Chemotherapy and immunity in murine African trypanosomiasis

Whitelaw, Douglas Dixon (1982) Chemotherapy and immunity in murine African trypanosomiasis. PhD thesis, University of Glasgow.

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The experiments described in this thesis investigated aspects of immunity and chemotherapy in mice infected with T. brucei and T. congolense. It was found that mice with infections of T. brucei of less than 7 days duration were completely cured if treated at this stage with trypanocidal drugs" However, if treatment was delayed beyond 14 days, a proportion of the mice relapsed, in some cases more than 3 months after chemotherapy. This was not due to drug resistance of the parasite, and tissue transfer experiments during the aparasitaemic period following chemotherapy indicated the presence of trypanosomes only in brain tissue. Transmission of immunity from mother to offspring was investigated in mice. Mothers with a T. brucei infection conferred immunity to homologous challenge of approximately 3 weeks duration in newborn mice. This immunity was by way of colostrum/milk after birth, since fostering experiments showed that mice born of infected mothers but suckled by an uninfected mother were susceptible to challenge. Furthermore there was an augmentative effect when chemoprophylaxis was given on the day of birth. This on its own afforded protection against infection for a similar period as passively acquired antibody, but young mice which received both drug and antibody resisted challenge for over 6 weeks. Genetic resistance to T. congolense infection was studied in C57B1 mice, which are able to repeatedly limit the numbers .of circulating parasites and survive for approximately 80 days, and CFLP mice which die within 10 days with an uncontrolled fulminating parasitaemia. No evidence was found to implicate pathophysiological factors in this resistance, but C57B1 mice were able to remove radiolabelled parasites from their circulation, and their immune response, as judged by in vitro immunological methods, was superior to the CFLP strain Attempts to enhance the response of susceptible mice by passive immunisation, priming of the immune system and activation of the mono" nuclear phagocytic system were unsuccessful, and it was concluded that the ability to produce and maintain levels of IgM in the plasma was essential for resistance. Finally, a reliable and simple technique for the in vivo labelling of trypanosomes with 75Se-methionine was developed" The fate of such trypanosomes after injection into normal and immune mice was investigated, and it was found that in immune mice the liver was the principal site of uptake. From this finding, studies were done on the mechanisms of hepatic uptake, which was found to be antibody dependent, and at low antibody titres also C3 dependents No evidence was found to suggest that intravascular lysis or activated macrophages were involved in immune clearance.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: G M Urquhart
Keywords: Parasitology
Date of Award: 1982
Depositing User: Enlighten Team
Unique ID: glathesis:1982-73635
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56

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