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Title: Immune modulation by the parasitic nematode Brugia malayi
Author: MacDonald, Andrew Scott
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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This thesis seeks to address the mechanisms that underlie the development of the profound cellular hyporesponsiveness in filariasis, and the relationship of this to the development of Th2-type responses. These questions were addressed using a murine model of infection with Brugia malayi, one of several species of parasitic nematode that are responsible for filarial disease. In this model, mice develop strong Th2 responses. The findings in this thesis relate to both parasite and host factors involved in the development of immune suppression. Adult and infective larval parasites, but not microfilaria, generated down-regulatory host cells. The excretory/secretory products of the adult parasite were sufficient to induce the generation of PEC that block proliferation. Suppressor cell generation correlated directly with systemic IL-4 production by the host. We were able to demonstrate that there was a direct link between host production of IL-4 and the generation of suppressive PEC, as IL-4-deficient mice failed to induce proliferative block. However, implanted IL-10-deficient mice resulted in T cell suppression, indicating that IL-10 is not essential for the induction of hyporesponsiveness. Experiments using transwell membranes or formaldehyde-fixing of PEC indicated that suppression was not effected by a soluble mediator, and required cell-cell contact. These data suggest that the mechanism of suppression exhibited by down-regulatory cells from filarial-infected mice appear to be unlike those previously described in other infectious disease systems, being dependent on host IL-4 production, and effected through a cell-contact-mediated mechanism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available