From the Symbolic Stimulus to the Pathophysiologic Response: Immune Mechanisms

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Abstract
Indirect evidence from a variety of sources, particularly clinical studies of emotional and stress factors in the onset and course of diseases associated with dysfunction or hypofunction of the immune system (infectious, allergic, autoimmune and neoplastic), support the notion that experiential factors can influence the functions of the immune system, presumably via neuroendocrine mediation. We dissect the immunologic system into its components in order to find identifiable targets within disease processes that are stress-responsive. The immune system can be divided into three limbs: afferent, comprising presentation of antigen; central, in which different classes of cells give rise to immune responses; and efferent, concerned with the sequelae of immunization. We must also consider sites in which the immune reaction occurs. We try to defend the assumption that emotional factors lead to small alterations in “immune balance” that can convert latent or mild illness to manifest or severe illness. We consider the interaction of specific components of the immune response with a variety of stress-responsive hormones and with cyclic AMP and cyclic GMP. We also speculate on the possibility of direct central nervous system influence on the immune response, particularly via the thymus which plays an endocrine role in immunologic competence. We outline a variety of influences hormones can play on specific components of each limb of the immune response. Since the interaction of neuroendocrine and immune systems no doubt involves an interplay of multiple mechanisms with multiple targets in the immune system, establishing and studying relationships within the entire matrix will be necessary. Evidence so far suggests that stress affects chiefly the efferent, and to some extent the afferent, limbs of the immune system and that macrophage activities are probably a major target.