The Genetic Control of the Antibody Repertoire During Infection With the Parasitic Nematode, Ascaris

The heterogeneity of host resistance or susceptibility to parasitic infection and the consequent overdispersion of the parasite population are well documented phenomena. This thesis presents an investigation of the genetic control of the antibody repertoire in infection with Ascaris, in a rodent model. Inbred and H-2 congenic strains of mice and rats were infected with A. suum, or a purified Ascaris component, and the antibody response was examined. The specificity of the response was studied using immunoprecipitation of radio-labelled antigens and SDS-PAGE. Infection sera were immunoprecipitated with excretory/secretory (ES) antigens, somatic antigen (ABF) or a purified 14kDa molecule, one of the main conponents of both ES and ABF. The level of antibody response was assessed using an ELISA system. The binding capacity of serum, from Asoaris infected animals, to the surface of living larvae was also examined, using immunofluorescence. All strains of mice and rats examined showed restricted recognition of the potentially antigenic components, in the context of infection. This restricted recognition could however, be overcome if a purified antigen was presented with adjuvant. The antibody repertoire produced as a result of Ascaris infection is controlled by MHC-linked genes, with non-MHC linked genes affecting the kinetics and level of antibody production. Helminth infections characteristically, induce high titres of IgE and special attention was, therefore, focused on the production and control of IgE, in this model, Parasite-specific IgE was examined using passive cutaneous anaphylaxis (PCA) and IgE-specific Western blotting. This analysis revealed that the repertoire of parasite-specific IgE, produced as a result of Ascaris infection, is identical to that of IgG antibody, exhibiting the same restricted recognition of parasite antigen and both MHC-linked and non-MHC linked genetic control, Finally, the antibody repertoire produced by human subjects, living in an endemic area, and naturally infected with A, lumbricaldes was examined, Serum from these individuals demonstrated restricted recognition of Ascaris components, There was variation in the level and specificity of the human antibody response, but no apparent correlation could be demonstrated between antibody production and infection status or age. The differences in antibody levels and specificity could also not be explained in terms of age or exposure to infection, suggesting that the differences observed may reveal that there is also genetic control of the human antibody response to infection with Ascaris. This system, therefore, provides a means of studying the genetic control of antibody production in response to infection, which may identify protective antigens or resistant host haplotypes