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Biomedical subjects

M Pinder

Publications and source records attributed to M Pinder.

At least 91 records · Page 5Linked to original sources
PubMed1987

Identification and selection of cattle naturally resistant to African trypanosomiasis.

Cattle were exposed to natural trypanosome challenge in an area of high Glossina density (Samandéni, Burkina Faso) for various periods of time during 1982, 1983, 1984 and 1985. All of 30 Zebu proved to be sensitive to trypanosomiasis i.e. they died or were treated in extremis in 10 +/- 4 weeks. Twenty-one (31%) Baoulé were as sensitive as the Zebu while 47 (69%) were resistant i.e. they survived in good condition. Twenty Ndama/Baoulé crosses, indigenous to Samandéni were all resistant. Weekly blood samples were taken (2,317 in total) for the determination of parasitaemia and packed cell volume (PCV) as a measure of anaemia, the most important pathological feature of cattle trypanosomiasis. In both Zebu and sensitive Baoulé 59% of the blood samples showed positive parasitaemia, of which 38% and 52% respectively were T. congolense the major cattle pathogen in the area considered. In resistant Baoulé and Ndama/Baoulé 11% and 10% of the samples were positive for trypanosomes of which only 4% and 2% were T. congolense respectively. PCV decreased from 35 to 20 in Zebu, 39 to 20 in sensitive Baoulé and 40 to 34 in resistant Baoulé, there was no change in the indigenous Ndama/Baoulé. Six Ndama/Baoulé indigenous to Samandéni remained resistant to trypanosomiasis when moved to another area of high Glossina challenge. Seven Ndama/Baoulé calves, conceived in Samandéni but born and kept for 2 1/2 years in a Glossina-free area, also proved to be resistant to challenge. Twelve Baoulé calves, born from cattle selected under natural field challenge, and which had not come in contact with trypanosomes for the first 10 months of their life, proved to be resistant when exposed in the field. These observations show that some, but not all, cattle from the Baoulé breed are naturally resistant to African trypanosomiasis, that this resistance does not need repeated exposure to trypanosomes early in life but appears to be inherited and functional against many types of antigenically different trypanosomes. Thus, selective breeding of trypanoresistant animals and their successful introduction, without trypanocidal drug protection, into areas of high Glossina density appears feasible.

Animals↗
PubMed1987

High density lipoprotein levels in the serum of trypanosensitive and trypanoresistant cattle. Changes during Trypanosoma congolense infection.

Nonpermissiveness to trypanosome infection has been correlated in some instances with the presence of toxic serum factors, e.g. high density lipoproteins (HDL) of human serum can lyse T.b. brucei. The present study examines the possibility of a role for such factors in West African cattle that are resistant to trypanosomiasis. Cattle used in this study were previously selected as resistant or sensitive to trypanosomiasis under heavy natural Glossina challenge. - A comparison of the direct effect of serum from trypanoresistant and trypanosensitive Baoulé cattle on the development of pathogenic bloodstream or metacyclic forms of T. congolense, using modifications of the blood infectivity incubation test, failed to demonstrate a difference between these cattle. High density lipoproteins and cholesterol levels were compared in 115 cattle of known sensibility to trypanosomiasis. HDL-cholesterol formed 91% of the total plasma cholesterol. HDL-cholesterol levels in Zebu (mean of 111.8 mg/100 ml) were significantly higher than those in Baoulé cattle (86.2 mg/100 ml). There was no significant difference, however, in these levels between trypanoresistant (73.4 mg/100 ml) and trypanosensitive (84.5 mg/100 ml) Baoulé. Alterations in HDL-cholesterol levels were monitored during an experimental cyclic infection with T. congolense in 5 Zebu and 9 Baoulé. HDL-cholesterol levels decreased in all animals concomitantly with the appearance of trypanosomes in the blood and returned rapidly to their starting values after parasite elimination following drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Mechanisms of self-cure from Trypanosoma congolense infection in mice.

