ALCOHOL: IMMUNOMODULATION AND DISEASE PATHOGENESIS

这项提议的总体目标是发展一个 将促进有关乙醇在以下方面的作用的研究：(1) 动物模型的细胞免疫功能，(2)免疫抑制 和获得性免疫缺陷疾病的发展，包括 逆转录病毒感染；(3)肝毒性的机制。 免疫调节。 我们的方法涉及多学科，以基础科学为导向， 研究努力。它将开发一个酒精研究中心，并 包括： 1)饮酒、逆转录病毒感染、 免疫调节和艾滋病的发展： -确定酒精对死亡率的影响 -深入研究酒精对人体免疫功能的影响 不同酒精摄入量的小鼠。 -详细研究酒精引起的免疫学变化 逆转录病毒感染过程中的辅因子对其他病毒的耐药性 病原体。 -确定刺激乙醇抑制的宿主防御的方法和 在逆转录病毒感染期间的抗病能力。 2)使用定义明确的动物模型系统来： -确定酒精使用、营养压力、 免疫结构变化及由此引起的抵抗力变化 小鼠逆转录病毒。 -研究酒精对细胞调节的长期影响 免疫功能，因为它们与化学增强相关- 诱发大鼠肝癌。 -确定毒素和酒精改变的库普弗细胞的作用 在大鼠肝损伤中的作用。 -研究酒精对正弦渗透性、组织的影响 淋巴中的氧合作用和细胞迁移。 -测量和研究巨噬细胞的宿主防御功能和 体内的Kupffer细胞，包括经修饰的体内显微镜 乙醇和逆转录病毒病。

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. - 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 defenses and disease resistance during retroviral infection. 2) The use of well-defined animal model systems to: - determine interactions between alcohol use, nutritional stresses, immunoarchitecture changes and the resulting changes in resistance to murine retrovirus. - 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.