Plasmodium chabaudi AS infections in mice result in lethal and non-lethal infections in a strain-dependent fashion. Resistant C57BL/6 mice exhibit moderate levels of peak parasitemia and anemia and survive the infection. Susceptible A/J mice develop significantly higher parasitemias, severe anemia and succumb to infection. Resistance is controlled by a single or tightly linked, dominant, autosomal, non-H-2 linked locus(i), and is associated with the development of enhanced splenomegaly during infection and enhanced reticulocytic response to phenylhydrazine-induced hemolytic anemia. In this thesis, the relationship between the splenic erythropoietic response and resistance to infection is examined. Impairment of splenic erythropoiesis is demonstrated in susceptible A/J mice. This impairment could not be explained by a deficiency in erythropoietin production or in the mobilization of erythroid progenitor cells from the marrow to the spleen. The kinetics and mechanism of the inhibition of erythropoiesis was examined using an in vitro erythroid proliferation assay. Increased inhibition was associated with the rise in parasitemia and was found to be invariant in resistant and susceptible mice. Evidence is presented to suggest that the inhibitor is erythroid-specific and is distinct from IL-1, TNF and IFN-gamma. In transfusion experiments, evidence was obtained for the importance of anemia in the mortality of susceptible A/J mice and in the induction of parasitologic crisis. In splenectomy and immune cell transfer experiments, evidence is presented for the conclusion that an intact spleen is required for the induction but not the expression of B cell-dependent immunity to Plasmodium chabaudi AS.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.41794 |
| Date | January 1994 |
| Creators | Yap, George So |
| Contributors | Stevenson, Mary M. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001397894, proquestno: NN94726, Theses scanned by UMI/ProQuest. |
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