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Title: Cytokine regulation and development of human anti-malarial immunity during Plasmodium falciparum infections
Author: Rhee, Michelle Sang Min
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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It is now widely accepted that clinical symptoms develop as a result of an excessive inflammatory response to malaria antigen. I hypothesise that inflammation is primarily due to a "Th-1-like" response and that the development of clinical immunity is associated with the downregulation of pro-inflammatory cytokines. I further hypothesise that immune responses of naïve and clinically immune individuals are mediated by different populations of mononuclear cells. In order to test these hypotheses, I first developed specific and sensitive methods to measure cytokine production. I then compared proliferative responses and IFN-g-production of peripheral blood mononuclear cells (PBMCs) to P. falciparum schizont extract (PfSE) from malaria naive, malaria-exposed (but not clinically immune) and malaria-immune individuals. In order to determine how PfSE-induced IFN-g production is regulated, I have also measured IL-12 p40, IL-12 p70 and IL-10 from PfSE-stimulated PBMCs and investigated the role of neutralising antibody to IL-12 in modulating IFN-g production. Finally, a combination of cell surface staining and intracellular cytokine staining was used in order to determine the phenotypes of cells responding to PfSE. Cells from all individuals proliferated vigorously in response to PfSE, but there were no significant differences between any of the groups. Cells from naïve individuals produced moderate levels of IFN-g which were mainly IL-12-dependent. Intracellular cytokine staining analysis indicated that IFN-g was primarily produced by ab+ T cells, although significant proportions of gd+ T cells and NK cells also produced IFN-g. IFN-g levels were significantly higher in PBMC cultures of exposed individuals than in cell cultures from naïve individuals and were only partially IL-12-dependent. In contrast, minimal levels of IFN-g were produced from PfSE-stimulated cells of immune individuals and were significantly lower than those found in either naïve or exposed populations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available