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 death rate and percentage of parasitized erythrocytes in mice infected with Plasmodium berghei were enhanced by injections of anti-interferon globulins. As, in the same time, parasite-induced interferon was neutralized by these globulins, it can be concluded that endogenous interferon plays an important inhibiting role during parasitic diseases, such as malaria, as it has been previously demonstrated in many virus infections.
 ...
PMID:The protective effect of endogenous interferon in mouse malaria, as demonstrated by the use of anti-interferon globulins. 36 60

Groups of mice were inoculated with either low or high intraperitoneal doses of Plasmodium berghei infected erythrocytes (PIE). The course of infection was observed daily by counting new PIE which appeared in the red blood cells (RBC) of infected mice. At the same time, circulating interferon (IF) was tested. When low doses of infecting PIE were used (400 per mouse), circulating IF was first detected on the 5th day after inoculation. It increased to a maximal rate, when 5% of RBC were affected. It disappeared on the 8th day despite of a continuous rise of PIE. With high doses of PIE (60,000 per mouse), IF was detected on the 3rd day, when only 0.5% of RBC were parasitized. The maximal rate was observed on the 5th day when 20% of the RBC were affected. It disappeared on the 7th day, though the PIE rate would continue to rise. Treatment of mice by chloroquine (0.01 per g), at the time of first PIE appearance after Plasmodium infection, rapidly reduced the amount of PIE. In this case, no IF production was observed. Splenectomy resulted in an increased resistance of mice to the lethal effect of Plasmodium infection. IF production in such splenectomized mice was less important than in control. It was concluded that P. berghei was a good inducer of circulating IF at the beginning of the active disease, soon after infection. The fact was proven by the striking lowering effect of chloroquine and splenectomy that both reduced Plasmodium development and IF production.
 ...
PMID:[Production of interferon after infection by various doses of "Plasmodium berghei" in mice (author's transl)]. 38 70

The major surface antigen p190 of the human malaria parasite Plasmodium falciparum contains nonpolymorphic, immunogenic stretches of amino acids which are attractive components for a subunit vaccine against malaria. One such polypeptide, termed 190L, is contained in the 80-kDa processing product of p190, which constitutes the major coat component of mature merozoites. We report here that immunization of Aotus monkeys with 190L gives only poor protection against P. falciparum challenge. However, addition by genetic engineering of a universal T-cell epitope (CS.T3) to 190L improved immunity, and as a result three of four monkeys were protected following challenge infection with blood-stage parasites. Neither antibody against the immunizing antigens or against blood-stage parasites nor the capacity of the monkeys' sera to inhibit in vitro parasite invasion correlated with protection. However, in contrast to sera from nonprotected monkeys, sera from protected animals contained elevated levels of gamma interferon. These results suggest that gamma interferon is directly or indirectly involved in the process of asexual parasite control in vivo.
 ...
PMID:Protection against malaria in Aotus monkeys immunized with a recombinant blood-stage antigen fused to a universal T-cell epitope: correlation of serum gamma interferon levels with protection. 137 Feb 71

The hybrid synthetic protein SPf(66), which contains small fragments of the 83-kD, 55-kD, 35-kD, and circumsporozoite antigens of Plasmodium falciparum, was studied to determine its protective capacity against malaria infection in Aotus lemurinus monkeys. Two groups of six monkeys each were immunized six times with this polymer, which was mixed with either Freund's adjuvant or aluminum hydroxide. Two groups of five animals each were used as controls and immunized with saline solution mixed with the same adjuvants. Neither antipeptide nor antimalarial antibodies developed after the six immunization doses. Regardless of this fact, the monkeys were challenged intravenously with 10(5) P. falciparum blood stage parasites, and the resultant parasitemia was followed daily on blood smears. Only one monkey from each of the groups immunized using Freund's adjuvant (both experimental and control) was protected. In those immunized using aluminum hydroxide, one animal was protected in the experimental group, but none were protected in the control group. Anti-parasite antibodies developed during the infection, but did not correlate with protection and failed to recognize SPf(66) peptide in an enzyme-linked immunosorbent assay. Immunization with the polymer did not boost natural antibodies present in two of the monkeys before the experiment. Low levels of gamma-interferon were produced in some animals, but were not correlated with protection.
 ...
PMID:Failure of a synthetic vaccine to protect Aotus lemurinus against asexual blood stages of Plasmodium falciparum. 144 9

