Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both antibody-dependent and antibody-independent mechanisms are involved in immune protection against the asexual blood stages of the malaria parasite. It is well established that T cells play a crucial role in both induction and maintenance of this immunity. Of the two T-cell subsets (CD4+, CD8+) carrying alpha/beta T-cell receptors, the CD4+ T cells are of major importance for the development of blood stage immunity in both experimental and human malaria. In mice, CD4+ T cells comprise at least two functionally distinct cell types (TH1, TH2), distinguished on the basis of their lymphokine production. The balance between these subsets is critical for the outcome of an infection. In some rodent malarias, TH1 cells producing IFN-gamma and IL-2 are important for controlling infection in its early phases, while TH2 cells, producing i.a. IL-4 and IL-10, together with antibodies, are important for parasite clearance in later phases of infection. Distinct CD4+ T cells of either TH1 or TH2 type also have regulatory functions in human P. falciparum infection. In contrast to the CD4+ T cells, the role of CD8+ T cells in blood stage infection appears to be limited, but suppression of some CD4+ activities has been reported for both experimental and human malaria. As in other infections, peripheral T cells equipped with gamma/delta receptors are strongly upregulated in malaria and also respond to parasite antigens in vitro by proliferation and lymphokine production. However, the importance of the gamma/delta T cells for protection when compared with pathogenesis is presently unclear. Rapid advances made in recent years in the characterization and cloning of plasmodial antigens eliciting immune protection have made it possible to define some of the antigenic structures involved in T-cell immunity. This, together with an improved understanding of cellular mechanisms, provides some basis for the development of modern malaria vaccines.
 ...
PMID:T-cell control of immunity to the asexual blood stages of the malaria parasite. 770 48

Six murine T cell clones expressing gamma delta TCR were generated from malaria immunized, alpha beta T cell-deficient mice. Phenotypic characterization of these clones has revealed that, in contrast to conventional alpha beta T cells, there is a considerable degree of heterogeneity among these gamma delta clones with regard to their surface markers and their lymphokine profile. One clone was found to display significant anti-parasite activity in vivo upon adoptive transfer. We attempted to determine whether the protective clone differs in one or more key characteristics from the non-protective clones. Although no obvious pattern peculiar to the protective gamma delta clone was observed, it appears that more than one parameter may, in combination, define a distinct protective phenotype, and thus explain the functional difference between the protective and non-protective gamma delta clones.
 ...
PMID:Phenotypic and functional properties of murine gamma delta T cell clones derived from malaria immunized, alpha beta T cell-deficient mice. 872 88

In this study we characterized the CD4+ T cell response directed against two distinct epitopes located in the circumsporozoite (CS) protein of Plasmodium yoelii. The immunization of mice with P. yoelii sporozoites induced CD4+ T cells which were mostly directed against one of these peptides, Py-1, previously reported to contain a CD4+ epitope. The CD4+ T cells directed against this immunodominant epitope were mostly of the Th-1 type. Another newly identified peptide, AS44, induced a specific CD4+ T cell response, which was mainly detectable after immunization with the corresponding peptide. Several CD4+ T cell clones, recognizing this epitope, were generated and their lymphokine expression was characterized, as well as their surface markers and their anti-parasite activity in vivo. It was noteworthy that some of these CD4+ T cell clones, which recognize this cryptic epitope and were of different Th subtypes, were shown to have a strong inhibitory effect on the development of liver stages of malaria parasites.
 ...
PMID:Plasmodium yoelii: peptide immunization induces protective CD4+ T cells against a previously unrecognized cryptic epitope of the circumsporozoite protein. 893 72

The reverse transcriptase-polymerase chain reaction (RT-PCR) was used to amplify selected lymphokine mRNAs from phytohemagglutinin-activated leukocytes of the owl monkey (Aotus trivirgatus). Interleukin-2 (IL-2), IL-4, IL-13, and interferon-gamma were selected as lymphokine mRNAs of interest, since expression of these cytokines helps define the type of T helper lymphocyte response (i.e., TH1 versus TH2). Because sequences for these lymphokine genes were not available for the owl monkey, multiple PCR primers for each lymphokine gene were designed based on published human sequences. Various PCR primer pairs were then used in the RT-PCR to determine the conditions for optimal amplification of each owl monkey cytokine mRNA. In addition, each PCR primer pair was compared for the ability to amplify lymphokine mRNAs from other primate species, including African green (Cercopithecus aethiops), squirrel (Saimiri sciureus), and rhesus (Macaca mulatta) monkeys. The specificity and sensitivity of optimal primer pair was also demonstrated by amplification of as little as 10 fg of each lymphokine gene in a background of 300 ng of irrelevant cDNA. Finally, partial sequences of owl monkey coding regions for IL-2, IL-13, and interferon-gamma were determined and compared for homology with their human counterparts. Together, these studies define specific and sensitive conditions for detection of lymphokine mRNA expression in the owl monkey and provide partial sequence information of the coding region for these lymphokines. This investigation should provide molecular probes to investigate the immune response against malaria and the effectiveness of malaria vaccines in the owl monkey that models this human disease.
 ...
PMID:Reverse transcriptase-polymerase chain reaction amplification and partial sequence of T helper 1- and T helper 2-type lymphokine genes from the owl monkey (Aotus trivirgatus). 912 42

