Masters Degrees (Molecular Biology and Human Genetics)
Permanent URI for this collection
Browse
Browsing Masters Degrees (Molecular Biology and Human Genetics) by browse.metadata.advisor "Beyers, A. D."
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- ItemImmune regulation in children and adults in a community with a high incidence of tuberculosis(Stellenbosch : Stellenbosch University, 1998-12) Adams, Joanita Frances Ann; Beyers, A. D.; Stellenbosch University. Faculty of Medicine & Health Sciences. Dept. of Biomedical Sciences.ENGLISH ABSTRACT: There is a progressive maturation of the immune system from infancy to adulthood. The immature immune system in early life is characterised by impaired macrophage function and antigen presentation as well as a higher naIve to memory T cell ratio with subsequent diminished IFN-y production. Children with tuberculosis often present with lymphadenopathy, the complications thereof or with systemic spread of the organisms. Adults generally manifest with pronounced systemic effects (such as weight loss and high fever) and immunopathology (such as cavitation and fibrosis). We hypothesised that the immunopathology in adults may be due to enhanced cytokine production in comparison to children. The first aim of this study was therefore to measure cytokine responses in healthy children and adults. Cytokine responses in patients with tuberculosis will be examined in future studies. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood obtained from 9 healthy children and 9 healthy adults. The cells were cultured in serum-free medium, unstimulated or polyclonally stimulated with Phytohaemagglutinin (PHA). Supernatants were harvested after which IFN-y, IL-2, TNF-a., IL-4 and IL-IO production was determined by means of ELISA analysis. Ri'J"A was ~ubsequently extracted from the cells followed by RT-PCR analysis for the semiquantitative determination of mRNA levels of these cytokines. PBMC isolated from healthy children produced significantly less IFN-y protein than adults. Futhermore, IFN-y production in the adults seemed to be trimodally distributed. No significant differences could be found in the production of IL-2, TNF-a, IL-4 and IL-] O. Although children produced low levels of IFN-y protein, their IFN-y, TNF-a, IL-2, IL-4 and IL-IO mRNA levels were comparable to that of adults. Tuberculosis is a major cause of mortality and morbidity, particularly in the third world. Ravensmead and Uitsig, two adjacent suburbs in the Western Cape, have a tuberculosis incidence of> I 000/100000 population. Also, up to 90 % of the children in the Western Cape have been reported to be infested by intestinal parasites such as Ascaris lumbricoides and Trichurius trichl/ria. Infection with M tuberculosis indut:es a Th 1 Stellenbosch University http://scholar.sun.ac.za iv In:.,c response, while intestinal parasites elicit a Th2 immune response. Th2 dominance induced by intestinal parasite infestations could predispose individuals to an enhanced susceptibility to M. tuberculosis. The second aim of this study was to investigate serum IgE levels, surrogate markers for Th2 activation, in the community. The serum 19B levels were subsequently correlated to the tuberculosis incidence per enumerator sub-district (ESD), crowding, female literacy and socio-economic levels. Similarly, the tuberculosis incidence per ESD was correlated with the above mentioned parameters. A significant positive correlation was found between tuberculosis incidence and the serum 19E levels in the community. However, further studies are needed to determine if intestinal parasites are the main cause of the high 19B levels in the community and to dCh111ine if parasite loads or Th2 dominance are causally linked to the incidence of tuberculosis. Correlation between serum 19E levels and tuberculosis incidence with the other parameters were significant, except in the case of crowding. The third aim of this study was to measure serum IgE and specific 19E levels against Ascaris and common allergens on presentation of tuberculosis and again after completion of successful treatment. Significant declines in serum 19B and Ascaris specific 19B levels were observed after completion of tuberculosis treatment. This down regulation of IgE levels may be due to an up regulation of ThI responses in patients following successful treatment for tuberculosis.