Lymphocyte-associated complement: role of C8 in certain cell-mediated lytic reactions.
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Biomedical subjects
Publications and source records attributed to H Perlmann.
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Chromium-51-labeled chicken erythrocytes (E), treated with rabbit anti-Forssman antibody (A) and the first four (C1-4) or the first seven (C1-7) components of human complement (C), released isotope upon exposure to human leukocytes. Isotope release from EACJ-7 cells proceeded more rapidly and was more extensive than that from EACI-3 cells. Lysis of these cells was suppressed by pretreatment of leukocytes with antimycinA. Monocyte-enriched leukocyte preparations affected both types of target cell-complement intermediates, whereas purified lymphocytes lysed EACI-7 cells but not EACI-3 cells.
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Fowl erythrocytes are lysed when exposed to an excess of fowl blood lymphocytes in the presence of phytohemagglutinin. No significant cell damage is seen in the absence of phytohemagglutinin, or when the lymphocytes are replaced by malignant lymphoid cells, thymus cells, or nonlymphoid cells. The lymphocytes remain viable during the reaction. Differences in histocompatibility between lymphocytes and erythrocytes are not required. Autologous lymphocytes are cytotoxic to the same extent as allogenic lymphocytes over a wide range of experimental conditions.
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118 adult Liberians from 2 villages were studied prospectively for one year with monthly blood examinations for malaria parasites. The crude parasite rate was 41.5% and the crude gametocyte rate was 6.1%. The inoculation rate varied between 0.075 in the dry season and almost 0.4 in the rainy season, which is in accordance with other data from holoendemic areas. 47.5% (56) had a titre to the Pf155/RESA antigen less than or equal to 1/50 ('low responders') and 52.5% (62) had a titre of greater than or equal to 1/250 ('high responders'). The response was not age-dependent in this adult population, which may suggest that genetic factors are determining whether the individual become a high or low responder. Antibodies against the Pf155/RESA antigen were measured in 2 surveys 8 months apart, and the mean antibody response to Pf155/RESA and its EENV sequence was constant without seasonal variation. Pf155/RESA high responders had lower parasite densities during all 3 seasons surveyed, and Pf155/RESA high responders, with high antibody reactivity against the (EENV)6 sequence from the 3' repeat region of Pf155/RESA, had significantly lower parasite densities in the rainy season of 1987. The data suggest that high titres of antibodies to the Pf155/RESA antigen, and especially to its EENV sequence, might play a role in protective immunity in adults.
We have measured cellular and humoral immune responses to short synthetic peptides representing epitopes of the malaria vaccine candidate antigen Pf155/RESA in a longitudinal, prospective study of clinical immunity to Plasmodium falciparum malaria in a cohort of 354 Gambian children aged 3-8 years. A significant association was observed between presence of antibodies to the 3' repeat region peptide (EENV)6 and resistance to clinical malaria. The prevalence of protective antipeptide antibodies varied significantly between different ethnic groups, suggesting that immune recognition of some Pf155/RESA epitopes may be genetically regulated. There was no obvious association between proliferative or interferon gamma responses to T cell epitopes of Pf155/RESA and resistance to malaria infection or disease. At an individual level, the presence of peptide-binding antibodies was associated with the induction of interleukin 4 messenger ribonucleic acid expression in T cells activated with the overlapping T cell epitope EENVEHDA(EENV)2. This suggests that measurement of interleukin 4 production by T cells may represent a functional assay for T helper activity.
The first purpose was to study the sensitivity of a spot hybridization assay for P. falciparum with a DNA probe. This assay was compared with light microscopy for the detection of low-grade parasitemia. The second purpose was to study in clinically immune individuals the seroreactivity, against a newly identified P. falciparum antigen, deposited in the erythrocyte membrane during merozoite invasion (Perlmann et al., 1984). This antigen is considered to be a potential component in a future vaccine against the blood stage of the parasite. In a holoendemic village in Yekepa area, Northern Liberia, 28 adult men with a high degree of protective immunity against malaria, were shown to have repeatedly low-grade parasitemias of varying density. The spot hybridization assay with the DNA probe was highly sensitive in detecting parasitic infection. The sensitivity was comparable to that of the examination of a blood film for about 15 min by an experienced microscopist. The seroreactivity against Pf 155 antigen varied between a high positive titer to negativity in different subjects, but the reactivity was constant over a period of 15 months for each subject despite numerous new infections and comparable protective immunity against malaria infection.