FETAL ALCOHOL EFFECTS AND IMMUNE DEVELOPMENT

描述：(改编自《调查者摘要》)致畸 酒精的潜在性是众所周知的，虐待母亲的后代 酒精已被证明具有广泛的反常现象， 被称为酒精相关出生缺陷(ARBD)。ARB SPAN的表现形式 从出生体重减轻到独特的特征星座，称为 胎儿酒精综合征(FAS)。Fas儿童是慢性疾病的后代 酗酒的女人。然而，临床研究表明，即使是中等程度的 怀孕期间饮酒会影响胎儿发育 酗酒可能是导致出生缺陷的主要原因之一。多数 对酒精致畸作用的研究主要集中在 患病婴儿的形态和神经学特征。然而， 最近的研究表明，ARBD儿童有很高的风险 免疫缺陷的程度以及随之而来的发病率和严重性的增加 感染的可能性。由于免疫系统在出生时还没有完全发育， 婴儿应对感染的能力是脆弱的。因此，它是 重要的是要确定可能延迟正常免疫的环境因素 发展，并将婴儿置于危险之中。这个实验室的最新研究 使用ARBD小鼠模型的研究表明，在子宫内暴露于酒精中 导致胎肝和新生儿B淋巴细胞发育迟缓 骨髓和脾。发育中间体的表型分析 在B血统中，有几个人受到宫内酒精暴露的影响。 特别值得一提的是，调查人员观察到一种以前未报告的B 新生鼠骨髓和脾细胞前体减少 在子宫中暴露在酒精中。在本提案中，申请者将使用 胎儿酒精暴露与配对喂养和饲料喂养对照模型 酒精对胚胎和胚胎B淋巴细胞生成影响的动物实验 新生儿的生命。他们将使用多参数流式细胞术来确定 B细胞中间体的绝对数量及其表型 在胎儿肝脏和新生儿的骨髓和脾内。这个 B细胞中间体的发展潜力将由以下因素决定 分选B系细胞和其他造血祖细胞和干细胞 并使用克隆分析来确定酒精暴露是否会改变 能够分化的细胞的频率。他们还将 跟踪胎儿酒精暴露的动物，直到成年，以确定是否 暴露会影响体液免疫系统的功能， 效果的长寿。

DESCRIPTION: (Adapted from the Investigator's Abstract) The teratogenic potential of alcohol is well known and the offspring of mothers who abuse alcohol have been shown to have a broad spectrum of anomalies that have been termed alcohol related birth defects (ARBD). The manifestation of ARB span from reduced birth weight to the unique constellation of features termed fetal alcohol syndrome (FAS). FAS children are the offspring of chronic alcoholic women. However, clinical studies have shown that even moderate drinking during pregnancy can affect fetal development suggesting that alcohol abuse may be one of the leading causes of birth defects. Most studies of the teratogenic effects of alcohol have focused on the morphological and neurological features of the affected infants. However, recent studies have shown ARBD children to be at high risk of having some degree of immune deficiency and consequent increased incidence and severity of infection. Since the immune system is not fully developed at birth the infant's ability to cope with infection is fragile. Therefore, it is important to identify environmental factors that might delay normal immune development and put infants at risk. Recent studies from this laboratory using a murine model of ARBD have shown that in utero exposure to alcohol caused a retarded development of B lymphocytes in fetal liver and neonatal bone marrow and spleen. Phenotypic analysis of developmental intermediates in the B lineage showed several to be affected by in utero alcohol exposure. In particular, the investigator's observed that a previously unreported B cell precursor was decreased in neonatal marrow and spleens of animals exposed in utero to alcohol. In this proposal the applicants will use a model consisting of fetal alcohol exposed and pair-fed and chow-fed control animals to assess the effects of alcohol on B lymphopoiesis during fetal and neonatal life. They will use multiparameter flow cytometry to ascertain the absolute number of B cell intermediates and the phenotype of these cells within the fetal liver and neonatal bone marrow and spleen. The developmental potential of the B cell intermediates will be determined by sorting B-lineage cells and other hematopoietic precursors and stem cells and using clonal analysis to determine if alcohol exposure alters the frequency of cells that are capable of differentiation. They will also follow fetal alcohol exposed animals in to adulthood to determine if the exposure affected the function of the humoral immune system and the longevity of the effect.