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Biomedical subjects

J H Playfair

Publications and source records attributed to J H Playfair.

At least 91 records · Page 5Linked to original sources
PubMed1984

Killing of human malaria parasites by macrophage secretory products.

The susceptibility of the human malaria parasite, Plasmodium falciparum, to killing in vitro by macrophage secretory products was investigated. The effect of O2 radicals and tumor necrosis factor on parasite viability was assessed both morphologically and by following the uptake of [3H]hypoxanthine. H2O2 produced by the interaction of glucose and glucose oxidase was found to reduce viability; this effect was reversed by the addition of exogenous catalase. Further studies indicated that the catalase level within the erythrocyte was not altered upon parasite invasion. O2 radicals produced during the xanthine-xanthine oxidase interaction also killed P. falciparum. The addition of various O2 radical scavengers (including catalase) did not reverse this effect; therefore, it was not possible to determine which of the O2 radicals were involved in the killing process. Samples from three different sources containing tumor necrosis factor, a nonspecific soluble mediator derived from Mycobacterium bovis BCG-activated macrophages treated with endotoxin, also killed the parasite. There was no evidence that tumor necrosis factor or the products of the xanthine-xanthine oxidase interaction caused damage to the erythrocyte membrane that could be implicated as an important aspect of the killing process. These findings all strongly suggest that such macrophage products play an important role in immunity to malaria.

Animals↗
PubMed1984

The control of antibody diversity during IgM and IgG anti-sheep red cell responses in mice.

The isoelectric heterogeneity of both IgM and IgG murine anti-sheep red cell serum antibodies has been examined using an adaptation of published methods. It was found that the IgM spectra were restricted in a characteristic manner, implying oligoclonality. In cell transfer experiments, the T cell dependency of the IgM responses was confirmed. Further, helper cells appeared to switch on IgG antibody production and, simultaneously, recruit many novel IgG-forming clones into the response. The pattern of the IgM oligoclonality was attributed in part to the inheritance of genes at, or closely linked to, the Igl heavy chain locus. These findings are discussed in relation to current research on the regulation of diversity.

Animals↗
PubMed1984

Maternal inhibition of malaria vaccination in mice can be overcome by giving a second dose of vaccine.

A single dose of a formalin-fixed malaria vaccine which normally protects mice against challenge with the live parasite, is ineffective in mice born to immune mothers. This inhibition of protection, which is due to maternally-derived IgG, can be overcome if a second dose of vaccine is given 10 or more days after the first. We show that this is related to the production of specific IgM antibody in response to the first dose of vaccine, which competitively blocks the inhibitory effect of the IgG. The implications of this finding in relation to immune regulation and immunization regimes are discussed.

Animals↗
PubMed1984

Malarial parasites and tumour cells are killed by the same component of tumour necrosis serum.

Tumour necrosis serum (TNS), from animals primed with macrophage activating agents and challenged with endotoxin, causes necrosis of some tumours and can kill certain tumour lines in vitro and malarial parasites in vitro and in vivo. We have tested the possibility that the same factor is responsible for killing both tumour cells and malarial parasites. In competitive inhibition experiments, parasitized erythrocytes, but not normal erythrocytes, inhibited the cytotoxicity of TNS against a tumour cell line. Conversely, the tumour cells inhibited the killing of Plasmodium yoelii in vitro by TNS. When rabbit TNS was fractionated by ion exchange chromatography followed by gel filtration and the fractions at each step were pooled according to their ability to kill the tumour cells, in vitro parasite killing activity was found to correlate with tumour cell cytotoxicity, to a final sample which was purified more than 600-fold. Our results suggest that in terms of function, at least, the same component of TNS is responsible for the killing of both tumour cells and malarial parasites.

Animals↗
PubMed1983

Effect of immunosuppressive or inflammatory agents on lymphatic dilatation in cats infected with Brugia pahangi.

