PubMed Health⌕ Search

Biomedical subjects

W I Morrison

Publications and source records attributed to W I Morrison.

At least 109 records · Page 6Linked to original sources
PubMed1985

Identification of an antigen specific to Trypanosoma congolense by using monoclonal antibodies.

Using indirect immunofluorescence assays on acetone-fixed smears of a series of different parasites, we have shown that two monoclonal antibodies bind specifically to Trypanosoma congolense organisms. The antibodies bind to both bloodstream trypomastigotes and procyclic culture forms of the parasite and are thus not stage specific. Immunoprecipitation and immunoblot analysis showed that both monoclonal reagents bound a protein of approximately 31,000 m.w. This antigen appeared to be located on the plasma membrane of T. congolense, but the epitope was not exposed on the surface of living bloodstream or procyclic organisms. The antigen was detectable on acetone-fixed organisms or in trypanosome lysates in enzyme-linked immunosorbent assays and may therefore by useful as a species-specific marker in field assays for epidemiologic and clinical investigations.

Animals↗
PubMed1985

New approaches to immunization of cattle against Theileria parva.

The protozoan parasite Theileria parva is the causal agent of an acute, usually fatal disease of cattle characterized by widespread parasitism and destruction of cells of the lymphoid system. Immunity against the parasite, can be induced by various infection and treatment regimes. Because of the necessity to use live organisms, these methods of immunization are cumbersome and there is the added problem of parasite strain heterogeneity. Present evidence suggests that immunity may operate at two levels of the infection, namely, the sporozoite and the macroschizont-infected cell. Antibodies with the capacity to neutralize the infectivity of sporozoites have been produced and have been used to identify a sporozoite surface antigen of approximately 68,000 daltons. The feasibility of using such an antigen for immunization is currently being explored. In cattle undergoing immunization against T. parva, cytotoxic T cells are produced which are specific for parasitized target cells and are restricted by class I major histocompatibility antigens. Similar effectors can now be generated and maintained in vitro and work is underway to obtain cloned populations of these cells. It is hoped that such effector cells may be of use, in conjunction with molecular biological techniques, in identification of the target antigens on the surface of parasitized lymphocytes.

Animals↗
PubMed1984

Titration in cattle of infectivity and immunogenicity of autologous cell lines infected with Theileria parva.

Cell lines infected with Theileria parva were derived by infection of bovine peripheral blood lymphocytes with sporozoites in vitro. Cattle were inoculated with doses of autologous infected cells ranging from 1 X 10(1) to 1 X 10(8). Infection became established in animals which received 1 X 10(2) or more cells. While 1 X 10(2) cells resulted in sub-patent infection with development of immunity to challenge with sporozoites, larger doses of cells gave rise to patent infections of increasing severity. Thus, doses of 1 X 10(5) and 1 X 10(6) cells sometimes produced lethal infections and with 1 X 10(7) and 1 X 10(8) the outcome was invariably lethal. Based on the previous observation that induction of immunity by allogeneic cells requires transfer of infection into the recipient-host cells, a comparison of the infections produced by autologous and allogeneic cells indicated that the transfer of infection from allogeneic cells occurs at a frequency of maximally 1 X 10(-5). Two pairs of cattle were identified as being mutually non-reactive in the mixed leukocyte reaction (MLR). Doses of 1 X 10(6) and 1 X 10(7) cells of cell lines derived from 1 animal of each pair were inoculated into the autologous host, the non-reactive partner and an animal which was shown to be strongly reactive to the donor in the MLR. In each instance, the reaction in the MLR non-reactive recipient was not significantly different from that of the MLR reactive recipient, but was markedly different from that of the autologous recipient.

Animals↗
PubMed1983

The early events of infection with Theileria parva in cattle: infectivity for cattle of leukocytes incubated in vitro with sporozoites.

Leukocytes were isolated from bovine blood and, after short periods of incubation in vitro with sporozoites of Theileria parva, were washed thoroughly, and their infectivity tested in autologous and allogeneic hosts. Using a standard inoculum of 10(6) viable cells, it was found that, after incubation in vitro for either 1 or 24 h, the cells initiated lethal infections in autologous cattle, but failed to infect allogeneic animals. Autologous and allogeneic erythrocytes and mouse lymphocytes similarly incubated with sporozoites failed to infect cattle. The supernatant from bovine lymphocyte suspensions incubated with sporozoites for 1 h produced lethal infections whereas after 24 h of incubation the supernatant was non-infective. All cattle which did not develop detectable infection were fully susceptible to subsequent challenge with a stabilate of sporozoites. By inoculating cattle with graded doses of autologous blood leukocytes which had been incubated for 24 h with sporozoites, it was found that as few as 2 X 10(3) cells gave rise to infection. The results indicate that this approach can be used to evaluate different cell populations as targets for infection and transformation by sporozoites of T. parva.

