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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of BALB/c mice to mosquitoes infected with irradiated Plasmodium berghei confers protective immunity against subsequent sporozoite challenge. Immunized mice challenged with viable sporozoites develop parasitemia when treated orally with substrate inhibitors of nitric oxide synthase (NOS). This suggests that the production of nitric oxide (NO) prevents the development of exoerythrocytic stages of malaria in liver. Liver tissue from immunized mice expressed maximal levels of mRNA for inducible NOS (iNOS) between 12 and 24 h after challenge with sporozoites. Intraperitoneal injection of neutralizing monoclonal antibody against interferon gamma (IFN-gamma) or in vivo depletion of CD8+ T cells, but not CD4+ T cells, at the time of challenge blocked expression of iNOS mRNA and ablated protection in immunized mice. These results show that both CD8+ T cells and IFN-gamma are important components in the regulation of iNOS in liver which contributes to the protective response of mice immunized with irradiated malaria sporozoites. IFN-gamma, likely provided by malaria-specific CD8+ T cells, induces liver cells, hepatocytes and/or Kupffer cells, to produce NO for the destruction of infected hepatocytes or the parasite within these cells.
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PMID:Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon gamma and CD8+ T cells. 751 12

Lysates of Plasmodium falciparum parasitized human erythrocytes stimulate U937 cells to secrete neopterin during a 48 hr co-culture period. Neopterin secretion by U937 cells was enhanced by the addition of human interferon gamma (IFN-gamma). Several P. falciparum antigens, 'FC27' (a synthetic 'S' antigen), Ag16 (a recombinant 'S' antigen) and Ag44/RHOP3 (a recombinant merozoite rhoptry protein), also activated U937 cells to neopterin secretion and produced a similar effect on peripheral blood mononuclear cells (PBMC) from 2 of 3 normal healthy donors cultured with the antigens for 7 days. Plasma from six Nigerian malaria patients contained high neopterin concentrations ranging from 5.06 to 14.17 ng/ml. This preliminary pilot study lends support for further investigation incorporating a larger number of malaria patients and further culture experiments with U937 cells and PBMC with the aim of defining the cause and source of the large quantities of plasma neopterin produced in this infection.
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PMID:Malaria antigens stimulate neopterin secretion by PBMC and U937 cells. 760 65

Immunization of rodents and humans with irradiation-attenuated malaria sporozoites confers preerythrocytic stage-specific protective immunity to challenge infection. This immunity is directed against intrahepatic parasites and involves T cells and interferon gamma, which prevent development of exoerythrocytic stages and subsequent blood infection. The present study was undertaken to determine how protective immunity is achieved after immunization of rodent hosts with irradiated Plasmodium berghei sporozoites. We present evidence that irradiated parasites persist in hepatocytes of rats and mice for up to 6 months after immunization. A relationship between the persistence of parasites and the maintenance of protective immunity was observed. Protective immunity was abrogated in irradiated-sporozoite-immunized rats following the application of chemotherapy to remove preexisting liver parasites. Additionally, protective immunity against sporozoite challenge was established in rats vaccinated with early and late hepatic stages of irradiated parasites. These results show that irradiation-attenuated sporozoites produce persistent intrahepatic stages in vivo necessary for the induction and maintenance of protective immunity.
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PMID:Maintenance of protective immunity against malaria by persistent hepatic parasites derived from irradiated sporozoites. 773 32

The relation between the immune response and the clinical features of severe falciparum malaria was studied in Burundian adults with (n = 31) and without (n = 17) cerebral involvement. At the time of admission, mean values for age, temperature, and blood levels of hemoglobin, creatinine, bilirubin, and glucose were similar in the two groups. Plasma levels of tumor necrosis factor alpha, interferon gamma, interleukin 10 (IL-10), and soluble intercellular adhesion molecule 1 were similarly elevated in the two groups. Mean parasite counts and mean plasma levels of soluble E-selectin were higher in severe noncerebral malaria than in cerebral malaria and were correlated with each other. After adjustment for parasitemia, levels of soluble E-selectin remained higher in noncerebral malaria. All seven patients who died had cerebral disease. These patients had higher levels of creatinine, bilirubin, IL-10, and soluble E-selectin than did patients with nonfatal cerebral malaria. After adjustment for creatinine and bilirubin levels, IL-10 and soluble E-selectin concentrations were similar in fatal and nonfatal cases of cerebral infection. In these African adults, none of the immunologic variables investigated was specific to cerebral malaria or to a fatal outcome.
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PMID:Immunologic and biochemical alterations in severe falciparum malaria: relation to neurological symptoms and outcome. 781 67

Intraperitoneal injection of recombinant Interleukin 12 (rIL-12) at 30 ng/day for 5 days beginning 1 to 2 days before sporozoite challenge or administration of a single dose of 150 ng of rIL-122 days before challenge protected 100% of BALB/c mice against challenge with 10(2) Plasmodium yoelii sporozoites. rIL-12-induced protection was eliminated in all mice by administration of a monoclonal antibody against interferon gamma and in 50% of mice by administration of NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthase. rIL-12 protected BALB/c mice treated with cytotoxic anti-CD4 and anti-CD8 monoclonal antibodies, as well as T-cell- and B-cell-deficient severe combined immunodeficiency mice. These data suggest that rIL-12 stimulates non-B, non-T cells to produce interferon gamma that kills intrahepatic parasites by stimulating nitric oxide production. If rIL-12 proves to be well tolerated by humans, our findings support consideration of rIL-12 as an immunoprophylactic against malaria.
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PMID:Interleukin 12 induction of interferon gamma-dependent protection against malaria. 793 13

