The work presented in this thesis is an investigation of the immune responses induced by chronic schistosomiasis in Gabonese schoolchildren. By investigating concurrently various aspects of the... Show moreThe work presented in this thesis is an investigation of the immune responses induced by chronic schistosomiasis in Gabonese schoolchildren. By investigating concurrently various aspects of the immune response, including innate, adaptive and regulatory responses, we are able to gain a more in-depth understanding of the dynamic changes brought about by infection. Through a number of cross-sectional and longitudinal studies we show that S. haematobium infection induces increased frequencies of regulatory B (Breg) and T (Treg) cell subsets which are associated with increased levels of IL-10 and adaptive immune hypo-responsiveness. Anti-schistosome treatment results in the reduction of regulatory subsets, an increase in effector T cells and alleviation of suppressed antigen immune responses. By showing that Treg cells are linked to effector responses and that schistosomes can induce Breg cells, the scene is set for future studies to determine antigen specificity of these cells as well as ways to control their activity. As regulatory responses have been shown to be not only important in chronic infectious disease, but also in chronic inflammatory diseases the knowledge gained here may be of substantial value to the health of those living in both low- to middle-income countries as well as high-income countries. Show less
Early childhood is a critical period where the maturation of the immune system occurs while it receives various challenges from the environment shared with the mother. Children growing in an... Show moreEarly childhood is a critical period where the maturation of the immune system occurs while it receives various challenges from the environment shared with the mother. Children growing in an environment rich in micro-organisms and parasites are thought to have a different pattern of immune response compared to those children growing in a more hygienic environment. This difference might contribute to the lower prevalence of allergic and autoimmune disorders in developing countries compared to affluent countries. Within this context, a number of cohort studies mostly performed in developed countries have focused on finding the link between the pattern of immune responses in early life and health outcomes in later life. In this thesis, we studied child__s innate and adaptive responses during the first 4 years of life in a helminth-endemic area in Indonesia Show less