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)

The electrophoretic and immunological techniques typically used to detect potentially useful biopharmaceutical proteins are sensitive with detection limits in the nanogram range. However, quantitation of a recombinant protein can be cumbersome, and involve large numbers of samples throughout process optimization schemes. Although electrophoretic methods (i.e., SDS-PAGE and Western blots) now avail themselves to quantitation by densitometry, these techniques are time consuming because of the lack of appropriate automated systems. Biological activity assays, when available, often require relatively pure material and are not suitable for analyzing and quantitating impure or semi-purified samples, typical of the fermentation milieu. The optimization of several rDNA-derived protein systems from both prokaryotic and eukaryotic hosts has been completed using PCFIA, a rapid, sensitive system with high throughput. The development of Particle Concentration Fluorescence Immunoassay (CFIA) procedures for several of these rDNA-derived proteins of interest as potential biopharmaceuticals (e.g., alpha-1-antitrypsin, tPA, soluble CD4, and a malaria vaccine candidate) are discussed.
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PMID:The use of particle concentration fluorescence immunoassay technology for the analysis of rDNA products. 136 91

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

The induction of immunity by irradiated sporozoites has been a bench-mark of immunological protection against the malaria parasite. Herein we confirm that different mouse strains exhibit different susceptibilities to sporozoite-induced infection of Plasmodium berghei. We note, however, that after hepatic schizogony, early parasite growth in the blood demonstrates no strain preference between C57BL/6 and BALB/c mice. Sporozoite-susceptible C57BL/6 mice, although initially protected by irradiated sporozoite immunisation against a challenge of 10(3) live sporozoites, progressively lose this protection; a challenge with fewer sporozoites 2 months later elicits a blood infection. BALB/c mice treated in parallel remain protected. Analysis of the kinetics of blood parasitaemia (a measure of hepatic schizont burden) with waning protection shows clearly that immunocompetence remains, as indicated by a reduction in the effective exo-erythrocytic schizont load. This immunocompetence can be shown to be absolutely protective, given an appropriately low dose of viable infective sporozoites. We discuss the testable proposition that this elicitation of protective memory is a consequence either of 'unsaturated' threshold levels of recirculating immunoeffector CD8+ cells or of CD4 cell activation by nonviable sporozoites.
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PMID:Immunoprotection in mice susceptible to waning memory against the pre-erythrocytic stages of malaria after validated immunisation with irradiated sporozoites of Plasmodium berghei. 149 22

A major goal of current candidate malaria vaccines is to stimulate the expansion of clones of malaria-specific lymphocytes. We have examined the in vitro T cell responses of a group of malaria exposed and non-exposed adult Caucasian donors to recombinant circumsporozoite (CS) proteins, one of which is undergoing clinical trials, to blood-stage parasites, and to synthetic peptides copying the CS protein and defined blood-stage proteins. In nearly all individuals tested, CD4 T cell proliferation or lymphokine production occurred in response to whole parasite or CS protein stimulation, and T cells from many individuals responded to synthetic peptides. T cell responses were major histocompatibility complex-restricted, and stimulation of T cells with malaria parasites or CS protein did not appear to expand a population of T cell receptor gamma/delta cells. Malaria-specific responses were independent of prior malaria exposure, and in some cases exceeded the magnitude of response to tetanus toxoid. Specific T cells are present in high frequency in the peripheral blood of many donors who have never been exposed to malaria. Although malaria-specific CD4 T cells play an important role in immunity, these data question whether vaccines need to stimulate such cells, and focus attention on other aspects of malaria immunity which may be more critical to a successful vaccine.
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PMID:High frequency of malaria-specific T cells in non-exposed humans. 154 14