Animals↗
PubMed1983

Regulation of the growth and differentiation of Trypanosoma (Trypanozoon) brucei brucei in resistant (C57Bl/6) and susceptible (C3H/He) mice.

While Trypanosoma brucei brucei GUTat 3 were equally infective for C3H/He and for C57Bl/6 mice at doses ranging from 5 to 5 x 10(3) organisms and had similar prepatent periods in both strains of mice, infected C57Bl/6 mice displayed lower parasitaemia, shorter times to parasite wave remission and survived for a longer time than infected C3H/He mice. Parasite growth and differentiation rates and host immune responses were similar for the first 5 days in both strains of mice after infection with 10(3) T.b.brucei GUTat 3 but, thereafter, parasite differentiation proceeded more rapidly and specific antibodies reached higher titres in C57Bl/6 than in C3H/He mice. In contrast, parasite growth and differentiation rates were similar in irradiated mice of both strains. Furthermore, following inoculation of intact mice with irradiated T.b.brucei GUTat 3, C3H/He mice actually mounted higher titred antibody responses than C57Bl/6 mice showing that they were not intrinsically defective in their capacity to respond to GUTat 3 antigens. Parasite differentiation occurred at the same rate in irradiated (650r) C57Bl/6 mice and in irradiated C57Bl/6 mice reconstituted with syngeneic spleen cells although T.b.brucei GUTat 3 specific antibody was detected in the latter mice prior to peak parasitaemia. Furthermore, it was shown directly in C57Bl/6 mice that there was no selective destruction of slender form T.b.brucei GUTat 3 parasites during the phase of accumulation of stumpy form parasites. These studies indicate that the more rapid differentiation of T.b.brucei GUTat 3 parasites in infected C57Bl/6 mice as compared to infected C3H/He mice was unlikely to be directly related to the more efficient antibody response in the infected C57Bl/6 mice. The observations suggest that there might be an association between host mechanisms which regulate differentiation of T.b.brucei parasites and those which regulate antibody responses.

Animals↗
PubMed1983

Host-parasite interactions which influence the virulence of Trypanosoma (Trypanozoon) brucei brucei organisms.

Subclones were prepared in mice from T. b. brucei ILTat 1.4 parasites. Subclones which did not differentiate to stumpy forms in mice were highly virulent and did not stimulate detectable antibody responses. A subclone which did give rise to stumpy forms in mice, was less virulent and did stimulate an antibody response specific for the trypanosome surface glycoprotein. Clones and subclones of T.b. brucei parasites which did not give rise to stumpy forms in mice, did give rise to stumpy forms in Bovidae. Plasma from cattle infected with those parasites did not stimulate differentiation of T.b. brucei parasites in mice. Murine pleomorphic and monomorphic T.b. brucei parasites retained their respective phenotypes in co-infected mice. Both types of parasites were equally pleomorphic in Bovidae. We conclude that some clones of T.b. brucei remain monomorphic in mice as a result of a high avidity interaction between slender forms and host molecules which inhibit differentiation of T.b. brucei parasites.

Animals↗
PubMed1982

Protective immunity and specificity of antibody responses elicited in cattle by irradiated Trypanosoma brucei.

The level and specificity of antibody responses elicited in cattle by irradiated non-infective Trypanosoma brucei were examined and related to the development of protective immunity. These responses were compared with those induced by infection and by inoculation with purified variable surface glycoprotein (VSG) in adjuvant. It was found that 10(7) or more irradiated trypanosomes inoculated intravenously into cattle conferred complete protection against challenge with 10(3) homologous trypanosomes 14 days later. Animals immunized with 10(6) organisms showed partial protection. Of the assays used for detection of antibody, neutralization of infectivity was slightly more sensitive than either the Farr assay or the immunofluorescence test which were both more sensitive than solid-phase radioimmunoassay (RIA). Detection of specific antibody correlated with immunity, in that all animals inoculated intravenously with 10(6) or more trypanosomes developed neutralizing activity in their sera. The antibody responses after intravenous inoculation were consistently superior to those induced by the subcutaneous route. By carrying out blocking assays, most of the antibody elicited by irradiated trypanosomes was found to be specific for antigenic determinants on the VSG exposed on the surface of live trypanosomes. A similar specificity was found for the antibody induced during infection with T. brucei. Conversely, a large component of the antibody induced by purified VSG in adjuvant appeared to be directed against determinants on the VSG which are not exposed on live trypanosomes and are probably not involved in protective immunity.

Animals↗
PubMed1982

Immunization of cattle with a variant-specific surface antigen of Trypanosoma brucei: influence of different adjuvants.