Tumor necrosis factor and related cytokines are thought to be implicated in cell-mediated immunity and pathophysiology in malaria, but their mechanism of action has not been ascertained. Tumor necrosis factor has been reported to generate nitric oxide in vitro, so we have measured levels of this molecule and its products in the plasma of mice after they have received an injection of tumor necrosis factor, lymphotoxin, interleukin-1, gamma interferon, or interleukin-6, all of which have been reported to be increased in malaria. Total reactive nitrogen intermediate levels in plasma were assayed spectrophotometrically after exposing plasma to a copper-cadmium-zinc catalyst to convert nitrate to nitrite and then to Griess reagent. Tumor necrosis factor, lymphotoxin, and interleukin-1 all induced reactive nitrogen intermediates in vivo, with interleukin-1 showing the most activity. Tumor necrosis factor was then examined more closely. It induced more reactive nitrogen intermediates in malaria-infected mice than in normal mice, and appreciably more was in the form of nitrate than was in the form of nitrite. NG-methyl-L-arginine inhibited the in vivo generation of reactive nitrogen intermediates by tumor necrosis factor in a dose-dependent manner, implying that these molecules were arginine derived. These results are consistent with the possibility that tumor necrosis factor, lymphotoxin, and interleukin-1 may contribute to host pathology and parasite suppression through generation of nitric oxide.
 ...
PMID:In vivo induction of nitrite and nitrate by tumor necrosis factor, lymphotoxin, and interleukin-1: possible roles in malaria. 150 Jan 82

Liposomes containing lipid A induced potent humoral immune responses in mice against an encapsulated malaria antigen (R32NS1) containing NANP epitopes. The immune response was not enhanced by lipid A alone or by empty liposomes containing lipid A. Experiments to investigate the adjuvant mechanisms of liposomes and lipid A revealed that liposome-encapsulated R32NS1 was actively presented by bone marrow-derived macrophages to NANP-specific cloned T cells. The degree of presentation was related to the amount of liposomal antigen added per macrophage in the culture medium. At high cell densities, poor presentation occurred when liposomes lacked lipid A but excellent presentation occurred when the liposomes contained lipid A. Liposomes containing lipid A and encapsulated antigen also activated gamma interferon-treated macrophages to produce nitric oxide. Macrophage activation and antigen presentation occurred with liposomes that could not be detected by the Limulus amebocyte lysis assay. Intraperitoneal injection of liposomal lipid A caused a marked increase in the recruitment of immature (peroxidase-positive) macrophages to the peritoneum. On the basis of these experiments, we propose that the mechanism of the adjuvant action of liposomal lipid A is partly due to increased antigen presentation by macrophages and partly due to recruitment of an increased number of macrophages serving as antigen-presenting cells.
 ...
PMID:Adjuvant effects of liposomes containing lipid A: enhancement of liposomal antigen presentation and recruitment of macrophages. 158 11