The mechanism(s) of resistance to African trypanosomiasis caused by Trypanosoma congolense was investigated by using the Dinderesso/80/CRTA/3 isolate to which C57B1/6 are resistant (low parasitemia and self-cure) and BALB/c sensitive (high parasitemia and death). The resistance of C57B1/6 is similar to that found in some natural hosts of African trypanosomes such as certain indigenous West African cattle and wild Bovidae. The antibody response to epitopes exposed on the variant surface glycoprotein of a clone obtained from the Dinderesso/80/CRTA/3 isolate was measured by a complement-mediated lysis assay in C57B1/6 and BALB/c. After infections with 10(4), 10(5), or 10(7) motile organisms, antibody appeared in C57B1/6 4 to 8 days earlier than in BALB/c. Peak antibody titers were similar in both strains but were reached about 4 days earlier in C57B1/6. In this strain, antibody appeared during and controlled the first wave of parasitemia, whereas in BALB/c, parasitemia reached a plateau above 10(8) organisms per ml before antibody could be detected, and at this time the animals were dying. At peak antibody response, the proportion of immunoglobulin (Ig) M and IgG antibody was the same in both strains. The antibody response had the same kinetics in C57B1/6 and BALB/c after injection of 10(4), 10(5), and 10(7) lethally irradiated but intact parasites, but the peak titers were 10(3) to 10(4) times lower than after live challenge. The response to nonirradiated trypanosomes appeared to be T cell independent, because the antibody titers were the same in congenitally athymic nu/nu and normal C57B1/6, and no evidence for the induction of T cell activity could be demonstrated in the infected nude mice. A role for trypanolytic serum factors in resistance could not be demonstrated. The extent of immunosuppression after infection with nonirradiated organisms was compared in the two strains by measuring the in vitro response of their splenic lymphocytes to concanavalin A, pokeweed mitogen, and allogeneic cells and their ability to mount an in vivo response to an unrelated trypanosome challenge. Both strains were partially immunosuppressed during rising parasitemia, but as C57B1/6 controlled parasitemia, immunosuppression was gradually reversed, whereas in BALB/c it became worse. Several explanations might account for the resistance of C57B1/6 to the Dinderesso/80/CRTA/3 isolate of T. congolense. It appears that an early immune response is a decisive factor in this resistance.

Animals↗
PubMed1986

Susceptibility and immune responses of zebu and taurine cattle of West Africa to infection with Trypanosoma congolense transmitted by Glossina morsitans centralis.

Following tsetse-transmitted infection with Trypanosoma congolense, major differences in development of localised skin reactions, the ability to control parasitaemia, the degree of anaemia and in antibody response to trypanosomes were found between the reputedly trypanotolerant breeds of cattle (N'Dama, N'Dama/Baoule crosses, Baoule) and the trypanosusceptible West African Zebu. The local skin reactions that developed in the Zebu were large and severe while those that occurred in the other breeds were smaller and less severe or mild. The timing of appearance of parasitaemia and the height of the first peaks were similar in all the animals, but the Zebu were less able to control subsequent waves of parasitaemia. Possibly reflecting these events, it was only in the Zebu that significant anaemia developed. Neutralizing antibody against homologous metacyclic trypanosomes developed between 14 to 18 days after infection in all breeds of cattle; however, marked differences were found when antibody to trypanosomes derived from first peak parasitaemias were tested in the Zebu and Baoule. Neutralizing antibody against these parasites appeared in the Baoule on day 24 but were not detected in Zebu until day 51. Furthermore, the antibody titres were 3 log2 higher in the Baoule. It was concluded that the trypanotolerance exhibited by the West African taurine cattle might be related to a) their ability to control trypanosome numbers in the skin and in the bloodstream, an outcome that was possibly brought about by the earlier and superior immune response and b) failure to develop anaemia which might be associated with their capacity to control parasitaemia.

