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)

Plasma and peripheral blood mononuclear cells (PBMC) were obtained from P. falciparum-infected individuals with and without the sickle cell trait at diagnosis and 7 days after treatment. HbAA and HbAS patients were compared for levels of plasma soluble IL-2 receptors (IL-2R) and the in vitro cellular reactivity to affinity-purified soluble P. falciparum antigens (SPAg), PPD and phytohaemagglutinin (PHA). At diagnosis, HbAS patients with clinical disease had lower plasma-soluble IL-2R levels and parasite counts than the corresponding HbAA patients, whereas HbAS and HbAA patients with asymptomatic infections had comparable soluble IL-2R levels and parasite counts. PBMC from HbAS patients had higher proliferation and IFN-gamma production in response to SPAg than PBMC from HbAA patients. The difference in the lymphoproliferative responses to SPAg between the two groups was evident in patients with asymptomatic infections. In all patients, the clinical severity, the soluble IL-2R levels and the parasite counts were directly related. The former two were inversely related to the proliferative responses to SPAg. After treatment, all the studied parameters were comparable in the two groups. The study indicates that during P. falciparum infection, HbAS compared with HbAA patients had lower in vivo cellular activation and higher in vitro cellular reactivity in response to soluble malaria antigens.
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PMID:Modulation of the cellular immune response during Plasmodium falciparum infections in sickle cell trait individuals. 156 96

Immunity to P. falciparum malaria is developed as a result of long term exposure to the parasite and depends on immunological memory. The key directors in immune recognition and regulation of the immunological responses are the T-cells. It seems reasonable to propose that immunity is acquired when a critical mass of T-cells, recognizing relevant malaria antigens, has been developed. These T-cells mediate immunity by regulating macrophage and B-cell activity, but they may also act directly as cytotoxic cells on infected hepatocytes and through production of parasite-toxic cytokines. The potential immune effector mechanisms against P. falciparum are many. The relative importance of each in protection is unknown and protection seems to be mediated through different mechanisms according to the degree of exposure to malaria and the pattern of malaria transmission. Since immunity to malaria is not an absolute phenomenon, many effector mechanisms are probably working together in (partially) protected individuals. Immunity to P. falciparum is acquired after years of exposure to the parasite and several disease episodes. The protracted course to clinical immunity indicates that the parasite interfere with development of immunity. Several mechanisms seem to be operating. 1) Induction of the immune response to some macromolecules is avoided because the parasites are living inside host cells during part of their life cycle, and the reaction to other molecules is apparently avoided by mimicry of host molecules. 2) Immune recognition is hampered by the extraordinary diversity of antigen phenotypes in the parasite population. 3) Immune regulation is obstructed by immune suppression. During P. falciparum malaria such suppression is characterized by a profoundly diminished in vitro proliferative response to malaria antigens, which probably is precipitated by defects in the early events of T-cell activation and inhibition of IL-2 function elucidated, but soluble factors secreted either by the parasites, or by host cells as a result of exposure to the parasite, seem to be involved. 4) Immune effector mechanisms in the liver and the spleen are avoided by sequestration of the mature parasites to the vascular endothelium. The interplay between the human defence system and the malaria parasite governs the symptomatology, the pathology and the development of immunity to the disease. These interactions are extremely complex, and only partly understood. Figure 1 summarizes my view on how these interactions could explain the characteristics of acquired immunity to P. falciparum.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Defence mechanisms and immune evasion in the interplay between the humane immune system and Plasmodium falciparum. 156 95

Serum cytokine profiles were evaluated in immunized and nonimmunized human volunteers after challenge with infectious Plasmodium falciparum sporozoites. Three volunteers had been immunized with x-irradiated sporozoites and were fully protected from infection. Four nonimmune volunteers all developed symptomatic infection at which time they were treated. Sera from all volunteers were collected at approximately 20 time points during the 28-d challenge period; levels of IL-1 alpha, IL-1 beta, IL-2, IFN-gamma, tumor necrosis factor-alpha, IL-4, IL-6, granulocyte macrophage-colony-stimulating factor, and soluble CD4, CD8, and IL-2 receptor (sCD4, sCD8, and sIL-2R, respectively) were determined by ELISA. C-reactive protein (CRP) was assayed by radial immunodiffusion. Parasitemic subjects developed increases in CRP and IFN-gamma, with less marked increases in sIL-2R and sCD8; the other cytokines tested did not change. CRP increases were abrupt and occurred at the onset of fever (day 14 after challenge). IFN-gamma increases were also abrupt, preceding those of fever and CRP by one day. Increases in sIL-2R and sCD8 were more gradual. Increases in fever, CRP, IFN-gamma, and sCD8 were concordant in each volunteer. Early IL-6 increases were noted in the protected vaccinees. Thus, after challenge with virulent P. falciparum, unique systemic cytokine profiles were detectable both in immunized, nonparasitemic volunteers and in unvaccinated, parasitemic subjects. The contrasting cytokine profiles in the two groups may relate to mechanisms of protection and immunopathology in experimental human malaria.
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PMID:Serum cytokine profiles in experimental human malaria. Relationship to protection and disease course after challenge. 164 22