Cats infected with Brugia pahangi were immunosuppressed and the development of lymphatic pathology, as measured xeroradiographically by dilatation of the vessels, in these animals was compared with that of normally infected cats. Individual cats showed wide variations in response. Niridazole and antilymphocyte serum both reduced dilatation, niridazole being particularly effective in the early stages of infection. When silica, used as an inflammatory agent, was injected subcutaneously in conjunction with worm infection lymphatic dilatation developed, this being potentiated in degree and rate of development as compared with control animals. The possible role of a non-filarial inflammatory response in the development of lymphatic dilatation is discussed.

Animals↗
PubMed1983

Antilymphocyte autoantibody in lethal mouse malaria and its suppression by non-lethal malaria.

Mice infected with lethal P. berghei or P. yoelii malaria develop anti-lymphocyte autoantibodies less than a week after infection. The autoantibodies are IgM, T-dependent and cytotoxic to a subpopulation of non-T lymphocytes at 37 degrees C in the presence of mouse or guinea-pig complement. Non-lethal P. yoelii and P. chabaudi do not induce these autoantibodies. X-irradiated P. berghei parasites induce autoantibodies in normal mice but not in mice infected with non-lethal P. yoelii suggesting an active suppressor mechanism in the non-lethal infection.

Animals↗
PubMed1983

Killing of blood-stage murine malaria parasites by hydrogen peroxide.

Both nonlethal Plasmodium yoelii and lethal Plasmodium berghei were killed in vitro by hydrogen peroxide at concentrations as low as 10(-5) M. Higher concentrations were required in the presence of added normal erythrocytes. Injection of hydrogen peroxide in vivo significantly reduced P. yoelii parasitemia but had less effect on P. berghei.

Animals↗
PubMed1983

Failure of malaria vaccination in mice born to immune mothers. II. Induction of specific suppressor cells by maternal IgG.

Female BALB/c mice were vaccinated against blood stage P. yoelii malaria, infected 2 weeks later and after recovery mated to C57B1/6 males. When their offspring were subsequently vaccinated, the effectiveness of vaccination, as assessed by survival after infection, was significantly impaired until 8 weeks of age. Cell and serum transfer experiments indicated that specific maternally derived IgG interferes with protection in two distinct ways: (1) directly by prevention of priming by the vaccine and (2) indirectly by the induction and maintenance of specific suppressor T cells (TS) which act to inhibit the generation of memory T helper cells involved in IgG production, as measured by the response to TNP-P. yoelii. Furthermore, it is shown that the maternal IgG and the TS cells act in synergy to abolish the protective effect of vaccination.

Aging↗
PubMed1983

Anti-lymphocyte antibodies in lethal mouse malaria. II. Induction of an autoantibody specific suppressor T cell by non-lethal P. yoelii.

The anti-lymphocyte autoantibody response to irradiated lethal Plasmodium berghei malaria parasites in normal mice was significantly reduced when recipients were pre-treated with splenic T cells from mice recovered from a non-lethal Plasmodium yoelii infection. Suppression was specific for the autoantibody and did not affect the antibody response to the parasite. Experiments involving sequential P. yoelii-P. berghei infections in situ revealed that recovery from P. berghei was possible when the interval between the two infections was 14 days or more. This ability to recover from P. berghei correlated with a progressive reduction of anti-lymphocyte autoantibody suggesting a useful role for the suppressor cell. The possible link between suppressor cells and anti-lymphocyte autoantibodies in malaria is discussed.

Animals↗
PubMed1983

T-independent macrophage changes in murine malaria.

A study to investigate the participation of T cells in macrophage-mediated responses during malaria was performed in nude (nu/nu) and littermate (nu/+) mice infected with Plasmodium berghei (PB). We found that in both groups of mice spleen cells suppressed the mitogenic response to LPS. Both nu/+ and nu/nu infected mice also showed liver macrophage activation, reflected by increased plasminogen activator release. These findings suggest that at least some of the macrophage changes during malaria infection are T-independent.

Animals↗
PubMed1982

Killing of the malarial parasite Plasmodium yoelii in vitro by cells of myeloid origin.

