The role of """"""""stress"""""""" in the modulation of immunity has recently come under intensive investigation. However, """"""""stress"""""""" is a highly ambiguous term and many of the stress manipulations in the laboratory bear little or no relation to stress as encountered in nature. This research application takes the novel approach of using the biologically relevant stress resulting from agonistic encounters and aggressive interactions between mice in a social conflict paradigm to gain an understanding of the mechanisms and interrelationships governing stress induced modulation of the immune system. Results from immunological experiments will form the basis for selection of experimental groups to be used for endocrinological analysis in order to identify presumably important pathways of endocrine mediation of immunity. Immunological responsiveness will be assessed through the in vivo and in vitro use of specific and non-specific immune stimulants, flow cytometer cell analysis and measurement of immunoregulatory molecules. Endocrinological analysis will include selective ablation of endocrine function by surgical, pharmacological and immunoneutralization techniques. Based on results obtained from the above, experiments will be designed to specifically test the degree to which immunological and endocrinological systems interact in response to the stress of social conflict. This research design will thus allow for a direct cause and effect relationship between the immune and endocrine systems to be examined. As such, this proposal seeks to address whether a biologically relevant stress can modulate immunological competence. This information may therefore be applicable to the study of Acquired Immune Deficiency Syndrome (AIDS), since it has been suggested that the progression of AIDS may be dependent, in part, on altered interactions between the endocrine and immune systems resulting from the psychological stress that is experienced by its victims.
