STRESSOR INDUCED IMMUNE ALTERATION

拟议的研究源自一种假设，即压力-- 诱导免疫抑制(SIIS)是由离散神经元介导的 中枢神经系统的通路。拟议研究的重点是 确定某些大脑区域在调解中的重要性 应激诱导的脾神经依赖免疫功能的变化 在大鼠身上的反应。具体目标是：(1)确定和 大脑中支配脾的神经元回路：(2) 确定抑制离散的大脑核团是否可以消除 用体外有丝分裂原试验评估脾中的SIIS； (3)确定抑制离散脑核团是否可以 消除应激诱导的抗体反应抑制 注射绵羊红细胞。来确定哪种神经元 大脑中的群体支配脾的交感神经 节前神经元--一种跨神经元逆行运输 将进行测绘研究；伪狂犬病病毒将 注射到脾里，然后通过这个 嗜神经病毒通过突触连接的神经回路 采用光镜、免疫组织化学技术进行检测。 为了研究SIIS中特定大脑区域的重要性，一个 将使用基于神经电路的方法来确定 急性脑部离散部位的神经功能抑制 足部电击应激改变了脾的SIIS。我们将对此进行评估 使用体外非特异性有丝分裂原试验(AIM 2)和 抗原特异性淋巴细胞反应试验(AIM 3)。平行 免疫组织化学方法检测Fos表达的研究 我们将采用各种方法来评估我们的 方法抑制神经功能。此外，这些研究将 提供关于特定大脑部位在压力中的重要性的数据- 诱导的Fos在神经元群体中的表达 大脑。拟议研究的结果将有助于勾勒出 调节SIIS的神经回路，并为 研究合理的治疗方法以减少 应激对免疫系统功能和疾病的影响 敏感度。

The proposed studies are derived from the hypothesis that stress- induced immunosuppression (SIIS) is mediated by discrete neuronal pathways in the CNS. The focus of the proposed studies is to determine the importance of certain brain regions in mediating stress-induced changes in splenic nerve-dependent immune responses in rats. The specific aims are to: (1) identify and neuronal circuits in the brain that innervate the spleen: (2) determine whether inhibition of discrete brain nuclei can eliminate SIIS in the spleen as assessed using an in vitro mitogen assay; and (3) determine whether inhibition of discrete brain nuclei can eliminate stress-induced suppression of the antibody response injection of sheep red blood cells. To determine which neuronal populations in the brain innervate the splenic sympathetic preganglionic neurons, a transneuronal retrograde transport mapping study will be performed; pseudorabies virus will be injected into the spleen, and the subsequent passage of this neurotropic virus through synaptically-linked neural circuits will be examined using light microscopy immunohistochemical techniques. To examine the importance of specific brain regions in SIIS, a neural-circuit based approach will be used to determine whether acute inhibition of neuronal function in discrete brain sites during footshock stress alters SIIS in the spleen. This will be assessed using both an in vitro non-specific mitogen assay (Aim 2), and an antigen-specific lymphocyte response assay (aim 3). Parallel studies examining Fos expression using immunohistochemical methods will be performed to evaluate the effectiveness of our methods to inhibit neuronal function. In addition, these studies will provide data on the importance of specific brain sites in stress- induced Fos expression in neuronal populations throughout the brain. Results from the proposed studies will help delineate the neural circuits that mediate SIIS, and provide the framework for examining rational therapeutic approaches to reduce the impact of stress-related effects on immune system function and disease susceptibility.