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)

We recently reported that parenteral injection of malaria palmitoyl-tailed peptides without adjuvant efficiently induces B, Th and CTL responses. We now show that intranasal (IN) or sub-lingual (SL) delivery of such lipopeptides induces strong systemic immune responses, as demonstrated by specific Th cell responses from the spleen as well as inguinal lymph nodes, and by the production ofhigh levels of serum antibodies. Overall, both types of responses were significantly higher than in parallel experiments in which the same lipopeptides were delivered by the subcutaneous (s.c.) route. Moreover, the mucosal route resulted in the preferential induction of IFN-gamma producing T cells and of IgG2a antibody production, as compared to the dominant IL-4 and IgG1 responses obtained by the s.c. route, thus bringing a distinct advantage in the field of many infectious diseases and allergy. Possibly related to this Th1 response, we found that dendritic cells, the principal immune-competent cells to encounter antigens within mucosal membranes, take up lipopeptide antigens more efficiently than macrophages. Mucosal immunization by lipidated peptides appears therefore as a novel, noninvasive vaccine approach that does not require the use of extraneous adjuvant and which, besides cost-effectiveness, has attractive practical and immunological features.
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PMID:Systemic immune responses induced by mucosal administration of lipopeptides without adjuvant. 1220 40

Alfa-Galactosyl Ceramide was isolated from Ocean sponge which has antitumor effect against several tumors in in vivo animal model with no cytotoxicity. KRN7000(KRN) is the most potent alpha-Galactosyl Ceramide modified from the one isolated from Ocean sponge. KRN is also active against metastatic tumors through the activation ofanimal immune system. Research efforts in learning the mechanism of action, we found the important role of dendritic cells(DC) and NKT cells. NKT cells was first characterized in 1988 which is overlap some part with NK cells and T-Cells and majority is different from NK and T. KRN is active through the activation of DC and NKT in giving antigen specific immune stimulation in animal. This antigen specific stimulation is memorized by immune system and can reject second tumor challenge. KRN is not active in nude mice and NKT deficient animal. NKT cells level in blood is lower in patients with autoimmune disease, cancer, HIV positive or aplastic anemia. NKT rapidly releases IL-4 and IFN-gamma at high level when activated. NKT is CD1d and TCR restricted. NKT plays important role in autoimmune disease such as Type 1 Diabetes, Scleroderma and Systemic Lupus Erythematosus, infections such as Mycobacteria, Listeria and Malaria, GVHD control and tumor rejection. NKT acts as double edge sword, aggressive and suppressive ways. KRN can prevent the onset of Type 1 Diabetes, inhibit replication of hepatitis virus B in liver and suppress malaria replication in activating NKT cells. KRN can activate NKT through DC and activated NKT activates NK, T and macrophage. KRN also expands NKT cells and expanded NKT has full function. Although the exact role of DC and NKT is not clear, KRN clinical study results in conjunction with DC and NKT cell activation are expected.
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PMID:Role of NKT cells and alpha-galactosyl ceramide. 1243 Aug 64

Non-human primates could prove to be suitable models for the study of infectious diseases such as malaria, tuberculosis, and hepatitis; the molecules of their immune systems are in the process of being fully characterized. Due to the relevance of cytokines in the modulation of the immune response, a molecular analysis of these proteins in non-human primates from the Aotus genus was carried out. Peripheral blood mononuclear cells from four species of Aotusmonkey were obtained and their mRNAs for interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-gamma (IFN), and tumor necrosis factor (TNF)-alpha were characterized. This study shows a high degree of conservation between nucleotide and amino acid sequences of cytokines from different Aotus species and those from humans. The TNF-alpha molecules were identical in amino acid sequences for both.
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PMID:Identification, cloning, and sequencing of different cytokine genes in four species of owl monkey. 1246 97

Although there is good evidence that immunity to the blood stages of malaria parasites can be mediated by different effector components of the adaptive immune system, target antigens for a principal component, effector CD4(+) T cells, have never been defined. We generated CD4(+) T cell lines to fractions of native antigens from the blood stages of the rodent parasite, Plasmodium yoelii, and identified fraction-specific T cells that had a Th1 phenotype (producing IL-2, IFN-gamma, and tumor necrosis factor-alpha, but not IL-4, after antigenic stimulation). These T cells could inhibit parasite growth in recipient severe combined immunodeficient mice. N-terminal sequencing of the fraction showed identity with hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT). Recombinant HGXPRT from the human malaria parasite, Plasmodium falciparum, activated the T cells in vitro, and immunization of normal mice with recombinant HGXPRT reduced parasite growth rates in all mice after challenge.
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PMID:The purine salvage enzyme hypoxanthine guanine xanthine phosphoribosyl transferase is a major target antigen for cell-mediated immunity to malaria. 1259 31