We compared the tumor necrosis factor (TNF-alpha), interferon gamma (IFN-gamma) and granulocyte-macrophage colony stimulating factor (GM-CSF) serum levels in 87 patients with malaria from the Brazilian Amazon. They included asymptomatic infected individuals and symptomatic patients with mild disease or severe malaria with or without cerebral involvement. As controls we examined individuals living in endemic areas without past history of malaria. The TNF-alpha serum levels were increased in patients with malaria and progressively decreased in those with severe disease 7 days after specific treatment. We found correlation between parasitaemia, TNF-alpha levels and severity of the disease. The correlation between high TNF-alpha levels and severe malaria was independent of cerebral involvement. The increase in both IFN-gamma and GM-CSF levels among malarious patients was not related to the degree of severity or mortality. IFN-gamma concentration, however, was associated with high parasitaemia at admission.
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PMID:Tumor necrosis factor alpha interferon gamma and macrophage stimulating factor in relation to the Severity of Plasmodium falciparum malaria in the Brazilian Amazon. 865 Jul 40

Intercellular adhesion molecule 1 (ICAM-1) mediates the binding of Plasmodium falciparum to vascular endothelium. In a case-control study of falciparum malaria in Gambian children, we have looked for evidence that a generalized increase in expression of ICAM-1 is associated with cerebral malaria. Plasma levels of circulating ICAM-1 (cICAM-1) were significantly higher in 246 children with acute malaria than in 156 children with non-malarial illnesses. cICAM-1 levels correlated with levels of tumour necrosis factor (TNF), interleukin 1 alpha (IL-1 alpha) and interferon gamma, supporting the view that these cytokines are responsible for a general upregulation of ICAM-1 expression in malaria. However, while it has been previously shown that TNF and IL-1 alpha levels were related to disease severity, this was not the case for cICAM-1. It may be that differences in the distribution of ICAM-1, rather than its total level of expression, are critical in determining the clinical outcome in malaria.
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PMID:Circulating ICAM-1 levels in falciparum malaria are high but unrelated to disease severity. 875 74

The immune response to malaria parasites includes T cell responses that reduce parasites by effector T cell responses and by providing help for antibody responses. Some parasites are more sensitive to antibody and others are more sensitive to cell-mediated immunity. We demonstrate that cultured CD4(+) T cells that produce interferon gamma and interleukin 2, but not interleukin 4, in response to stimulation with the rodent parasite Plasmodium berghei can reduce but not eliminate parasites in vivo after adoptive transfer. Although cells can persist in vivo for up to 9 months in uninfected mice, infection results in elimination of up to 99% of specific T cells in different tissues, as judged by tracking T cells labeled with the fluorescent dye 5-(and -6)-carboxyfluorescein diacetate succinimidyl ester. T cells specific for ovalbumin are unaffected. In vivo activation and division of transferred T cells per se are not responsible for deletion because T cells positive for 5-(and -6)-carboxyfluorescein diacetate succinimidyl ester divide up to six times within 7 days in uninfected mice and are not deleted. Understanding the factors responsible for parasite-mediated specific deletion of T cells would enhance our knowledge of parasite immunity.
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PMID:Deletion of Plasmodium berghei-specific CD4+ T cells adoptively transferred into recipient mice after challenge with homologous parasite. 946 82

A prospective longitudinal study to examine the relationship between cellular immune responses to the synthetic malarial peptide SPf66 and malaria infection and morbidity was carried out in 187 children aged 0.5-15 years in the Wosera area of Papua New Guinea. Cellular responses were assessed by proliferation and stimulation of cytokines representing the Th1 and Th2 cell subsets (interferon gamma [IFN gamma] and interleukin-4 [IL-4]. Most children (66%) did not respond to SPf66 by any measure. Among the responders, the highest response was obtained for IL-4 (19%) followed by IFN gamma (10%), and the least for proliferation (5%). Analyses of the relation of T cell response to malaria infection showed that the IFN gamma response to SPf66 was positively correlated with parasite density (r = 0.27, P = 0.001). There was no association between the cellular response to SPf66 and concurrent or subsequent malaria morbidity, whichever clinical definition was used. Thus none of these cellular immune responses predicted efficacy of SPf66 in this highly endemic area.
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PMID:Naturally acquired cellular immune responses to the synthetic malarial peptide SPf66 in children in Papua New Guinea. 950 86

Extensive studies on protective immunity to rodent malaria provided the basis for the current experiments in which mice were immunized with recombinant (re) influenza and vaccinia viruses expressing selected sequences of the circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum. Mice of different H-2 haplotypes immunized with re influenza viruses expressing the immunodominant B cell epitope of this CS protein produced high titers of antibodies to the parasite. A cytotoxic T lymphocyte epitope of the CS protein of P. falciparum, PF3, recognized by CD8+ T cells of H-2(k) mice, was expressed in a re vaccinia virus (VacPf) and a re influenza virus (FluPf). Immunization of mice with either FluPf or VacPf elicited a modest CS-specific CD8+ T cell response detected by interferon gamma secretion of individual immune cells. Priming of mice with FluPf, followed by a booster with VacPf, resulted in a striking enhancement of this T cell response. The reverse protocol, i.e., priming with VacPf followed by a booster with FluPf, failed to enhance the primary response. VacPf also greatly enhanced the primary response of mice injected with P. falciparum sporozoites or with a lipopeptide containing PF3. A booster with FluPf also amplified the response of lipopeptide- or sporozoite-primed mice but less than a VacPf booster did. Although mice are not susceptible to infection by P. falciparum sporozoites, we demonstrated that administration of two distinct immunogens expressing PF3 elicited activated, extravasating CS-specific T cells that protected against an intracerebral VacPf challenge.
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PMID:Recombinant viruses expressing a human malaria antigen can elicit potentially protective immune CD8+ responses in mice. 952 Apr 74


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