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)

Specific CD8(-) T-lymphocyte (CTL) activity against Plasmodium pre-erythrocytic stages (P-ES) derived antigens is considered one of the most important mechanisms for malaria protection. Plasmodium vivax is the second most prevalent human malaria parasite species distributed worldwide. Although several CTL epitopes have been identified in Plasmodium falciparum P-ES derived antigens, none has been described for P. vivax to date. In this study, we analysed HLA-A*0201 specific CD8(-) T-lymphocyte responses to the P. vivax circumsporozoite (CS) protein in both malaria exposed and non-exposed populations from the Colombian Pacific Coast. First, we analysed the prevalence of HLA-A2 allele in the study populations and found that approximately 38 of the individuals expressed this molecule and that 50 of them were HLA-A*0201. We then selected, on the P. vivax CS, five peptide sequences containing the HLA-A*0201 binding motifs and used the corresponding synthetic peptides to evaluate the CD8(-) T-lymphocyte interferon (IFN)-gamma response. Peripheral blood mononuclear cells from the HLA-A*0201 donors were in vitro stimulated with these peptides and IFN-gamma production was determined by an ELISPOT assay. Specific CD8(-) T-lymphocyte responses were detected for three peptides located in the C-terminal region of the protein. Specific responses to these peptides were also detected in several individuals expressing different HLA-A*02 subtypes. The potential of these peptides to induce specific cytolysis and that of long synthetic peptides comprising these epitopes as P. vivax malaria vaccine subunits are being studied.
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PMID:Identification of HLA-A2 restricted CD8(+) T-lymphocyte responses to Plasmodium vivax circumsporozoite protein in individuals naturally exposed to malaria. 1207 50

Malaria sporozoites induce swift activation of antigen-specific CD8(+) T cells that inhibit the intracellular development of liver-stage parasites. The length of time of functional in vivo antigen presentation, estimated by monitoring the activation of antigen-specific CD8(+) T cells, is of short duration, with maximum T cell activation occurring within the first 8 h after immunization and lasting approximately 48 h. Although the magnitude of the CD8(+) T cell response closely correlates with the number of parasites used for immunization, increasing the time of antigen presentation by daily immunizations does not enhance the magnitude of this response. Thus, once a primary clonal burst is established, the CD8(+) T cell response becomes refractory or unresponsive to further antigenic stimulation. These findings strongly suggest that the most efficient strategy for the induction of primary CD8(+) T cell responses is the delivery of a maximal amount of antigen in a single dose, thereby ensuring a clonal burst that involves the largest number of precursors to become memory cells.
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PMID:Short-term antigen presentation and single clonal burst limit the magnitude of the CD8(+) T cell responses to malaria liver stages. 1218 51

Fifty subjects living in a malaria endemic area were studied at diagnosis of a Plasmodium falciparum attack and 3 weeks later. Absolute numbers of CD3(+), CD4(+) and CD8(+) lymphocytes as well as plasma cytokines and secreted cytokines after in vitro mitogenic stimulation were measured. At enrollment, lymphopenia was observed, lending support to the reallocation hypothesis during the acute phase. A significant elevation of the number of CD8(+) cells was present in the peripheral blood during the recovery phase. During the acute phase, plasma IL-6 levels peaked while in vitro production capacity was high at both phases. Plasma IL-6 concentrations were positively related to blood parasite density at D0, as IL-4 and IFN-gamma, suggesting an early intervention of these cytokines. Plasma IL-2 levels were low at diagnosis although cells retained their ability to produce IL-2, which was found more frequently in plasma after cure. Acquisition of immunity with age was in relation with greater secretion abilities of cells for type 1 and type 2 cytokines during the parasite clearance phase. We conclude to an early implication of type 2 cytokines and IFN-gamma, with particularly high levels of IL-6.
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PMID:Plasma and in vitro levels of cytokines during and after a Plasmodium falciparum malaria attack in Gabon. 1220 92

