RESTRAINT STRESS: SUPPRESSION OF IA EXPRESSION

在过去的几年里，有证据表明， 导致人类免疫能力的抑制， 最终导致对疾病的易感性增加。该抑制性 压力的影响可能不一定会导致 在表面上健康的人身上。相反，压力导致 免疫抑制和免疫应答抑制 与癌症化疗或人类感染相关 免疫缺陷病毒（艾滋病毒），可能会打破平衡，有利于 通过潜在致病性确定传染病 微生物的大约50%的艾滋病毒感染者 分枝杆菌病。对这组微生物的天然抵抗力 由单核吞噬细胞介导。控制生长的能力 这些微生物定位于小鼠1号染色体上的基因（Bcg）。卡介苗 该基因还调节MHC II Ia类糖蛋白的表达。的 本研究的目的是评估压力对Ia的影响， 表达和分枝杆菌耐药性的同源小鼠， 仅仅是对卡介苗的抵抗力。为了完成这个任务， 通过克制。Ia表达水平和分枝杆菌生长水平将 将评价腹腔巨噬细胞的功能能力， 应激小鼠 我们将评估巨噬细胞差异反应的机制 从BCG抗性和BCG敏感小鼠到ACTH、α-MSH和 通过测定这些激素对巨噬细胞Ia的影响， 表达和体外抗分枝杆菌活性。农村妇女在消除 控制MHC II类基因的转录和翻译将是 评估。这些激素与其他压力相关的 还将探索肽激素。理解压力是如何 由Bcg基因控制的巨噬细胞功能可能提供 了解巨噬细胞如何控制生长的基础知识 分枝杆菌和最终如何感染巨噬细胞与艾滋病毒可能会改变 Ia型糖蛋白的表达和分枝杆菌的生长。

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.