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Parasite antigens and cellular interactions associated with the membrane of Plasmidium falciparum infected erythrocytes
Stockholm University.
1991 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The asexual erythrocytic stages of malaria parasites are the cause of the pathological manifestations of the disease, Plasmodium falciparum being the species notorious for causing serious complications. This thesis describes studies on parasite-host cell interactions at two different stages of the P.falciparum erythrocytic cycle, the merozoite invasion and the cytoadherence to endothelial cells of mature infected erythrocytes. At both these stages the parasite expresses antigens with potential to induce immune responses with capacity to interfere with parasite development.

At merozoite invasion the antigen Pf 155/RES A is translocated from dense granules in the merozoite to the erythrocyte membrane. For further analysis of Pfl55/RESA and its interaction with the erythrocyte membrane, mouse monoclonal antibodies were produced to an octapeptide corresponding to a repeated sequence in the C-terminal part of the antigen. One mAb was studied in detail and was shown to recognize Pfl55/RESA both in denatured and native form. Furthermore, the mAb was an efficient inhibitor of merozoite invasion in vitro indicating that it recognizes a biologically important epitope.

The location of Pfl55/RESA in the membrane of infected erythrocytes was analysed. The antigen was found to be associated with the cytoplasmic phase of the erythrocyte membrane with no part exposed on the surface of intact erythrocytes. In concordance with this Pfl55/RESA bound to inside out vesicles of normal erythrocytes as well as to cytoskeletal shells of such vesicles but failed to bind to right-side out membrane vesicles. Protein depletion studies indicated that Pfl55/RESA association with the erythrocyte cytoskeleton is mediated by spectrin.

Mature stages of infected erythrocytes sequester from the host defense systems by adhering either to the endothelium of blood vessels or to uninfected erythrocytes forming rosettes. It was previously believed that only P.falciparum of knob expressing phenotype (K+) were capable to cytoadhere and survive in vivo. We showed that also infected erythrocytes of knobless phenotype (K') are present in fresh clinical P.falciparum isolates. Furthermore, both K+ and K" parasites may cytoadhere to melanoma cells as well as form rosettes and both types of cytoadherence can be exerted by the same infected erythrocyte. Cytoadherence of infected erythrocytes of both phenotypes to leukocytes was also demonstrated in fresh clinical isolates as well as in laboratory strains of P.falciparum. The binding of infected erythrocytes to leukocytes induced cellular aggregations which may play a role in the host defence against the parasite.

Cytoadherence of P.falciparum infected erythrocytes to melanoma cells or endothelial cells has earlier been shown to involve three receptors, CD36, thrombospondin and ICAM-1. CD36 was shown to be the major receptor on melanoma cells for both K+ and K' phenotypes. The cytoadherence of K+ infected erythrocytes was of higher affinity and the interaction of the two phenotypes with melanoma cells also differed ultrastructurally. While K+ erythrocytes showed intimate interdigitations with microvilli on the melanoma cells, K' erythrocytes displayed more separated interactions with fewer sites of contact.

Place, publisher, year, edition, pages
Stockholm: Stockholm University, 1991. , p. 51
National Category
Immunology
Identifiers
URN: urn:nbn:se:su:diva-161415ISBN: 91-7146-888-9 (print)OAI: oai:DiVA.org:su-161415DiVA, id: diva2:1258329
Note

Härtill 4 uppsatser

Available from: 2018-10-24 Created: 2018-10-24 Last updated: 2018-10-24

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