STRESS & IMMUNITY--BEHAVIORAL & PHYSIOLOGICAL MECHANISMS

描述(改编自申请者的摘要)：尽管身体在成长 关于压力和免疫之间相互作用的研究，有 对神经、内分泌和免疫学的了解相对较少 环境应激源最终改变某些措施的机制 对免疫功能的影响。应激源没有直接免疫的途径 细胞和器官。相反，它们会改变神经活动，进而 调节神经内分泌和自主神经过程，这反过来又影响 免疫系统的器官和细胞。在上一次授权期内， 研究表明，各种压力源都会干扰 抗原(Ag)抗体的产生。这项研究进一步表明， 假说来解释这些发现。假设是，应激源可以 诱导脑内IL-1b下调I型糖皮质激素 在海马区的受体功能，并导致外流 来自大脑的产品，激活了典型的急性时相反应 外围设备。因此巨噬细胞被激活，肝脏向 急性期蛋白(阳性反应物)的生产和远离 白蛋白和载体蛋白(阴性反应物)等下调 海马I型糖皮质激素受体的表达可提高基础水平 血浆中的皮质类固醇。这种效果，再加上减少的 由肝脏产生的皮质类固醇结合球蛋白(一种载体蛋白)， 导致2-3天内游离皮质酮的大幅增加 以下是，这反过来会导致Th1样细胞的减少 抗原特异性T辅助细胞亚群的变化 T-Abd-B细胞发育(Ag和IS后4天)。激活的巨噬细胞 也被视为抑制T细胞功能。从而形成T细胞和B细胞 接受不足的Th细胞因子以充分发育，这是 推测是Ig最终减少为Ag的最终原因。 这项拟议的研究旨在检验这一假设的每一步。

DESCRIPTION (Adapted from applicant's abstract): Despite the growing body of research concerning interactions between stress and immunity, there is relatively little understanding of the neural, endocrine, and immunologic mechanisms by which an environmental stressor ultimately alters some measure of immune function. Stressors do not have a pathway directly to immune cells and organs. Rather, they alter neural activity, which in turn regulates neuronendocrine and autonomic processes, which in turn impact on organs andcells of the immune system. During the previous grant period the research has indicated that a variety of stressors interfere with the generation of antibody to an antigen (Ag). The research further suggested a hypothesis to explain these findings. The hypothesis is that stressors can induce IL-1b in brain which both downregulates Type I glucocorticoid receptor function in the hippocampus and in addition leads to an outflow of products from brain that activate a classic acute phase response in the periphery. Thus macrophages became activated, the liver shifts towards the production of acute phase proteins (positive reactants) and away from albumin and carrier proteins (negative reactants), etc. The downregulation of Type I glucocorticoid receptors in the hippocampus elevates basal levels of plasma corticosteroids. This effect, in combination with the reduced corticosteroid binding globulin (a carrier protin) production by the liver, leads to large increases in free corticosterone for a 2-3 day period following IS, which in turn produces a reduction in the Th1-like "subpopulation" of T-helper cell during the time period in which Ag-specific T abd B cells develop (4 days after Ag and IS). The activated macrophage also is seen as suppressing T cell function. Thus developing T and B-cells receive insufficient Th cytokines to develop adequately, and this is hypothesized to be the ultimate cause of the eventual reduction in Ig to Ag. The proposed research is designed to test each step of this hypothesis.