Nine different adjuvants were examined for their ability to potentiate the humoral and cell-mediated immune responses of cattle to a soluble glycoprotein antigen prepared from Trypanosoma brucei. Serological responses as measured by the Farr assay were best augmented by the oil-based adjuvants and saponin. Cell-mediated immunity, as assessed by specific lymphocyte transformation in vitro, was enhanced by all oil-based adjuvants at different intervals after immunization. Results from a challenge infection of immunized cattle with the homologous clone of T. brucei and from neutralization tests indicated that protection against infection was better correlated with specific antibodies than with cell-mediated responses. From these considerations, and the absence of tissue reactions at the site of inoculation, saponin was considered more practical than the oil-based or bacterial adjuvants for the elicitation in cattle of antibodies to purified soluble antigens.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Generation of cell-mediated cytotoxicity to Theileria parva (East Coast fever) after inoculation of cattle with parasitized lymphoblasts.

The participation of genetically restricted cell-mediated lympholysis (CML) in protective immunity against Theileria parva was examined in cattle inoculated with autologous and allogeneic parasitized lymphoblasts. The majority of cattle given 10(7) infected allogeneic cells were protected against infection with the homologous parasite. Animals inoculated with drug-cured lymphoblasts, normal allogeneic lymph node cells (LNC), or a combination of LNC and parasitized allogeneic cells were fully susceptible. The magnitude of the primary CML responses against autologous infected targets (as opposed to that against the allogeneic lymphoblasts inoculated or 3rd-party targets) more accurately correlated with a decreased severity of infection after challenge. Autologous CML responses appeared earlier as cattle were given increasing numbers of parasitized autologous lymphoblasts, and were higher and more persistent with increasing parasitosis. Between 10(2) and 10(5) autologous infected cells induced immunity to T. parva, whereas at least 10(7) allogeneic lymphoblasts were required for comparable protection. The findings provide additional evidence for a protective role of restricted CML responses against T. parva in vivo. When allogeneic infected cells are used for immunization, viable T. parva need to establish infection in host cells to induce adequate protective immunity.

Animals↗
PubMed1982

Interference in the establishment of superinfections with Trypanosoma congolense in cattle.

To examine the influence of an established infection on subsequent challenge with another unrelated trypanosome serodeme, cattle were subjected to two challenges, 5 to 6 wk apart, with unrelated isolates of Trypanosoma congolense. The primary infection inhibited the establishment of the second infection despite the initial absence of detectable antibody to the trypanosomes used for the second challenge. This was true whether the second challenge consisted of bloodstream forms of the parasite or metacyclics from infected Glossina m. morsitans. Rechallenge with bloodstream forms resulted in a slight antibody response, which was only detectable by immunofluorescence and was much less than in the challenge controls. Although animals subjected to the second challenge by tsetse flies showed no appreciable increase in parasitemia and, in most instances, no chancre reaction at the site where the tsetse bit, they developed readily detectable neutralizing antibody to the metacyclic trypanosomes. That this interference effect was not the result of specific immunity and required an active infection was confirmed by the finding that when infected animals were treated with Berenil prior to rechallenge, they were fully susceptible to the infection.

Animals↗
PubMed1981

The pathogenesis of experimentally induced Trypanosoma brucei infection in the dog. I. Tissue and organ damage.

Inoculation of dogs with Trypanosoma brucei produced an acute fetal disease similar to that seen following natural infection. The disease was characterised by high levels of parasitaemia, moderately severe anemia, and marked changes in the lymphoid system. Extravascular invasion by large numbers of trypanosomes was widespread throughout the body and was accompanied by severe tissue damage. Tissue invasion by trypanosomes was associated with marked cellular infiltration involving lymphoid cells and plasma cells followed by macrophages and polymorphonuclear leukocytes. Associated with these reactions, severe cellular degeneration and focal necrosis occurred. While these changes were widespread and were found in the majority of tissues examined, consistently severe lesions were found in the heart, eyes and central nervous system. In many organs, lymphatic vessels were distended with fluid, trypanosomes, and a cell population similar to that in the surrounding tissue; fibrin deposition and thrombus formation was sometimes observed within the lymphatic lumens. Thrombosis was also found in the blood vessels of the pampiniform plexus, the venous plexus of the ovary, and branches of the renal vein. A severe necrotizing vasculitis affecting only the coronary vessels was a prominent feature in some animals.

Animals↗
PubMed1981

The pathogenesis of experimentally induced Trypanosoma brucei infection in the dog. II. Change in the lymphoid organs.