Secretion of gamma interferon (IFN-gamma) in response to stimulation of Plasmodium falciparum-primed T cells by specific antigens may be a useful indicator of cellular immunity to malaria. An enzyme-linked immunospot (ELISPOT) assay designed to detect IFN-gamma at the single-cell level was used to study IFN-gamma-producing cells from P. falciparum-primed donors from The Gambia after in vitro stimulation with various malarial antigens. IFN-gamma secreted into the culture supernatant was measured by conventional enzyme-linked immunosorbent assay (ELISA). There was a good correlation in individual donors between the level of IFN-gamma secreted into the culture supernatant and the number of IFN-gamma-secreting cells. However, the ELISPOT assay was apparently more sensitive in demonstrating low levels of IFN-gamma production than the ELISA was. Thus after stimulation with crude P. falciparum antigen from infected erythrocytes, 72% of the primed donors responded positively in the ELISPOT assay but only 55% responded positively in the ELISA. When stimulated with synthetic peptides representing immunodominant epitopes of the malarial antigen Pf155/RESA, a vaccine candidate, 31 to 55% responded in the ELISPOT assay and 21 to 36% responded in the ELISA. Unprimed Europeans did not respond positively to these antigens in either of the assays, and background in antigen-free controls was generally low. These results indicate that measurement of IFN-gamma by the ELISPOT assay or ELISA should have wide applications in large-scale epidemiological studies of malaria immunity. In addition, the ELISPOT assay makes it possible to analyze the T cells responding to malarial antigens in terms of both numbers and functional heterogeneity.
 ...
PMID:Number of cells from Plasmodium falciparum-immune donors that produce gamma interferon in vitro in response to Pf155/RESA, a malaria vaccine candidate antigen. 169 35

Cellular immune responses to the Plasmodium falciparum circumsporozoite (CS) protein were measured by proliferation and interferon-gamma production in a cohort of children aged 3 to 8 years, living in The Gambia. Anti-CS antibody titres, malariometric indices and sickle cell status were also determined. Malaria morbidity in the ensuing malaria transmission season was monitored by weekly health questionnaire, axillary temperature measurements and examination of blood films. Exposure to malaria was inferred from entomological data collected during the transmission season. Immunological and parasitological measurements were repeated at the end of the rainy season. Immunological findings were compared between children who experienced clinical malaria or asymptomatic infection and children who had no evidence of infection. No association was found between cellular immune responses to the CS protein at the beginning of the transmission season and subsequent susceptibility to infection except among children with high titres of antibody to (NANP)40. Seropositive children who did not become infected had a higher mean proliferative response to the Th3R epitope than seropositive children who did become infected. High titres of anti-(NANP)40 antibodies alone were not protective. Responses to the Th2R epitope were significantly higher at the end of the rainy season than at the beginning in children who experienced an asymptomatic infection. Responses to variant sequences of the 2 epitopes were highly correlated at an individual level but there was no correlation between proliferative and interferon responses to a particular epitope.
 ...
PMID:Recognition of dominant T cell-stimulating epitopes from the circumsporozoite protein of Plasmodium falciparum and relationship to malaria morbidity in Gambian children. 170 74

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.
 ...
PMID:[Use a of DNA probe to detect cellular immunity against intracellular parasitism]. 172 69

Linear B- and T-cell epitopes have been identified in the Plasmodium falciparum clustered-asparagine-rich-protein (CARP). Twenty-six synthetic peptides, 15-25 amino acids in length, were assayed for their ability to stimulate purified, human T-cells primed to P.falciparum by natural infection to proliferate and/or secrete gamma-interferon (IFN gamma). The plasma of malaria exposed individuals were tested for antibody reactivity with peptides coupled to bovine serum albumin in a semiquantitative ELISA. Two of the peptides (NNFMNRNMKNKNMN/NAKNVNDMYRDGEMS) induced T-cells from many malaria exposed donors to proliferate and/or secrete-IFN gamma. Six peptides bound antibodies from a large number of the plasma samples, the amounts ranging from ten to more than 200 micrograms specific antibody/ml. T-cell activation was most pronounced when the T-cells were from highly immune donors. In contrast, high anti-peptide specific antibody levels were usually detected in the plasma of less immune donors, recently exposed to infection. One short sequence (NAKNVNDMYRDGEMS) was found to contain both T- and B-cell epitopes. Thus, CARP includes both T- and B-cell reactive elements recognized by the human immune system following exposure to the parasite by natural infection.
 ...
PMID:Epitopes of the Plasmodium falciparum clustered-asparagine-rich protein (CARP) recognized by human T-cells and antibodies. 172 21


1 2 3 4 5 6 7 8 9 10 Next >>