Kwa, S. fen; (2006) Cellular and structural factors influencing the induction of Th1 mucosal responses against an enteric pathogen. Doctoral thesis , University of London.

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Abstract

Secondary lymphoid structures are organised networks which support the generation of efficient immune responses by facilitating antigen presentation between an antigen presenting cell (APC) and an antigen-specific naive T cell. Professional APC such as dendritic cells (DC) are potent primers of T cells and have the capacity to determine the T-helper type 1 or 2 direction of the immune response. Lymphotoxin (LT) is a cytokine of the TNF family which has diverse biological roles, including one as a cytotoxic mediator of immunity. Moreover LT-mediated signals are required for the organogenesis and maintenance of lymphoid structures. The role of various lymphoid structures may have profound effects on the co-ordination of primary immune responses and LT-disruption has been used to examine these requirements. To date, most studies have focussed on systemic infection and here, the roles of LT and various gut-associated lymphoid tissues (GALT) were addressed in the context of enteric infection with the gut-tropic apicomplexan parasite, Eimeria vermiformis. Immunity to infection and the induction of protective gut Th1 responses were dependent upon the rapid recruitment of DC to lymphoid structures. Deficiency in lymphoid structures affected the induction of protective immunity and increased susceptibility to infection. Despite the lack of infection in the PP (E. vermiformis targets crypt enterocytes), a role for PP was established in the rapid induction of immunity. The anti-parasite response required a co-operative interaction between PP and mesenteric lymph nodes (MLN) with the PP influencing the time of induction of responses in the MLN. Examination of DC numbers and phenotypes revealed a delay in accumulation of DC subsets in PP-deficient mice and supports the role for DC traffic between these lymphoid structures in the induction of rapid gut immune responses.

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