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Biomedical subjects

G H Mitchell

Publications and source records attributed to G H Mitchell.

59 records · Page 4Linked to original sources
PubMed1974

Mechanisms of immunity to malaria.

The erythrocytic phase of malarial infection provides a potent stimulus for the production of specific malarial antibody. Serologic tests do not provide any indication of immune status, so that much specific antibody has no protective function. The role of serum antibody in acquired malarial immunity has, however, been established by passive transfer tests, and in the case of P. knowlesi by specific inhibition of the cyclic growth of parasites in vitro. The inhibitory antibody appears to combine with merozoites and prevents their attachment to red cells, thus interrupting the cyclic proliferation of the parasite. The inhibitory antibody response is predominantly variant-specific, but cross-reacting antibody occurs in sufficient amount to suppress proliferation of most other variants of the species. The occurrence of cross-immunity between variants is encouraging from the point of view of vaccination. If it were possible to isolate cross-reacting antigens, these could provide the basis for a malarial vaccine effective against erythrocytic forms of the parasite.

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PubMedDate not supplied

Gamma delta T cells in the peripheral blood of individuals from an area of holoendemic Plasmodium falciparum transmission.

gamma delta T cells bearing V gamma 9 T cell receptors from unexposed Caucasian donors make large responses to Plasmodium falciparum in vitro. This finding, together with observations of others showing high levels of V gamma 9+ T cells in the blood of infected non-immune individuals, led us to hypothesize that the response of these cells might contribute to the pathology of P. falciparum malaria. Acquisition of immunity to disease in people naturally exposed to infection may therefore be due in part to down-regulation or alteration of the function of gamma delta T cells. Supporting this view, and in contrast to infection in non-immune individuals, V gamma 9+ T cells are not elevated in peripheral blood of children or adults living in an endemic area despite constant exposure to P. falciparum. After in vitro stimulation with P. falciparum, however, the expansion of V gamma 9+ cells from the African donors is of similar magnitude to that observed for non-exposed Europeans. Thus, although these cells are not elevated in peripheral blood, they are still able to respond to P. falciparum antigens. In adult European donors the major gamma delta T cell population in peripheral blood is V gamma 9+ (approximately 70% of all gamma delta cells), whereas in the majority of adult Africans V delta 1+ V gamma 9- T cells predominated (approximately 70% of total gamma delta cells).

Adult↗
PubMedDate not supplied

The fine structure of secretion by Plasmodium knowlesi merozoites during red cell invasion.

The secretory organelles of Plasmodium knowlesi were studied ultrastructurally to examine their mode of action during invasion. The formation of lamellar structures in merozoite rhoptries within late stage schizonts is prevented by the protease inhibitors chymostatin and leupeptin. Under normal conditions vesicles lined by 6-nm membranes are formed in rhoptries during erythrocyte invasion. Stereoscopic viewing of tilted sections shows that where the merozoite apex contacts the parasitophorous vacuole (PV) membrane during invasion, a domed elevation of the PV surface lies within the mouth of the rhoptry duct in contact with the secretory matrix. The membrane of the early invasion pit is thinner (6 nm) than the red cell membrane elsewhere, and sheets of lamellar material are frequently present on the invasion pit surface. These findings support the proposal that the rhoptry-microneme complex is capable of generating membranous material and inserting it into the red cell surface in a controlled manner to create the parasitophorous vacuole. On the basis of this model, measurements from serial sections show that the rhoptries could provide enough material to create a membrane lining the parasitophorous vacuole, and, with the contribution of the microspheres, could double it to accommodate the early ring stage of the parasite.

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