Title page for ETD etd-09072005-115430

Document Type Master's Dissertation
Author Lombard, Denise Carol
URN etd-09072005-115430
Document Title The effect of mycobacterial mycolic acids on the cytokine profile of the immune response in murine tuberculosis
Degree MSc (Biochemistry)
Department Biochemistry
Advisor Name Title
Prof J A Verschoor Committee Chair
  • Mycobacterium tuberculosis
  • immune response molecular aspects
  • tuberculosis in animals
Date 2003-09-01
Availability unrestricted
Mycobacterium tuberculosis (M. tuberculosis) , the etiological agent of tuberculosis, is an intracellular bacterium which persists within macrophages. Successful control of tuberculosis depends on T-cell-mediated immunity. Immune protection involves the development of a Th1 response characterised by the secretion of cytokines such as IL-12, IFN-γ and TNF-α. The progression towards disease in humans and mice is often associated with a Th2 response characterised by the secretion of cytokines such as I L-4 and I L-10.

Mycolic acids, the major cell wall lipid of M. tuberculosis, were previously shown to have a marginally protective effect on the development of disease in Balb/c mice when administered intravenously at an optimal dose of 25 g one week before intravenous M. tuberculosis infection. Here it is shown that the protective effect is highly significant when infection is done intranasally. The protective effect of 25 g mycolic acids against tuberculosis could not be explained by induction of a longer lasting Th1 response in Balb/c mice. This was determined by using semi-quantitative RT-PCR on the mRNA of cytokines characteristic of the different immune responses. It was observed that maximum sensitivity was obtained at the lowest possible PCR cycle and template concentrations for the samples.

Mycolic acids were the first non-protein antigens shown to induce an immune response after presentation on CD1 membrane proteins. Balb/c mice predominantly generate a Th1 response during the first 3 - 4 weeks of M. tuberculosis infection, whereas they generate a Th2 response in the following weeks. Even though the protective effect of 25 g mycolic acids could not be associated with a prolonged Th1 immune response in infected mice, it did induce IL-12 and IL-10 mRNA in uninfected mice. These cytokines are primarily.

2003 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.

Please cite as follows:

Lombard, DC 2003, The effect of mycobacterial mycolic acids on the cytokine profile of the immune response in murine tuberculosis, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-09072005-115430/ >


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