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)

Studies using experimental models of malaria in immunodeficient mice and chickens have shown that resistance to blood-stage infection is mediated by protective antibodies and T cell-dependent cell-mediated mechanisms of immunity. Depending on the infecting species of Plasmodium and prior experience of the host, either humoral or cell-mediated immune mechanisms predominate. Cell-mediated immunity has been adoptively transferred with CD4+ splenic T cells, and with antigen-specific T cell lines and clones. Since ascending parasitemia occurs in all instances, the transferred cells do not kill plasmodia directly but appear to activate effector mechanisms capable of destroying the invading parasites. Both CD4+ and CD8+ T cells were found to increase in the spleens of malarious mice. Depletion of CD4+ T cells prevented nude mice adoptively transferred with immune splenic T cells from clearing parasitemia. In contrast, late treatment with anti-CD4 antibody had little if any effect. The converse was true when anti-CD8 antibody was utilized, i.e., a significant number of mice treated with anti-CD8 antibody after parasitemia became patent and had difficulty clearing blood parasites. These data suggest that during infection CD8+ T cells may become activated by CD4+ T cells responding to malarial antigens. These CD8+ T cells may be directly cytotoxic or secrete additional cytokines thereby amplifying the role of CD4+ T cells in the activation of anti-parasite effector mechanisms. Finally, a hypothesis is presented to explain how the parasite in natural infections may activate T cell-dependent effector mechanisms in order to control its numbers in host tissues thereby ensuring the survival of both parasite and host.
 ...
PMID:Cell-mediated immunity to the asexual blood stages of malarial parasites: animal models. 212 29

Plasmodium falciparum schizont extract and purified protein derivative were used to stimulate peripheral blood mononuclear cells obtained from healthy aparasitemic Gabonese individuals with lifelong exposure to malaria infection and non-Gabonese control subjects who have had had no clinical malaria. In vitro lymphoproliferation was measured by uptake of tritiated thymidine, while production of interleukin-2, interferon-gamma, and soluble CD8+ were measured by immunoenzymatic assays. Enumeration of interferon-gamma-producing cells was done using a modified immunoenzyme spot assay. Twenty-eight percent of Gabonese subjects were determined to be low responders in the lymphoproliferative assay, with a tritiated thymidine uptake of less than 6000 c.p.m. The proportions of T cell subsets and the kinetics of the proliferative response were similar in the low and the high responders. Removal of CD8+ T cells from mononuclear cells of low responders or culture of purified CD4+ T cells from the same individuals resulted in a 7-fold increase in the proliferative response to the schizont antigen but not to purified protein derivative (PPD). A similar increase in the proliferative response was seen in the low but not the high responder mononuclear cell cultures stimulated with the schizont antigen in the presence of exogenous interleukin 2 (IL-2) or in the presence of anti-HLA-DQ antibody. Low responder mononuclear cell cultures stimulated with schizont antigen but not PPD produced 3-fold less IL-2, 14-fold less interferon-gamma (IFN-gamma), and 3-fold more soluble CD8 than high responder mononuclear cell cultures. Removal of CD8+ T cells from low responder mononuclear cells resulted in a 2-fold increase in IL-2 production and a 4-fold increase in IFN-gamma production in response to schizont antigen. High responder mononuclear cells stimulated with schizont antigen contained four times as much IFN-gamma-producing cells as low responder cultures, with each IFN-gamma-producing cell producing three times the amount of IFN-gamma as that produced by an IFN-gamma-producing cell in low responder cultures. Removal of CD8+ T cells from low responder mononuclear cells led to a significant increase in the amount of IFN-gamma produced at the single cell level in response to schizont antigen stimulation. In such cultures, the amount of IFN-gamma produced by a single cell was similar between high and low responders. We conclude that in certain individuals, T cell responses to schizont antigen are actively down-regulated by activated schizont-specific CD8+ suppressor T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:In vitro cell-mediated immune responses to Plasmodium falciparum schizont antigens in adults from a malaria endemic area: CD8+ T lymphocytes inhibit the response of low responder individuals. 215 Oct 24

