RESTRAINT STRESS: SUPPRESSION OF IA EXPRESSION

在过去的几年里，有证据表明这种压力已经开始累积

During the past several years evidence has begun to accumulate that stress results in a suppression of immunological competence in man that may ultimately result in increased susceptibility to disease. The suppressive effects of stress may not necessarily result in an increased incidence of disease in apparently healthy individuals. Instead, stress induced immunosuppression together with suppression of immune responsiveness associated with cancer chemotherapy or infection by the Human Immunodeficiency Virus (HIV), may tip the balance to favor the establishment of infectious disease by potentially pathogenic microorganisms. Approximately 50% of individuals infected with HIV have Mycobacterial disease. Natural resistance to this group of microorganisms is mediated by mononuclear phagocytes. The ability to control the growth of these microorganisms maps to a gene (Bcg) on chromosome 1 in mice. The Bcg gene also regulates the expression of MHC class II Ia glycoproteins. The purpose of this investigation is to assess the effect of stress on Ia expression and on Mycobacterial resistance of congenic mice that differ only in their resistance to BCG. To accomplish this mice will be stressed by restraint. The level of Ia expression and of Mycobacterial growth will be evaluated as will the functional capacity of peritoneal macrophages from stressed mice. We will evaluate the mechanism of the differential response of macrophages from BCG resistant and BCG susceptible mice to ACTH, alpha-MSH, and corticosterone by determining the effect of these hormones on macrophage Ia expression and antimycobacterial activity in vitro. Their role in controlling the transcription and translation of MHC class II genes will be evaluated. The interaction of these hormones with other stress-related peptide hormones will also be explored. An understanding of how stress effects macrophage function controlled by the Bcg gene may provide fundamental knowledge to understand how macrophages control the growth of Mycobacteria and ultimately how infection of macrophages with HIV may alter the expression of Ia glycoprotein and the growth of Mycobacteria.