Africa, Western↗
PubMed1985

Trypanosoma brucei: analysis of relapsing populations in sensitive and resistant breeds of cattle.

The clone DiTat 1.1 of Trypanosoma brucei brucei was injected into four bovids, and clones obtained from successive waves of parasitemia were used to study the expressed variant-specific surface glycoprotein repertoire. Twenty-four clones were obtained which could be classified into 12 different variable antigen types, in addition to the clone injected, using agglutination or immunofluorescence with monospecific antisera. The variable surface glycoproteins of the 25 clones were extracted using the detergent octyl-beta-D-glucopyranoside in the presence of the protease inhibitor, N-cbz-L-phenylalaninechloromethylketone. The molecular weights varied from 52,000 to 69,000 and the pI from 5.0 to 8.8. The virulence of 14 clones representing 13 variable antigen types was ascertained in mice. The mean survival time ranged from 20.5 to 43.0 days. Clones isolated from early peaks of parasitemia in the bovid were the most virulent while clones derived from later peaks were less virulent. It seems that organisms of diminishing virulence appear in bovids, leading to self-cure of the disease. All clones were sensitive to human serum in a blood infectivity inhibition test. Antibody against all virulent clones appeared in 20 cattle (10 Zebus, 10 Baoulés) which had been injected with T. brucei DiTat 1.1. There was no evidence for parasites of high or low virulence being preferentially expressed in resistant or sensitive hosts.

Agglutination Tests↗
PubMed1985

High and low responsiveness of bovine lymphocytes to Trypanosoma brucei in vitro: lack of correlation with resistance to trypanosomiasis.

Bovine peripheral blood lymphocytes (PBL) were stimulated to proliferate in vitro by live, irradiated or freeze-thawed Trypanosoma brucei, but not by the isolated variant surface glycoprotein. The optimal dose was 10(5) trypanosomes per 5 X 10(5) lymphocytes in 0.2 ml. Maximal proliferation was at day 5. Of the 98 cattle tested, 36 were high-responders (stimulation indexes 20-104), 49 were low or non-responders (SI 1-10) and 13 were intermediate. The responder status of individual animals did not change over a period of 1 year, nor did it alter following deliberate trypanosome infection. The stimulation was dependent on macrophage/monocyte type accessory cells, and this co-operation did not seem to be MHC restricted. Lack of stimulation of non-responder PBL did not appear to be due to the activation of suppressor cells. Accessory cells from non-responder animals could complement PBL from responders, but accessory cells from responders could not complement non-responder PBL. Responsiveness is therefore a characteristic of lymphocytes. Analysis of the surface markers of these lymphocytes or the blast cells generated in culture showed that they were a subpopulation of T cells, possibly TH cells. Analysis of PBL from 98 animals, which had been selected for trypanoresistance or trypanosensitivity under natural tsetse fly challenge, failed to establish a correlation between resistance and level of lymphocyte stimulation by trypanosomes in vitro.

Animals↗
PubMed1984

Trypanosoma congolense: genetic control of resistance to infection in mice.

Primary isolates of Trypanosoma congolense show a range of virulence in NMRI mice. Stabiliates derived from an isolate (Dinderesso/80/CRTA/3) which showed moderate virulence in most NMRI mice (moderate parasitemia and survival) were used in inbred mice. C57Bl/6 were resistant with low parasitemia and survival. Parasitemias were higher in males than females. BALB/c were the most sensitive of the strains tested and died with fulminating parasitemia. Inheritance of resistance, defined as low parasitemia, was studied using these two strains. Male F1 showed high parasitemia; the backcrosses of F1 to the resistant parent had a ratio of one susceptible to one resistant product; the product of F1 to susceptible parent were all susceptible; and the F2 crosses showed a ratio of three susceptible to one resistant product. The results obtained with female F1, backcrosses, and F2 mice showed similar segregation to that found using males, but the range of parasitemia was always 1-2 log10 lower, except for the F1 backcrossed to BALB/c, where female and male parasitemia were undistinguishable. The segregation ratios were identical whether resistant females were crossed with sensitive males or vice-versa. The results obtained are compatible with resistance being a recessive trait controlled by a single autosomal gene (or gene cluster). In addition, sex-associated factors appear to confer higher resistance in females.

