Mammals use two different routes to passively transfer protective antibodies from the mother to her offspring; one is through the placenta, the other is via breast milk. Only IgG travels by the former route whereas IgG and IgA travel by the latter. Without these means of providing antibody to the neonate and growing offspring, the young mammal would be at tremendous risk to its natural pathogens. A relatively short time after birth, the young is able to mount an immune response to protein antigens, but it remains unresponsive or weakly responsive to polysaccharide antigens (e.g., capsules of bacteria) for a long time. The basis for this responsiveness is unknown, but it is directly correlated in man and mouse with an inability to make an IgG response in the subclass that normally arises in response to polysaccharides in adults. Thus, the offspring is susceptible to a number of microbes, resistance to which is dependent upon antibodies to carbohydrate antigens on the infectious agents. We have found that in the mouse IgG3 antibody, the major responding subclass to polysaccharide antigens, readily passes from the mother to her offspring via the placenta and breast milk. We propose to study passive immunity by both routes and investigate the potential protective role maternal IgG3 and IgA offer the offspring against lethal infection by the encapsulated microorganism, Streptococcus pneumoniae. We will use hybridoma antibodies to study the dynamics of IgG3 transmission, including accumulation and retention of antibody. Maternal serum and breast milk and offspring serum will be examined. We will evaluate how well IgG3 and IgA from actively and passively immunized mothers protect the infant mouse. Additionally, we plan to investigate the selectivity in binding of IgG3 to the brush border cells of the jejunal epithelium, with a view toward determining the number and characteristics of Fc receptors. Finally we propose to investigate how passively transferred antibody from the mother affects the immune status of the offspring when they are immunized as adults with the complementary antigen.
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