The enormous mortality burden exerted by P. falciparum malaria has evolutionarily selected for red blood cell (RBC) polymorphisms which confer protection against the severe manifestations of this disease. Although the epidemiological protection by these polymorphisms has been well-established for the past half-century, the mechanisms underlying this protection are still being uncovered. Recent studies implicate impaired cytoadherence to microvascular endothelial cells (MVECs) due to reduced surface levels and altered display of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as a mechanism of protection against severe malaria by sickle hemoglobin (Hb) S and HbC. Consequently, in this thesis, I have described three separate, but related investigations into whether hemoglobins S and C influence a parasite’s cytoadherence binding phenotype (Chapter 3), the PfEMP1 variants that parasites express in vivo (Chapter 4), and the IgG recognition of PfEMP1 domains in Malian children (Chapter 5). We found that parasites from HbAS children show statistically insignificant increased binding to MVECs and that parasites did not express a restricted subset of var genes in HbAS and HbAC children. Compared to HbAA and HbAC children, HbAS children demonstrated a slower rate of acquisition of IgG responses to a repertoire of PfEMP1 domains. These findings suggest that, although hemoglobin type influences the binding phenotype of P. falciparum isolates and the acquisition of PfEMP1-specific IgG responses, other factors more likely determine the expressed var gene repertoire within parasites than hemoglobin type.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:581180 |
| Date | January 2012 |
| Creators | Beaudry, Jeanette T. |
| Contributors | White, Nicholas J.; Fairhurst, Rick M. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:21f27887-e7e8-4480-a8e4-c7072f3b392c |
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