Showing papers on "Plasmodium berghei published in 1976"
TL;DR: It is suggested that Mycobacterium bovis strain BCG protects by increasing the release of non-antibody soluble mediators of immunity postulated to cause the death of B.microti inside red cells2.
Abstract: Babesia spp. are haemoprotozoans, and some cause diseases of considerable economic importance in cattle. Complete protection against challenge has been recorded only in animals recovered from artificial1 or natural infections with a virulent strain of the organism. We have achieved the same result with B.microti and B.rodhaini, two of the species which parasitise mice, by previous infection with Mycobacterium bovis strain BCG (Bacillus Calmette-Guerin). Evidence is provided that neither antibody specific for surface antigens of the parasites nor increased phagocytic capacity is responsible for this protection. We suggest that BCG protects by increasing the release of non-antibody soluble mediators of immunity postulated to cause the death of B.microti inside red cells2. Preliminary observations on protection against Plasmodium berghei yoelii and P.vinckei are also presented.
269 citations
Journal Article•
TL;DR: The model of mu suppression was shown to be a valuable tool for an evaluation of the cellular basis of immunity to an infectious disease and the requirement for both T cells and B cells for effective resistance to an intercurrent infection with 17XNL P.b. yoelii is established.
Abstract: The course of infection with 17X nonlethal Plasmodium berghei yoelii was examined in BALB/c mice which were deficient in either T cells or B cells. Markedly increased parasitemia and mortality were observed in athymic (nude) mice which had been backcrossed on a BALB/c background (T cell deficient) compared to similar mice which had been grafted with neonatal BALB/c thymus, and were also observed in BALB/c mice suppressed from birth with goat antiserum to mouse mu-chain (B cell deficient) compared to age- and sex-matched BALB/c controls. These results establish the requirement for the presence of both T cells and B cells for effective resistance to an intercurrent infection with 17XNL P.b. yoelii in adult BALB/c mice. Mechanisms by which the requirement for both T cells and B cells could be explained were discussed. The model of mu suppression was shown to be a valuable tool for an evaluation of the cellular basis of immunity to an infectious disease.
105 citations
TL;DR: In vitro experiments suggest a decrease in the capacity of the glass adhering peritoneal exudate cells in vitamin A deficient mice to clear the infection and addition of non glassAdhering cells from sensitized control mice was improved.
Abstract: The ability of vitamin A deficient rats to resist infection with P. berghei was investigated. When 10 × 10 6 erythrocytes bearing the parasite/100 g body weight were given to the vitamin A protein energy undernourished rats, parasitemia developed in these animals at a faster pace than the controls. A high number (60% to 95% ) of red blood cells (RBC) carrying the parasite were noticeable within 6 to 7 days after infection, at which time most animals in this group died. The pair-fed controls (protein-energy undernourished but supplemented with vitamin A) fared perceptibly better with an equivalent load of infection. Control ad libitum fed littermates were able to restrict the infection and neither high parasitemia nor death was noted in this group. Oral supplements of retinyl acetate to vitamin A deficient rats enabled the animals to recover from infection. A subclinical dose of 500 parasitized RBC given at an early stage of the vitamin A deficiency precipitated the deficiency symptoms at a faster rate and led to the development of higher order of parasitemia in these rats beginning from the 10th day after infection as compared to pair fed controls. The yield of glass adhering cells obtainable from peritoneal exudates was low in deficient rats. In vitro experiments further suggest a decrease in the capacity of the glass adhering peritoneal exudate cells in vitamin A deficient mice to clear the infection. This capacity was improved by addition of non glass adhering cells from sensitized control mice.
52 citations
Journal Article•
TL;DR: T dependent responsiveness of spleen cells from uninoculated control animals to the 17XL antigen preparation was observed, but demonstrated a much different (delayed) kinetics from that observed with immune cells.
Abstract: After infection with a nonlethal strain of murine malaria (17XNL Plasmodium berghei yoelli), BALB/c mice are then resistant to a lethal strain (17XL P. b. yoelli). BALB/c mice were infected with 17XNL, and challenged 3 weeks later, after clearing their parasitemias, with 17XL. Three weeks thereafter, spleen cells from such immune animals were used to define an early peaking T-dependent (anti-ϑ sensitive) antigen-specific proliferative response when incubated in vitro with 17XL infected RBC, or a saline soluble 17XL antigen preparation. T dependent responsiveness of spleen cells from uninoculated control animals to the 17XL antigen preparation was also observed, but demonstrated a much different (delayed) kinetics from that observed with immune cells.
