Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood mononuclear cells from 63 Gambian children with acute Plasmodium falciparum malaria were examined for lymphoproliferation and interferon-gamma (IFN) production in response to stimulation by mitogens, malaria antigens and other soluble antigens. Mitogen or Candida-induced proliferation was not depressed during acute infection but was enhanced 2 to 4 weeks after treatment. Responses to partially purified soluble P. falciparum antigens were minimal or absent in all children in the acute phase but approximately 50% of the children responded by proliferation or IFN-gamma production during the 2 to 8 week convalescent period. These proliferative responses were severely depressed in the presence of the patient's own serum. Nine children with significant convalescent phase proliferative responses were re-examined several months after acute infection. Of these, four remained responsive for at least 8 months in the probable absence of reinfection.
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PMID:Cellular immune responses to Plasmodium falciparum antigens in Gambian children during and after an acute attack of falciparum malaria. 313 43

The present study concerns the interferon (IFN) compartment of the immune response in human malaria. It was undertaken with Plasmodium falciparum parasitized human red blood cell culture supernatants (PF-RBCS). Investigations were conducted in order to verify whether supernatants of such protozoa cultures had the capacity to induce gamma interferon previously identified in sera of P. falciparum infected patients and to verify whether a T-cell mitogen recently characterized in vitro could be correlated with the eventual IFN-inducing activity. Investigations were performed with nonsynchronized P. falciparum cultures and highly synchronized PF-RBC cycles. Results obtained with the first type of experiment demonstrated the presence of an immune interferon inductor in PF-RBCS controlled for their positive mitogenic activity. In supernatants from highly synchronized PF-RBC cycles it was possible to further correlate the mitogen activity with the capacity to induce IFN-gamma. Both activities were found in the time-interval situated near the end of the parasite cycle shortly previous of the merozoite stage. At an earlier time, at the peak of the ring stage, when no mitogen activity was detected, an interferon-induction activity, solely of IFN-alpha, was also demonstrated.
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PMID:The interferon compartment of the immune response in human malaria: I. Interferon inducers in Plasmodium falciparum cultures. 392 27

The present study concerns the monitoring of serum-interferon (serum-IFN) levels among 189 patients followed after and sometimes during an acute episode of malaria due mainly to Plasmodium falciparum (P. falciparum). Of these patients, 110 known to have no other parasitic or infectious disease were followed in France; 79 were from Thailand, among which 25 cases of neuromalaria were diagnosed. In a first four-month survey conducted in France, among 100 patients seen after the acute attack, serum-IFN-gamma was characterized among 87% cases for which at least two sera were controlled, whereas in a healthy population no serum-IFN was present. When efforts were concentrated on screening ten cases during the first 48 h of the febrile attack, serum-IFN-alpha was mainly characterized, whereas serum-IFN-gamma was present only once. Elevated leukocyte 2',5' oligoadenylate synthetase levels were found among several IFN-alpha positive patients of this study group. A peculiarity pertaining to the patients from Thailand was that one-third (25 cases) were cerebral malaria cases. Among these, 15 were followed under hospitalization during the first 96 h. In this study group, the onset of circulating immune interferon was found to be preceded or accompanied by that of IFN-alpha. Thus, if serum-IFN-gamma is largely characterized among malaria patients followed after the acute attack, it is possible that the onset of circulating immune interferon is generally preceded by that of IFN-alpha.
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PMID:The interferon compartment of the immune response in human malaria: II. Presence of serum-interferon gamma following the acute attack. 392 28

We have previously identified a Plasmodium falciparum liver stage-specific Ag (LSA-1) found to encode tandem 17 amino acid repeats harboring B cell determinants. Here we extend this study in terms of sequence analysis, protein localization, and immunologic properties. Analysis of the N- and C-terminal regions of LSA-1 from the T9/96 clone reveals high sequence conservation with LSA-1 from NF54. This 200-kDa protein is detected throughout liver schizogony and accumulates in the parasitophorous vacuole space. In our investigation of T and B cell responses to LSA-1, we have focused on both the area of the C-terminal, nonrepetitive "hinge" region and the conserved repetitive region and derived synthetic peptides. These were found to contain major B and T cell determinants. High prevalences and elevated Ab levels to LSA-1, directed primarily, although not exclusively, to the repetitive region, were detected in sera of individuals from one moderately high and two low transmission malaria-endemic areas (prevalences of 97%, 75, and 77%, respectively). In one of these low transmission areas, secretion of the cytokine IFN-gamma, known to inhibit malaria liver stages, and T cell proliferation were detected in PBMC of 22 to 48% and 6 to 20%, respectively, of individuals in response to separate LSA-1 peptides. These results complement the recent finding of conserved CTL epitopes in LSA-1 and support the assertion that immune responses to LS Ag are involved in protection against malaria pre-erythrocytic stages.
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PMID:Plasmodium falciparum liver stage antigen-1 is well conserved and contains potent B and T cell determinants. 751 22

