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)

In malaria endemic areas, pregnancy predisposes previously immune women to clinical and subclinical malaria infection. While parameters of humoral immunity do not seem to be affected by pregnancy, suppression of cellular immunity has been demonstrated for a number of antigens. In this study of women from a rural area of the Gambia where falciparum malaria is holoendemic, we show that lymphoproliferative responses to Plasmodium falciparum antigens are depressed in pregnant women compared to parity matched non-pregnant women, and that this effect is particularly marked in primigravidae. The data also indicate that malaria antigen induced gamma-interferon production may be depressed in pregnant women. There was no significant difference in antimalarial antibody titers between the 2 groups.
 ...
PMID:Suppression of cell-mediated immune responses to malaria antigens in pregnant Gambian women. 249

Fifty-two Gambian children who had received fortnightly chemoprophylaxis with maloprim, (pyrimethamine and dapsone), and 45 receiving placebo, were studied. Cellular immune responses to malaria antigens, measured by lymphoproliferative responses and interferon production, were higher in children who had received prophylaxis than in controls, although the anti-malarial antibody levels were lower. During a one-year period after termination of prophylaxis, there was no increase in the frequency of clinical episodes of malaria in the children who had received Maloprim. These results suggest that chemoprophylaxis for 3 years may lower malaria antibody levels, but does not interfere with the development of protective immunity, perhaps by enhancing cell-mediated immune responses to malaria in protected children.
 ...
PMID:Cellular immune responses to Plasmodium falciparum antigens in children receiving long term anti-malarial chemoprophylaxis. 251 34

Infection with Plasmodium falciparum induces marked disturbances in normal immunoregulatory functions. Antigen-specific immunosuppression is a feature of acute malaria and has been linked to activation of CD8+ T suppressor cells. Among immune adults, cell-mediated immune responses to malaria antigens are extremely variable when measured in vitro, and there is no obvious relation between responsiveness and resistance to clinical disease. In this study, when CD8+ cells were removed from peripheral blood mononuclear cell preparations obtained from individuals who responded poorly to a soluble malaria antigen preparation, both lymphoproliferation and gamma interferon production were significantly enhanced, but responses to other soluble antigens and mitogen were unaffected. No effect of CD8+ cell depletion was seen in individuals whose undepleted mononuclear cells gave a high response to the malaria antigen. This suggests that for some malaria-exposed individuals, CD8+ cells activated in vitro by exposure to malaria antigens suppress other cellular responses and may obscure the presence of potentially protective immune mechanisms.
 ...
PMID:CD8+ T cells inhibit Plasmodium falciparum-induced lymphoproliferation and gamma interferon production in cell preparations from some malaria-immune individuals. 252 21

The functional heterogeneity of the CD4+ T cell response to Plasmodium chabaudi has been evaluated. Using a limiting dilution assay system and a variety of assays to detect gamma-interferon (IFN-gamma), interleukin-2 (IL-2), IL-3, and T helper (Th) cells for malaria-specific antibody production, the precursor frequencies of P. chabaudi-reactive T cells have been calculated. The patterns of lymphokines produced by individual microcultures of the limiting dilution assay generally supported the idea of two functionally distinct CD4+ subsets: one which produces IFN-gamma and IL-2 (Th1) and one which is an effective helper cell for antibody production (Th2). However, it could not be determined whether the overlapping functions observed in some cultures represented T cells which could produce all factors or separate clones which were developing in the same wells. During the first 14 days of an erythrocytic infection of P. chabaudi the predominant T cell response was of the Th1-type. The frequency of these cells decreased after 14 days. By 3 weeks after infection the CD4+ T cell response was characterized by Th2 cells, as defined by their ability to act as helper cells in the production of malaria-specific antibody. These data support the hypothesis that early clearance of P. chabaudi may be antibody-independent but that the final clearance mechanism coincides with the appearance of helper cells and antibody.
 ...
PMID:Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. 253 35

A specific DNA probe was used to study the effect of recombinant rat, mouse, and human gamma-interferon (gamma-IFN) on the course of sporozoite-induced malaria infections. In mice and rats infected with sporozoites of Plasmodium berghei, mouse and rat gamma-IFN's strongly inhibited the development of the exoerythrocytic forms in the liver liver cells of the hosts, but not the development of the erythrocytic stages. The degree of inhibition of the exoerythrocytic forms was proportional to the dose of gamma-IFN administered, but was independent of the number of sporozoites used for challenge. A 30 percent reduction in the development of exoerythrocytic forms in rat liver was achieved when 150 units (about 15 nanograms of protein) of rat gamma-IFN were injected a few hours before sporozoite challenge; the reduction was 90 percent or more with higher doses of gamma-IFN. The effect was less pronounced if the gamma-IFN was administered 18 hours before or a few hours after challenge. Human gamma-IFN also diminished the parasitemia in chimpanzees infected with sporozoites of the human malaria parasite Plasmodium vivax. The target of gamma-IFN activity may be the infected hepatocytes themselves, as shown by in vitro experiments in which small doses of the human lymphokine inhibited the development of exoerythrocytic forms of Plasmodium berghei in a human hepatoma cell line. These results suggest that immunologically induced interferon may be involved in controlling malaria infection under natural conditions.
 ...
PMID:Inhibition of development of exoerythrocytic forms of malaria parasites by gamma-interferon. 308 18