Cytokines regulate cellular immune activity and are produced by a variety of cells, especially lymphocytes, monocytes, and macrophages. Multiparameter flow cytometry is often used to examine cell-specific cytokine production after in vitro phorbol 12-myristate 13-acetate and ionomycin induction, with brefeldin A or other agents added to inhibit protein secretion. Spontaneous ex vivo production reportedly rarely occurs. We examined the spontaneous production of interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) by peripheral-blood B lymphocytes, T cells, CD8(-) T cells, CD8(+) T cells, CD3(-) CD16/56(+) lymphocytes (natural killer [NK] cells), CD3(+) CD16/56(+) lymphocytes (natural T [NT] cells), and/or monocytes of 316 acutely ill hospitalized persons and 62 healthy adults in Malawi, Africa. We also evaluated the relationship between spontaneous and induced cytokine production. In patients, spontaneous TNF-alpha production occurred most frequently, followed in descending order by IFN-gamma, IL-8, IL-4, IL-10, IL-6, and IL-2. Various cells of 60 patients spontaneously produced TNF-alpha; for 12 of these patients, TNF-alpha was the only cytokine produced spontaneously. Spontaneous cytokine production was most frequent in the immunoregulatory cells, NK and NT. For IL-2, IL-4, IL-6, IL-8, and IL-10, spontaneous cytokine production was associated with greater induced production. For TNF-alpha and IFN-gamma, the relationships varied by cell type. For healthy adults, IL-6 was the cytokine most often produced spontaneously. Spontaneous cytokine production was not unusual in these acutely ill and healthy persons living in an area where human immunodeficiency virus, mycobacterial, malaria, and assorted parasitic infections are endemic. In such populations, spontaneous, as well as induced, cell-specific cytokine production should be measured and evaluated in relation to various disease states.
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PMID:Spontaneous cytokine production and its effect on induced production. 1220 58

People in Asia often use a medicinal plant, bitter melon (Mamordica charantia), to treat various diseases (e.g., malaria). It has anti-viral, anti-tumor, and immune system boosting properties. Some Asians, especially Filipinos, eat bitter melon. They believe that bitter melon cleanses the blood and boosts the immune system. Rural Filipino midwives place a strong bitter melon extract in a newborn's mouth to activate the immune system. An HIV-infected man in California uses bitter melon therapy. Bitter melon therapy can be prepared by extracting juices from fresh leaves and fruits and adding purified water to the extract to control the potency. Another preparation involves bringing two pounds of leaves and fruits in a gallon of purified water to a boil, allowing it to simmer for five minutes, filtering the decoction in a sterile strainer, and storing it in the refrigerator. The therapy can be administered either orally or via the rectum. The HIV-infected California man drank 10 ounces of the juices or a combination of juices and decoction each day for five days a week during the first year. He then switched to rectal retention enema due to the bad taste. He increased the dosage to 16 ounces/day and the duration to seven days a week. He held an inserted enema bag or rectal syringe until the juices/decoction had been absorbed. Sometimes he would infuse most of the therapy two times a day. Within seven days of rectal retention enema delivery of the bitter melon therapy, his energy level increased rapidly and his physical stamina and appetite improved. One year after therapy began, his CD4 count increased greatly. Later, his CD4/CD8 ratios had returned to normal. He no longer experiences acute sinusitis or recurrent respiratory infections. He has had no serious side effects.
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PMID:Bitter melon therapy: an experimental treatment of HIV infection. 1234 31

Human immunodeficiency virus (HIV) infection is the primary cause of morbidity and mortality in Malawi, Africa, because of its many effects on the immune system. Immune cells communicate through cytokines; therefore, we examined the relationships between HIV serostatus and cell-specific cytokine production for 40 asymptomatic, employed adults and 312 acutely ill, hospitalized patients in Malawi. We also measured the plasma HIV-1 RNA levels of 13 asymptomatic persons and 83 patients found to be HIV(+). We incubated peripheral whole blood with brefeldin-A +/- phorbol 12-myristate 13-acetate and ionomycin and then permeabilized, fixed, fluorescently stained, and examined the mononuclear cells with four-color, six-parameter flow cytometry. The percentage of lymphocytes expressing CD4 did not differ significantly between the HIV(+) and HIV(-) healthy adults (medians, 35.2 vs. 40.8%, respectively), but a wide array of cytokine parameters were lower in the HIV(+) than in the HIV(-) asymptomatic persons, for example, median percentages of T cells producing induced interleukin 2 (IL-2) (8.7 vs. 16.5%, respectively) and spontaneously producing IL-6 (0.7 vs. 11.0%, respectively). Also, four T cell parameters reflecting type 2-to-type 1 cytokine balances (T2/T1) were higher in the HIV(+), versus HIV(-), asymptomatic persons. Unlike the healthy adults, for patients with mycobacteremia/fungemia or malaria, the HIV(+) patients had higher median percentages of T cells and CD8(+) T cells producing induced interferon gamma than did the HIV(-) PATIENTS: For both asymptomatic and acutely ill persons, HIV-1 plasma levels were positively correlated with T2/T1 parameters. Cell-specific cytokine effects of HIV infection may precede measurable effects on CD4 expression. Cytokine therapies, even beyond periodic administration of IL-2, may improve the responses of HIV-infected persons to both HIV and coinfections.
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PMID:Peripheral blood cell-specific cytokines in persons with untreated HIV infection in Malawi, Africa. 1248 8