Peripheral blood lymphocytes from healthy, Epstein-Barr virus (EB-virus)-seropositive donors and from patients with acute Plasmodium falciparum malaria were tested for their cytotoxicity towards autologous EB-virus-infected B-cells using an in vitro regression assay. Of the 18 cultures from control donors, 88.8% showed the normal pattern of regression. Of the 20 malaria patients in the study, 40% failed to exhibit the normal pattern observed in the control group. Analysis of the lymphocyte subsets showed a high incidence of inverted CD4:CD8 ratios in the patient group due to an absolute rise in the CD8 population. This data suggests that the immunosuppressive effects of acute malaria extend to defective control over EB-virus. The relevance of the observations to the aetiology of EB-virus-associated, endemic Burkitt's lymphoma (eBL) is discussed.
 ...
PMID:In vitro analysis of Epstein-Barr virus: host balance in patients with acute Plasmodium falciparum malaria. I. Defective T-cell control. 216 84

We studied immunity to the blood stage of the rodent malaria, Plasmodium vinckei vinckei, which is uniformly lethal to mice. BALB/c mice develop solid immunity after two infections and drug cure. The following experiments define the basis of this immunity. Transfer of pooled serum from such immune mice renders very limited protection to BALB/c mice and no protection to athymic nu/nu mice. Moreover, B cell-deficient C3H/HeN mice develop immunity to P. vinckei reinfection in the same manner as immunologically intact mice, an observation made earlier. In vivo depletion of CD4+ T cells in immune mice abrogates their immunity. This loss of immunity could be reversed through reconstitution of in vivo CD4-depleted mice with fractionated B-, CD8-, CD4+ immune spleen cells; however, adoptive transfer of fractionated CD4+ T cells from immune spleen into naive BALB/c or histocompatible BALB/c nude mice does not render recipients immune. In vivo depletion of CD8+ T cells did not influence the parasitemia in nonimmune or immune mice. Splenectomy of immune mice completely reverses their immunity. Repletion of splenectomized mice with their own spleen cells does not reconstitute their immunity. We conclude that some feature of the malaria-modified spleen acts in concert with the effector/inducer function of CD4+ T cells to provide protection from P. vinckei. To be consistent with this finding, a malaria vaccine may require a combination of malaria Ag to induce immune CD4+ T cells and an adjuvant or other vaccine vehicle to alter the spleen.
 ...
PMID:Interdependence of CD4+ T cells and malarial spleen in immunity to Plasmodium vinckei vinckei. Relevance to vaccine development. 257 Aug 2

T cells are critical for immunity to malaria, not only because they function as helper cells for an antibody response, but also because they serve as effector cells. Such cellular immunity is directly implicated in protection from sporozoites and plays an important role in protection from blood-stage parasites. It also can block transmission of malaria from mammalian host to the mosquito. Both CD8 and CD4 effector cells have important roles. The parasite's defence from immune attack, however, is designed to minimize activation of T cells. Thus, there appears to be limitation of the number of T sites within many malaria proteins and variation within these limited sites. Homology to host proteins and resultant immune-escape due to tolerance may be another mechanism. These parasite defence mechanisms highlight both the importance of T-cell immunity in malaria and the challenge of designing effective vaccines to stimulate T cells.
 ...
PMID:Involvement of T cells in malaria immunity: implications for vaccine development. 265 42

In recent malaria sporozoite vaccine trials in humans and mice, antibodies to the sporozoite coat protein have given only modest protection against sporozoite challenge. In contrast, irradiated sporozoites can protect mice against massive sporozoite infections. Evidence suggests that immunity in these mice is mediated by T cells. To identify the mechanism of immunity, we used monoclonal antibodies specific for either the CD4 or CD8 molecule to selectively deplete sporozoite-immunized mice of T-cell subsets. Though in vivo depletion of CD4+ T cells did not reduce immunity, depletion of CD8+ T cells abolished protection. Monoclonal antibody treatment did not affect anti-sporozoite antibody levels. Our data indicate that cytotoxic T cells are critical for immunity to large numbers of sporozoites and suggest that vaccine development should be reoriented toward stimulating cellular as well as humoral immunity.
 ...
PMID:CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. 296 34