Both CD8+ T cells and IFN-gamma (IFN-gamma) are important components in the regulation of inducible-nitric oxide synthase (iNOS) which contribute to liver stage anti-malarial activity in rodents immunized with irradiated sporozoites. IFN-gamma, provided by malaria-specific CD8+ T cells, stimulates liver cells to produce nitric oxide (NO) for the destruction of infected hepatocytes or the parasite within these cells. To identify the cell source of iNOS in livers from Brown Norway rats challenged with Plasmodium berghei sporozoites, we probed tissue sections with antisera that recognize iNOS and the malarial exoerythrocytic stage parasite. Immunofluorescence analysis of parasitized livers demonstrate that 1) iNOS was found in infected hepatocytes, not Kupffer or endothelial cells; and 2) a higher proportion of infected hepatocytes express iNOS in immunized rats compared with naive animals after challenge. There was no immunoreactivity to the iNOS antisera in liver sections of immunized rats 15 h after sporozoite challenge, however, iNOS activity was present in 18% of the infected hepatocytes by 24 h and reached 81% by 31 h. In contrast, < 10% of the infected hepatocytes displayed iNOS activity in naive or immune animals 48 h after challenge. We also found a significant decrease in the ability of the immunized animals to express iNOS in response to sporozoite challenge by accelerating the removal of pre-existing irradiated-attenuated parasites from hepatocytes with the antimalarial drug, primaquine. Therefore, induction and maintenance of iNOS activity were dependent on intrahepatic persistence of the irradiated-attenuated parasite. These results suggest that liver-iNOS expression following sporozoite challenge is restricted to the infected hepatocyte and dependent on the presence of the irradiated-attenuated parasite in immune animals.
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PMID:Co-localization of inducible-nitric oxide synthase and Plasmodium berghei in hepatocytes from rats immunized with irradiated sporozoites. 753 96

Localization of human MHC class I-restricted T cell epitopes in the circumsporozoite (CS) protein of the human parasite Plasmodium falciparum is an important objective in the development of antimalarial vaccines. To this purpose, we synthesized a series of overlapping synthetic 20-mer peptides, spanning the entire sequence of the 7G8 CS molecule except for the central repeat B cell domain. The P.f.CS peptides were first tested for their ability to bind to the human MHC class I HLA-A2.1 molecule on T2, a human cell line. Subsequently, the use of a series of shorter peptide analogues allowed us to determine the optimal A2.1 binding sequence present in several of the 20-mers. Binding P.f.CS peptides were further tested for their capacity to activate PBL from HLA-A2.1+ immune donors living in a malaria-endemic area. Specific IFN-gamma production was detected in the supernatant of cultures of PBL from exposed individuals. Cytotoxic T cell lines and clones were derived from the PBL of one responder, and their activity was shown to be HLA-A2.1-restricted and specific for the peptide 334-342 of the CS protein. In addition, double transgenic HLA-A2.1 x human beta 2-microglobulin mice were immunized with peptide 1-10 of the CS protein. T cells derived from immune lymph nodes displayed a peptide-specific HLA-A2.1-restricted cytolytic activity after one in vitro stimulation.
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PMID:Localization of HLA-A2.1-restricted T cell epitopes in the circumsporozoite protein of Plasmodium falciparum. 753 17

IFN-gamma receptor deficient (IFN-gamma R-/-) mice, immunized with different developmental stages of malaria parasites, were used to define the mechanisms of protection against the various stages of this infection. IFN-gamma R-/- mice failed to develop protective immunity against Plasmodium yoelii sporozoites or liver stages, upon immunization with a single dose of irradiated sporozoites, whereas in immunized wild-type mice, parasite development was strongly inhibited. Immunized wild-type mice expressed high levels of inducible nitric oxide synthase (iNOS) mRNA in their liver, upon challenge with viable sporozoites, whereas only background levels of iNOS were detected in immunized IFN-gamma R-/- mice. In contrast, after immunization with multiple doses of irradiated sporozoites, both IFN-gamma R-/- and wild-type mice mounted an immune response, which strongly inhibited the development of liver stage parasites. In both types of mice, protection occurred in the absence of appreciable expression of liver iNOS mRNA. As for the course of the erythrocytic phase of infection by nonlethal malaria species, P. yoelii yoelii and P. chabaudi adami, we observed only a moderately prolonged parasitemia in IFN-gamma R-/- mice compared with wild-type mice, indicating that IFN-gamma may only play a modest role in immunity against erythrocytic stages. These results indicate that IFN-gamma is the main mediator of the protective mechanism that develops first upon immunization with sporozoites. However, the nature of the anti-parasite mechanism(s) changes in the course of immunization, so that multiple immunizing doses elicit additional protective mechanisms, which are independent of IFN-gamma and its receptor.
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PMID:Development of antimalaria immunity in mice lacking IFN-gamma receptor. 753 5

