Immunologic consequences of cryosurgery. I. Serum proteins.
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Biomedical subjects
Publications and source records attributed to J B Robbins.
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Employing a sensitive and immunoglobulin-specific assay method based upon antiglobulin augmentation, quantitative and qualitative aspects of the primary and secondary response of the rabbit to Salmonella typhimurium O antigens have been evaluated. These studies examine the validity of the method of assay for detecting and measuring gammaG- and gammaM-antibodies produced in response to whole organisms or its lipopolysaccharide. The results show that during the primary response gammaG-antibodies, not detectable by usual techniques, are produced in a pattern similar to that reported in animals stimulated by other classes of antigens. Moreover, the gammaG response following reinjection is characteristic of a secondary-type response. In contrast, gammaM-antibody levels after both primary and secondary stimulation rose equally to levels between 1 and 4 mg/ml. Despite increased sensitivity of detection and quantitative estimates of the actual molar concentration of each immunoglobulin, the minimal interval between gammaM and gammaG appearance in serum was not less than 1.5 days. The variable degree of augmentation of agglutination by antiglobulin reagent found during the immune response severely limits the quantitative usefulness of the methods developed. However, the data suggest that qualitative changes in anti-O antibodies interpretable as changes in avidity occur regularly during the immune response.
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Herzberg, Mendel (University of Florida, Gainesville), Kathryn V. Kenny, and John B. Robbins. Nonabsorbable rabbit anti-Salmonella typhimurium antibody as detected by the complement-mediated bactericidal reaction. J. Bacteriol. 91:1548-1555. 1966.-A portion of antibody active in the complement-mediated bactericidal reaction against Salmonella typhimurium from hyperimmune rabbit serum has been shown to be nonabsorbable by repeated serial absorptions with whole heat-killed or living bacteria. The first two absorptions remove 90 to 95% of the activity, but 1 to 5% cannot be removed by subsequent absorptions. The nonabsorbable antibody appears to be a macroglobulin by density-gradient centrifugation and by comparison of activity and absorbability of purified gamma-M and gamma-G immune globulins. Alternative hypotheses involving low avidity antibody or antibody to minor cell antigenic components are offered in explanation of the phenomenon.
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The blood group P1 antigenic trisaccharide (3), which is the receptor-binding ligand of Shiga-like toxins, is synthesized in a spacer-equipped form (32) from 2-(trimethylsilyl)ethyl glucoside 5 and the 1-thiogalactoside building blocks 10 and 22 in a stereocontrolled, stepwise fashion. Covalent attachment of 32 to hydrazine group-containing agarose gel by reductive amination provided the P1 trisaccharide-containing affinity sorbent which was used for preparative scale isolation of subunit B of Shiga toxin.
Only indirect evidence has been cited to document that lipopolysaccharide-mediated virulence at the bacterial level and serum antibodies to the O-specific side chain of the lipopolysaccharide molecule may prevent shigellosis. Our proposed use of the B subunit of Shiga toxin as a carrier protein is based upon evidence (even more indirect) that serum antitoxin may reduce the severity of dysentery and diarrhea. Because animal models of disease may provide information inapplicable to the prediction of vaccine-induced protective immunity, we suggest that clinical trials in the population at risk should be started after successful completion of the safety and immunogenicity phases of vaccine development in laboratory animals and in the target population. Clinical studies of shigella vaccines are difficult because of the many causes of dysentery in a population with a high rate of intestinal disease.
The epidemiologic and experimental data upon which the proposed second and more expanded formulation for the pneumococcal capsular polysaccharide was based has been reviewed. The use of a functional (opsonization) and quantitative (radioimmunoassay) for assaying the human serum antibody response in order to predict the efficacy of pneumococcal vaccine should permit further examination of its usefulness in various clinical settings. New developments in the area of improved pneumococcal and other polysaccharide vaccines were examined.