Animals↗
PubMed1984

The appearance of isometamidium resistant Trypanosoma congolense in West Africa.

The frequent reappearance of patent parasitemia, mainly Trypanosoma congolense, in cattle maintained under isometamidium prophylaxis in the Upper Volta indicated that drug-resistant forms might be appearing. To investigate this possibility, trypanosome stocks were isolated in mice, their isometamidium sensitivity estimated and compared to that of stocks isolated before drug use was widespread. Most T. congolense stocks isolated in 1982-1983 were 4-8 times less sensitive to isometamidium than those isolated in 1979-1980.

Animals↗
PubMed1984

Anti-trypanosome specific immune responses in bovids of differing susceptibility to African trypanosomiasis.

A clone of Trypanosoma brucei brucei (DiTat 1.1) was injected into 32 bovids of various breeds, 11 animals being kept as controls. Five animals, Simmental-Ndama F1 crosses, were extremely sensitive. They showed overt symptoms and one died on day 18 of infection despite treatment with a trypanocidal drug. Seven other animals became ill but recovered progressively and cleared the infection. Twenty animals, of breeds generally considered to be trypanosensitive as well as ones from trypanotolerant breeds, did not show symptoms apart from anaemia and cleared the infection. Putative protective antibody, i.e. directed against exposed determinants on the coat variant-specific glycoprotein, was detected by agglutination, complement-mediated lysis and inhibition of infectivity. All animals showed a primary immune response consisting of IgM whose kinetics and amplitude were indistinguishable between animals of differing sensitivity. The response was long-lasting, whether the animals had been treated or not with a trypanocidal drug 3 weeks after infection, and antibody of IgG1 and IgG2 types were detected in certain sensitive as well as resistant animals after 2 months. Some animals were rechallenged with DiTat 1.1 either 1 year after the primary infection or 6 months after inoculation of irradiated trypanosomes. Peak titres of antibody were lower than was the case following primary infection but higher levels of mercaptoenthanol-resistant antibodies were seen. In no case was there any difference in the response of sensitive or tolerant animals. Our results do not support the idea that resistance of certain bovids to African trypanosomiasis is due to a better protective antibody response.

Animals↗
PubMed1983

Trypanotolerance. an individual not a breed character.

Ten animals from a reputedly trypanosensitive bovine breed, the Zebu, and ten from a reputedly trypanotolerant breed, the Baoulé, were exposed to natural trypanosome challenge in an area of high Glossina density. The ten Zebus and five of the Baoulés died within 6 to 11 weeks with heavy parasitaemia and severe anaemia. The five other Baoulés showed little or no parasitaemia, no anaemia and were all in good condition after weeks of exposure: Seven animals of a herd of Baoulé/Ndama crosses indigenous to the same area were followed concurrently and showed very rare or no patent parasitaemia. Clearly, only some individuals within a "trypanotolerant breed" are able to withstand natural fly challenge. Selection of trypanotolerant animals has to be done on an individual basis and not on the biometrical characteristics of the breed.

Animals↗
PubMed1981

Proliferation and lymphocyte stimulatory capacity of Theileria-infected lymphoblastoid cells before and after the elimination of intracellular parasites.