51 citations
TL;DR: The syntheses of a number of substituted 1,2,4-triazines as potential antimalarials are described and of the compounds tested, 2,5, and 7 produced cures in mice infected with plasmodium berghei.
Abstract: The syntheses of a number of substituted 1,2,4-triazines as potential antimalarials are described. The structural requirements for antimalarial activity are discussed with reference to the substituents of a phenyl group in the 6 position and amino groups at the 3 and 5 positions. Of the compounds tested, 2,5, and 7 produced cures in mice infected with plasmodium berghei. Compounds 2(3,5-diamino-6-(4-trifluoromethylphenyl)-1,2,4-triazine),3,5,8,12,and 37 produced cures in chicks infected with Plasmodium gallinaceum.
43 citations
TL;DR: It was shown that unfractionated spleen cells, and T cells alone, could transfer protection to syngenic recipients as early as 11 days after infection of the cell donors, and the protection conferred by T cells increased with the duration of the infection in the donors, at least up to 100 days.
Abstract: Experiments were carried out in which unfractionated spleen cells, and T lymphocyte subpopulations characterized by certain experimental criteria, were isolated at various times from rats infected with Plasmodium berghei. By adoptive transfer it was shown that unfractionated spleen cells, and T cells alone, could transfer protection to syngenic recipients as early as 11 days after infection of the cell donors. The protection conferred by T cells increased with the duration of the infection in the donors, at least up to 100 days. The additional presence of B cells in transferred lymphocyte populations enhanced their protective capacity over that shown by T cells alone. The role of T cells in protective immunity to malaria is discussed.
39 citations
TL;DR: Erythromycin inhibits chloroquine-induced pigment clumping in Plasmodium berghei in vitro and potentiated the action of chloroquines against two chloroquINE-resistant strains of rodent malaria, the mildly resistant NS, and the highly resistant RC strains of P. b Berghei, but not against the drug-sensitive N strain.
Abstract: Erythromycin inhibits chloroquine-induced pigment clumping in Plasmodium berghei in vitro. The drug was therefore tested against infections of P. berghei in mice and was found to be active at non-toxic doses. Given orally, the stearate salt was more effective than the base, but subcutaneously the base was more effective than the stearate. Erythromycin potentiated the action of chloroquine against two chloroquine-resistant strains of rodent malaria, the mildly resistant NS, and the highly resistant RC strains of P. berghei, but not against the drug-sensitive N strain.
29 citations
TL;DR: Investigation of the immunological basis of Severity of malarial infection in young rats found it related to the inability of their lymphocytes to respond to Plasmodium berghei antigens early in infection in a way that leads to immunity.
Abstract: Malaria infection in young rats is characterized by high parasitemia, severe anemia, and death. Parasitemia is lower in older rats, and the rats usually survive. This study was designed to investigate the immunological basis of this difference. T cell numbers in the thymuses and spleens of young (4 weeks old) and in adult (18 weeks old) infected and control rats were determined by killing with anti-theta serum and complement. The number of complement receptor lymphocytes (B cells) in spleens was determined after these cells had formed rosettes with sensitized, complement-coated sheep erythrocytes. Infection in young rats was characterized by progressive and severe thymic involution and by decreasing numbers of T and B cells in the spleen. In 18-week-old rats, T cell numbers in the spleen were slightly below those of controls early in infection but exceeded normal values by day 15. Progressive thymic involution was not a feature of infection in adult rats. The number of complement receptor lymphocytes in the spleens of adult rats decreased dramatically early in infection but were nearly normal by day 15. Severity of malarial infection in young rats is related to the inability of their lymphocytes to respond to Plasmodium berghei antigens early in infection in a way that leads to immunity.
26 citations
Journal Article•
TL;DR: The model of µ suppression was shown to be a valuable tool for an evaluation of the cellular basis of immunity to an infectious disease and establishes the requirement for the presence of both T cells and B cells for effective resistance to an intercurrent infection with 17XNL P.b. yoelii.
Abstract: The course of infection with 17X nonlethal Plasmodium berghei yoelii was examined in BALB/c mice which were deficient in either T cells or B cells. Markedly increased parasitemia and mortality were observed in athymic (nude) mice which had been backcrossed on a BALB/c background (T cell deficient) compared to similar mice which had been grafted with neonatal BALB/c thymus, and were also observed in BALB/c mice suppressed from birth with goat antiserum to mouse µ-chain (B cell deficient) compared to age- and sex-matched BALB/c controls. These results establish the requirement for the presence of both T cells and B cells for effective resistance to an intercurrent infection with 17XNL P.b. yoelii in adult BALB/c mice. Mechanisms by which the requirement for both T cells and B cells could be explained were discussed. The model of µ suppression was shown to be a valuable tool for an evaluation of the cellular basis of immunity to an infectious disease.