P. falciparum malaria is associated with increased activation among peripheral lymphocytes. In the present study, we investigated markers of susceptibility to apoptosis and expression of IFN-gamma and IL-4 by CD28-and CD28+T cells in West African children with acute P. falciparum malaria. The study showed increased susceptibility to apoptosis and cytokine production among T lymphocytes during acute malaria but also that T cells, in particular IFN-gamma producing CD28-T cells, were substantially reduced. These results are in line with previous studies suggesting that certain T cell subsets are sequestered away from the peripheral blood during P. falciparum malaria.
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PMID:Acute P. falciparum malaria induces a loss of CD28- T IFN-gamma producing cells. 1269 5

Human basophils are potent producers of IL-4 following cross-linking of the high affinity receptor for IgE (Fc epsilon R1). Elevated levels of both total- and malaria-specific IgE have been demonstrated in sera from people living in malaria-endemic regions. Whether or not these IgE antibodies are pathogenic is unclear. Serum containing high IgE levels obtained from malaria individuals was used to establish whether IgE-immune complexes could induce IL-4 production in human basophils. The basophils, obtained from healthy donors, were primed with 10 ng/ml of IL-3 before being transferred to wells containing goat anti-human IgE or human antimalarial IgE-immune complexes. IL-4 was induced upon stimulation of human basophils by plate bound IgE-containing immune complexes. Basophils treated similarly but with goat anti-IgG/human antimalarial- IgG-immune complexes did not secrete IL-4. Similarly mononuclear cells depleted of basophils in parallel culture did not secrete IL-4. Thus, human basophils may contribute to the polarization of T-helper type 2 in the (Th2) responses in malaria hosts via IgE-induced IL-4 production.
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PMID:Immunoglobulin E (IgE) containing complexes induce IL-4 production in human basophils: effect on Th1-Th2 balance in malaria. 1271 Nov 3

An important aspect of malaria vaccine development is the identification of an appropriate adjuvant which is both capable of stimulating a protective immune response and safe for use by humans. Here, we investigated the feasibility of using novel immunostimulatory molecules as adjuvants combined with a crude antigen preparation and coadsorbed to aluminum hydroxide (alum) as a vaccine against blood-stage Plasmodium chabaudi AS malaria. Prior to challenge infection, immunization of genetically susceptible A/J mice with the combination of malaria antigen plus recombinant interleukin-12 (IL-12) in alum induced a Th1 immune response with production of high levels of gamma interferon (IFN-gamma) and diminished IL-4 levels by spleen cells stimulated in vitro with parasite antigen compared to mice immunized with antigen alone, antigen in alum, or antigen plus IL-12. Mice immunized with malaria antigen plus recombinant IL-12 in alum had high levels of total malaria-specific antibody and immunoglobulin G2a. Compared to unimmunized mice, immunization with antigen plus IL-12 in alum induced the highest level of protective immunity against challenge infection with P. chabaudi AS, which was evident as a significantly decreased peak parasitemia level and 100% survival. Protective immunity was dependent on CD4(+) T cells, IFN-gamma, and B cells and was long-lasting. Replacement of IL-12 as an adjuvant by synthetic oligodeoxynucleotides (ODN) containing CpG motifs induced a similar level of vaccine-induced protection against challenge infection with P. chabaudi AS. These results illustrate that it is possible to enhance the potency of a crude malaria antigen preparation delivered in alum by inclusion of immunostimulatory molecules, such as IL-12 or CpG-ODN.
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PMID:Vaccination with novel immunostimulatory adjuvants against blood-stage malaria in mice. 1293 62

