Genetic Control of the Antibody Response in Experimental and Human Ascariasis

The immune response of both infected laboratory animals and humans from an endemic area to the parasitic nematode Ascaris lumbricoides was investigated. Initially, some biochemical characteristics of various components of the parasite were examined. The four parasite preparations were the adult body fluid (ABF), Ascaris body fluid alleregn-1 (ABA-1), excretory/secretory products from infective larvae kept in culture (L2 ES) and excretory/secretory products from lung stage larvae kept in culture (L3/4 ES). Biochemical studies showed that the preparations (except the ABA-1) were complex mixtures of glycoproteins. The ABA-1 is a 14kDa molecule with very little carbohydrate content. The IgG antibody response to these preparations of different strains of mice and rats infected both with infective Ascaris eggs and parasite preparations in adjuvant were analysed by immunoprecipitation of radiolabelled antigen fallowed by SDS-PAGE analysis. Results showed that the IgG antibody repertoire was affected both by the MHC type of the animal and the mode of presentation of antigen. Similarly, the IgE response to ABA-1 was investigated in PCAs. Positive IgE responses to this molecule corresponded with positive IgG responses to it in strains of mice which possess the s allele at the I-A region of their H-2 and were infected with infective eggs. However, administration of ABA-1 in adjuvant altered the recognition patterns of the ABA-1 molecule by both IgG and IgE In mice and rats to that seen when generated in the context of infection. The IgG antibody responses of humans from an area endemic for Ascaris in Nigeria were examined by ELISAs against all four parasite preparations. Considerable heterogeneity in the levels of response was displayed but no correlations between these levels and any of the epidemiological data were discovered. Analysis of the antibody response in immunoprecipitations followed by SDS-PAGE analysis also revealed heterogeneity in the antigens recognised by individuals. Of particular interest was the restricted recognition of the ABA-1 which was also seen in humans from enedenic Ascaris areas in the Gambia and Karachi. IgG responses were also analysed by a Western blotting method. Human IgE responses were investigated in a blotting method and revealed that a wide range of parasite components are the target of an IgE response. The antibody response to the surface of the two larval stages was examined by means of a quantitative fluorescent antibody labelling technique. These studies revealed stage specificity of antigen expression and were suggestive of surface shedding contributing to ES products. Investigations with human sera revealed considerable heterogeneity not only in antibody responses but within the parasite population itself