25 citations
TL;DR: Treatment with glucocorticoid, immunosuppressive, platelet function inhibiting and/or anticoagulant drugs, or indomethacin from the 1st day of infection failed to prevent development of the disease or to lead to its early cure.
Abstract: Mice were infected with 1X 107 Plasmodium berghei Yoelii parasites intraperitoneally. Circulating parasite, malaria antibody and C3 concentrations were measures: parasitaemia and hypocomplementaemia were transient, but the antibody response was persistent. Animals were sacrificed at intervals and their kidneys examined: a glomerulonephritis associates with predominantly mesangial deposits of C3, IgG1, IgM and some IgA always developed after 7 days and persisted for up to 6 mth. Malaria antigen and antibody were demonstrated within the glomeruli. Microscopic haematuria occurred with proteinuria but without marked deterioration in renal function. Strains producing high and low affinity antibody were equally susceptible to the disease. Treatment with glucocorticoid, immunosuppressive, platelet function inhibiting and/or anticoagulant drugs, or indomethacin from the 1st day of infection failed to prevent development of the disease or to lead to its early cure. Eradication of the infection within its first 3 days prevented glomerular deposition of antibody and complement, and infection with a smaller antigen load followed by later treatment also produced subsequent cure.
22 citations
Journal Article•
TL;DR: The reaction of spleen cells from rats infected with Plasmodium berghei to non-specific mitogens has been measured and the reactivity of macrophages, as measured by the release of LAF, was not altered by the disease.
Abstract: The reaction of spleen cells from rats infected with Plasmodium berghei to non-specific mitogens has been measured. The cells have been stimulated in vitro by phytohaemagglutinin, concanavalin-A and by bacterial lypopolysaccharide. In addition the release of lymphocyte activating factor (LAF) by splenic macrophages has been assayed using a heterologous thymocyte culture. The reactivity of spleen lymphocytes from malarious rats is severly affected. The cells do not react either to the T cell-specific mitogens or to the B-cell stimulant. The reactivity of macrophages, as measured by the release of LAF, was not altered by the disease.
TL;DR: A warning is given against the widescale use of WR 122,455 or similar new drugs for human malaria other than in a suitable combination, in order to minimize the danger of the development of resistance to them.
Abstract: The phenanthrenemethanol compound WR 122,455 is an effective blood schizontocide against lines of Plasmodium berghei that are highly resistant to primaquine, sulphonamides, pyrimethamine and cycloguanil. It is also active against the NS line that is moderately resistant to chloroquine. WR 122,455 is inactive against the RC line which is highly resistant to chloroquine. Resistance to WR 122,455 is fairly readily developed by the drug-sensitive N strain of P. berghei, using a relapse technique. Resistance develops very readily to the NS line of P. berghei. Both resistant lines exhibit cross-resistance to quinine, but a roughly normal response to chloroquine, primaquine, sulphonamides, dapsone, pyrimethamine and cycloguanil. Resistance to WR 122,455 is stable through cyclical transmission and through cryopreservation, as well as in the absence of drug selection pressure. The resistant parasites have an essentially normal morphology and virulence. A warning is given against the widescale use of WR 122,455 or similar new drugs for human malaria other than in a suitable combination, in order to minimize the danger of the development of resistance to them.
TL;DR: The synthesis of 1-alkyl-8-(aminoalkylamino)-6-methyl1-1,2,3,4-tetrahydroquinolines, and most of the intermediates used in their preparation were tested against Plasmodium berghei in mice, and a few compounds were tested for prophylactic activity against PlAsmodium cynomolgi in rhesus monkeys.
Abstract: The synthesis of 1-alkyl-8-(aminoalkylamino)-6-methyl1-1,2,3,4-tetrahydroquinolines, 8-(4'-amino-1'-methylbutylamino)-6-methoxy-1-methyl1-1,2-dihydroquinoline, 5-substituted 8-(4'-amino-1'-methylbutylamino)-1-methyl-1,2-dihydroquinolines, 8-alkylamino-1-(2-N,N-diethylaminoethyl)-6-methoxy-1,2,3,4-tetrahydroquinolines, 1-)2-N,N-diethylaminoethyl)-6-methoxy-1,2,3,4-tetrahydroquinoline, 1-(2-N,N-diethylaminoethyl)-8-(2-N,N-diethylaminoethylamino)-6-methoxy-1,2,3,4-tetrahydroquinoline, and 2-substituted 8-methoxy-5,6,-dihydro-4-imidazo [i,j]quinolines is described. These compounds as well as most of the intermediates used in their preparation were tested against Plasmodium berghei in mice, and a few compounds were tested for prophylactic activity against Plasmodium cynomolgi in rhesus monkeys.