Live vectors expressing foreign antigens have been used to induce immunity against several pathogens. However, for the virulent rodent malaria parasite Plasmodium yoelii, the use of recombinant vaccinia virus, pseudorabies virus, or Salmonella, expressing the circumsporozoite protein of this parasite, failed to induce protection. We generated a recombinant influenza virus expressing an epitope from the circumsporozoite protein of P. yoelii known to be recognized by CD8+ T cells and demonstrated that this vector induced class I major histocompatibility complex-restricted cytotoxic T cells against this foreign epitope. Immunization of mice with this recombinant influenza virus, followed by a recombinant vaccinia virus expressing the entire circumsporozoite protein, induced protective immunity against sporozoite-induced malaria. The sequence of immunization appears to be crucial, since a primer injection with recombinant vaccinia virus, followed by a booster injection with recombinant influenza virus, failed to induce protection. The protection induced by immunization with these recombinant viruses is mostly mediated by CD8+ T cells, as treatment of mice with anti-CD8 monoclonal antibody abolishes the anti-malarial immunity. The use of different live vectors for primer and booster injections has a synergistic effect on the immune response and might represent an effective general strategy for eliciting protective immune responses to key antigens of microbial pathogens.
 ...
PMID:Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. 768 19

We have isolated, characterized and quantified the immunocompetent cells present in the extravascular hepatic compartment at various stages after Plasmodium yoelii malaria infection with sporozoites. Cytological analyses revealed a predominantly lymphoid population. In mice with a primary infection, the predominant cells were CD4+, CD8+ and B lymphocytes. In fully protected mice, CD3+ CD4- CD8- and polymorphonuclear cells, particularly eosinophils, were most common. The significance of changes in subpopulations is discussed in relation to antigen presentation and host-protective mechanisms.
 ...
PMID:Characterization of liver lymphomyeloid cells in mice infected with Plasmodium yoelii sporozoites. 783 30

In a community survey of 312 children aged 3-6 years in urban Guinea-Bissau, we examined Plasmodium falciparum parasitaemia and T cell subsets. 183 children (59%) had parasites in their blood, 13 had fever > or = 37.5 degrees C, and 9 (3%) had fever and a parasite density > 5000/microL (clinical malaria). Compared with children with no parasitaemia or asymptomatic parasitaemia, children with acute malaria had lymphopenia and significantly lower total CD4 and CD8 cell counts, but there was no significant difference in white blood cell count percentages of CD4 and CD8 cells, or the CD4/CD8 ratio. Children with parasitaemia but without fever had a significantly lower percentage of CD4 cells than children without parasites (P = 0.031), but did not differ in any other haematological index. Controlling for other factors, the CD4 cell percentage was inversely correlated with the density of malaria parasites (P = 0.024), whereas there was no association with CD8 cell percentage or the CD4/CD8 ratio. Asymptomatic parasitaemia may be an important confounder in general community studies of T cell subsets in the tropics.
 ...
PMID:A community study of T lymphocyte subsets and malaria parasitaemia. 788 82

Intraperitoneal injection of recombinant Interleukin 12 (rIL-12) at 30 ng/day for 5 days beginning 1 to 2 days before sporozoite challenge or administration of a single dose of 150 ng of rIL-122 days before challenge protected 100% of BALB/c mice against challenge with 10(2) Plasmodium yoelii sporozoites. rIL-12-induced protection was eliminated in all mice by administration of a monoclonal antibody against interferon gamma and in 50% of mice by administration of NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthase. rIL-12 protected BALB/c mice treated with cytotoxic anti-CD4 and anti-CD8 monoclonal antibodies, as well as T-cell- and B-cell-deficient severe combined immunodeficiency mice. These data suggest that rIL-12 stimulates non-B, non-T cells to produce interferon gamma that kills intrahepatic parasites by stimulating nitric oxide production. If rIL-12 proves to be well tolerated by humans, our findings support consideration of rIL-12 as an immunoprophylactic against malaria.
 ...
PMID:Interleukin 12 induction of interferon gamma-dependent protection against malaria. 793 13


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