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The study of the interactions among behavioral, neural and endocrine, and immune functions. This convergence of disciplines has evolved to achieve a more complete understanding of adaptive processes. At one time, the immune system was considered an independent agency of defense that protected the organism against foreign material (that is, proteins that were not part of one's “self”). Indeed, the immune system is capable of considerable self-regulation. However, converging data from the behavioral and brain sciences indicate that the brain plays a critical role in the regulation or modulation of immunity. Thus, psychoneuroimmunology emphasizes the study of the functional significance of the relationship between these systems—not in place of, but in addition to, the more traditional analysis of the mechanisms governing the functions within a single system—and the significance of these interactions for health and disease. See Neuroimmunology

Brain–immune system interactions

Evidence for nervous system–immune system interactions exists at several biological levels. Primary and secondary lymphoid organs are innervated by the sympathetic nervous system, and lymphoid cells bear receptors for many hormones and neurotransmitters. These substances, secreted by the pituitary gland, are thus able to influence lymphocyte function. Moreover, lymphocytes themselves can produce neuropeptide substances. Thus, there are anatomical and neurochemical channels of communication that provide a structural foundation for the several observations of functional relationships between the nervous and immune systems.

Stress and immunity

The link between behavior and immune function is suggested by experimental and clinical observations of a relationship between psychosocial factors, including stress, and susceptibility to or progression of disease processes that involve immunologic mechanisms. Abundant data document an association between stressful life experiences and changes in immunologic reactivity. The death of a family member and other, less severe, stressful experiences (such as taking examinations) result in transient impairments in several parameters of immune function. See Stress (psychology)

In animals, a variety of stressors can influence a variety of immune responses. Since immune responses are themselves capable of altering levels of circulating hormones and neurotransmitters, these interactions probably include complex feedback and feedforward mechanisms. See Endocrinology

The direction, magnitude, and duration of stress-induced alterations of immunity are influenced by (1) the quality and quantity of stressful stimulation; (2) the capacity of the individual to cope effectively with stressful events; (3) the quality and quantity of immunogenic stimulation; (4) the temporal relationship between stressful stimulation and immunogenic stimulation; (5) the sampling times and the particular aspect of immune function chosen for measurement; (6) the experiential history of the individual and the existing social and environmental conditions upon which stressful and immunogenic stimulation are superimposed; (7) a variety of host factors such as species, strain, age, sex, and nutritional state; and (8) interactions among these variables.


Central nervous system involvement in the modulation of immunity is dramatically illustrated by the classical (Pavlovian) conditioning of the acquisition and extinction of suppressed and enhanced antibody- and cell-mediated immune responses. In a one-trial taste-aversion conditioning situation, a distinctively flavored drinking solution (the conditioned stimulus) was paired with an injection of the immunosuppressive drug cyclophosphamide (the unconditioned stimulus). When subsequently immunized with sheep red blood cells, conditioned animals reexposed to the conditioned stimulus showed a reduced antibody response compared to nonconditioned animals and conditioned animals that were not reexposed to the conditioned stimulus. See Conditioned reflex

The acquisition and the extinction (elimination of the conditioned response by exposures to the conditioned stimulus without the unconditioned stimulus) of the conditioned enhancement and suppression of both antibody- and cell-mediated immune responses—and nonimmunologically specific host defense responses as well—have been demonstrated under a variety of experimental conditions.


An elaboration of the integrative nature of neural, endocrine, and immune processes and the mechanisms underlying behaviorally induced alterations of immune function is likely to have clinical and therapeutic implications that will not be fully appreciated until more is known about the extent of these interrelationships in normal and pathophysiological states. See Endocrine system (vertebrate), Immunology, Nervous system (vertebrate)

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