An ELISPOT assay to detect and determine the number of antigen specific CD8+ T cells was standardized using cloned murine CD8+ T cells specific for the epitope SYVPSAEQI of a rodent malaria antigen. This assay is based on the detection of IFN-gamma secretion by single cells after their stimulation with antigen. The interferon secretion is visualized as spots revealed by using enzyme labeled anti-IFN-gamma monoclonal antibodies. Using known numbers of cloned murine CD8+ T cells it was determined that the assay detects 80-95% of these CD8+ T cells. The optimal culture conditions for the stimulation of the CD8+ T cells were determined and the antigen concentration, number of antigen presenting cells and supplement of growth factors required to perform the assay were defined. This ELISPOT assay can be performed with spleen cells from immunized mice, and provide the precise number of antigen specific CD8+ T cells present in mixed lymphocyte populations. This method is more sensitive than the chromium-51 release assay, and much simpler than the conventional precursor frequency analysis, providing the number of antigen specific CD8+ T cells in 36-48 h.
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PMID:Quantification of antigen specific CD8+ T cells using an ELISPOT assay. 753 12

T- and B-cell responses to the Plasmodium falciparum blood-stage antigen Pf155/RESA were investigated in 104 Cameroonian women, half of whom were pregnant. We used purified protein and six synthetic peptides representing T- and B-cell epitopes. In vitro T-cell responses were measured by proliferation and IL2, IFN-gamma, and IL4 release. B-cell responses were assessed by plasma antibodies. All peptides induced a cellular response in some individuals. A proliferative response was induced in 25% of the donors by Pf155/RESA, and in 7 to 11% by any peptide. Cytokine release occurred in 23 to 30% of the Pf155/RESA-stimulated cultures, and in 8 to 25% of the peptide-stimulated cultures. Overall, each peptide induced a cellular response (proliferation and/or cytokine release) in 44% of the donors. T-cells from 23% of the donors failed to respond to any peptide. Responding cells did not usually respond in all readouts, and proliferation and release of any of the three cytokines were not correlated. Similarly, antibody and T-cell responses were not related. Selected epitopes of Pf155/RESA, an important vaccine candidate, are well recognized in naturally exposed individuals and are able to activate T-cells to proliferate and to produce various lymphokines in numerous individuals from a malaria endemic area.
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PMID:Humoral and cellular immune responses to synthetic peptides from the Plasmodium falciparum blood-stage antigen, Pf155/RESA, in Cameroonian women. 761 35

The enzyme-linked immunospot (ELISPOT) assay was used to enumerate the number of IFN-gamma and IL-4 producing cells after in vitro stimulation with a highly purified recombinant malaria vaccine candidate antigen (r-Pf155/RESA) or synthetic peptides corresponding to its major T-cell epitopes. Two groups of naturally primed individuals living in rural areas of Burkina Faso were studied. The donors comprised one group of healthy (non-parasitemic) mainly adult people and one parasitemic mainly younger people. IL-4 producing cells were detected in response to PHA but no such cells were detected in response to the malarial antigens. The most frequent IFN-gamma responses were seen with r-Pf155/RESA. Thus, after stimulation with this antigen 52% of the donors responded positively in the ELISPOT assay, while only 17% responded to the synthetic peptides, suggesting that the rPf155/RESA contained T-cell epitopes not covered by the peptides used in this study. The number of IFN-gamma producing cells in response to the malarial antigens did not differ between the two groups. However, IFN-gamma levels found in sera from the parasitemic individuals were significantly higher than in those from healthy donors. This latter finding and the lack of differences seen in the number of IFN-gamma producing spots in the two groups indicate that IFN-gamma producing cells may have sequestered to other organs in the parasitemic group.
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PMID:Comparison of the number of IL-4 and IFN-gamma secreting cells in response to the malaria vaccine candidate antigen Pf155/RESA in two groups of naturally primed individuals living in a malaria endemic area in Burkina Faso. 763 Nov 43


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