Masters Degrees (Anatomical Pathology)

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Browsing Masters Degrees (Anatomical Pathology) by browse.metadata.advisor "Kollmann, Tobias"

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    Ontogeny of the innate immune response in healthy South African infants
    (Stellenbosch : Stellenbosch University, 2012-12) Adams, Rozanne Charlene McChary; Esser, Monika Maria; Kollmann, Tobias; Bouic, Patrick J. D.; De Beer, Corena; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology.
    ENGLISH ABSTRACT: Infection is a major cause of morbidity and mortality in infants within the first few months of life. Susceptibility to infectious disease in this vulnerable population is more prevalent in resource-limited regions, with a higher disease burden. Due to certain deficiencies in their adaptive immune system, neonates rely predominantly on their innate immune system for protection against infection, a vital component in the early host defence against pathogens. Several studies have described differences in neonatal innate toll-like receptor-mediated responses compared to adult counterparts, though very little is known about these receptor responses within resource-limited settings. To address this issue, we assessed the longitudinal development of cytokine-specific responses of TLR4 and TLR7/8 in monocytes, myeloid dendritic cells and plasmacytoid dendritic cells in infants from a resource-limited setting, South Africa, within the first 12 months of life and compared it to adults. Contrary to previously published literature, we observed heightened production of TH-1 cytokines: we showed increased responsiveness to TLR4 and TLR7/8 stimulation in infants at two and six weeks of age, which may be due to vaccination administered at birth. Unexpectedly, the hyper-inflammatory response persisted at six months in response to the LPS (TLR4) stimulus. This increased response at six months may be attributed to decreased passive immunity through infant weaning as well as increased exposure to microbial pathogens in this setting. Maturation of most cytokine responses was reached at twelve months for the TLR4 receptor, and at six months for the TLR7/8 receptor. The first year of life represents a critical period for maturation of the immune response. Data from this study point towards an elevated response within the first six months of life. This heightened response reflects both an ability to mount a sufficient TH-1 response in infancy, but more likely, the increased exposure to microbial stimuli in the environment. Thus, we speculate that these age-specific inflammatory responses may influence the outcome of immune responses to various vaccines administered, which may result in altered responsiveness to immunisation in infancy.