Thesis

Immunological control of Toxoplasma gondii infection

Creator
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Awarding institution
  • University of Strathclyde
Date of award
  • 1993
Thesis identifier
  • T7583
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Studies using B10 H-2 congenic and recombinant mice indicated that control of brain cyst number in T. gondii infected mice mapped to the D region of the MHC complex. Further studies using BALB MHC congenic mice demonstrated that a drop in cyst number coincided with a dramatic change in the ratio of splenic CD4: CD8 T lymphocytes in favour of the latter. Adoptive transfer and selective depletion of T lymphocyte populations demonstrated a role for both CD8+ and CD4+ T cell populations in the acute phase of infection while CD8+ T cells play the dominant role in the control of cyst numbers. The Lsh gene was found to have a route of infection dependent influence on early mortality in congenic Lshr and Lshs BALB/c and C57BL/10ScSn mice. Mice homozygous for the beige allele were more susceptible to T. gondii infection as demonstrated by high rates of mortality and increased cyst burdens. Mice carrying the Lpsd allele were found also to have increased susceptibility to acute mortality, but developed fewer cysts in their brains. The use of the polymerase chain reaction revealed the presence of transcripts for TNFα, IL-6, MIP-1β, IL-4, IL-2, and IFN-γ in the brains of C57BL/10ScSn mice, with progressive meningoencephalitis. Analysis of the kinetics of cytokine production revealed temporal differences in their production which were related to neuropathological effects. The development of a murine model of congenital toxoplasmosis facilitated the testing of a vaccine preparation consisting of non ionic surfactant vesicles (NISV) and the soluble fraction of a tachyzoite lysate (STAg). Vaccination was found to result in fewer brain cysts, prevent foetal death and reduce congenital transmission.
Advisor / supervisor
  • Alexander, J
Resource Type
DOI
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