A two-phase study was initiated to delineate the peripheral blood lymphocyte populations present in owl monkeys and to correlate those populations with immune response and parasitism during malaria infection. The goal of phase I of the study was to elucidate a monoclonal antibody panel that could be used to characterize peripheral blood mononuclear cell (PBMC) populations with flow cytometric techniques. Forty-two monoclonal antibodies (reported to be reactive with human and macaque lymphocyte antigens) were screened for activity to owl monkey PBMC. Eleven monoclonals were found to react: anti-H42A (MHC Class II DP-like); anti-TH14B (MHC Class II DR-like); and anti-TH81A5 (MHC Class II DQ-like); anti-H58A (MHC Class I); anti-DH59B (granulocyte and monocyte); anti-B1 (B cell); anti-T4 (CD4); anti-Leu3a (CD4); anti-Leu11a (CD16); anti-60.3 (CD18); and anti-OKM1 (NK and monocyte). In a preliminary retrospective study correlating antibody titers, parasitemia values, and MHC Class I and Class II marker profiles on PBMC to test antigens used in malaria vaccine trials, a significant negative association was observed between cells bearing MHC Class II molecules and the other elements of the comparison. In summary, an appropriate panel of monoclonal antibodies has been identified for characterizing PBMC in owl monkeys, and preliminary studies indicate a possible association between clinical outcome and expressed phenotypic PBMC markers.
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PMID:Immunophenotypic characterization of owl monkey peripheral blood mononuclear cells. 162 63

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

Mice can be immunized to Plasmodium vinckei by repeated infections followed by cure. Such immunity is dependent on CD4 T cells and an architecturally modified spleen, but has little requirement for antibody. Thus, athymic mice can be exposed to P. vinckei and cured, but do not develop immunity. They are resistant to challenge with parasites, however, if they are then given spleen cells from euthymic immunized animals. Such immune spleen cells, however, cannot transfer resistance to normal mice which have been exposed to BCG, Salmonella typhimurium, or vaccinia virus, and are only partially effective in transferring resistance to mice which have been previously immunized with heterologous plasmodia, P. yoelii, P. chabaudi and P. berghei. Mice exposed to varying numbers of irradiated P. vinckei-pRBC do not develop immunity and nor are such animals protected following adoptive transfer of immune spleen cells. Cellular immunity to malaria may not only be dependent on a population of immune CD4 T cells, but may require a specifically architecturally modified spleen which may not occur following either exposure to candidate vaccine vectors, heterologous plasmodia or non-viable homologous plasmodia.
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PMID:Inability of Plasmodium vinckei-immune spleen cells to transfer protection to recipient mice exposed to vaccine 'vectors' or heterologous species of plasmodium. 168 80

After reminding the epidemiology of the HTLV1 infection the authors sum up the actually recommended diagnosis procedure. --Case finding by ELISA, confirmation by WESTERN-BLOT and/or RIPA (anti-gag and anti-env specificities), or even PCR which makes specific diagnosis of HTLV1/2. --Or if possible directly by PCR which has helped some authors to find provirus in seronegative people. Coinfections caused by HIV and by Strongyloides are the best documented. As a rule, HTLV1 seems to have rather a worsening effect on evolutiveness and on seriousness of the clinical picture caused by mixed infections, than the contrary (possibly for lack of experience and owing to slow evolution of HTLV1 pathology). Several mechanisms have been proposed concerning coinfections with HTLV1 and HIV (in vitro studies). --Immortalization of CD4 lymphocytes infected with HTLV1 by stimulating both IL2 and its receptor, and by activating lymphocytes with translocation of the replicating factor NF k B in the nucleus, on a promoting sequence of HIV-LTR by stimulating its replication. --The product of HTLV1 tax gene would also have a transactivating effect on the provirus HIV-LTR replication. And finally infection with HTLV1 may facilitate HIV by inducing CD4, molecule expression in non-expressing cells. In Strongyloides modulating effects of HTLV1 on the immune response would facilitate and predispose Strongyloides stercoralis multiplication. As far as other coinfections are concerned (caused by viruses, by parasites: such as malaria, filariasis, trypanosomiasis or by bacteria), epidemiological convergence (risk factors, and geographic distribution) on the one hand, and immunological dysregulation induced by the other, on the other hand, would be of varying importance. In conclusion, these data ask more questions than they answer. But it seems to be established that detection of HIV and Strongyloides should performed in every case HTLV1 carries and vice versa.
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PMID:[HTLV1 and coinfections]. 180 Aug 78

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


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