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K D Murrell

Publications and source records attributed to K D Murrell.

At least 127 records · Page 7Linked to original sources

Characterization of the immunosuppressive state during Schistosoma mansoni infection.

Analysis of a murine model of schistosomiasis revealed that both the thymus (T)- and bursa (B)-derived compartments of the immune system are modified during acute infection. The functional capacity of T and B lymphocytes to respond to mitogenic stimuli and the humoral response to thymus-dependent (SRBC) and thymus-independent (DNP-Ficoll) antigens are severely depressed. In addition, it was found that suppressor cells capable of inhibiting the response of normal lymphocytes to SRBC arise during acute infection. Although the splenic frequency of T (theta) and B (Ig+) cells remained constant during chronic infection, quantitative changes were detected in each population. In the T cell pool there was a decrease in the percentage of Ly-1+ cells and a concomitant increase in Ly-1+, 2+, 3+, cells, whereas the B cell pool showed a progressive loss of complement receptor-bearing lymphocytes, which apparently was the result of inactivation of surface complement receptor by a serum factor specifically found in infected mice. Characterization of the serum factor strongly suggests it is an immune complex. Thus, it appears that both suppressor cells and immune complexes contribute to changes noted in the immune system during acute schistosomiasis. Additional studies carried out in mice after unisexual infection revealed that egg production is not a necessary prerequisite for several of the immunologic phenomena associated with acute schistosomiasis.

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Isolation and characterization of surface antigens from Schistosoma mansoni. I. Evaluation of techniques for radioisotope labeling of surface proteins from adult worms.

Radiolabeled surface proteins of adult Schistosoma mansoni were prepared by in vitro labeling of whole worms, and by labeling freeze-thaw surface membrane extracts. Incorporation of 125I into surface proteins was attempted using the lactoperoxidase, chloramine-T, iodosulfanilic acid, and Bolton-Hunter methods. Radiolabeling of whole worms with lactoperoxidase, chloramine-T and iodosulfanilic acid yielded a single protein peak (mol wt greater than 100,000) on SDS-PAGE, and showed considerable incorporation of label in the lipid fraction. Bolton-Hunter labeling of whole worms yielded four major peaks with molecular weights of 100,000, 60,000, 30,000 and 21,000, and minor peaks with molecular weights of 26,000, 36,000, 43,000, 68,000 and 78,000; three of the four major peaks corresponded to prominent bands in Coomassie blue-stained gels. Although carbohydrate-labeling techniques were not successful, a single carbohydrate band, molecular weight greater than 100,000, was detected was PAS staining. Radiolabeling of freeze-thaw extracts yielded results similar to those obtained with whole worms. Electron microscopy revealed the tegument to be left intact and undamaged after labeling with the Bolton-Hunter reagent.

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Isolation and characterization of surface antigens from Schistosoma mansoni. II. Antigenicity of radiolabeled proteins from adult worms.

Adult Schistosoma mansoni were radiolabeled in vitro with 125I Bolton-Hunter reagent. Surface membrane antigens were solubilized with non-ionic detergent, then reacted with infection or normal serum. The antigen-antibody complexes were then precipitated with staphylococcal protein A immunoadsorbent, eluted with urea and SDS, and fractionated by SDS-PAGE. The results indicated the presence of 6 to 8 tegument antigens, depending on the type of antisera used. Human antisera to S. japonicum and S. haematobium reacted with some but not all of the antigens identified with human S. mansoni infection serum; this implies the presence of species-specific tegument antigens. The molecular weights of the radiolabeled antigens ranged from 10,000 to 100,000. A large (greater than 100,000) molecular weight glycoprotein and an uncharacterized lipid fraction appeared to be precipitated nonspecifically. Immunoprecipitation methods with anti-mouse IgG and anti-mouse whole serum failed to detect the presence of hostlike antigens in the labeled extracts. Several of the labeled proteins from S. mansoni were found to react with serum from patients infected with either S. haematobium or with S. japonicum.

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Immunization of mice with cobalt-60 irradiated Schistosoma mansoni cercariae.

Parameters of immunization of mice with 60Cobalt-irradiated Schistosoma mansoni cercariae are described and related to protection against subsequent challenge infection. Such immunization was found to be dependent on dose of irradiation, number of immunizing cercariae, and number and time course of infections. Low levels of resistance were obtained with low irradiation doses, in contrast to previous studies in mice. In general, resistance increased with increasing irradiation doses, up to approximately 48-56 Kr. Maximal resistance (70-80%) was induced by a single exposure to 250-500 cercariae, irradiated at a dose rate of 2 Kr/minute to a total dose of 56 Kr, administered percutaneously 4-6 wk prior to challenge. Challenge could be delayed for at least 15 wk after immunization without a decrease in resistance. The resistance obtained was not attributable to a delayed migration of challenge worms.

