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A N Jayawardena

Publications and source records attributed to A N Jayawardena.

15 recordsLinked to original sources
PubMed1983

Enhanced expression of H-2K and H-2D antigens on reticulocytes infected with Plasmodium yoelii.

The 17XNL strain of Plasmodium yoelii induces a highly effective and permanent T-cell dependent immunity in mice of the CBA strain; the lethal variant P. yoelii 17XL and P. berghei (ANKA) fail to activate an effective immune response in the same host. These differences in immunogenicity are unexplained. We recently observed that in CBA/CaJ mice the intracellular blood stages of P. yoelii 17XNL were almost exclusively within reticulocytes whereas lethal P. yoelii 17XL and P. berghei (ANKA), at comparable stages of infection, were predominantly erythrocytic. Induction of a reticulocytosis converted the normally lethal P. yoelii 17XL infection into a nonlethal one, and reticulocytic P. yoelii was shown to be more immunogenic than the erythrocytic form. Since one of the differences between reticulocytes and erythrocytes that might have influenced the development of immunity was greater expression of MHC antigens of the former cell type we examined the expression of H-2K, H-2D and Ia on reticulocytes infected with P. yoelii 17XNL. These cells showed a very marked increase in H-2K and D antigen expression compared to normal reticulocytes or erythrocytes. No Ia was detected. Red blood cells (RBC) infected with lethal P. yoelii 17XL or P. berghei showed no increase in H-2K or H-2D antigen expression. Finally, the level of expression of H-2K on P. yoelii 17XNL parasitized red blood cells from different strains of mice correlated closely with the ability of these strains to control the infection.

Animals↗
PubMed1982

Surface coat variant antigen of Trypanosoma brucei brucei: its clearance from blood and concentration in organs of normal, infected, and immune mice.

Experiments were conducted to determine the fate of variant antigen once it was shed from the surface of Trypanosoma brucei brucei. Radioiodinated variant antigen was administered intravenously to normal mice, mice immunized to the homologous variant antigen, and mice infected with an antigenically dissimilar (heterologous) T. brucei brucei variant. The variant antigen was cleared slightly faster in infected and immune animals. Though over 80% of the variant antigen was cleared in all animals within 4 h, traces of radioactivity could be detected in the peripheral blood at 48 h postinjection. At 1 h postinjection, most of the variant antigen had collected in the liver, kidneys, bone marrow, spleen, lungs, thymus, and lymph nodes (listed in the order of decreasing radioactivity). At 24 h, the kidneys, liver, and spleen retained the most radioactivity. The kidneys had 10 to 20 times, the liver had 8 to 10 times, and the spleen had 5 to 7 times more variant antigen than was present in the organs' blood supply. At 48 h postinjection, two-thirds of the radioactivity present at 24 h remained in these tissues. The livers and spleens from infected animals had, on a per gram of tissue weight basis, reduced uptake of the soluble antigen whereas their lungs had an increased uptake. Radioactivity in blood and organs was proved to be associated with protein by electrophoresis/autoradiography and precipitation of radioactive protein of tissue extracts.

Animals↗
PubMed1982

T cell-mediated immunity in malaria. I. The Ly phenotype of T cells mediating resistance to Plasmodium yoelii.

CBA mice that recover from Plasmodium yoelii 17X infection are resistant to reinfection. T cells from these mice transfer immunity to nonimmune recipients. To analyze the nature and mode of action of these T cells, we transferred selected subsets into T cell-deprived recipients. Treatment of the T cells with anti-Ly-1 but not anti-Ly-2 serum and C abrogated their ability to transfer immunity. A mixture of anti-Ly-1 and anti-Ly-2 serum-treated cells (i.e., a population devoid of Ly-123 cells) transferred a level of immunity comparable to that of unselected T cells. Hence, the T cells mediating resistance to P. yoelii 17X were primarily of the Ly-1+23- phenotype. T cell-deprived mice reconstituted with these immune Ly-1 cells developed a) high levels of IgM and IgG antibodies, b) DTH responses to parasitized RBC, and c) enhanced blood monocyte responses. The addition of immune B cells to the Ly-1 population dramatically increased its ability to transfer immunity and induce antibody production. B cells from immune CBA/N mice had no such effect. Thus, the transfer of optimal protective immunity against malaria stems from an interaction between Ly-1 cells and a select B cell subset that CBA/N mice lack. This "selective synergy" is a protective mechanism against pathogens that has not been previously appreciated.