TL;DR: It was demonstrated in vitro, with one strain of P. berghei, that phagocytes more readily ingested parasites in the presence of immune serum than inThe presence of normal serum, which suggests thatPhagocytosis of the antibody coated parasite probably was required to prevent infection.
TL;DR: It is suggested that a direct vascular exposure of the splenic lymphoid-macrophage elements to the parasite may be responsible for the initial early alterations in the PFC response while the impairment in serum antibody titers and splenic phagocytic activity may be a result of the pathological alterations occurring later in the infection.
Abstract: Malaria-induced immunosuppression has been demonstrated in humans and experimental animals. The suppressed immune response has been suggested to be primarily humoral and not cellular in nature, since classical lymphocytic cell-mediated responses have been reported to be normal. Since previous results have demonstrated that an impairment in macrophage antigen processing may be a contributing factor in malaria-induced immunosuppression, the present studies were conducted to determine if the macrophage/reticuloendothelial system (RES) alteration occurs parallel to the course of the malarial infection and if the impairment in antibody formation is temporally related to the RES alteration. The present study has demonstrated that a profound impairment in splenic direct plaque forming cell (PFC) formation occurs in malaria-infected Balb/c mice which had been immunized with sheep erythrocytes (SRBC) either 2 or 4 days after inoculation with Plasmodium berghei, NYU-2 strain. Serum hemagglutinin titers were significantly depressed in mice which received the SRBC 4 days post-inoculation; however, no alterations in antibody titers were observed in mice immunized with SRBC 2 days post-inoculation. Coincident with the depression of serum antibody titers at the day 4 immunization period was a profound increase in the vascular clearance of 51Cr-SRBC with an enhanced hepatic uptake of the 51Cr-SRBC and a decreased splenic localization of the labelled erythrocytes. It is suggested that a direct vascular exposure of the splenic lymphoid-macrophage elements to the parasite may be responsible for the initial early alterations in the PFC response while the impairment in serum antibody titers and splenic phagocytic activity may be a result of the pathological alterations occurring later in the infection, e.g., tissue anoxia, anemia, and hemolysis.
TL;DR: Seruminduced hypersensitivity protected some mice against intraperitoneal sporozoite challenge but not against intravenous challenge, and it was concluded that hypersensitivity may possibly be at least partly responsible for protection by injections of 70 salivary glands, but that sporozoites immunity is not primarily due to hypersensitivity.
TL;DR: Results indicate that these obligate intracellular parasites have a wide range of osmotic sensitivities and that they are capable of existing for short periods in various osmosis environments ranging from 100–2500 mOsm without complete loss of infectivity.
TL;DR: Incubation of blood cells of malaria-infected animals with normal serum "in vitro" resulted in a significant inhibition of the CRA of the normal serum, and this inhibition was shown to operate through the alternate complement pathway.
Abstract: In the course of rodent malaria, the ability of mouse serum to release immune complexes from lymphocytes (complex-release, or CRA), a complement dependent function, becomes profoundly altered. These alterations occur in parallel with changes in the serum levels of the third complement component (C3). A transitory but significant increase in CRA and C3 was noticed during the first 3 days after blood-induced Plasmodium berghei infection. This was followed by a progressive decrease in CRA, which was extremely low in the 2nd week after injection. At this time, C3 levels were about 25% of those found in normal mouse serum. Incubation of blood cells of malaria-infected animals with normal serum “in vitro” resulted in a significant inhibition of the CRA of the normal serum. This inhibition was shown to operate through the alternate complement pathway. In addition, a considerable proportion of hypocomplementemic malarious sera also had an inhibitory effect on the CRA of normal sera.
TL;DR: In this article, a series of 9-phenanthrene amino alcohols has been prepared in which each compound bears from one to five halogen or halogen-containing moieties.
Abstract: A series of new 9-phenanthrene amino alcohols has been prepared in which each compound bears from one to five halogen or halogen-containing moieties. A number of these compounds are extremely active against Plasmodium berghei in the mouse. Some structural requirements for optimal efficacy are considered.
TL;DR: Immunization of mice with extracts of mosquito thorax failed to protect them, indicating that mosquito antigens were not directly responsible for the immunity observed in the basic experiments.
