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Title: Age-dependent susceptibility and immune hypo-responsiveness to Schistosoma mansoni
Author: Gibbons, J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2003
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It has been observed that adults and children have differences in their susceptibility to schistosome infection and reinfection. The relative importance of the various factors that may influence age-dependent innate resistance and acquired immunity to schistosome infection is uncertain. In order to assess this, juvenile and adult female Fischer rats were exposed to primary and secondary infections of Schistosomia mansoni. In contrast to the adult rats, juveniles were found to be harbouring significantly more worms at day 21 post-infection. After reinfection, both groups were equally resistant to challenge. Similar age-dependent susceptibility to infection was observed in rat mouse infections with Nippostrongylus brasiliensis. The effect of host hormones was assessed on larval schistosomes. Testosterone (but not DHEAS) was found to be schistosomicidal in vitro. Antibody responses (antigen-specific IgG, IgG1, IgG2a, IgG2b and IgG2c) were found to be lower in juvenile animals after primary infection. No significant differences were observed in the relative levels of anti-carbohydrate antibodies to parasite antigens. Intra-cellular cytokine staining revealed juveniles to have a more Th1 dominated cytokine profile than adults. Immunisation of juvenile and adult rats with ovalbumin resulted in lower levels of antigen-specific antibody in the juvenile group, even after subsequent boosting whilst sexually mature. To provide an experimental bridge between rodents and humans, juvenile and adult female. Rhesus monkeys were infected with S. mansoni. Juvenile monkeys had higher worm burdens (non-significant) with greater tissue and faecal egg counts compared to adults. However, circulating schistosome antigens (CAA) were significantly greater in infected juvenile monkeys. PBMC production of IL-4 and IL-5 was lower in juvenile animals following primary schistosome infection, as were parasite-specific antibody responses (IgG, IgG2, IgM and IgA).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available