Our goal continues to be the elaboration and mediation of behaviorally conditioned alterations in immunologic reactivity. Current emphasis is on experimental paradigms using naturally-occurring or endogenous immunomodulating stimuli rather than immunopharmacologic agents as unconditioned stimuli (UCSs) for the conditioned modulation of immunity. Based on recently collected data, we propose to condition an enhancement of antibody production using antigens as UCSs. Reexposing conditioned mice to a gustatory CS previously paired with antigen potentiates the subsequent antibody response to a minimally effective dose of that antigen. We propose to: - address methodological issues calculated to optimize the experimental protocol and, in addition to the primary comparison between conditioned animals that are or are not reexposed to the CS at the time of testing, mice preexposed to the CS (which should attenuate the conditioned response) or given unreinforced exposures to the CS between conditioning and testing (experimental extinction) will be included to confirm that associative processes are involved in the conditioned enhancement of antibody production; -assess the generality of the conditioned response by using different antigenic UCSs; and -assess the specificity of the response (i.e., determine if the conditioned changes responsible for enhanced antibody production are a consequence of immune reactions specific to the antigen used as the UCS or are mediated by nonspecific immunologic or neuroendocrine reactions induced by immunization). In pursuing the mediating mechanisms, the effects of conditioning on B and T cell functions and on cytokines (interleukin-1 and -2) will be examined. The proposed research will increase our understanding of the means by which behavior can serve an immunoregulatory function and provide an experimental foundation for and new approaches to the study of adaptive processes in health and in a variety of disease processes such as autoimmune diseases, infectious diseases, and AIDS which involve disordered regulation of the immune system.
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