Effect of hemoglobins S and C on the in vivo expression and immune recognition of Plasmodium falciparum erythrocyte membrane protein 1 variants in Malian children
<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 ha...
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| Άλλοι συγγραφείς: | |
| Μορφή: | Thesis |
| Γλώσσα: | English |
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2012
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| _version_ | 1826315900391784448 |
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| author | Beaudry, J |
| author2 | White, N |
| author_facet | White, N Beaudry, J |
| author_sort | Beaudry, J |
| collection | OXFORD |
| description | <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> |
| first_indexed | 2024-03-06T19:44:53Z |
| format | Thesis |
| id | oxford-uuid:21f27887-e7e8-4480-a8e4-c7072f3b392c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:34:33Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:21f27887-e7e8-4480-a8e4-c7072f3b392c2024-12-01T18:07:41ZEffect of hemoglobins S and C on the in vivo expression and immune recognition of Plasmodium falciparum erythrocyte membrane protein 1 variants in Malian childrenThesishttp://purl.org/coar/resource_type/c_db06uuid:21f27887-e7e8-4480-a8e4-c7072f3b392cMalariaInfectious diseasesBiologyParasitologyEnglishOxford University Research Archive - Valet2012Beaudry, JWhite, NFairhurst, R<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> |
| spellingShingle | Malaria Infectious diseases Biology Parasitology Beaudry, J Effect of hemoglobins S and C on the in vivo expression and immune recognition of Plasmodium falciparum erythrocyte membrane protein 1 variants in Malian children |
| title | Effect of hemoglobins S and C on the in vivo expression and immune recognition of Plasmodium falciparum erythrocyte membrane protein 1 variants in Malian children |
| title_full | Effect of hemoglobins S and C on the in vivo expression and immune recognition of Plasmodium falciparum erythrocyte membrane protein 1 variants in Malian children |
| title_fullStr | Effect of hemoglobins S and C on the in vivo expression and immune recognition of Plasmodium falciparum erythrocyte membrane protein 1 variants in Malian children |
| title_full_unstemmed | Effect of hemoglobins S and C on the in vivo expression and immune recognition of Plasmodium falciparum erythrocyte membrane protein 1 variants in Malian children |
| title_short | Effect of hemoglobins S and C on the in vivo expression and immune recognition of Plasmodium falciparum erythrocyte membrane protein 1 variants in Malian children |
| title_sort | effect of hemoglobins s and c on the in vivo expression and immune recognition of plasmodium falciparum erythrocyte membrane protein 1 variants in malian children |
| topic | Malaria Infectious diseases Biology Parasitology |
| work_keys_str_mv | AT beaudryj effectofhemoglobinssandcontheinvivoexpressionandimmunerecognitionofplasmodiumfalciparumerythrocytemembraneprotein1variantsinmalianchildren |