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)

PBL from individuals with no history of malaria exposure, as well as cord blood lymphocytes, were tested for proliferation to T cell epitopes from the malaria circumsporozoite proteins of Plasmodium falciparum and Plasmodium vivax. Cells from many individuals proliferated in response to these peptides, but for two peptides (P. vivax317-336 and P. falciparum CS331-350) the response rate ranged from 64 to 93%, with the specific stimulation indices reaching as high as 38. The phenotype of the cells responding to PfCS331-350 was predominantly CD4+,CD8-,CD45Ra+,CD45Ro-, which was the inverse of the phenotype of the cells responding to tetanus toxoid with respect to CD45 isoforms. T cell clones from different individuals specific for PfCS331-350 were restricted by at least four different HLA-DR molecules and there was no evidence that the peptide was a "superantigen." Overlapping peptides were used to demonstrate that clones had different fine specificities although the peptide specificities of the DR4-restricted and DR11-restricted clones were similar. Although the individuals tested here have had no history of malaria exposure, these data demonstrate that they have T cells specific for malaria sequences present in high frequency that proliferate as intensely as some memory responses. Although one clone from an individual with a history of BCG vaccination did react strongly with PPD, the phenotype of these cells suggests that they are not classical memory cells for a cross-reactive recall Ag. Such cells may affect the induction or expression of malaria immunity.
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PMID:Promiscuous malaria peptide epitope stimulates CD45Ra T cells from peripheral blood of nonexposed donors. 137 May 23

CTL lines specific for two different proteins derived from the human pathogens, Plasmodium falciparum (malaria) circumsporozoite protein and HIV-1 reverse transcriptase, were obtained by immunizing mice with protein-pulsed syngeneic spleen cells. The lysis of the target cells was dependent on a class I MHC molecule and the accessory molecule CD8. Immunodominant epitopic peptides were identified previously in the two proteins using murine CTL derived after immunization with recombinant virus or sporozoites, or using CTL from HIV-1-infected patients. These peptides were also recognized by the CTL lines obtained after protein-pulsed spleen-cell immunization. A new CTL antigenic determinant was localized in HIV-1 reverse transcriptase to residues 514 to 528, a sequence that, if folded as an alpha-helix, would be strongly amphipathic. The determinant was tentatively narrowed, using overlapping peptides, to a core of at least nine residues, 515 to 523. This site was also recognized by CTL obtained by the two different methods of immunization. Therefore, extracellular proteins incubated with spleen cells can be processed and presented in vivo in the same way as intracellular proteins, resulting in recognition of the same epitopes in association with the same class I MHC molecules. The potential implications for vaccine development and for the understanding of class I-restricted Ag presentation are discussed.
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PMID:Immunization with soluble protein-pulsed spleen cells induces class I-restricted cytotoxic T lymphocytes that recognize immunodominant epitopic peptides from Plasmodium falciparum and HIV-1. 138 39

Inbred strains of mice were immunized with p190-3, a 38-kDa recombinant protein derived from p190, a major merozoite surface Ag of the malaria parasite Plasmodium falciparum. Ag-specific proliferative T cell responses were obtained in H-2b, H-2d, and H-2k mouse strains. Surprisingly, mice of the H-2b haplotype (e.g., C57BL/6) did not give a measurable antibody response to the recombinant protein administered in Freund's adjuvant, but CD8+/CD4- as well as CD4+/CD8- T cells specific for p190-3 could be obtained after in vivo priming and in vitro selection with Ag. Distinct epitopes of p190-3 recognized by the CD8+ and CD4+ T cells from C57BL/6 mice were identified. The CD8+ T cells could kill H-2b APC in the presence of the appropriate epitope-containing peptide. The p190-3-specific CD4+ cells isolated from C57BL/6 mice were of the Th1 type. In contrast, Th2 cells, but no CD8+ T cells were present in a p190-3-specific line from BALB/c mice, which give good antibody responses to p190-3.
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PMID:A recombinant malaria protein that can induce Th1 and CD8+ T cell responses without antibody formation. 138 40

