ALCOHOL: IMMUNOMODULATION AND DISEASE PATHOGENESIS

该提案的总体目标是建立一个中心， 将促进关于乙醇作用的研究：（1） 动物模型的细胞免疫功能，（2）免疫抑制 艾滋病的预防和发展， 逆转录病毒感染，和（3）肝毒性机制，通过 免疫调节 我们的方法涉及多学科，基础科学为导向， 研究工作。 它将建立一个酒精研究中心， 包括以下步骤： 1)酒精使用，逆转录病毒感染， 免疫调节和艾滋病发展： - 确定酒精对死亡率的影响 - 深入研究酒精对免疫功能的作用， 不同酒精摄入水平的小鼠。 - 测量停止大量饮酒对细胞的影响 免疫功能 - 详细研究酒精作为一种免疫系统的变化， 逆转录病毒感染期间对其他 病原体 - 确定刺激乙醇抑制的宿主防御的方法， 逆转录病毒感染期间的抗病性。 2)使用定义明确的动物模型系统： - 确定饮酒、营养压力 免疫结构的变化和由此产生的耐药性变化 鼠疱疹病毒。 - 研究酒精对调节细胞的长期影响， 免疫功能，因为它们与增强化学- 诱发大鼠肝癌。 - 确定毒素和酒精改变的枯否细胞的作用 在大鼠肝损伤中的作用。 - 研究酒精对窦通透性、组织 氧合，淋巴细胞迁移。 - 测量和研究巨噬细胞和枯否细胞的宿主防御功能 体内细胞，包括乙醇修饰的体内显微镜检查 和逆转录病毒病。

The overall goals of this proposal are to develop a center which will foster research concerning the role of ethanol on: (1) cellular immune function in animal models, (2) immunosuppression and development of acquired immunodeficiency diseases including retrovirus infection, and (3) mechanisms of liver toxicity via immunomodulation. Our approaches involve a multidisciplinary, basic science-oriented, research effort. It will develop an alcohol research center and include: 1) The relationships of alcohol use, retrovirus infection, immunomodulation and AIDS development to: - determine alcohol's effects on death rates - investigate in depth alcohol's actions on immune functions in mice with various levels of alcohol intake. -measure the effects of cessation of high alcohol use on cellular immune function -study in detail the immunological changes due to alcohol as a cofactor during retroviral infection on resistance to other pathogens -determine ways to stimulate ethanol-suppressed host defense and disease resistance during retroviral infection. 2) The use of well-defined animal model systems to: - determine interactions between alcohol use, nutritional stresses, immuno-architecture changes and the resulting changes in resistance to murine retorvirus. - investigate the long-term effects of alcohol to modulate cellular immune functions as they correlate with enhancement of chemically- induced liver cancer in rats. -determine the role of toxin and alcohol-altered Kupffer cell functions in liver damage in rats. - study alcohol's effects on sinusoidal permeability, tissue oxygenation, cell migration in lymph. -measure and study host defense function of macrophages and Kupffer cells in vivo including in vivo microscopy as modified by ethanol and retroviral disease.