Animals↗
PubMed1982

Comparative analysis of procedures used to isolate variant antigen from Trypanosoma brucei rhodesiense.

Comparisons made among various procedures leading to the isolation of variant antigen from Trypanosoma brucei rhodesiense bloodstream trypomastigotes. As a means of parasite disruption, freeze-thawing solubilized 36% more variant antigen than did sonication. Protease inhibitors were important additions to the suspension prior to cellular disruption. If trypanosomal extracts were frozen for at least 1 wk prior to chromatographic isolation of variant antigen, recovery of the antigen was reduced by 70%. Ion exchange chromatography was more efficient in the isolation of variant antigen than either lentil-lectin or antibody-affinity columns. All three methods yielded qualitatively similar variant antigen preparations. Using the most efficient isolation procedure tested, about 4 mg of variant antigen was isolated per 10(10) bloodstream trypomastigotes. The most efficient means of isolating variant antigen from plasma of infected rats began with passage of fresh plasma with protease inhibitors through an ion exchange column followed by antibody-affinity chromatography. This resulted in a preparation that was 52% variant antigen, a 370-fold concentration over plasma levels.

Animals↗
PubMed1979

Immunity to Plasmodium yoelii and Babesia microti: modulation by the CBA/N X-chromosome.

CBA/N mice carry an X-linked recessive defect expressed in cells of the B cell lineage. The major deficiency in these mice is an almost complete inability to respond to certain thymus-independent antigens, such as pneumococcal polysaccharide type III (S III). We have examined the responses of mice carrying the CBA/N X-chromosome to the malaria parasite Plasmodium yoelii and the piroplasm Babesia microti. We have found that the duration and severity of these infections is increased in mice carrying the CBA/N X-chromosome and that this is associated with a markedly defective IgM antibody response to the parasitized red cell and a failure to produce autoantibodies to bromelain-treated mouse RBCs. An autoimmune response directed at modified determinants on the red cell membrane may be one of the factors involved in the control of these infections.

Babesia↗
PubMed1979

Experimental malaria in the CBA/N mouse.

CBA/N mice carry an X-linked, recessive gene, which results in the absence of a B cell subset, and is expressed primarily as an inability to respond to a certain class of thymus-independent antigens. We have examined the responses of these mice to the malaria parasite Plasmodium yoelii and found that primary infections induced by this parasite are more severe and last longer in mice with X-linked defect than in normal controls. The decreased resistance of the defective mice is associated with a striking deficiency in their IgM antibody response. After recovery from a primary infection, defective mice resist reinfection with the homologous parasite as well as normal mice. Although as resistant as normal controls, B cells from defective mice transfer considerably less immunity to naive recipients than B cells from normal animals. Hence, two modes of thymus-dependent protective immunity may contribute to the host response to P. yoelii. Control of an acute primary infection appears to involve a thymus-dependent antibody response that CBA/N mice are deficient in. Resistance to reinfection may be mediated primarily by a different mechanism.

Animals↗
PubMed1978

The immunological response of CBA mice to P. yoelii. II. The passive transfer of immunity with serum and cells.