It is now generally accepted that peripheral blood of humans not exposed previously to malaria contains T cells which proliferate vigorously in response to malaria parasites and antigens. Although it has been claimed that these cells express a memory phenotype, their origin is uncertain. We have examined the phenotype and immunological responses of such cells. We confirm that these cells do express the 'memory phenotype', CD45Ro, in that depletion of such cells, but not of CD45Ra (virgin) cells, abrogates the immune response to malaria parasites. In an effort to define the genesis of these responses, numerous malaria-specific T cell clones have been generated from non-exposed individuals. These were tested for reactivity to a large panel of common bacterial, viral, and fungal pathogenic and non-pathogenic organisms. Most clones proliferated vigorously in response to one or more such organisms, while many clones demonstrated smaller but significant degrees of proliferation in response to many different organisms. Our data offers insights into the maintenance of immunological memory. All clones examined were CD3+, CD4+, CD8-, TCR alpha beta+, and TCR delta-. The ratio of TCR alpha beta+ to TCR delta+ cells among peripheral blood lymphocytes increased during polyclonal culture in the presence of parasite. The high frequency of such cells in peripheral blood (1/800-1/9000), and their response to a wide range of geographically different Plasmodium falciparum isolates and clones by both proliferation and lymphokine secretion (predominantly IFN-gamma) with a high degree of sensitivity (less than 1 parasite/microliters blood in some cases) suggests that these cells must be quickly activated following malaria infection. Their contribution to the outcome of the disease (protection/immunopathology) may be significant.
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PMID:'Natural' T cells responsive to malaria: evidence implicating immunological cross-reactivity in the maintenance of TCR alpha beta+ malaria-specific responses from non-exposed donors. 139 Apr 41

Clone B is a cytotoxic T cell clone induced by immunization with Plasmodium yoelii sporozoites which recognizes an epitope on both the P. yoelii and Plasmodium berghei circumsporozoite proteins. It is CD8, uses the V beta 8.1 TCR, and is Kd restricted. When adoptively transferred, it protects mice against infection by both species of malaria sporozoites, and this protection is dependent on IFN-gamma. Clone B cells are more broadly reactive and protective than previously described murine T cell clones against malaria. Clone B may be an important model for immune protection against the spectrum of variant parasites in nature.
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PMID:A T cell clone directed at the circumsporozoite protein which protects mice against both Plasmodium yoelii and Plasmodium berghei. 151 74

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

By using a specific, repetitive DNA probe, we have been able to detect picograms of P. berghei DNA. With this probe we have determined that: a) P. berghei, inoculated into Norway Brown rats, reaches its peak of proliferation in the liver 44 h after infection; b) gamma interferon inhibits in a dose-dependent fashion the development of liver exoerythrocytic forms (EEF) in vivo and in vitro, and; c) endogenous gamma interferon inhibits the development of EEF in hosts immunized with irradiated sporozoites. Related with and derived from these findings, we have found that, in order to obtain an effective immunity against malaria in experimental animal models, effector mechanisms mediated by T cells are required. This is substantiated by the following facts: a) immune hosts inoculated with monoclonal antibodies against gamma interferon reversed their immunity against a sporozoite challenge; b) This immunity was also reversed when the animals were depleted from their CD8 positive cytotoxic T cells. Therefore, sterile immunity against this parasite requires not only the presence of antibodies but also the inhibition of the EEF by gamma interferon with participation of CD8 positive T cells.
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PMID:[Use a of DNA probe to detect cellular immunity against intracellular parasitism]. 172 69