Cytotoxic effects of mouse cells on Plasmodium yoelii were sought directly by incubating parasitized red cells with cells of various kinds for 16 h and then determining the percentage parasite survival in vivo, in terms of infectivity for the mouse. Cell populations rich in lymphocytes, e.g. lymph node and spleen, were less active than peritoneal cells and blood. Parasite killing by peritoneal cells was associated with macrophages: treatment with anti-macrophage serum (AMS) or depletion by adherence or centrifugation on Ficoll decreased activity. Polymorphonuclear leucocytes (PMN) in induced exudates may have contributed to killing, although not as actively cell for cell, and an effect of eosinophils in worm-induced exudates was not excluded. White blood cells were most active of all and fractionation on Ficoll confirmed that lymphocytes were relatively ineffective. The effector cell was phagocytic but it was insensitive to AMS. Tests on populations wih high or low proportions of PMN showed that parasite killing was independent of PMN number. It is concluded that the effector cell belongs to the monocyte-macrophage series and has acquired the ability to kill the parasite before becoming fully differentiated into a macrophage.

Animals↗
PubMed1982

Differential sensitivity in vivo of lethal and nonlethal malarial parasites to endotoxin-induced serum factor.

Sera from mice infected with Plasmodium yoelii or Plasmodium berghei and given endotoxin contained nonspecific mediators which killed both species of parasite and tumor cells in vitro. The sera resembled tumor necrosis sera obtained from mice given macrophage-activating agents such as Propionibacterium acnes (formerly designated Corynebacterium acnes) or Mycobacterium bovis BCG and then endotoxin. Cytotoxicity developed parallel to parasite killing activity and indicated that macrophages were activated. Activation occurred sooner with P. berghei, which is lethal, and serum activity remained on a plateau until the mice died. In nonlethal P. yoelii infections, activation was related to the course of parasitemia. Endotoxin given to mice infected with P. yoelii caused an immediate decrease in parasitemia, presumably through the release of parasite killing factors. The extent of the decrease depended upon the time of administration. No immediate drop in the parasitemia caused by P. berghei was observed at any time. Early administration of endotoxin prolonged survival; late administration accelerated death. Passive transfer of rabbit tumor necrosis serum to infected mice decreased the parasitemia caused by P. yoelii but not that caused by P. berghei. Other components of the immune response appeared to act together with these soluble mediators to eliminate P. yoelii; they may be absent or suppressed in infections with P. berghei.

Animals↗
PubMed1982

Failure of malaria vaccination in mice born to immune mothers.

Female BALB/c mice were vaccinated against blood stage P. yoelii (17XL strain), infected 2 weeks later and after recovery mated to normal C57B1/6 males. Control matings were with normal BALB/c females. The (C57B1/6 x BALB/c)F1 progeny were vaccinated at 4, 6, 8 or 10 weeks of age and infected 2 weeks later with lethal P. yoelii. All control mice were fully protected, but in the offspring of immune mothers mortality was 100, 87, 50, and 0% respectively. Mice in which the protective effect of vaccination had been abolished showed greatly reduced specific IgG and delayed hypersensitivity (DH) responses to challenge with parasite antigen. Results indicate that this failure of vaccination is due to the transmission of maternal IgG to the offspring which acts to suppress both priming by the vaccine and the generation of specific T helper cells involved in IgG production, as measured by the response to TNP-P. yoelii.

Animals↗
PubMed1982

Lymphocyte traffic and lymphocyte destruction in murine malaria.

Normal lymphocytes labelled with 51Cr were injected into mice at various stages of lethal and non-lethal malaria infections. Marked alterations were seen in the uptake into spleen and liver, which correlated with the outcome of the infection. Non-lethal infections and lethal infections in mice protected by vaccination caused increased uptakes, especially in the liver. In lethal infections, particularly Plasmodium berghei, uptakes were below normal values at certain times: this was apparently due to destruction of lymphocytes, probably caused by autoantibody.

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