CBA mice infected with the malaria parasite Plasmodium berghei yoelii (P. yoelii) develop a self-resolving infection lasting 15-18 days; on recovery from a primary infection they are immune to further infection. Cell and serum transfers from immune to non-immune mice were used to analyse the mechanism of resistance. Whereas serum from mice which had recovered from a single infection was ineffective in transferring immunity, hyperimmune serum (from mice repeatedly challenged with P. yoelii) protected against challenge inocula of 10(4) and 5 X 10(4) but was ineffective against higher inocula (10(5)). Doses of serum which completely protected intact mice were ineffective when administered to T-cell deprived recipients. The injection of spleen cells from recovered mice conferred immunity on both normal and T cell deprived mice. Pretreatment of immune cell donors with cyclophosphamide reduce the ability of spleen cells to transfer immunity. Treatment of the immune cells with an anti-Thy 1 antiserum and complement in vitro did not abrogate their protective effect. The significance of these results is discussed in relation to the effector mechanisms which might operate in murine malaria.

Animals↗
PubMed1978

Activation of distinct helper and suppressor T cells in experimental trypanosomiasis.

Spleen cells taken from mice soon after infection with Trypanosoma brucei S 42 enhance the primary in vitro antibody response of normal spleen cells to sheep red blood cells (SRBC), but do not affect their response to DNP-Ficoll. Spleen cells harvested later in the infection (day 6 onwards) suppress the antibody response of normal spleen cells to both SRBC and DNP-Ficoll. The enhancing and suppressive effects of "infected" spleen cells are sensitive to treatment with anti-Thy 1.2 anti-serum and complement, and can be mediated by nylon wool-purified populations of T cells. The enhancing T cell is sensitive to ALS, not lost within 4 weeks of adult thymectomy, and bears the Ly-1+, 23- phenotype. The suppressor T cell is insensitive to ALS, lost within 20 weeks of adult thymectomy, and bears the Ly-1+, 23+ phenotype. The significance of the activation of distinct helper and suppressor T cells is discussed in relation to the pathogenesis of trypanosomiasis.

Animals↗
PubMed1977

Suppressor cells in mice infected with Trypanosoma brucei.

Within 2 to 3 days of infection with Trypanosoma brucei strain S42, the ability of spleen cells from infected CBA mice to mount a primary in vitro antibody response to sheep red blood cells (SRBC) is profoundly reduced, and suppressor cells are generated as detected by cell mixture experiments. Suppressor cell activity lies in the T and adherent cell compartments of spleens from infected mice, but not in the B cell compartment, although antibody responses to a thymus-independent antigen, DNP-Ficoll, are significantly reduced. Suppression of antibody responses of normal spleen cells depends on viable cells from infected mice. The trypanosome, itself, plays no direct role in suppression, and we have ruled out the possibility of antigenic competition as a mechanism of suppression. Our data is consistent with the model of suppressor T cells induced by concanavalin A mitogenesis. We hypothesize that trypanosome antigens may directly stimulate T cells with the concomitant release of factors with affinity for macrophage surfaces thus becoming suppressive for T and B cell responses.

Animals↗
PubMed1977

The immunological response of CBA mice to P. yoelii. I. General characteristics, the effects of T-cell deprivation and reconstitution with thymus grafts.

Experimental infection of normal CBA mice with the parasite Plasmodium berghei yoelii (P. yoelii) resulted in a mild, non-fatal and self-limiting infection which lasted for 15-17 days. Animals which recovered from the primary infection were immune to reinfection though parasites could be detected in the kidneys of such mice 4 weeks after recovery from infection. (No plasmodia were demonstrated in the peripheral blood and other tissues examined.) In T cell-deprived mice, P. yoelii infections resulted in a progressive parasitaemia and proved fatal in 35-40 days. Studies of fluorescent antibody levels and morphological changes in the spleens of infected normal and T cell-deprived mice showed that while normal mice produced high levels of IgG1, IgG2 and IgM antiplasmodial antibodies and developed a strong and sustained germinal centre response, in T cell-deprived animals the production of IgG1 antibodies was almost completely abolished and the germinal centre response severely impaired. Reconstitution of T cell-deprived mice with syngeneic thymus grafts resulted in partial restoration of immunological responsiveness. P. yoelii infections in these reconstituted animals ran a self-limiting course akin to that seen in normal CBA mice; the level of protective immunity and the germinal centre response correlated with the degree of reconstitution achieved.

Animals↗