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Title: Immunological factors mediating the resistance and susceptibility to filarial nematodes
Author: Lamb, Tracey Jane
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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None of the nematodes that cause human falarial disease readily establish and develop in laboratory mice. However the rodent filarial nematode Litomosoides sigmodontis can complete development to patency in BALB/c inbred mice. The studies in this thesis have utilised this rodent model to study factors that influence the establishment of filarial infection. Filarial nematodes evoke strong type 2 host immense responses characterised by the cytokine interleukin 4 (IL4). By infecting mice that are unable to produce IL4 we have discovered that IL4 can mediate resistance to the establishment of L. sigmodontis infection. Infections of chimeric mice that can only produce IL4 from the innate or the acquired immune response indicate that IL4 needs to be produced from both arms of the immune system to confer protection. We have also studied the impact of co-infecting protozoan pathogens that induce strong type 1 responses. Co-infection with the protozoan parasites Plasmodium chabaudi or Leishmania major resulted in the accelerated death of established adult L. sigmodontis. Immunological analysis indicates that this was correlated with a decrease in type 2- like responses against L. sigmodontis parasites in both cases. However we did not detect any increase in type 1-like responses against L. sigmodontis in either of these studies. Finally we investigated the role of the filarial intracellular bacteria Wolbachia. We established that anti-Wolbachia immune responses do occur in human filarial infection, in individuals not treated with anti-filarial drugs. Using general linear modelling we determined that anti-Wolbachia surface protein (WSP) antibodies are generated mainly by the L3 stage. In support of this, analysis of life cycle stages of L. sigmodontis indicate that, per gram of nematode material, the L3 stage evokes by far the greatest antibody responses against WSP. Additionally we have shown that anti-WSP immune responses can, in some circumstances, promote the establishment of primary L. sigmodontis infection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available