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.
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