We have mapped a T cell epitope in the circumsporozoite (CS) protein of the murine malaria parasite, Plasmodium yoelii. A 21-mer synthetic peptide corresponding to the amino acid positions 59-79 (referred to as Py1), induced specific proliferation in BALB/c and C57BL/6 mice, and provided help for the production of antibodies to peptides from the repetitive region, (QGPGAP)n, of the same CS protein, when mice were immunized with the Py1 peptide conjugated to the repetitive peptide. Long-term CD3+CD4+CD8-TCR alpha beta+ T cell lines and clones were derived from both strains of mice. These lines and clones, that proliferated in an MHC-restricted fashion, did not recognize peptides from the homologous region of another murine malaria parasite, P. berghei. About 50% of these clones produced detectable amounts of IFN-gamma and IL-2, whereas the remaining produced IL-4, IL-5, and IL-6. In preliminary experiments, some of these clones specifically inhibited P. yoelii sporozoite development in vitro and conferred protection in vivo in passive transfer experiments. These findings show that heterogenous T cell populations are activated in mice upon immunization with a short peptide from the P. yoelii CS protein and that some of these cells could be active in the effector arm of the immune response against malaria sporozoites.
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PMID:Peptide-primed CD4+ cells and malaria sporozoites. 170 50

We report here on functional aspects of squirrel monkey T cells isolated either from peripheral blood mononuclear cells or in the presence of accessory cells or accessory-cell-secreted cytokines. The T-cell response triggered by polyclonal activators was measured through proliferation, T-cell growth factor production and transient expression of receptors to growth factors. We also sought to delineate mechanisms by which antimitogenic molecules might prevent lymphocytes from being able to express "activation antigens" and/or from proliferating. Under these conditions, we mainly explored the inducible IL2/IL2R pathway and phenomena occurring in lymphocyte "non-activation" in terms of early and late cellular events; indeed, defects in the IL2/IL2R pathway represent one of the dysregulation events presumed to occur during the acute phase of human malaria, disease for which. Saimiri monkeys have been selected as experimental hosts.
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PMID:Peripheral blood mononuclear cells in the squirrel monkey Saimiri sciureus. II. Exploration of the IL2/IL2R pathway of T-cell activation. 179 9

Quantification of human peripheral blood NK subsets has been made in a group of Kenyan adults and children with acute P. falciparum malaria. Results were compared with data obtained from three age- and sex-matched control cohorts: parasitaemic but asymptomatic children; aparasitaemic children and adults; and adult Caucasians with no previous history of malaria. Separated NK subsets were tested in vitro for cytotoxicity to erythrocytic schizonts of P. falciparum in the presence and absence of cytokines. There was a statistically significant quantitative and qualitative depression of the CD3-CD56+ subset in patients with acute malaria and this was accompanied by an expansion of the 'non-functional' CD3-CD57+CD16-CD56- subset. Both CD3-CD16+ and CD3-CD56+ NK cells from all patients and donors lysed schizonts, and this cytotoxicity was enhanced by the addition of recombinant interferon-alpha and/or IL-2, notably with the CD3-CD56+ subset. Interestingly, asymptomatic donors had the highest levels of CD3-CD56+ NK cells, which also demonstrated an enhanced response to cytokine stimulation. Cytotoxicity to schizonts was accompanied by the release of soluble NK cell lytic factors. Neomycin suppressed cytotoxicity in a dose-dependent manner, indicating that the lysis of schizonts by NK cells involves phospholipase C-mediated phosphoinositide metabolism. Our findings define a role for NK cells in immunity to malaria through the lysis of infected erythrocytes as a first-line defence against the parasite.
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PMID:Cytotoxicity of human natural killer (NK) cell subsets for Plasmodium falciparum erythrocytic schizonts: stimulation by cytokines and inhibition by neomycin. 183

