MODIFICATION OF SPECIFIC IMMUNE RESPONSES BY ALCOHOL

酒精对特异性免疫反应的改变

• 批准号: 3112322
• 负责人: CARL WALTENBAUGH
• 金额: $ 14.64万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3112322
• 关键词: T lymphocyte; alcoholic beverage consumption; cell type; cellular immunity; chemical synthesis; drug tolerance; genetic strain; humoral immunity; immune tolerance /unresponsiveness; immunoglobulin G; immunoglobulin isotypes; immunoregulation; infection; laboratory mouse; synthetic antigens; toxicology

APPLICANT'S ABSTRACT: Excessive alcohol consumption represents a major human health threat. Both clinical and laboratory evidence suggests that alcohol alters normal host defense mechanisms making alcoholic patients more prone to a variety of infections. The immune system is major defense against infection and mounts both humoral (antibody) and cell-mediated responses to infectious organisms. Ethanol apparently has a two-fold effect on the immune system of alcoholic patients; it enhances humoral immunity and impairs cell-mediated immunity. Most immune responses are regulated by helper T (Th) or suppressor T (Ts) lymphocytes with effector cells. In the mouse, Th cells can be divided into two subsets based upon function Th1 cells help cell-mediated immune response and Th2 are responsible for most humoral immunity. Recent studies show that Th1 and Th2 are coregulatory, e.g., IFN-gamma (interferon-gamma) produced by Th1 down-regulates Th2. We hypothesize that ethanol enhances humoral immunity by the impairment of Ts which regulate humoral immunity and/or by adversely affecting Th1 cell function. Our preliminary studies concur with this interpretation. Impairment of Th1 function by alcohol would limit down-regulation of Th2 and enhance the humoral immune response. Here we propose to examine the effect of alcohol consumption, in a controlled manner, on immune responses in inbred strains of mice to synthetic copolymer antigens. We have previously shown that the poly(Glu50Tyr50)(GT) and poly(Glu60Ala30Tyr10)(GAT) antigens are powerful tools in eliciting the genetic control of the role of regulatory T cells in both cellular and humoral immune responses. We will use these antigens to immunize alcohol-preferring inbred strains of mice. We will define the conditions under which ethanol alters the immune response and determine which cells of the immune system are affected by ethanol consumption. Both humoral and cell-mediated immune functions will be assayed in order to monitor Th2 and Th1 activity, respectively. This study should help elucidate the underlying mechanism(s) of the effect of ethanol on the immune response.

申请人的摘要：过量的饮酒代表了主要的 人类健康威胁。 临床和实验室证据都表明 酒精改变了正常的宿主防御机制 更容易感染各种感染。 免疫系统是主要防御 反对感染并固定体液（抗体）和细胞介导的 对感染生物的反应。 乙醇显然有两个方 对酒精患者免疫系统的影响；它增强了体液 免疫力并损害细胞介导的免疫力。 大多数免疫反应是 由助手t（th）或抑制剂t（ts）淋巴细胞调节 细胞。 在小鼠中，TH细胞可以根据 功能Th1细胞有助于细胞介导的免疫反应，Th2是 负责大多数体液免疫。 最近的研究表明TH1和 Th2是核心调节的，例如，Th1产生 下调TH2。 我们假设乙醇增强了体液免疫力 通过调节体液免疫和/或不利的TS损害 影响Th1细胞功能。 我们的初步研究同意 解释。 酒精对Th1功能的损害将限制 TH2的下调并增强体液免疫反应。 我们在这里 建议在受控的 方式，在小鼠近交菌株中的免疫反应上 共聚物抗原。 我们以前已经表明poly（GLU50TYR50）（GT） 和poly（glu60ala30tyr10）（GAT）抗原是吸引该抗原的强大工具 调节性T细胞在细胞和细胞中的作用的遗传控制 体液免疫反应。 我们将使用这些抗原免疫 饮酒的小鼠养育菌株。 我们将定义条件 在其中，乙醇改变了免疫反应并确定哪些细胞 免疫系统受乙醇消耗的影响。 两者都有体液和 将分析细胞介导的免疫功能，以监测Th2和 TH1活性分别。 这项研究应有助于阐明 乙醇对免疫反应的影响的基本机制。