BIOLOGICAL DEFINITION OF HOST DEFENSE DEFECTS IN MAN

人类宿主防御缺陷的生物学定义

• 批准号: 6303041
• 负责人: Max Dale Cooper
• 金额: $ 2.95万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6303041
• 关键词: B lymphocyte; cell differentiation; clinical research; developmental immunology; disease /disorder proneness /risk; family genetics; genetic mapping; host organism interaction; human subject; hypogammaglobulinemia; immunodeficiency; immunogenetics; immunoregulation; leukocyte activation /transformation; major histocompatibility complex; phenotype; sex linked trait

The major goals are to define the defects in lymphocyte differentiation or function associated with immune deficiency diseases, lymphoid malignancies, and disorders of immunoregulation. The underlying thesis is that some of the gaps in knowledge about the human immune system can be addressed by the comparative analysis of the normal ontogeny of the immune system and the immune system defects in primary immunodeficiency diseases. Emphasis is on (1) the ontogeny of B cell development in humans, (2) the genetic basis of immunodeficiency, and (3) the influence of gene defects on the differentiation of immunocompetent cells. A major predictor of childhood atopy is the concentration of IgE in the cord blood, but whether the source of the IgE is maternal or fetal remains unclear. Through examination of fetal, neonatal, and infant samples; we sought to determine the developmental pattern of in situ IgE production during fetal and neonatal life. We found that B lymphocytes, especially from individuals with IL-4R A1902G allele, appear primed to undergo IgE class switching from the earliest stages of ontogeny and can produce IgE, but IgE producing cells are rare in the blood until nine months after birth.

主要目标是确定与免疫缺陷疾病、淋巴恶性肿瘤和免疫调节疾病相关的淋巴细胞分化或功能缺陷。 基本论点是，通过对免疫系统的正常个体发育和原发性免疫缺陷疾病中的免疫系统缺陷进行比较分析，可以解决有关人类免疫系统的一些知识空白。 重点是（1）人类B细胞发育的个体发育，（2）免疫缺陷的遗传基础，以及（3）基因缺陷对免疫活性细胞分化的影响。 儿童特应性的一个主要预测因素是脐带血中 IgE 的浓度，但 IgE 的来源是母体还是胎儿仍不清楚。 通过检查胎儿、新生儿和婴儿样本；我们试图确定胎儿和新生儿生命期间原位 IgE 产生的发育模式。 我们发现，B 淋巴细胞，尤其是带有 IL-4R A1902G 等位基因的个体，似乎从个体发育的最早阶段就准备好进行 IgE 类别转换，并且可以产生 IgE，但产生 IgE 的细胞在出生后 9 个月之前在血液中很少见。