FETAL ALCOHOL EFFECTS AND IMMUNE DEVELOPMENT

描述：（改编自研究者摘要）致畸 酒精的潜在作用是众所周知的，而酗酒母亲的后代 酒精已经被证明具有广泛的异常， 酒精相关的出生缺陷（ARBD） ARB跨度的表现 从出生体重减轻到被称为 胎儿酒精综合征（FAS）。 FAS儿童是慢性 酗酒的女人 然而，临床研究表明，即使是温和的， 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。 最 关于酒精致畸作用的研究主要集中在 受影响婴儿的形态学和神经学特征。 然而，在这方面， 最近的研究表明，ARBD儿童患某些疾病的风险很高， 免疫缺陷的程度以及随之而来的发病率和严重程度的增加 感染 由于免疫系统在出生时尚未发育完全， 婴儿科普感染能力很弱。 因此有 识别可能延迟正常免疫的环境因素很重要 使婴儿处于危险之中。 这个实验室最近的研究 使用ARBD的小鼠模型显示，在子宫内暴露于酒精 导致胎儿肝脏和新生儿B淋巴细胞发育迟缓 骨髓和脾脏。 发育中间体的表型分析 在B谱系中，有几个受子宫内酒精暴露的影响。 特别是，研究者观察到以前未报告的B 新生动物骨髓和脾脏中的细胞前体减少 在子宫内接触酒精 在本建议书中，申请人将使用 由暴露于酒精的胎儿和成对喂养和普通饲料喂养的对照组成的模型 评估酒精对胎儿和胎儿期B淋巴细胞生成的影响。 新生儿生命 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和这些细胞的表型 在胎儿肝脏和新生儿骨髓和脾脏中。 的 B细胞中间体的发育潜力将通过以下方法确定： 分选B系细胞和其他造血前体细胞和干细胞 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到成年，以确定是否 暴露影响体液免疫系统的功能， 长寿的效果。

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.