STRESS & IMMUNITY--BEHAVIORAL & PHYSIOLOGICAL MECHANISMS

描述（改编自申请人的摘要）：尽管身体不断增长， 关于压力和免疫力之间相互作用的研究， 对神经、内分泌和免疫系统的了解相对较少。 环境压力源最终改变某些措施的机制 免疫功能。 应激源没有直接的免疫途径， 细胞和器官。 相反，它们会改变神经活动， 调节神经内分泌和自主过程，这反过来又影响 免疫系统的器官和细胞。 在上一个赠款期间， 研究表明，各种各样的压力干扰了 产生针对抗原（Ag）的抗体。 研究进一步表明， 假设来解释这些发现。 假设压力源可以 诱导脑内IL-1b同时下调I型糖皮质激素 海马体中的受体功能，此外还导致 大脑中的一种典型的急性期反应， 外围 因此，巨噬细胞被激活，肝脏向 产生急性期蛋白（阳性反应物），并远离 白蛋白和载体蛋白（阴性反应物）等。 海马中I型糖皮质激素受体的水平升高 血浆皮质类固醇 这种效果与减少的 肝脏产生皮质类固醇结合球蛋白（载体蛋白）， 导致2-3天内游离皮质酮大量增加 IS后，这反过来又导致Th 1样细胞减少， T辅助细胞的“亚群”在其中Ag特异性 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。 从而产生T细胞和B细胞 没有足够的Th细胞因子来充分发育，这是 假设这是IG最终降低为Ag的最终原因。 拟议的研究旨在测试这一假设的每一步。

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.