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.

新生儿抵御细菌和病毒感染的主要防御之一 是母源性 IgG。 经胎盘获得的 IgG 水平低 可能是早产儿易感性增加的一个因素 新生儿容易感染。 除了提供瞬态保护外 通过针对潜在感染因子的抗体，被动获得 抗独特型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。 在子宫内从患病母亲获得的抗体可能 干扰新生儿疾病的早期血清诊断。 从患有某些自身免疫性疾病的母亲那里被动获得抗体 不仅妨碍血清诊断，而且还可能诱发短暂形式的血清学检查。 新生儿疾病。 拟议研究的长期目标是 建立更可靠的疾病早期血清诊断方法 新生儿并制定增强新生儿抵抗力的策略 通过调节选定抗体的经胎盘通道来治疗疾病 子宫内的特殊性。 提议的 IgG 向胎儿转运模型 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运输 IgG 被释放到胎儿循环中。 大量研究 表明在 IgG 亚类内转运速率差异很大 不同个体之间以及个体内部都存在 不同抗体特异性的选择性转移。 假设 该提案要测试的是抗体向胎儿的转运 通过一种可以优先选择抗体的机制发生 它们的抗原特异性或其他独特型特征。 这 选择模式会受到特定免疫复合物的影响 存在于正常免疫反应期间。 为了解决这个假设 具有确定抗原性的单克隆抗体的运输 将使用独特型特异性。 本提案的具体目标 是： 1) 确定 IgG 分子发生了什么修饰（如果有） 当它穿过胎盘时； 2) 评估抗原/抗体的效果 或独特型/抗独特型免疫复合物对转移率的影响 单克隆抗体可穿过胎盘； 3) 确定效果 抗体经胎盘传递的母体免疫状态。 这些 研究将深入了解经胎盘的机制 抗体传代，母源抗体克隆型的鉴定 胎儿血清中的成分，以及母体免疫系统可能的方式 旨在增强新生儿对感染的抵抗力。