on the degree and persistence of the stressor; the species, age, sex, and genetics of the subject; and the immune cells that are the targets of the stress. Not all stressors result in the same immune response, such as isolation compared to restraint stress. But, in general, most psychological and environmental stressors lead to impaired immune functions, especially those that regulate inflammatory and cytotoxic responses. The deleterious effects of stress are readily observed at an early gene expression level in cells of the innate (not requiring prior exposure to foreign antigen) and adaptive (requiring prior exposure to foreign antigen) immune systems. Thus, stress-immune interactions usually have significant physiological consequences even before behavioral or gross pathogenic changes are observed.

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