Marked changes were found in the spleen and lymph nodes of dogs experimentally infected with Trypanosoma brucei. These changes were considered to occur in two phases. First, in animals examined on Days 8 and 16 after inoculation, there was an intense proliferative response; this involved particularly the B-dependent follicular areas and was accompanied by a dramatic increase in the number of plasma cells in the splenic red pulp and medullary cords of the lymph nodes. Although numerous large proliferating lymphoblasts were found in the periarteriolar regions of the spleen and in the peripheral part of the paracortical areas of the lymph nodes, the presence of cells containing Ig in these regions made it difficult to evaluate the degree of involvement of thymus-derived cells. The plasma cell response involved both IgM and IgG, although the increase in IgM-containing cells was most striking. During this initial phase there was focal hemorrhage, deposition of fibrin, necrosis, and infiltration of polymorphonuclear leukocytes in the spleen, these changes being most severe in the peripheral follicular areas. Following the initial proliferative phase and prior to the death of the host during the fourth week of the infection, the spleen and lymph nodes became less reactive, and there was marked disorganization and disruption of their architecture. Compared with characteristics earlier in the infection there was greatly decreased proliferative activity and a reduction in size of the splenic white pulp and lymph node cortices. Germinal centers were reduced in number, size, and activity, had a disorganized appearance, and, by immunofluorescence, showed a reduction of immunoglobulin on the dendritic reticular cells. The lymph node sinuses exhibited a decrease in content of lymphocytes and contained massive numbers of macrophages, including numerous multinucleated giant cells. There was also severe disruption of the reticulum cell network of the sinuses; and accumulations of polymorphonuclear leukocytes, along with extensive deposition of fibrin, were commonly found in the subcapsular sinuses. During this period, foci of erythropoietic cells were present throughout the red pulp of the spleen.

Animals↗
PubMed1981

Response of the murine lymphoid system to a chronic infection with Trypanosoma congolense. I. The spleen.

The response within the different cellular compartments of the spleen in mice infected with Trypanosoma congolense was evaluated using histologic and cytologic methods and immunofluorescence to detect intracellular and cell surface immunoglobulin. The isolate of T. congolense used produces a chronic infection in C3H/He mice leading to death 40 to 70 days after inoculation. Previous studies had shown that this infection resulted in a marked immunodepression as judged by a range of in vitro assays of splenic cellular responses. It was found that the splenic cellular changes occurred in two phases. First, coincident with and following the first peak of parasitemia, there was a marked proliferative phase characterized by widespread hyperplasia of the white pulp with the production of large numbers of plasma cells and an expansion of the erythropoietic component of the red pulp. During this period, there was a marked decrease in the intensity of staining for surface Ig on cells of the follicular regions of the white pulp. Following the initial proliferative changes, a more protracted phase ensued during which, although the proliferative activity continued, there was a gradual disorganization of the white pulp with eventual lymphoid depletion. This was accompanied by a progressive expansion of the red pulp due to increased numbers of erythropoietic cells and to a lesser extent granulopoietic cells and macrophages. At the same time, there was a gradual decrease in the number of plasma cells found in the red pulp, although many were still present in the periarteriolar regions. The end result of these changes was an approximately 17-fold increase in total splenic cellularity of which erythropoietic cells contributed more than 50 per cent, and lymphocytes were reduced in absolute numbers to below control levels. A striking feature during both phases of the infection was the lack of discrete germinal centers.

Animals↗
PubMed1981

Evaluation of the structural and functional changes in the lymphoid organs of Boran cattle infected with Trypanosoma vivax.

Experimental infection of Boran cattle with Trypanosoma vivax resulted in fluctuating parasitemia detectable in peripheral blood which, as the infection progressed, diminished to undetectable levels. In animals necropsied during the initial stages of the infection, trypanosomes were detected in lymph and in the sinuses of the lymph nodes. The lymph nodes and spleen exhibited marked proliferative response which was maximal in animals killed on days 10 and 17 of infection. The response was characterized by an increase in the size and activity of the germinal centers accompanied by increased numbers of large proliferating lymphocytes in the medullary cords and peripheral part of the paracortex of the lymph nodes and in the periarteriolar regions and peripheral follicular areas of the spleen. This was associated with the production of large numbers of plasma cells which were present in the red pulp of the spleen, in the medullary cords of the lymph nodes, and focally in the peripheral paracortical areas of the lymph nodes. By immunofluorescence, many of these plasma cells were found to contain immunoglobulin (Ig) M. There was also increased number of follicles which exhibited granular deposits of IgM and reduction in the areas containing small lymphocytes bearing IgM. During the remainder of the infection and paralleling the decrease in parasitemia, there was gradual reduction in the reactivity of the lymphoid organs. Accompanying the initial proliferative response was a marked increase in plasma concentration of IgM; this decreased to base line during the 3rd week of the infection. The response to phytohemagglutinin, pokeweed mitogen, and lipopolysaccharide of leukocytes obtained from peripheral blood lymph nodes and spleen at intervals during the infection was not significantly different from controls.

Animals↗