MATERNAL INFLUENCES ON MUCOSAL IMMUNITY IN INFANTS

母亲对婴儿粘膜免疫的影响

• 批准号: 6104901
• 负责人: MICHAEL W RUSSELL
• 金额: $ 21.78万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104901
• 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.

Center应用程序的此组件涉及 新生儿粘膜和全身免疫反应的发展 和儿童，与他们获得口腔微生物有关 （特别是那些参与斑块形成和启动 龋齿），以及母源性抗体对 婴儿粘膜免疫力的发展。 出生前，胎儿 接受母体IgG抗体通过胎盘转移到其 流通 出生后，如果是母乳喂养，婴儿接受母乳喂养。 初乳中主要为分泌型伊加（S-IgA）同种型的抗体， 牛奶，但这些不会被吸收到循环中，因此 为口腔-胃肠和上消化道提供被动保护 呼吸道 动物和体外实验表明， IgG抗体，对相应抗原的模块免疫应答， 反应的增强或抑制取决于 抗原和IgG亚类的性质。 S-IgA通过调节 共生生物（通常来源于 母亲或他们的共同环境），从而会影响接触 婴儿对微生物抗原的免疫系统 其目的是 因此，建议：（1）确定母性的影响 血清IgG和初乳S-IgA抗体，以确定的抗原， 口腔链球菌对内源性抗体反应的发展， 新生儿;（2）确定母体来源的影响 口腔链球菌确定抗原的抗体 这些生物在口腔微生物群;（3）以确定 产生血清（IgM、IgG和伊加）和分泌性（S-IgA）抗体 婴儿口腔链球菌的确定抗原， 获取这些生物。 这些将使用以下方法进行调查： 从核心部分招募的母婴对中获得的样本 这个中心。 特定链球菌特异性IgG抗体 抗原（AgI/II、AgIII、葡糖基转移酶和血清型 多糖）将在母体血清和脐带血清中进行测定， 评估胎盘转移。 S-IgA 1和S-IgA 2抗体 将在初乳和乳汁的连续样品中测定抗原， 评估出生后对婴儿的转移，以及婴儿的抗体 将在唾液（S-IgA 1和S-IgA 2）和血清中测定应答 (IgM，IgG，IgA 1和IgA 2），以评估内源性 免疫反应在研究过程中的顺序。 免疫 应答数据将与抗体从 母亲和获得口腔链球菌在婴儿， 在这个中心的项目#1中确定。 结果将阐明 关于免疫系统作用的重要问题 控制儿童早期致龋细菌的获得， 在婴儿最容易受到这种影响的时候， 关于儿童免疫力早期个体发育的知识。