Search PubMed⌕ Search

Biomedical subjects

J H Playfair

Publications and source records attributed to J H Playfair.

At least 109 records · Page 6Linked to original sources
PubMed1981

Endotoxin-induced serum factor kills malarial parasites in vitro.

We investigated the possibility that malarial parasites may be killed by nonspecific soluble mediators, such as those in tumor necrosis serum, that are obtained from mice given macrophage-activating agents like Corynebacterium parvum or Mycobacterium bovis BCG, followed by endotoxin. Such sera killed parasites in vitro after overnight incubation; killing was measured directly by using an in vivo infectivity assay. Parasite infectivity was not decreased by incubation in sera from mice given C. parvum or BCG alone (no endotoxin) or by incubation in sera from normal mice given endotoxin. Plasmodium yoelii, its lethal variant, and Plasmodium berghei were equally susceptible to inactivation. Sera obtained from mice given endotoxin during the course of infection with these parasites also contained parasite-killing factor. The activity of this factor appeared to be proportional to parasitemia in that it was higher in the sera from mice infected with the lethal parasites than in the sera from mice with infections which resolved either spontaneously or after vaccination.

Animals↗
PubMed1981

Differential involvement of non-specific suppressor T cells in two lethal murine malaria infections.

The suppression of the contact sensitivity of oxazolone in murine malaria is shown to be mediated by non-specific T suppressor cells, but to a different extent in infection caused by two different species of parasite. Depletion of T suppressor cells in vivo and/or anti-Thy 1.2 treatment in vitro indicated that in mice infected with P. berghei the suppressor effect was largely mediated by T cells. By contrast, in mice infected with a lethal strain of P. yoelii it was only partly due to T cells; B suppressor cells and/or macrophages may also be involved. However, depletion of T suppressor cells in vivo had no effect on the course of the parasitaemia or on the survival time. Therefore, we postulate that this kind of non-specific immunosuppression cannot be regarded as a major cause of lethality.

Animals↗
PubMed1980

The role of T cells in regulating immunoglobulin class and subclass.

A plaque-forming cell assay was used to follow the changes in Ig class and subclass during the response of mice to repeated injections of sheep red cells. The proportion of IgG1 rose, and that of IgG2b fell, as the response proceeded. In cell-transfer experiments both B and T cells displayed this tendency, and when asynchronously primed cells co-operated together, the pattern was characteristic of the longer-primed population. Thus T cells can advance, but cannot reverse, the progress of isotype changes in B cells. Evidence is presented for two physically separable T-cell subpopulations which need to interact in order the help B cells produce certain isotypes.

Animals↗
PubMed1980

Two distinct types of non-specific immunosuppression in murine malaria.

A comparative study of non-specific immunosuppression by malaria has been carried out in five situations: in both unvaccinated and vaccinated mice infected with the lethal Plasmodium yoelii or the lethal Plasmodium berghei, and in the unvaccinated non-lethal P. yoelii infection. Spleen cells showed a suppressive effect on the normal blastogenic response to mitogens. This suppression was strongest in the mice vaccinated before infection with the lethal P. yoelii and in those infected with non-lethal P. yoelii, suggesting that the suppressive effect did not interfere with recovery. Silica, anti-Thy-1, and indomethacin treatment suggested that this suppression was caused by macrophages. However, the plaque-forming cell response to sheep RBC in vivo was suppressed equally in every case at the peak of the parasitaemia, whereas the suppression of contact sensitivity to oxazolone was strongest in mice with fatal infections. We suggest that different suppressor mechanisms operate in malaria, some being harmful to the host and others possibly beneficial.

Animals↗
PubMed1980

The role of the liver in immunity to blood-stage murine malaria.

Mice vaccinated with fixed parasitized red blood cells and Bordetella pertussis can clear an otherwise lethal Plasmodium yoelii infection in 7 days; this protection is abolished by splenectomy before vaccination. Most mice splenectomized following vaccination were able to clear their infections, although their recovery was delayed. When labelled parasitized red cells were injected into mice during an infection, splenic uptake fell from day 3 onwards while uptake by the liver increased. Lymphocytes (mainly T cells) formed the majority of the live cells extracted from livers 7 days after infection, although blasts and myeloid cells were also present. Infected livers from vaccinated mice contained most cells. Less marked increases were observed 7 days after P. berghei infection of vaccinated mice. Examination of liver tissue showed that the sinusoids contained increased numbers of cells and suggested that activation of Kupffer cells was occurring, particularly in vaccinated mice infected with P. yoelii. Homing experiments confirmed the increased trapping of various cells in livers of vaccinated mice infected with P. yoelii. These results suggest an important role for the liver in recovery from blood-stage malaria infection.

Animals↗
PubMed1979

Cell-mediated immunity in the liver of mice vaccinated against malaria.

Mice can be protected against several species of lethal malaria infection by vaccination, and their recovery correlates well with increased anti-malarial antibody levels, particularly IgG (ref.2). However, there is also a good correlation between protection by vaccines and priming for delayed-type hypersensitivity in the skin, although there is no obvious explanation for this effect. We now report an apparent relationship between protection and a cell-mediated immune response involving the migration of various types of cell capable of killing malaria parasites in vitro to the liver. We suggest that the effect of vaccination is to bring together parasites, specific antibody and nonspecific cytotoxic cells, and that the liver may be a major site for their interaction.