Levels of TNF alpha, IL-6-, soluble R IL-2, and fibronectin, were evaluated in fifteen patients with cerebral malaria. Relations between cytokines levels and parasitemia were assessed. Concentration of IL-6, and soluble R IL-2, correlated with parasitic density on admission. It was appeared, that IL-6, would be a prognostic factor, as interesting as TNF alpha.
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PMID:[Neuromalaria and cytokines]. 184 81

We have tested the prophylactic effect of Escherichia coli-derived recombinant human interferon gamma (rHuIFN-(gamma] against sporozoite- or trophozoite-induced Plasmodium cynomolgi B malaria infection in rhesus monkeys. Data show that treatment with only five doses of rHuIFN-(gamma) (0.1 mg/kg body weight) given on days -2, 0, and +2 after infection protected the monkeys against sporozoite-induced P. cynomolgi infection. Animals initially protected by rHuIFN-(gamma) treatment remained susceptible to reinfection. No inhibitory effect of rHuIFN-(gamma) was seen against trophozoite-induced infection. We have also tested the effect of recombinant human tumour necrosis factor (rHuTNF) in rhesus monkeys. No significant activity of TNF was seen against trophozoite-induced P. cynomolgi B infection. rHuIFN-(gamma) inhibited schizogony in functional human hepatocytes infected with P. falciparum sporozoites. These results suggest that the inhibitory effect of IFN is limited to the exoerythrocytic stage of parasite development. Interleukin-1 (IL-1) also inhibited hepatic development of P. falciparum sporozoites; however, IL-1 treatment was effective only when applied before sporozoite inoculation. IL-2 and TNF were effective in higher doses.
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PMID:The role of cytokines in malaria infection. 212 26

The kinetics of indicators of lymphocyte activation were determined in non- and semiimmune patients with uncomplicated Plasmodium falciparum infection and in control subjects in Acre, Brazil. Delayed type hypersensitivity (DTH) to seven recall antigens was weakest in nonimmune patients. Both patient groups differed significantly from controls on admission (P less than .001 for both) and improved considerably after clindamycin therapy. Total serum IgG and IgM, but not antimalarial antibodies, were highest in nonimmune patients compared with semiimmune patients and controls during acute malaria. Immunoglobulin levels normalized after chemotherapy. A striking decrease of CD4+ peripheral blood lymphocytes, normalizing after chemotherapy, was seen in both patient groups, and was more pronounced in nonimmune patients. A slight increase in interleukin-2 receptor (IL-2R)-bearing cells was found in nonimmune patients. In addition, soluble plasma IL-2R was significantly elevated in them (P less than .001) and to a lesser extent in semiimmune patients. These findings were paralleled by significantly decreased IL-2 concentrations in plasma (P less than .001) during the acute phase of malaria, suggesting pronounced general immunosuppression in nonimmune malaria patients.
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PMID:Immune response in patients during and after Plasmodium falciparum infection. 218 25

We have studied the role of CD4+ T cells in the immune response to Plasmodium chabaudi chabaudi. From in vivo experiments in which the different subsets of T cells were depleted, it is clear that CD4+ T cells are essential for the generation of protective immunity. Our limiting dilution analysis show that the CD4 T-cell response to P. chabaudi antigens is heterogeneous, in that distinct functions can be performed by different responding T cells, and these responses change during infection. During the first phase of the infection the predominant response is that of a TH1-type cell, producing IL-2 and IFN-gamma. This correlates with the appearance of IFN-gamma in the serum of infected animals. After the clearance of the acute parasitemia, i.e. in the second phase of the infection, the specific response is characterised by TH2 cells, which are effective helper cells for antibody production and presumably are necessary for the switch of IgM to IgG. CD4+ T cells are effector cells are not necessary in the second phase of the infection; mice which have been depleted of CD4+ T cells at this time are able to control their infection in a manner similar to untreated mice. This ability to control parasitemia coincides with the production of specific IgG but not IgM antibodies and the predominance of TH2 type helper cells. Therefore, our data suggest that malaria-specific IgG antibodies are important effectors in the second phase of an infection with P. chabaudi chabaudi.
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PMID:The response of CD4+ T cells to Plasmodium chabaudi chabaudi. 257 75


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