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)

T lymphocyte responses to malaria-specific antigens during acute falciparum malaria were studied to determine host-parasite interaction and its relation to the manifestations of the disease. The results indicate that while there is antigen-specific immunodepression, markedly elevated levels of soluble factors such as IL2 receptor, CD8 antigen and IFN-gamma suggest that there is intense concurrent cellular activation which however does not seem to be effective in controlling the infection. It is proposed that the cellular activation is to a large extent non-specific and polyclonal, and leads to the exaggerated production of cytokines and eventually immunopathology. Various mechanisms of immunodepression are discussed.
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PMID:T cell responses in acute falciparum malaria. 228 44

The C-terminal (3') amino acid repeat region of the Plasmodium falciparum Ag Pf155/RESA, a vaccine candidate, contains immunodominant T and B cell epitopes. In order to identify additional T cell epitopes in the molecule, synthetic peptides corresponding to the centrally (5') located repeat region, as well as to four nonrepeated regions, were synthesized. T cells from 46 P. falciparum-primed individuals living in a holoendemic area of The Gambia where malaria transmission is seasonal were tested for their responsiveness to the peptides by thymidine incorporation and IFN-gamma release. There was a considerable variation in the response to different peptides. Proliferation and IFN-gamma release were not correlated in individual donors, underlining the importance of measuring both activities when screening donor populations for total T cell responsiveness to a given Ag. Whereas 72% of the donors responded with proliferation and/or IFN-gamma release to the intact protein the mean % responders to the peptides was 40%. The most frequent responses (up to 60%) were induced with peptides from the 3'- and 5'-repeat region of the protein. Analysis of some closely related sequences in the 3'-repeat region indicated that they contained at least two epitopes that were either distinct or cross-reacting in different donors, suggesting difference in the genetic control of these responses. When the same peptides were investigated for reactivity with antibodies, the best T cell inducing sequences also displayed the best antibody reactivities. However, in individual donors, T and B cell responses were not correlated. T cell responses were shown to persist after a period with no P. falciparum transmission, whereas antibody concentrations tended to decrease, suggesting differences in the requirements of boosting at the T and B cell levels, respectively.
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PMID:T and B cell responses of Plasmodium falciparum malaria-immune individuals to synthetic peptides corresponding to sequences in different regions of the P. falciparum antigen Pf155/RESA. 247 32

A Plasmodium falciparum sporozoite vaccine, composed of a synthetic dodecapeptide (NANP)3 coupled to tetanus toxoid (TT), was injected, at weeks 0 and 8, into non-immune volunteers in two randomized double-blind placebo-controlled trials. In the first trial, 37 volunteers received the vaccine simultaneously with placebo (group 1), 0.5 x 10(6-) (group 2), or 1.5 x 10(6) U (group 3) of recombinant human interferon-alpha (= IFN-alpha). In the second trial, 35 other volunteers received the vaccine with placebo (group 4), 0.25 x 10(6) (group 5), or 1.0 x 10(6) IU (group 6) of interferon-gamma (= IFN-gamma). Immunizations were well tolerated and resulted in seroconversion rates (greater than or equal to 4-fold increase of antibody titre in immunofluorescence or enzyme-linked immunosorbent assays) of 67-100% of volunteers. IFN-alpha significantly enhanced the IgG antibody titres in ELISA to malaria peptide.
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PMID:Effects of interferons on immune response to a synthetic peptide malaria sporozoite vaccine in non-immune adults. 247 87

IFN-gamma plays an important role in host defense against microbial disease. Here, we studied the role of IFN-gamma in lethal and nonlethal murine malaria. Administration of recombinant murine IFN-gamma resulted in a dose-dependent protection of SW, BALB/cByJ, and CBA/J mice from the lethal variant of Plasmodium yoelii 17x (PyL) but had little effect on the course of the nonlethal variant of this parasite (PyNL). Administration of recombinant IFN-gamma also resulted in the activation of peritoneal macrophages for increased phagocytosis of malaria-infected erythrocytes and release of H2O2, as measured in vitro. The ability of spleen cells from infected mice to produce endogenous IFN-gamma and release H2O2 during the course of malaria was also studied. In BALB/cByJ mice, which are relatively susceptible to PyL and PyNL, there was an initial burst of IFN-gamma only in response to PyNL whereas in CBA/J mice, which are relatively resistant to these parasites, there was an initial burst of IFN-gamma in response to both PyL and PyNL. The kinetics of H2O2 release corresponded to that of IFN-gamma. In all infections, levels of IFN-gamma declined as parasitemia increased; however, nonlethal infections were characterized by a recovery of both IFN-gamma activity and H2O2 release as parasitemia declined. These data suggest that IFN-gamma may play an important role in modulating the course of malaria infections by activating macrophages for both intracellular and extracellular parasite destruction.
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PMID:Role of IFN-gamma in lethal and nonlethal malaria in susceptible and resistant murine hosts. 250 74

Studies are reviewed in which the role of IFN-gamma in different models of inflammation in mice is examined: LPS-induced generalized Shwartzman reaction, experimental allergic encephalomyelitis (EAE) and experimental cerebral malaria (ECM). The particular role of the cytokine was studied by systemic administration and by blocking the endogenously produced cytokine by the use of neutralizing antibodies. IFN-gamma was found, depending on the model and circumstances, to exert an anti- or a pro-inflammatory effect. In the generalized Shwartzman reaction and ECM this cytokine has a disease promoting role. In EAE, on the contrary, endogenous as well as exogenous IFN-gamma exert a down-regulating effect.
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PMID:The role of cytokines in various animal models of inflammation. 250 97