Experimental cerebral malaria (ECM) resulting from Plasmodium berghei ANKA infection involves T lymphocytes. However, the mechanisms of T cell-mediated pathogenesis remain unknown. We found that, in contrast to ECM-susceptible C57BL6 mice, perforin-deficient (PFP-KO) mice were resistant to ECM in the absence of brain lesions, whereas cytoadherence of parasitized erythrocytes and massive accumulation of activated/effector CD8 lymphocytes were observed in both groups of mice. ECM is induced in PFP-KO mice after adoptive transfer of cytotoxic CD8+ cells from infected C57BL6 mice, which were directed to the brain of PFP-KO mice. This specific recruitment might involve chemokine/chemokine receptors, since their expression was up-regulated on activated CD8 cells, and susceptibility to ECM was delayed in CCR5-KO mice. Thus, lymphocyte cytotoxicity and cell trafficking are key players in ECM pathogenesis.
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PMID:Perforin-dependent brain-infiltrating cytotoxic CD8+ T lymphocytes mediate experimental cerebral malaria pathogenesis. 1257 96

T cells from different subsets play a major role in protective immunity against pre-erythrocytic stages of malaria parasites. Exposure of humans and animals to malaria sporozoites induces (alphabeta CD8(+) and CD4(+) T cells specific for antigens expressed in pre-erythrocytic stages of Plasmodium. These T cells inhibit parasite development in the liver, and immunization with subunit vaccines expressing the respective antigenic moieties confers protection against sporozoite challenge. gammadelta and natural killer T cells can also play a role in protective immunity. Recent studies with mice transgenic for the alphabeta T-cell receptor have revealed the existence of complex mechanisms regulating the induction and development of these responses.
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PMID:T cells as mediators of protective immunity against liver stages of Plasmodium. 1258 77

Cell-mediated immunity plays a crucial role in the control of many infectious diseases, necessitating the need for adjuvants that can augment cellular immune responses elicited by vaccines. It is well established that protection against one such disease, malaria, requires strong CD8(+) T cell responses targeted against the liver stages of the causative agent, Plasmodium spp. In this report we show that the dendritic cell-specific chemokine, dendritic cell-derived CC chemokine 1 (DC-CK1), which is produced in humans and acts on naive lymphocytes, can enhance Ag-specific CD8(+) T cell responses when coadministered with either irradiated Plasmodium yoelii sporozoites or a recombinant adenovirus expressing the P. yoelii circumsporozoite protein in mice. We further show that these enhanced T cell responses result in increased protection to malaria in immunized mice challenged with live P. yoelii sporozoites, revealing an adjuvant activity for DC-CK1. DC-CK1 appears to act preferentially on naive mouse lymphocytes, and its adjuvant effect requires IL-12, but not IFN-gamma or CD40. Overall, our results show for the first time an in vivo role for DC-CK1 in the establishment of primary T cell responses and indicate the potential of this chemokine as an adjuvant for vaccines against malaria as well as other diseases in which cellular immune responses are important.
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PMID:The dendritic cell-specific chemokine, dendritic cell-derived CC chemokine 1, enhances protective cell-mediated immunity to murine malaria. 1262 78

The occurrence and intensity of lymphocyte apoptosis in blood samples from 79 outclinic patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria and 30 healthy individuals were investigated. No difference in apoptosis percentages was detected between healthy individuals and malaria patients when ex vivo lymphocytes were analyzed. However, significantly increased apoptosis levels were observed in lymphocytes from both P. falciparum- and P. vivax-infected patients when the cells were cultured for 24 h. CD4(+)and CD8(+) T cells were affected to a comparable extent in P.falciparum- and P.vivax-infected patients. However, when we compared apoptosis values in infected and non-infected individuals it appeared that CD4(+) T cells were more susceptible than CD8(+) T cells. A significant increase in the sIL-2R plasma levels was observed in malaria patients when compared with healthy individuals and a positive correlation was observed between sIL-2R levels and apoptosis rates in infected patients presenting increased rates of apoptosis. An increased expression of Fas antigen was recorded after stimulation with P. falciparum antigen or anti-CD3 monoclonal antibody. These data show that a consistent proportion of the lymphocyte population dies by apoptosis during a malaria infection and that a period of time is necessary before in vivo activated cells can express the apoptotic process in vitro.
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PMID:Malaria associated apoptosis is not significantly correlated with either parasitemia or the number of previous malaria attacks. 1274 99


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