| Özet: | <p>The enormous mortality burden exerted by <em>P. falciparum</em> 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 <em>Plasmodium falciparum</em> 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 (<strong>Chapter 3</strong>), the PfEMP1 variants that parasites express <em>in vivo</em> (<strong>Chapter 4</strong>), and the IgG recognition of PfEMP1 domains in Malian children (<strong>Chapter 5</strong>). 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 <em>P. falciparum</em> isolates and the acquisition of PfEMP1-specific IgG responses, other factors more likely determine the expressed <em>var</em> gene repertoire within parasites than hemoglobin type.</p>
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