In the present study, the contribution of CD4+ and CD8+ T lymphocytes to acquired immunity to blood-stage infection with the murine malaria species Plasmodium chabaudi AS was investigated. C57BL/6 mice, which are genetically resistant to infection with this hemoprotozoan parasite and exhibit a transient course of infection, were treated intraperitoneally with monoclonal antibodies to T-cell epitopes, either anti-Thy-1, anti-CD4, or anti-CD8. After intraperitoneal infection with 10(6) parasitized erythrocytes, control C57BL/6 mice exhibited a peak parasitemia on day 9 of approximately 35% parasitized erythrocytes and eliminated the infection within 4 weeks. Mice depleted of Thy-1+ or CD4+ T cells had significantly higher parasitemias on day 7 as well as significantly higher peak parasitemias. These mice were unable to control the infection and developed a persistent, high parasitemia that fluctuated between 40 and 60% until the experiment was terminated on day 56 postinfection. Depletion of CD8+ T lymphocytes was found to have no effect on the early course of parasitemia or on the level of peak parasitemia. However, mice depleted of CD8+ T cells experienced two recurrent bouts of parasitemia during the later stage of the infection and required more than 5 weeks to eliminate the parasites. After the peak parasitemia, which occurred in control and experimental animals on day 9, there was a sharp drop in parasitemia coinciding with a wave of reticulocytosis. Therefore, the contribution of the influx of reticulocytes, which are not the preferred host cell of this hemoprotozoan parasite, to limiting the parasitemia was also examined by determining the course of reticulocytosis during infection in control and T cell-depleted animals. Early in infection, there was a marked and comparable reticulocytosis in the peripheral blood of control and T cell-depleted mice; the reticulocytosis peaked on day 12 and coincided with the dramatic and sudden reduction in parasitemia occurring in all groups. In both control and CD8-depleted mice the percentage of reticulocytes decreased as the infection was resolved, whereas in CD4-depleted mice marked reticulocytosis correlated with high, persistent parasitemia. These results thus demonstrate that both CD4+ and CD8+ T cells are involved in acquired immunity to blood-stage P. chabaudi AS and that the influx of reticulocytes into the blood that occurs just after the peak parasitemia may contribute temporarily to limiting the parasitemia.
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PMID:CD4+ and CD8+ T lymphocytes both contribute to acquired immunity to blood-stage Plasmodium chabaudi AS. 189 2

The malaria parasite, Plasmodium yoelii 17X, causes a self-limited, nonlethal infection characterized, in the blood stage, by preferential invasion of reticulocytes. Previous studies have suggested that immunity to the blood stage infection may be related to enhanced levels of class I MHC Ag on the parasitized reticulocyte surface and can be adoptively transferred to immunodeficient mice by immune CD8+ T cells in the absence of CD4+ T cells. To further examine the mechanisms of CD8+ T cell involvement in immunity to blood stage P. yoelii infection, we performed in vivo CD8 depletion and adoptive transfer experiments. Depletion of CD8+ T cells during primary blood stage infection in BALB/c mice did not diminish the ability of the mice to resolve their infections. Spleen cells from immune BALB/c and C57BL/10 mice were transferred to BALB/c-nu/nu and C57BL/10-nu/nu mice, respectively. The recipient mice were CD4 depleted in vivo to kill any transferred CD4+ T cells. The mice failed to control the infection. Populations of CD4-, CD8+ T cells were transferred from immune CBA/CaJ donors to in vivo CD4-depleted CBA/CaJ recipients. The mice were unable to control the infection. Although immune unfractionated spleen cells transferred rapid protection in all three mouse strains and immune CD4+ T cells transferred immunity in the two mouse strains studied, CD8+ T cells by themselves were neither protective nor did they enhance immunity.
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PMID:Adoptive transfer of CD8+ T cells from immune animals does not transfer immunity to blood stage Plasmodium yoelii malaria. 196 71

Children living in hyperendemic malarious regions have high immunoglobulin levels and an increased frequency of Burkitt's lymphoma. In a study of Gambian children which endeavours to explain these findings we showed that acute P. falciparum malaria caused spontaneous activation and growth of their B lymphocytes in vitro. A high proportion of these cells contained Epstein-Barr nuclear antigen (EBNA). In ancillary experiments aimed at explaining these findings. CD4 helper cells from adult donors were destroyed with monoclonal antibody and complement. This manoeuvre resulted in loss of cytotoxic T cell control of their B lymphocytes when infected with Epstein-Barr virus (EBV). In children with acute malaria, both spontaneous immunoglobulin and antibody production by B cells was increased yet CD4 helper cell control over these cells, as measured by responses to pokeweed mitogen, was found to be intact. Spontaneous and concanavalin A-driven lymphocyte proliferation was depressed. We infer from these findings that in patients with P. falciparum malaria loss of cytotoxic T cell control of the EBV in B cells, possibly due to destruction or dysfunction of a subset of CD4 cells responsible for induction of suppressor/cytotoxic CD8 cells, leads to activation and proliferation of foci of B cells containing EBV. The expanded pool and rapid turnover of these cells may increase chances of malignant transformation leading to the genesis of Burkitt's tumor. Partial loss of suppressor mechanisms coupled with normal CD4 helper/inducer activity may result in high serum levels of immunoglobulin which are characteristic of persons living in malarious regions.
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PMID:The effects of Plasmodium falciparum malaria on immune control of B lymphocytes in Gambian children. 197 71


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