Mice were protected against lethal Plasmodium yoelii malaria by vaccination with a Triton X-100 lysate of whole parasitized erythrocytes. For full effectiveness this vaccine required an adjuvant, and we have found that recombinant gamma-interferon has strong adjuvanticity in this model when given either intraperitoneally or subcutaneously. Specific immune responses that were enhanced included antibody, T cell help, and delayed hypersensitivity.
 ...
PMID:Recombinant gamma interferon is a potent adjuvant for a malaria vaccine in mice. 311 84

This study was designed to test the hypothesis that T-cell effector mechanisms are required for protective immunity to malaria sporozoites. Administration of neutralizing monoclonal antibodies against gamma interferon (gamma IFN) to immune hosts, reversed sterile immunity to sporozoite challenge, by allowing the growth of exoerythrocytic forms (EEF) and thus the development of parasitaemia. Immune animals also developed infections when depleted in vivo of their suppressor/cytotoxic T cells expressing the CD8 antigen (CD8+) but not when depleted of helper T cells expressing CD4 antigen (CD4+), before sporozoite challenge. Passive transfer of immune immunoglobin alone, or adoptive transfer of immune T cells alone, conferred partial protection to naive recipients. Transfer of both immune components resulted in significantly greater protection. This transferred immunity was reversed by the in vivo neutralization of gamma IFN. Thus, sterile immunity to sporozoite challenge requires the neutralization of sporozoites by antibodies and the inhibition of EEF development by gamma IFN with the participation of CD8+ cells.
 ...
PMID:Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. 312 15

Early experiments in mice suggested that tumour necrosis factor (TNF) might be cytotoxic to asexual blood-stage malaria parasites. This was based on the striking activity of tumour necrosis serum (TNS) on the parasite both in vitro and in vivo, and the inability to separate by physical means the parasite-killing and tumour-killing components. However, recombinant TNF does not have this cytotoxic effect in vitro, while its antiparasitic activity in vivo, though significant, is not as strong as that of an equivalent amount of TNS. Thus it appears that TNS contains another cytotoxic molecule and that TNF itself may act indirectly in vivo, perhaps by activating an effector cell. An example of this has been found in murine schistosomiasis, where macrophage-derived TNF is able to activate eosinophils to attack the infecting worms. One mechanism of schistosomule damage is by eosinophil cationic proteins, and these have also been found to be cytotoxic to blood-stage malaria. There may therefore be a pathway of TNF activity common to both parasites. In a similar way, the crisis-forming factor (CFF) found in the serum of certain immune Sudanese adults is clearly distinct from TNF, since CFF-containing sera do not kill TNF-susceptible tumour cells and rTNF does not kill Plasmodium falciparum in vitro. This confirms that there are other cytotoxic molecules, still to be identified, with a role in immunity to malaria and perhaps other parasites. TNF is also active against intracellular Trypanosoma cruzi and against some viruses but in both cases this appears to be an interferon-like mediatory effect and not direct cytotoxicity. It is not yet clear whether these antiparasitic activities are part of the biological role of TNF.
 ...
PMID:Antiparasitic effects of tumour necrosis factor in vivo and in vitro. 313 Oct 74

In vitro, neopterin, a pyrazino-[2, 3-d]-pyrimidine compound, is produced by human monocytes-macrophages following induction by either supernatants from activated T lymphocytes or by recombinant gamma interferon. In vivo, its determination in urine or serum provides a sensitive and specific test for the activation grade of cell-mediated immune reactions. Urinary neopterin levels were measured in 128 Tanzanian individuals (age 6 months to 54 years) with parasitologically proven malaria. Levels in a subgroup of 117 previously untreated patients were compared with those previously reported from 19 untreated malarial patients from Bangkok, Thailand (age 7 to 62 years). The influence of concomitant variables such as age, fever, parasitaemia, duration of symptoms and local endemicity of malaria upon neopterin excretion levels was analysed. In the Thai patients, levels were considerably higher than in Tanzanian subjects of similar age. Among the Tanzanian patients, an overwhelming influence of age was detected, children showing extremely high neopterin excretion levels. The other variables did not influence neopterin levels significantly. Our findings are in accord with recent data on the prevalence and mean titres of antibodies to the circumsporozoite protein of Plasmodium falciparum, which indicate that in endemic areas acquired humoral immunity develops slowly with increasing age, while prevalence and severity of disease decline.
 ...
PMID:The dependence of cell-mediated immune activation in malaria on age and endemicity. 332 84

The present study concerns the interferon (IFN) compartment of the immune response in human malaria. It was undertaken with Plasmodium falciparum parasitized human red blood cell culture supernatants (PF-RBCS). Investigations were conducted in order to verify whether supernatants of such protozoa cultures had the capacity to induce gamma interferon previously identified in sera of P. falciparum infected patients and to verify whether a T-cell mitogen recently characterized in vitro could be correlated with the eventual IFN-inducing activity. Investigations were performed with nonsynchronized P. falciparum cultures and highly synchronized PF-RBC cycles. Results obtained with the first type of experiment demonstrated the presence of an immune interferon inductor in PF-RBCS controlled for their positive mitogenic activity. In supernatants from highly synchronized PF-RBC cycles it was possible to further correlate the mitogen activity with the capacity to induce IFN-gamma. Both activities were found in the time-interval situated near the end of the parasite cycle shortly previous of the merozoite stage. At an earlier time, at the peak of the ring stage, when no mitogen activity was detected, an interferon-induction activity, solely of IFN-alpha, was also demonstrated.
 ...
PMID:The interferon compartment of the immune response in human malaria: I. Interferon inducers in Plasmodium falciparum cultures. 392 27


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