TL;DR: It was found that the course of the L. enriettii infection was affected by P. yoelii and that this effect depended on the relative timing of the two infections.
Abstract: Plasmodium yoelii infection was established in hamsters, and the effect of this type of malaria on concurrent Leishmania enriettii infection was examined. It was found that the course of the L. enriettii infection was affected by P. yoelii and that this effect depended on the relative timing of the two infections. A chronic malarial infection with Plasmodium berghei was also established in hamsters, and this was found to affect the course of a concurrent L. enriettii infection in a similar manner to P. yoelii. These results are discussed in relation to current knowledge of the immunosuppressive effects of plasmodia.
TL;DR: Mouse erythrocytes parasitized with PlasModium berghei or Plasmodium yoelii were separated by ultracentrifugation using preformed isodensity gradients of the discontinuous type and cells are not altered morphologically or physiologically (as assessed by infectivity) by the treatment.
Abstract: Mouse erythrocytes parasitized with Plasmodium berghei or Plasmodium yoelii were separated by ultracentrifugation using preformed isodensity gradients of the discontinuous type. Three fractions were obtained following centrifugation, the upper of which contained greater than 90% of all schizont-infected cells added to the gradient. The gradient material, Stractan II, is an arabinogalactan polysaccharide and appears to yield results similar to those available using gradients of bovine serum albumin. Cells are not altered morphologically or physiologically (as assessed by infectivity) by the treatment.
Journal Article•
TL;DR: The drugs 2,4-diamino-6-(2-naphthyl-sulfonyl)-quinazoline and its tetrahydro analog were found to act synergistically in reducing the parasitemia of Plasmodium berghei infected mice.
Journal Article•
TL;DR: The characteristics of a selected population of small blood stage parasites obtained by differential centrifugation of a population of P. berghei parasites freed by continuous flow sonication are described.
Abstract: The characteristics of a selected population of small blood stage parasites obtained by differential centrifugation of a population of P. berghei parasites freed by continuous flow sonication are described. About 10% of these free parasites are merozoites, many others are transitional forms having some merozoite characteristics. The parasite preparations are infectious and sufficiently resistant to incubation at 37 degrees C to be useful experimentally. Disc gel electrophoresis analysis indicates that these small parasites differ in composition from an unselected intraerythrocytic P. berghei population.
Journal Article•
TL;DR: Comparison of the antigens found in the sera of infected animals with antIGens prepared by physical desintegration of parasite material showed that in theSera antigen appeared which could not be demonstrated in the plasmodial extracts.
Abstract: Using the fluorescent antibody technique it was possible to demonstrate antibodies in the sera of F1(C57B1 x DBA)-mice already during the first week of infection with Plasmodium berghei, strain K 173. These antibodies reached high titers during the second and third week, but, nevertheless, the animals died from the infection. Coincidently with the FAT-antibodies plasmodial antigens could be found in the sera of infected mice. The numbers of these antigens increased in the course of the infection. Finally up to seven could be precipitated by using a double diffusion technique in cellulose acetate membranes. Since antibodies directed against these antigens were only found in immune animals they must be different from the antibodies measured in the FAT. Comparison of the antigens found in the sera of infected animals with antigens prepared by physical desintegration of parasite material showed that in the sera antigens appeared which could not be demonstrated in the plasmodial extracts. If parasite material was phagocytized by macrophages in cell cultures in the culture supernatant also antigens appeared which could not be found in the plasmodial extracts. Similar antigens were found if isolated parasites were allowed to degrade without the action of phagocytic cells.
TL;DR: 5-(p-Anisyloxy)-6-methoxy-8-(5-isopropylaminopentylamino)quinoline was resynthesized for evaluation in the Plasmodium berghei and monkey prophylactic tests and showed significant antimalarial or proPHylactic activity.
TL;DR: Immunogenicity was found to depend upon the continued survival of some (noninfective) parasites in the host, and appears to be determined by antigens different from those responsible for infectivity.
Journal Article•
TL;DR: Serum-soluble malaria antigen in probably responsible for forming the soluble immune complex which causes glomerulonephritis in infected mice.
Abstract: Swiss albino mice infected with Plasmodium berghei berghi showed the serum-soluble malarial antigen and antibody on day 10 of infection onward. Immune complex nephritis in these mice developed on the seventh day after inoculation. The infected kidneys revealed the deposition of mouse gamma globulin, mouse beta1C globulin and malaria antigen along the capillary wall of the glomeruli. Proteinuria was detected on seventh day of infection. Serum-soluble malaria antigen in probably responsible for forming the soluble immune complex which causes glomerulonephritis in infected mice.