MECHANISM OF ETHANOL INDUCED IMPAIRMENTS IN IMMUNITY

描述：(改编自《调查者摘要》)研究结果来自 我的实验室和其他研究人员的报告表明，乙醇 (乙醇)实验动物和人类的消费是相关的 对传染病的易感性增加。总体而言，这是 主要与细胞免疫生成的缺陷有关 淋巴样细胞的反应和效应功能，包括T和 自然杀伤细胞和巨噬细胞。我们和其他人已经证明了 乙醇的消耗也与 下丘脑-垂体-肾上腺(HPA)轴的许多变化 淋巴样细胞的数量和功能可以归因于所产生的 作为这种激活的结果而产生的皮质类固醇。这位将军 在本申请中提出的研究中要检验的假设是 喂食乙醇的动物产生的皮质类固醇抑制先天和 获得性免疫反应是宿主防御所必需的 有传染性的微生物。这一假设和其他更具体的假设 由一般假设产生的假设将通过使用 小鼠双喂流食中乙醇摄入模型的建立 范例。通过使用切除肾上腺的小鼠，我们将确定 模型T细胞依赖抗原如磷胆碱的免疫应答 与钥匙孔帽状血蓝蛋白或感染性微生物结合， 包括单核细胞增多性李斯特氏菌、鼠伤寒沙门氏菌、尼波斯特氏菌 巴西人和小鼠巨细胞病毒被皮质类固醇减少 作为乙醇消费的结果生产的。在这种方法下， 乙醇相关的皮质类固醇激素在细胞效应器上的产生 免疫，包括自然杀伤细胞、CD4和CD8 T细胞，以及 巨噬细胞将接受测试。通过使用各种传染病模型系统 在这个实验室中，乙醇对亚群的影响 辅助T细胞(TH-1和TH-2)也将被定义。

DESCRIPTION: (Adapted from the Investigator's Abstract) Study results from my laboratory and reported by other researchers have shown that ethanol (ETOH) consumption by experimental animals and human beings is associated with an increased susceptibility to infectious diseases. Overall, this is associated mostly with defects in the generation of cell-mediated immune responses and the effector functions of lymphoid cells, including T and natural killer cells as well as macrophages. We and others have shown that ETOH consumption is also associated with activation of the hypothalamic-pituitary- adrenal (HPA) axis and that many of the changes in lymphoid cell numbers and function can be attributed to the resulting corticosteroids produced as a result of this activation. The general hypothesis to be tested in the studies proposed in this application is that the corticosteroids produced by ETOH-fed animals suppress innate and acquired immune responses that are necessary for host defenses against infectious microorganisms. This hypothesis and other more specific hypotheses resulting from the general hypothesis will be tested by using a murine model of ETOH consumption in a liquid diet with a pair-feeding paradigm. With the use of adrenalectomized mice we will determine whether immune responses to model T-cell-dependent antigens such as phosphocholine conjugated to key hole limpet hemocyananin or infectious microorganisms, including Listeria monocytogenes, Salmonella typhimurium, Nippostrongylus brasiliensis, and murine cytomegalovirus, are decreased by corticosteroids produced as a result of ETOH consumption. With this approach the role of ETOH-associated corticosteroid production on the cellular effectors of immunity, including natural killer cells, CD4+ and CD8+T cells, and macrophages will be tested. By using the various infectious model systems in place in this laboratory the ETOH-mediated effects on the subsets of helper T cells (TH-1 and TH-2) will also be defined.