Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.460769
Title: Thymus dependency of the immune response in murine malaria
Author: Jayawardena, A. N.
ISNI:       0000 0001 3589 5914
Awarding Body: London School of Hygiene & Tropical Medicine
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 1975
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Abstract:
Studies were carried out to elucidate the role of the thymus and thymus derived lymphocyte population in the immune response of mice to malaria. Infection of normal CBA mice with the malaria parasite P. b. yoelii resulted in a mild, non fatal infection which lasted 15 to 16 days. Mice which recovered from a primary infection were immune to reinfection. Parasites could be demonstrated in the kidneys of such mice 3 to 4 weeks after recovery from infection, but were not detected in the peripheral blood and other tissues examined. In T cell deprived CBA mice P. b. yoelii infections followed a fulminant course and proved fatal within 30 to 35 days, thus demonstrating the absolute thymus dependency of these infections. In ATS treated mice P. b. yoelii infections followed an essentially similar pattern, but 30% of the treated mice recovered. Studies of fluorescent antibody levels and the histopathological changes in the spleens of normal and T cell deprived mice during infection showed that while normal CBA mice made high levels of IgG1, IgG2 and IgM antibodies and showed a strong and sustained germinal centre response, in T cell deprived mice the production of IgG1 antibodies was almost completely abolished and the germinal centre response was severely impaired. Reconstitution of T cell deprived mice with syngeneic thymus grafts resulted in restoration of immune responsiveness; the level of protective immunity and the germinal centre response correlated well with the degree of reconstitution achieved. The response of the CBA mouse to P. b. berghei, a progressive infection which proved fatal in 20 to 25 days, was also examined. These infections were found to provoke antibody and germinal centre responses intermediate between those elicited by P. b. yoelii infections in normal and T cell deprived mice. The T cell mitotic response to P. b. yoelii and P. b. berghei was defined in CBA/Lac - CBA/H.T6T6 mouse radiation chimaeras carrying a chromosomally distinguishable population of T cells. While P. b. yoelii provoked a rapid and sustained burst of T cell mitosis, the T cell response evoked by P. b. berghei was feeble and failed early in the infection despite the progressive parasitaemia. The functional state of the T cell pool was assayed by examining the responses of infected CBA mice to Oxazolone and of spleen cells to PHA (Phytohaemagglutinin). P. b. yoelii infected mice responded normally to oxazolone and despite a decrease in the proportion of PHA responsive cells there was a net increase in the absolute number of such cells in the spleen. In contrast, P. b. berghei infections resulted in marked depression of the response to oxazolone and of the absolute number of PHA responsive cells in the spleen. Both infections caused a decrease in the proportion of LPS responsive (B), cells, but when the response was computed on a per spleen basis there was no significant impairment of the response. Mechanisms of resistance in P. b. yoelii infections were further analysed by carrying out a series of cell and serum transfers from immune to non immune mice. While hyperimmune serum was protective against low parasite innocula, immune serum had no protective effect. Doses of hyperimmune serum which protected intact recipients completely, caused orly transient inhibition of infection in T cell deprived recipients. Immune spleen cells were the most effective in transferring immunity to normal and T cell deprived recipients. Treatment of these cells with anti theta antiserum did not remove their protective effect, suggesting that the effector cells in the immune spleen cell population were non T cells. These results ar e discussed in relation to their significance in effector and suppressor responses elicited during malarial infections.
Supervisor: Targett, G. A. T. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.460769  DOI:
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