CD1d-restricted NKT cells are a novel T cell lineage with unusual features. They co-express some NK cell receptors and recognize glycolipid antigens through an invariant T cell receptor (TCR) in the context of CD1d molecules. Upon activation through the TCR, NKT cells produce large amounts of IFN-gamma and IL-4. It has been proposed that rapid cytokine output by activated NKT cells may induce bystander activation of other lymphoid lineages. The impact of CD1d-restricted NKT cell activation in the induction of B cell-mediated immune responses to infection is still unclear. We show here that CD1-restricted NKT cells contribute to malarial splenomegaly associated with expansion of the splenic B cell pool and enhance parasite-specific antibody formation in response to Plasmodium berghei infection. The increased B cell-mediated response correlates with the ability of NKT cells to promote Th2 immune responses. Additionally, antibody responses against the glycosylphosphatidylinositol (GPI)-anchored protein merozoite surface protein 1 (MSP-1) were found to be significantly lower in CD1(-/-) mice compared to wild-type animals. P. berghei-infected MHC class II (MHCII)(-/-) mice also generated antibodies against MSP-1, suggesting that antibody production against GPI-anchored antigens in response to malaria infection can arise from both MHCII-dependent and independent pathways.
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PMID:CD1d-restricted NKT cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses. 1293 35

Plasmodium yoelli sporozoite surface protein 2 (pySSP2) is considered as an important antigen for protection studies in malaria vaccine development. For the liver stage protection, anti-pySSP2 cytotoxic T lymphocyte (CTL) activity in BALB/c mice was investigated by immunization of genetically engineered bone marrow-derived dendritic cells (DCs) expressing pySSP2 peptides. Retrovirus-transfected bone marrow cells cultured with GMCSF and IL-4 for 7 days demonstrated 70-80% of DCs with high CD11c, CD80, CD86, and MHC class I (I-Kd) expression. Dividing bone marrow cells were infected with retrovirus expressing SSP2 on fifth, sixth, and seventh days of culture by prolonged centrifugation for 1 h at 32 degrees C. Transfection efficacy of DCs was assessed using retrovirus-shuttled green fluorescence vector (pMSCV-EGFP neo). A total of 64% of CD11c positive transfected DCs showed green fluorescence. The degree of SSP2 expression in transfected DCs was assessed by immunoprecipitation with SSP2 antibody. Both SSP2 and EGFP transfected DCs had prolonged expression of the engineered gene until day 6 since the transfection. Antigen presentation to nai;ve CTLs was assessed by immunization of retrovirus-infected DCs into BALB/c mice. Kd restricted, antigen-specific two new MHC class I (I-Kd) binding motifs were identified (A and C) in pySSP2 protein. Both A and C induced peptide-specific, IFN-gamma-secreting cytolytic CTLs upon antigen recognition on target cells. Taken together, these data indicate that genetically modified DCs by prolonged centrifugation is effective in enhanced antigen presentation. Immunization of DCs encoding SSP2 gene resulted in identification of two K(d) restricted CTL epitopes and induction of IFN-gamma-secreting cytolytic CD8+ T cells.
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PMID:Immunization of retrovirus-transfected dendritic cells induces specific cytotoxic T lymphocytes for two distinct malarial peptides presented by Kd molecule. 1294 36

The choice of the host in studying host-parasite interactions is of crucial importance, and the use of a natural host is most appropriate in answering pertinent questions related to human malaria. The Grammomys surdaster is the natural host and reservoir of the rodent malaria parasite Plasmodium berghei. This natural host is difficult to protect by irradiated sporozoite immunization, a situation comparable to what has been observed in humans with P. falciparum. This is in contrast to the complete protection that can be induced in artificial hosts like inbred mice strains. The natural host is highly susceptible to P. berghei hepatic stage infections. Immunization with irradiated sporozoites in Grammomys generates blocked hepatic stage parasites and immunized Grammomys protected upon live sporozoite challenge generate antibody and T cell proliferative responses to these hepatic stages. Associated with proliferation, cytokines are secreted into culture supernatants constituted mainly of Interferon gamma, negligible amounts of TNF-alpha, and no IL-4. Natural host-parasite interactions of Grammomys surdaster-P. berghei can help define the effector mechanism(s) in the Plasmodium falciparum-human interaction.
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PMID:Rodent malaria in the natural host--irradiated sporozoites of Plasmodium berghei induce liver-stage specific immune responses in the natural host Grammomys surdaster and protect immunized Grammomys against P. berghei sporozoite challenge. 1451 35


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