MATERNAL INFLUENCES ON MUCOSAL IMMUNITY IN INFANTS

母亲对婴儿粘膜免疫的影响

• 批准号: 6238572
• 负责人: MICHAEL W RUSSELL
• 金额: $ 21.22万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6238572
• 关键词: Streptococcus; colostrums; communicable disease transmission; dental caries; human milk; human subject; immunity; immunoglobulin A; immunoglobulin G; immunoglobulins; infant human (0-1 year); microorganism interaction; mother child interaction; mucosal immunity; oral bacteria; perinatal; placental transfer

This component of the Center application is concerned with the development of mucosal and systemic immune responses in newborn infants and children, in relation to their acquisition of oral microorganisms (especially those involved in plaque formation and the initiation of dental caries), and the influence of maternally derived antibodies on the development of mucosal immunity in the infant. Prior to birth, the fetus receives maternal IgG antibodies transferred across the placenta into its circulation. After birth, if breast-fed, the infant receives maternal antibodies largely of the secretory IgA (S-IgA) isotype in colostrum and milk, but these are not absorbed into the circulation and therefore provide passive protection of the oro-gastrointestinal and upper respiratory tracts. Experiments in animals and in vitro have shown that IgG antibodies, module immune responses to corresponding antigen, with enhancement or suppression of the response depending upon the nature of the antigen and the properties of the IgG subclass. S-IgA, by regulating colonization of the infant with commensal organisms (usually derived from the mother or their common environment), will thereby affect exposure of the infant's immune system to microbial antigens. The aims of this proposal are therefore: (1) to determine the influence of maternally derived serum IgG and colostral S-IgA antibodies to defined antigens of oral streptococci on the development of endogenous antibody responses in the neonate; (2) to determine the influence of maternally derived antibodies to defined antigens of oral streptococci on the acquisition of these organisms in the oral microbiota; (3) to determine the development of serum (IgM, IgG, and IgA) and secretory (S-IgA) antibodies to defined antigens of oral streptococci in the infant, in relation to the acquisition of these organisms. These will be investigated using samples obtained from mother-infant pairs recruited in the Core Component of this Center. Specific IgG antibodies to defined streptococcal antigens (AgI/II, AgIII, glucosyltransferase, and serotype polysaccharide) will be assayed in maternal serum and cord serum to assess placental transfer. S-IgA1 and S-IgA2 antibodies to the same antigens will be assayed in sequential samples of colostrum and milk, to assess post-natal transfer to the infant, and the infants' antibody responses will be assayed in saliva (S-IgA1 and S-IgA2) and in serum (IgM, IgG, IgA1, and IgA2), to evaluate the development of endogenous immune responses sequentially over the course of the study. The immune response data will be correlated with transfer of antibodies from the mother and the acquisition of oral streptococci in the infants, as determined in Project #1 of this Center. The results will elucidate important questions concerning the role of the immune system in controlling the acquisition of cariogenic bacteria in early childhood, at a time when infants are most susceptible to this, and add new knowledge concerning the early ontogeny of immunity in children.

中心应用程序的此组件与 新生儿黏膜免疫和全身免疫反应的研究进展 和儿童获得口腔微生物的关系 (尤其是那些参与斑块形成和启动的 龋齿)，以及母源抗体对 婴幼儿黏膜免疫功能的发育。在出生之前，胎儿 接受母体免疫球蛋白抗体通过胎盘转移到其 发行量。出生后，如果母乳喂养，婴儿将收到母亲的 初乳和乳汁中主要分泌型免疫球蛋白A(S-免疫球蛋白A)抗体 牛奶，但它们不会被吸收到循环中，因此 为口腔、胃肠和上段提供被动保护 呼吸道。在动物和体外的实验表明， 免疫球蛋白抗体，对相应抗原的免疫反应模块，具有 响应的增强或抑制取决于 免疫球蛋白亚类的抗原和性质。S-IgA，通过调节 婴儿与共生生物体(通常来自 母亲或他们的共同环境)，将因此影响接触 婴儿对微生物抗原的免疫系统。这样做的目的是 因此建议：(1)确定对母体的影响 针对猪瘟确定抗原的血清Ig G和初乳S Ig A抗体 口服链球菌对儿童内源性抗体反应发展的影响 对新生儿的影响；(2)确定母源的影响 获得时口腔链球菌特定抗原的抗体 口腔微生物区系中这些微生物的数量；(3)测定 血清(IgM、Ig G、Ig A)和分泌型(S-Ig A)抗体的研制 确定婴儿口腔链球菌的抗原，与 对这些生物的获取。这些问题将通过以下方式进行调查 从核心部分招募的母婴配对中获得的样本 这个中心的。针对明确的链球菌的特异性抗体 抗原(AgI/II、AgIII、葡萄糖基转移酶和血清型 将检测母体血清和脐带血清中的多糖)，以 评估胎盘移植。S-IgA_1和S-免疫球蛋白A_2的抗体 将在连续的初乳和牛奶样本中检测抗原，以 评估出生后对婴儿的转移，以及婴儿的抗体 将在唾液(S-Ig A1和S-Ig A 2)和血清中检测反应 (IGM、Ig G、Ig A1、Ig A2)，以评价内源性疾病的发展。 在研究过程中依次进行免疫反应。免疫者 反应数据将与抗体从 母亲与婴儿口腔链球菌的获得性 在本中心的项目#1中确定。结果将会阐明 关于免疫系统在免疫系统中的作用的重要问题 在儿童早期控制致龋性细菌的获取， 在婴儿最容易受此影响的时候，并增加了新的 关于儿童免疫早期个体发生的知识。