STRESS & IMMUNITY; BEHAVIORAL & PHYSIOLOGICAL MECHANISMS

最近，人们对以下方面的潜在关系产生了相当大的兴趣： 暴露于压力源和免疫系统的功能。 这是 因为免疫功能的改变可能介导 从艾滋病到癌症的疾病发展的压力因素。 事实上，有人认为，有关的个人差异， 艾滋病病毒感染引起的艾滋病症状的发展和表现可能 部分原因是心理或生理上的 在对病毒的免疫反应级联的关键阶段的压力。 该提案侧重于免疫功能的体内变化。 具体 该提案的目的是：1）研究行为因素， 重要的是确定是否以及如何应激暴露将改变 特异性抗体（Ab）和Ab分泌细胞（ASC）的形成 抗原（Ag）KLH。 尽管有很多示威活动， 暴露于痛苦或令人厌恶的事件可以改变免疫系统的某些方面。 功能，很少有分析工作针对隔离 重要的行为调节因素。 在这里，我们将重点放在2 因素：a）应激源的行为可控性，无论是在休克 和失败范例，B）优势。2)研究神经和神经内分泌 研究的应激条件改变Ab水平的介质。 重点 是两个不同但相关的问题A.中枢神经系统 在压力源和周围变化之间进行调解的过程， 可以接触免疫器官和细胞。 去甲肾上腺素能（NE）过程 与下丘脑室旁核（PVN）相关的神经元， 受到特别关注。 PVN是一种控制 垂体肾上腺和交感肾上腺髓质活动，NE PVN的输入是主要的刺激因素。B）外围设备 神经内分泌介质，负责应激产生的抗体 变化 这里重点将阐明肾上腺的作用， 肾上腺髓质释放的皮质类固醇和血浆儿茶酚胺 和交感神经末梢 3)目的：研究应激源及其神经、 神经内分泌后遗症，可能是负责减少抗体 形成，重点将是压力源产生的细胞内的变化， 免疫区室之间的运输，导致免疫区室的比例发生变化 淋巴细胞表型

There is considerable recent interest in potential relationships between exposure to stressors and the functioning of the immune system. This is because alterations in immune function might mediate the impact of stressors on the development of diseases ranging from AIDS to cancer. Indeed, it has been argued that individual differences concerning the development and expression of AIDS symptoms from infection with HIV might be partially accounted for by the occurrence of psychological or physical stress at a critical stage in the cascade of immune reactions to the virus. This proposal focuses on in vivo changes in immune function. The specific aims of the proposal are: 1) To study behavioral factors which are important in determining whether and how stressor exposure will alter the formation of specific antibody (Ab) and Ab secreting cells (ASCs) to the antigen (Ag) KLH. Although there have been numerous demonstrations that exposure to painful or aversive events can alter some aspect of immune function, there has been very little analytic work directed at isolating important behavioral modulating factors. Here we wish to focus on 2 factors: a) Behavioral controllability of the stressor, both in the shock and defeat paradigms, b) Dominance. 2) To study neural and neuroendocrine mediators by which the stress conditions studied alter Ab levels. Focus is on 2 different but related issues. a) The central nervous system processes that mediate between the stressor and the peripheral changes that could contact immune organs and cells. Noradrenergic (NE) processes associated with the paraventricular nucleus (PVN) of the hypothalamus will receive particular attention. The PVN is a key structure in controlling both pituitary-adrenal and sympathoadrenomedullary activity, and the NE input to the PVN is a major stimulatory factor. b) The peripheral neuroendocrine mediators that are responsible for the stress-produced Ab changes. Here emphasis will be on elucidating the roles of adrenal corticosteroids and plasma catecholamines released by the adrenal medulla and sympathetic terminals. 3) To study immunologic changes produced by stressors and their neural and neuroendocrin sequelae that might be responsible for the reduced Ab formation, the focus will be on stressor produced alterations in cell trafficking between immune compartments, resulting in changed ratios of lymphocyte phenotypes.