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Effect of immunization on migration of Schistosoma mansoni through lungs.

Schistosoma mansoni schistosomula migrate through the lungs of infected mice; peak recovery occurs 6 days following infection. When cercariae were irradiated at 60Cobalt doses of 24 to 64 Kr, the number of schistosomula recovered from lungs 6 days after infection decreased in a dose-dependent fashion. The pattern of lung migration of schistosomes irradiated at 56 Kr prior to infection was similar to that of nonirradiated schistosomes, but greatly reduced numbers were recovered. When mice were immunized by a single infection with 56 Kr attenuated cercariae 6 wk prior to challenge, the pattern of challenge migration through the lungs was altered. The number of schistosomes recovered increased rapidly between 2 and 6 days post-infection, and showed a plateau between 8 and 10 days with peak recovery occurring 10 days post-infection. This peak recovery was reduced in comparison to that of non-immunized mice, but did not account for all of the reduction observed at the adult worm stage.

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Resistance of mice to secondary infection with Schistosoma mansoni. I. Comparison of bisexual and unisexual initial infections.

Mice receiving a unisexual primary infection with either sex of Schistosoma mansoni did not develop detectable resistance to reinfection. In contrast, mice receiving a bisexual primary infection developed a high degree of resistance. The number of adult worms developing from the challenge infection was reduced, relative to controls, by 72--100% at challenge times of 6 weeks or greater.

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Resistance of mice to secondary infection with Schistosoma mansoni. II. Evidence for a correlation between egg deposition and work elimination.

Mice reinfected with Schistosoma mansoni 6--8 weeks after a primary infection largely or completely eliminated the second infection prior to the 7-week adult worm stage. In contrast, challenge worm counts were not lower than controls at the 6-day lung schistosomulum stage. At reinfection intervals of 12 or more weeks, worm counts were reduced at both stages. The reduction in lung schistosomulum count was proportional to the number of schistosome eggs present in the lungs, with no significant reduction being detected at any challenge time in mice free of lung eggs. Isolated schistosome eggs injected intravenously into the lungs of normal mice induced moderate to high levels of resistance to infection, while eggs injected subcutaneously or imtraperitoneally did not. It is concluded that the deposition of schistosome eggs in sites encountered by migrating schistosomula may be essential for mice to become resistant to reinfection with S. mansoni.

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Proteolytic, antigenic and immunogenic properties of Schistosoma mansoni cercarial secretion material.

Schistosoma mansoni cercariae secrete preacetabular gland material in association with skin penetration. The material is heterogeneous and contains proteolytic enzyme(s) which comprise a small proportion of the total protein. We have immunized mice with cercarial secretion material in several protocols designed to induce a variety of antibody responses. The cercarial secretion material is sufficiently immunogenic to induce precipitating and reaginic antibody production. The antibodies obtained were not of the necessary quantity and/or quality to afford protection from a challenge infection.

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Enzyme- and 125I-labeled anti-immunoglobulin assays in the immunodiagnosis of schistosomiasis.

An enzyme-linked immunosorbent assay (ELISA), and radioimmunoassays using antigen bound to plastic tubes or microcrystalline particles, were adapted for the indirect serological measurement of anti-schistosome antibodies. These alkaline phosphatase and 125I-labeled anti-immunoglobulin techniques were found to be highly quantitative and adaptable. Comparison showed them to be considerably more sensitive than the indirect hemagglutination and indirect fluorescent antibody techniques. Using adult S. mansoni freeze-thaw antigen, anti-schistosome antibodies were detected in sera from patients infected with Schistosoma mansoni and S. haematobium. However, results in patients with schistosomiasis haematobium were generally intermediate between those of patients with schistosomiasis mansoni and normal, uninfected controls.

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The development of anti-immunoglobulin antibodies in rhesus monkeys repeatedly exposed to Schistosoma japonicum.

The development of anti-immunoglobulin (Ig) antibodies in rhesus monkeys repeatedly exposed to Schistosoma japonicum cercariae was studied. Anti-Ig developed in all 8 monkeys exposed 5 times to cercariae of the Formosan strain, while none of 4 monkeys exposed once to the Philippine strain developed such antibodies in the same period. All monkeys developing anti-Ig had specificities for IgA, 6 of 8 for IgM and IgG, and 7 of 8 for rabbit Ig. The persistence of anti-Ig was greatly extended in the monkeys exposed initially to the Formosan strain and then challenged with the Philippine strain. A single monkey exposed once to the Philippine strain developed anti-IgA and anti-rabbit Ig 85 weeks postinfection. No relationship between host reaction to trapped eggs and the development of anti-Ig was discerned. The results suggest that immunization protocols designed for humans be carefully examined for their potential immunopathological side effects.

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