IMMUNOREACTIVE EFFECTS OF FETAL ETHANOL EXPOSURE

胎儿乙醇暴露的免疫反应影响

• 批准号: 2045972
• 负责人: JOANNE WEINBERG
• 金额: $ 9.24万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2045972
• 关键词: B lymphocyte; T lymphocyte; cell cell interaction; concanavalin A; cytotoxic T lymphocyte; embryo /fetus toxicology; ethanol; fetal alcohol syndrome; flow cytometry; gender difference; hypothalamic pituitary axis; immune system; immunoglobulins; laboratory rat; lipopolysaccharides; lymphokines; mitogens; prenatal stress; suppressor T lymphocyte

Fetal alcohol syndrome is a significant preventable health problem world wide. Studies in humans and animals suggest that prenatal ethanol exposure (E) also disrupts the normal development of the immune system, resulting in immune disfunction that may persist well into adult life. Data also indicate that stress can have a profound negative impact on immunocompetence. The proposed research is the first to investigate the interactive effects of prenatal ethanol and postweaning stress on immunocompetence. We have shown that E results in: 1) long-term effects on offspring immunocompetence; 2) alterations in the hypothalamic-pituitary-adrenal (HPA) response to stress, Our preliminary studies demonstrate interactive effects of prenatal ethanol and stress in adulthood on lymphocyte populations. The proposed research will focus on one critical aspen of the immune response, T cell--B cell interactions. The ability of T helper cells to facilitate immunoglobulin production by B cells, and conversely, the ability of B cells to respond to T lymphocyte-derived activation and proliferation signals, will be assessed. In adulthood, offspring will be subjected to a 3 week chronic intermittent stress regimen or will remain undisturbed. Experiments in which mitogen-activated T cell supernatants from both prenatally treated and control animals are cultured with activated B cells from both prenatally treated and control animals will allow us to determine if the potential defect lies on the T cell or the B cell side of this system, or if both cell types are functioning abnormally. Our working hypothesis is that prenatal ethanol will cause abnormal T cell--B cell interactions, via either defective T cell activation or aberrant lymphokine production by activated T cells. Our experimental paradigm will also enable us to determine whether B cells are affected. We also hypothesize that stress will exacerbate the immunosuppressive effects of prenatal ethanol, and based on our previous data, that males will be more affected than females by exposure to prenatal ethanol and stress. This approach will increase our understanding of two fundamentally important issues: the nature of the immunoteratogenic effects of ethanol, and the possible role of stress in exacerbating these effects.

胎儿酒精综合征是一个重大的可预防的健康问题的世界 宽对人类和动物的研究表明，产前接触乙醇 (E)也会破坏免疫系统的正常发育， 免疫功能紊乱可能会持续到成年。 数据还 表明压力会对 免疫活性这项研究是第一次调查 产前乙醇和断奶后应激的相互影响 免疫活性 我们已经表明，E的结果：1）对后代的长期影响 免疫活性; 2）下丘脑-垂体-肾上腺的改变 (HPA)我们的初步研究表明， 产前乙醇和成年应激对淋巴细胞的影响 人口。拟议的研究将集中在一个关键的白杨的 免疫反应，T细胞-B细胞相互作用。T辅助细胞的能力 细胞以促进B细胞产生免疫球蛋白，反之， B细胞应答T淋巴细胞衍生的活化的能力， 将评估增殖信号。 成年后，后代将 进行为期3周的慢性间歇性应激方案，或将保持 不受干扰其中丝裂原活化的T细胞上清液 来自产前处理和对照动物的细胞培养物， 来自产前处理和对照动物的活化B细胞将 使我们能够确定潜在的缺陷是否位于T细胞或B细胞上 或者如果两种细胞类型都在运行， 反常地。 我们的工作假设是产前酒精会导致T细胞异常 细胞-B细胞相互作用，通过缺陷性T细胞活化或 活化T细胞产生异常淋巴因子。我们的实验 这一范例也将使我们能够确定B细胞是否受到影响。我们 我还假设压力会加剧免疫抑制作用， 产前酒精，并根据我们以前的数据，男性将 比女性更容易受到产前酒精和压力的影响。 这种方法将从根本上增加我们对两个问题的理解 重要问题：乙醇的免疫致畸作用的性质， 以及压力在加剧这些影响中的可能作用。