SELECTIVE TRANSMISSION OF ANTIBODIES TO THE FETUS

选择性地将抗体传递给胎儿

• 批准号: 3456199
• 负责人: KEITH ALAN KNISLEY
• 金额: $ 10.64万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3456199
• 关键词: affinity chromatography; antibody receptor; antibody specificity; antigen antibody reaction; antigen receptors; autoradiography; bactericidal immunity; embryo /fetus; enzyme linked immunosorbent assay; immune complex; immunity; immunoglobulin G; immunoglobulin structure; laboratory mouse; monoclonal antibody; placental transfer; radiotracer; scintillation counter; western blottings

One of the major neonatal defenses against bacterial and viral infection is maternally-derived IgG. Low levels of transplacentally-acquired IgG may be a contributing factor in the increased susceptibility of premature neonates to infection. In addition to the transient protection afforded by antibody against potentially infectious agents, passively acquired anti-idiotypic antibody can alter the development of active immunity in the neonate. In certain situations passively acquired antibody may not be desirable. Antibody acquired in utero from diseased mothers may interfere with early serodiagnosis of the disease in the neonate. Passively acquired antibody from mothers with certain autoimmune diseases not only hinder serodiagnosis but may also induce a transient form of the disease in the neonate. The long term goal of the proposed study is to establish more reliable methods for early serodiagnosis of disease in the neonate and to develop strategies that will enhance neonatal resistance to disease by regulating transplacental passage of selected antibody specificities in utero. Proposed models of IgG transport to the fetus involve binding to Fc receptors on placental tissues followed by endocytosis of the receptor-ligand complex and transport across the cell where IgG is released into the fetal circulation. Numerous studies suggest that within an IgG subclass transport rates vary considerable among different individuals and that within an individual there is selective transfer of different antibody specificities. The hypothesis to be tested in this proposal is that transport of antibody to the fetus occurs by a mechanism that can preferentially select antibodies based on their antigenic specificity or other idiotypic characteristics. This mode of selection would be influenced by specific immune complexes that exist during normal immune responses. To address this hypothesis transport of monoclonal antibodies that have defined antigenic and idiotypic specificities will be used. The specific aims of this proposal are: 1) To determine what modification if any occurs to an IgG molecule as it crosses the placenta; 2) To assess the effect of antigen/antibody or idiotype/anti-idiotype immune complexes on the rate of transfer of a monoclonal antibody across the placenta; and 3) To determine the effect of maternal immune status on transplacental passage of antibodies. These studies will provide insight into the mechanisms of transplacental passage of antibodies, the identification of maternal antibody clonotypes in fetal serum, and ways by which the maternal immune system might be manipulated to enhance neonatal resistance to infection.

针对细菌和病毒感染的主要新生儿防御措施之一 是母体衍生的IgG。 低水平的移植获得IgG 可能是提高过早易感性的因素 新生儿感染。 除了提供瞬态保护 通过针对潜在感染剂的抗体，被动地获得 抗IDiotypic抗体可以改变主动免疫的发展 新生儿。 在某些情况下，被动获得的抗体可能不会 是理想的。 从患病母亲获得子宫内获得的抗体可能 干扰新生儿中疾病的早期血清诊断。 从患有某些自身免疫性疾病的母亲的被动获得的抗体 不仅会阻碍血清诊断，而且还可能引起瞬态形式 新生儿中的疾病。 拟议研究的长期目标是 建立更可靠的方法来早期疾病的早期诊断 新生儿并制定将增强新生儿抵抗力的策略 通过调节选定抗体的移植通过来疾病 子宫内的特异性。 提议的IgG转运到胎儿的模型 涉及与胎盘组织上的FC受体结合，然后 受体配体复合物的内吞作用和跨细胞的转运 IgG被释放到胎儿循环中。 许多研究 建议在IgG子类传输率中有所不同 在不同的个人中，一个人内部有 不同抗体特异性的选择性转移。 假设 在此提案中进行测试是抗体向胎儿的运输 通过一种可以优先选择基于基于的抗体的机制发生 它们的抗原特异性或其他白痴特征。 这 选择方式将受到特定免疫复合物的影响 在正常免疫反应中存在。 解决这一假设 已定义抗原和的单克隆抗体的运输 将使用白痴型特异性。 该提议的具体目的 是：1）确定如果发生在IgG分子的情况下发生什么修饰 当它越过胎盘时； 2）评估抗原/抗体的影响 或白痴型/抗IDiotype Anmune复合物的传递速率 胎盘上的单克隆抗体； 3）确定效果 母体免疫状态在抗体的移植通过。 这些 研究将提供有关移植机制的见解 抗体的通过，鉴定母体抗体clonotypes 在胎儿血清以及孕产妇免疫系统的方式中 操纵以增强新生儿对感染的抗性。