T cells are central to immunity in malaria. CD4+ helper T cells favour the generation of high-affinity antibodies that are effective against blood stages and they are necessary to establish immunological memory. The intrahepatic stage of infection can be eliminated by specific CD8+ cytotoxic T cells (CTL). Cytokines secreted by CD4+ T cells may also contribute to liver stage immunity. Evolution has selected varied mechanisms in pathogens to avoid recognition by T cells. T cells recognize foreign epitopes as complexes with host major histocompatibility (MHC) molecules. Thus, a simple form of evasion is to mutate amino acid residues which allow binding to an MHC allele. Recently, more sophisticated forms of polymorphic evasion have been described. In altered peptide ligand (APL) antagonism, the concurrent presentation of particular closely related epitope variants can prevent memory T cell effector functions such as cytotoxicity, lymphokine production and proliferation. In immune interference, the effect of the concurrent presentation of such related epitope variants can go a step further and prevent the induction of memory T cells from naive precursors. The analysis of immune responses to a protein of P. falciparum, the circumsporozoite protein (CSP), indicates that the malaria parasite may utilize these evasion strategies.
 ...
PMID:Immune evasion in malaria: altered peptide ligands of the circumsporozoite protein. 957 91

The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by lymphocytes was examined in murine malaria. When spleen cells or lymph node cells from P. berghei-infected mice were cultured in vitro with malaria antigen, the GM-CSF production correlated with the incubation time up to 72 hours. When lymphocytes obtained at various days after infection were cultured with the antigen, GM-CSF became detectable as early as 2 days after infection, reached a peak at day 9 and then rapidly decreased. Production of GM-CSF was antigen-specific, and related to the dose of antigen. Treatment of lymphocytes with anti-Thy-1.2 antibody and complement resulted in almost complete loss of GM-CSF-producing activity, while treatment with either anti-CD4 or anti-CD8 antibody and complement resulted in partial loss of GM-CSF-producing activity, indicating that both CD4+ and CD8+ T cells are involved in GM-CSF production in malaria. GM-CSF exhibits glycoprotein nature, and has an apparent molecular weight of 36,000. The molecular properties of this T-cell derived GM-CSF were compared with those of known lymphokine GM-CSF.
 ...
PMID:Granulocyte-macrophage colony-stimulating factor production by T lymphocytes in Plasmodium berghei-infected mice. 965 99

Both antibody dependent and cell mediated mechanisms contribute to immunity in malaria. The parasites vary in sensitivity to antibody mediated inhibition due to underlying antigenic variation. When Plasmodium falciparum isolates are tested with antibodies from the donor originally harbouring the parasites or with those from other donors, growth inhibition is usually lowest in the autologous combinations. Parasites with decreased sensitivity are also generated in vitro by culturing them for prolonged periods in the presence of certain anti-plasmodial antibodies. When the antibodies are removed, a successive return of sensitivity develops. The decrease in sensitivity to inhibition may either be due to down-regulation of synthesis of the antigen or a selection of parasites with low antigen expression from the heterogeneous original populations. Both T lymphocytes carrying alpha/beta and gamma/delta antigen-receptors play a role in malaria immunity. However, although gamma/delta T cells may expand 40-fold or more in the peripheral immune system in acutely infected humans and also inhibit parasite growth in vitro and in vivo, their relative importance for protection or pathogenicity is presently unclear. Of the two major T cell subsets (CD4+, CD8+) carrying alpha/beta T cell receptors, the role of CD8+ T cells in blood stage infections appears to be limited. Instead, CD4+ T cells are of major importance. These cells comprise at least two functionally different subsets (Th1, Th2), distinguished on the basis of lymphokine secretion. In some rodent malaria models, Th1 cells producing primarily IL2 and IFN gamma give rise to protection in early infection while Th2 cells producing IL4 are essential for parasite clearance in late infection. In other mouse strains, the same parasites induce a strong Th2 response in early infection, resulting in a lethal course. CD4+ T cells of either Th1 or Th2 type also have regulatory functions in human P. falciparum malaria. Most humans living in areas of high endemicity have significantly elevated blood levels of IgE, reflecting a skewing of the underlying T helper cell ratio in favour of Th2, responsible for the switch in immunoglobulin isotypes. Less than 5% of the IgE in malaria represents antibodies to P. falciparum. IgE elevation is highest in patients with severe and particularly cerebral malaria and is frequently associated with an elevation of tumour necrosis factor alpha (TNF). The release of this cytokine from monocytes/macrophages may reflect crosslinking of their low affinity receptors for IgE (CD23) by IgE containing immune complexes from malarial sera. Local overproduction of TNF is considered a major pathogenic mechanism, responsible for fever and tissue lesions in severe malaria. Although TNF overproduction in malaria is generally assumed to be due to direct stimulation of effector cells by certain parasite derived toxins, the present results suggest that IgE elevation constitutes yet another mechanism contributing to the pathogenicity of P. falciparum in human malaria.
 ...
PMID:Selected problems of malaria blood stage immunity. 1002 76


<< Previous 1 2