Animals↗
PubMed1979

Development and suppression of a population of late-adhering macrophages in mouse malaria.

Changes in phagocytic and adherent cell numbers were compared during the course of infections of mice with Plasmodium yoelii (Py) and P. berghei (Pb) and in vaccinated mice challenged with homologous parasites. Nucleated cells in the spleen increased in number in Py-infected mice and were maximal at the time of recovery. The number of phagocytic cells increased in parallel, as did the number of blood leucocytes. Rates of increase were accelerated in vaccinated mice. Changes in Pb-infected mice resembled controls and blood leucocytes showed no consistent increase. In infected mice, the number of spleen and bone marrow cells which adhered to plastic rose above normal. At some stages of infection, cells which did not adhere in 24 h did so in 72 h. Such late-adhering cells, which resembled macrophages in morphology, were most numerous at the time of recovery. They appeared to be derived from monocyte precursors which matured in culture. Sometimes cells adherent at 24 h suppressed the development of the late-adhering population. Silica invactivated these suppressive macrophages but did not affect the precursors which developed into late-adhering cells. It is concluded that malarial infection stimulates the production of precursors of the macrophage-monocyte series and that their development is regulated by the presence of mature macrophages.

Animals↗
PubMed1979

Antibody responses in mice protected against malaria by vaccination.

Mice were vaccinated against lethal P. yoelii or P. berghei malaria and their immunofluorescent anti-parasite antibody levels followed after infection with live homologous parasites. There was a good correlation between antibody titres (especially IgG) and protection, under various experimental conditions, including: different doses of vaccine, different strains of mice, and increase or decrease of macrophage function. When antiserum was passively transferred to normal recipients, protection against challenge also correlated with antibody titre, though even with high titres only a small number of parasites could be completely eliminated. P. berghei was much more difficult to protect against than P. yoelii, despite similar antibody responses. We conclude that antibody is important in the protective effect of vaccination, but that other properties of both the host and the parasite influence its effectiveness.

Animals↗
PubMed1979

Lethal Plasmodium yoelii malaria: the role of macrophages in normal and immunized mice.

Mice were injected with silica or Corynebacterium parvum, which, respectively, inhibit and stimulate macrophages in vivo, in an attempt to study the role of macrophages in lethal Plasmodium yoelii infection and in mice protected by immunization. In the normal infection, macrophages were able to control parasitaemia for up to 1 week, whereas in immunized mice they appeared to inhibit the sterilizing immune response. A model is proposed in which this dual role of activated macrophages may account for the chronic non-sterilizing course of natural malaria infections.

Animals↗
PubMed1978

Ontogeny of murine-B-lymphocytes. Avidity of antigen binding cells in neonatal and adult mice.

The heterogeneity of avidity of DNP-binding (rosetting) cells has been studied in mice of various ages, in an attempt to learn more about the development of antibody diversity. The results indicate that during the neonatal period murine B cells show a limited heterogeneity of avidity with no "high" avidity ABC being detectable. This implies that the full repertoire of anti-DNP antibodies is only gradually acquired during ontogeny. The results are interpreted as favouring the hypothesis that somatic events are important in the generation of antibody diversity.

Aging↗
PubMed1978

Cell-mediated immunity in mice vaccinated against malaria.

Mice vaccinated with a formalin-fixed preparation of either Plasmodium berghei or P. yoelli exhibited delayed type hypersensitivity (DTH) to the homologous antigen. This manifested itself in increased delayed thickening of antigen-challenged pinnae of the vaccinated mice as compared to the non-vaccinated controls. DTH was also evident in the vaccinated mice using the homing of radio-labelled bone marrow cells (BMC) to the delayed lesion as a criterion of reactivity. When P. yoelii vaccinated mice were given a live infection P. yoelii, a marked migration of BMC into the spleen occurred, with a peak at 48 hr, and it is suggested that this was a systemic response of DTH. The splenic T-cells of P. yoelii-vaccinated animals transformed in vitro with a soluble extract of the homologous parasite. The potential function of cell-mediated mechanisms in immunity to malarial infections is discussed.

Animals↗
PubMed1978

Differential tolerance of thymus-independent and thymus-dependent antibody responses.

The effect of pre-immunization with soluble haptenated serum proteins or haptenated carbohydrates on the subsequent responses to the hapten in thymus-dependent or thymus-independent form was investigated. In certain cases both thymus-dependent and -independent responses were suppressed whilst in others a differential suppression of thymus-independent responsiveness was observed. These results are discussed in terms of B-cell subpopulations and mechanisms of tolerance induction.

Animals↗
PubMed1978

Generation of immunological memory in tolerant mice.

Adult mice pretreated with dinitrophenylated isologous gamma globulins respond very poorly to the hapten presented in immunogenic form. However, the responses of such tolerized and primed animals, or the spleen cells from such mice on adoptive transfer, to small doses of soluble antigen revealed normal secondary responsiveness in terms of size of response, relative affinities of the antibodies produced and antigenic sensitivity. In contrast, mice tolerized in early life and subsequently primed showed diminished responsiveness to secondary challenge, both in the original animals and on adoptive transfer. In this instance cells producing high affinity antibodies seemed to be preferentially deleted.

Animals↗