A prominent pathogenic facet of Theileria infections is that the parasite infects lymphocytes and 'transforms' them into parasitized lymphoblastoid cells which are highly proliferative and can be cultured indefinitely in vitro. To analyse the relationship between the intracellular parasite and lymphocyte transformation we have studied the effects of eliminating parasites from these lymphoblastoid cells using the naphthoquinone derivative 993.C. Treatment of Theileria-infected lymphoblastoid cells with 993.C gradually eliminates intracellular parasites but cell proliferation is not inhibited until several days after parasite elimination. The proliferating cells no longer contain schizont particles and are medium-sized lymphocytes and small blast cells. The surface phenotype of these cells, as defined by lectins and monoclonal antibodies, remains unchanged after parasite elimination. The division of non-parasitized cells, under the culture conditions examined, was not indefinite. The compound 993.C itself does not appear to be mitogenic and possible mechanisms for this continued division are discussed. It has been previously reported that co-cultivation of irradiated Theileria-infected lymphoblastoid cells with autologous lymphocytes induces marked DNA synthesis in the latter. We examined further the relevance of this observation for immunity to Theileria by using lymphoblastoid cells treated with 993.C. Elimination of intracellular parasites by this compound does not impair the ability of these cells to stimulate DNA synthesis in autologous lymphocytes. Furthermore, lymphocytes from Theileria-immune or non-immune cattle react similarly. The reaction differs from a classical mixed lymphocyte reaction induced by antigens encoded in the main histocompatibility complex since the stimulator cells are exclusively T lymphocyte-derived cells, the magnitude of response is greater and stimulated lymphocytes are able to act as 'stimulator cells' to fresh autologous lymphocytes. Thus we question the immunological relevance of the observed lymphocyte division. The possibility that Theileria-infected lymphoblastoid cells carry viral genomes or infectious virus particles is discussed. Preliminary electron microscopic studies have not revealed any virus particles.

Animals↗
PubMed1981

[Deleterious effect of levamisole on experimental trypanosomiasis in mice].

One outbred strain, NMRI, and 4 inbred strains of mice, BALB/c A/J, CBA and C57B1/6, of widely differing susceptibilities to infection by Trypanosoma (Nannomonas) congolense, stock Dinderesso/80/CRTA/3, were treated throughout the course of infection with levamisole, an immunomodulating drug. Under the regime used this drug is capable of restoring depressed immune responses. Surprisingly, levamisole was not beneficial to the course of infection. In all of the strains except BALB/c, levamisole treatment increased mortality and in three of the strains parasitaemia was enhanced. The authors discuss possible reason for these findings which highlight the fact that the protective immune mechanisms operating in African trypanosomiasis are still poorly understood.

Animals↗
PubMed1980

Methods for derivation and detection of anti-parasite monoclonal antibodies.

We describe detailed methods for derivation and cloning of myeloma hybrids which secrete antibodies specific for antigens of protozoan parasites. The methods were designed to enable the derivation of large numbers of specific monoclonal antibodies and to give high cloning efficiencies of desired hybrids. Although special attention is paid to derivation and detection of anti-parasite antibodies, the methods can be applied to many different antibody-antigen systems. Using the described methods we have isolated more than 90 myeloma hybrids which secrete antibodies specific for antigens of African trypanosomes and Theileria parasites, thus illustrating their effectiveness.

Animals↗
PubMed1980

The bovine lymphoid system: II. Derivation and partial characterlzation of monoclonal antibodies against bovine peripheral blood lymphocytes.

We have raised monoclonal antibodies to produce reagents specific for bovine lymphocyte subpopulations. Spleen cells from mice immunized with bovine peripheral blood lymphocytes were fused with X63-Ag8 myeloma cells and eleven myeloma-hybrids which secreted antibody specific for bovine lymphocytes were doubly cloned. Five of the hybrids secreted antibodies which bound to the majority of bovine lymphocytes. Two of these antibodies were specific for polymorphic antigens. One antibody bound to B lymphocytes and serum IgM molecules. The remaining five bound to subpopulations of lymphocytes. Four monoclonal antibodies bound only to bovine cells while six also bound to lymphocytes from other bovidae. None bound to human lymphocytes. We discuss the difficulty of correlating the specificities of monoclonal antibodies to functional lymphocyte subpopulations in outbred animals where few other defined markers are available.

Animals↗