The functional heterogeneity of the CD4+ T cell response to Plasmodium chabaudi has been evaluated. Using a limiting dilution assay system and a variety of assays to detect gamma-interferon (IFN-gamma), interleukin-2 (IL-2), IL-3, and T helper (Th) cells for malaria-specific antibody production, the precursor frequencies of P. chabaudi-reactive T cells have been calculated. The patterns of lymphokines produced by individual microcultures of the limiting dilution assay generally supported the idea of two functionally distinct CD4+ subsets: one which produces IFN-gamma and IL-2 (Th1) and one which is an effective helper cell for antibody production (Th2). However, it could not be determined whether the overlapping functions observed in some cultures represented T cells which could produce all factors or separate clones which were developing in the same wells. During the first 14 days of an erythrocytic infection of P. chabaudi the predominant T cell response was of the Th1-type. The frequency of these cells decreased after 14 days. By 3 weeks after infection the CD4+ T cell response was characterized by Th2 cells, as defined by their ability to act as helper cells in the production of malaria-specific antibody. These data support the hypothesis that early clearance of P. chabaudi may be antibody-independent but that the final clearance mechanism coincides with the appearance of helper cells and antibody.
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PMID:Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. 253 35

Evidence is presented here that tumor necrosis factor/cachectin (TNF), is of crucial importance in the pathogenesis of cerebral malaria. First, the central lesion of CM, hemorrhagic necrosis of cerebral vessels, corresponds to lesions observed during other pathological conditions associated with high serum TNF levels, such as endotoxemic shock or administration of TNF. Second, in both mouse and human, there is a close correlation between high serum TNF levels and CM. At least in mouse, high TNF levels and CM depend upon T lymphocytes of the CD4+ phenotype. Third, passive immunization against mouse TNF significantly prolongs the survival of P. berghei-infected CBA/Ca mice, and prevents the development of neurologic signs. Treatment with the anti-TNF antibody also prevents hemorrhagic necrosis of brain vessels. Fourth, in the mouse model, a cytokine cascade including at least GM-CSF, IL-3 and IFN-gamma is required for the elevation of TNF level. This cascade appears to involve two components: (a) a quantitative component: increased accumulation of macrophages results from the concomitant release of IL-3 and GM-CSF, and (b) a qualitative component: macrophage number has not only to be raised, but macrophages need to be activated by IFN-gamma. Fifth, metabolic parameters of CM and its main lesion in both mouse and human, i.e. the hemorrhagic necrosis of small brain vessels, correspond to the known properties of TNF.
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PMID:Tumor-necrosis factor and other cytokines in cerebral malaria: experimental and clinical data. 257 74

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

We investigated the seroreactivity and T cell reactivity against the Plasmodium falciparum antigen Pf155/RESA, different oligopeptides from the 3' and 5' repeat regions of the Pf155/RESA antigen, and crude Plasmodium falciparum antigens in 164 adult Liberians. We compared 2 long-term residential groups with high and low exposure to malaria. The seropositive rate to the peptides was significantly higher with increased exposure. There was no significant difference in response rates to the Pf155/RESA. This may indicate the level of persistent T cell memory in previously primed donors. The seropositive rates to 3 Pf155/RESA peptides and the rates measured by either 3H-thymidine incorporation or IFN-gamma release after stimulation with Pf155/RESA and the peptides were all lower in parasite positive individuals. Even low grade, asymptomatic parasitemia can impair the T cell response in vitro. The lower antibody response in parasite positive subjects may be explained by either antibody consumption or lower protection against malaria parasitemia in subjects with low concentrations of antibodies against the Pf155/RESA antigen.
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PMID:An epidemiological study of humoral and cell-mediated immune response to the Plasmodium falciparum antigen PF155/RESA in adult Liberians. 267 67

T cell-dependent, cell-mediated immune mechanisms have been shown to contribute to resistance against malaria. Because the identity of plasmodial Ag responsible for the activation of these protective immune responses remains unknown, a major step in isolating these potential immunizing agents will be the development of adequate screening procedures designed to identify important T cell Ag. This study focused on the isolation of protective T cell clones that may play a pivotal role in this process. A T cell clone designated CTR2.1 and two subclones derived from it adoptively transferred protection to athymic nude mice infected with Plasmodium chabaudi adami, a murine malarial parasite known to be recognized by protective thymus-dependent immune mechanisms. The protective T cell clone displayed a L3T4+, Lyt-2- surface phenotype and secreted both IFN-gamma and IL-2 after stimulation with solubilized parasites in vitro. This is the first report of results demonstrating a cloned T cell line capable of providing adoptive protection against malaria in vivo. More importantly, CTR2.1 and other protective T cell clones may provide for the identification of plasmodial antigenic epitopes recognized by important cell-mediated immune mechanisms during acute malarial infection.
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PMID:Adoptive protection against Plasmodium chabaudi adami malaria in athymic nude mice by a cloned T cell line. 312 38


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