PubMed Health⌕ Search

Biomedical subjects

E C Gotschlich

Publications and source records attributed to E C Gotschlich.

At least 127 records · Page 7Linked to original sources

Quantitative determination of the human immune response to immunization with meningococcal vaccines.

Radioactive antigen binding tests have been developed to measure quantitatively the antibody response of 167 adults, 84 children, and 51 infants to several different preparations of group A and group C meningococcal polysaccharides. Almost all the adults injected responded and the geometric mean responses were approximately 15 mug/ml of antibody protein in individuals vaccinated subcutaneously with two preparations of group A vaccine. The geometric mean antibody concentration after immunization with two preparations of group C vaccine was approximately 35 mug/ml. Most children aged 7 yr responded to immunization with two group A vaccines, and their mean response was only slightly less than that seen in adults. There was no difference between the subcutaneous and the intradermal route if both were given with jet gun. The majority of infants aged 6-13 months responded to a preparation of group A vaccine and the geometric mean titer was approximately 1.2 mug/ml. Adults, children, and infants responded significantly less to a preparation of group A polysaccharide which was of low molceular weight.

Adult↗

Studies on gonococcus infection. I. Pili and zones of adhesion: their relation to gonococcal growth patterns.

The four colony types of several different strains of gonococci were isolated by selective transfers on agar. These colony variants differed in the degree of autoagglutination which occurred when they were grown in fluid medium. It was found that this clumping behavior was related to the colonial type, with type 2 isolates exhibiting the greatest autoagglutination followed by types 3, 1, and 4. Electron microscopic examination of thin sections indicated that the clumping in fluid medium was mediated by peculiar zones of adherence of the outer membranes of gonococci. These resembled the gap junctions seen in animal cell systems but differed in that the gonococcal membranes involved in the zone of adherence did not bear typical surface modifications. Electron microscopic study of negatively stained specimens of gonococci revealed that pili with a diameter of approximately 85 A and a length up to 4 micro were present on the surfaces of all type 1 and type 2 gonococci examined, and were not seen on any type 3 or 4 gonococci. The consistent presence of pili on type 1 and type 2 gonococci which are virulent colony forms and the lack of pili on avirulent colony types 3 and 4 suggests a relationship between the gonococcal pili and pathogenetic potential of the organisms.

Agar↗

Purification and physical properties of group C streptococcal phage-associated lysin.

A purification procedure for the Group C phage-associated lysin is described utilizing tetrathionate to protect the enzyme's -SH group(s) from thiol-inactivating agents. A 652-fold purification has been accomplished yielding a solution in which the enzyme activity corresponds to essentially a single band on polyacrylamide gel which accounts for 70% of the total protein in the preparation. A molecular weight of 101,000 and frictional ratio of 1.526 was determined for the lysin utilizing experimentally determined values for its Stokes radius and sedimentation coefficient.

Acrylates↗

Degradation of a pneumococcal type-specific polysaccharide with exposure of group-specificity.

Pyruvic acid is an immunological determinant of the quite rigorously type-specific capsular polysaccharide of pneumococcal type IV (S IV). Removal of pyruvic acid by mild hydrolysis converts the capsular polysaccharide of type IV into an analog of the pneumococcal group-specific C-substance. Depyruvylated S IV resembles C-substance so closely immunologically that it not only precipitates a high proportion of the anti-C in antipneumococcal sera, regardless of their immunological types, but also, like C, precipitates human C-reactive protein in the presence of calcium ions. Apparently, the removal of pyruvic acid ketal rings from adjacent sugars unmasks N-acetylgalactosamine residues which must be linked and spaced much as are those in C-substance. Groupings reactive with suitably linked N-acetylgalactosamine, therefore, appear to be located on the surfaces of molecules of human C-reactive protein.

Antigen-Antibody Reactions↗

Electron microscopic studies on streptococci. I. M antigen.

The presence of M antigens on group A streptococci is associated with hairlike fimbriae that cover the surface of the streptococcal cell wall and are demonstrable by electron microscopy. These fimbriae also may be associated with R antigen. Like M protein, the surface fimbriae are destroyed by trypsin treatment and reappear when "trypsinized" streptococci are reincubated in fresh, trypsin-free broth. Ferritin-conjugated, type-specific antibodies localize on homologous M+ cells in a pattern suggestive of several M antigenic sites along the length of individual surface fimbria. The M-associated fimbriae remain on the residual cell wall after removal of the bulk of group-specific polysaccharide through nitrous acid extraction. This suggests attachment of the fimbriae to the mucopeptide and minor polysaccharide components remaining in the nitrous acid-extracted wall. The pattern of localization of ferritin-conjugated antibodies on homologous streptococci before and after trypsin exposure and upon reincubation of the trypsinized cells in fresh medium suggests the following hypothesis: M antigen is secreted by the cell, is partially excreted through the otherwise intact cell wall, and is bound by the wall so that M protein occupies a peripheral, exposed position on the surfaces of the streptococcal cell wall.

Antigens↗

Human immunity to the meningococcus. I. The role of humoral antibodies.

Susceptibility to systemic meningococcal disease is related to a selective deficiency of humoral antibodies to pathogenic strains of meningococci. In a study of the age-specific incidence of meningococcal meningitis in the United States, it was found that the proportion of individuals with serum bactericidal activity to meningococci of serogroups A, B, and C was reciprocally related to the incidence of disease. The prevalence of bactericidal activity was highest at birth and among adults, and lowest in infants between 6 and 24 months of age. Sera from 51 of 54 prospective cases of meningococcal disease among military recruits were deficient in antibodies to homologous and heterologous strains of pathogenic meningococci as determined by serum bactericidal activity and indirect immunofluorescence. Such sera, however, could support the bactericidal activity of purified human gamma globulin (Cohn fraction II), and such individuals could respond immunologically to infection with meningococci. The implication is that susceptible persons are deficient in antimeningococcal antibodies because they have not received significant exposure to meningococcal antigens in the past. The fate of individuals who lack bactericidal antibodies to pathogenic meningococci was determined during an outbreak of group C meningitis among military recruits. The incidence of disease was found to be primarily associated with the incidence of exposure of susceptibles to the pathogenic strains. Whereas 81.5% of the presumed susceptibles acquired a meningococcal strain, only 24.1% acquired an organism similar to the prevalent disease-producing strains. Of the exposed susceptibles, 38.5% developed systemic meningococcal disease.

Adolescent↗

Human immunity to the meningococcus. II. Development of natural immunity.

Results of the present study suggest that natural immunity to meningococcal disease is initiated, reinforced, and broadened by intermittent carriage of different strains of meningococci throughout life. In young adults, carriage of meningococci in the nasopharynx is an efficient process of immune sensitization. 92% of carriers of serogroup B, C, or Bo meningococci were found to develop increased titers of serum bactericidal activity to their own meningococcal isolate, and 87% developed bactericidal activity to heterologous strains of pathogenic meningococci. The rise in bactericidal titer occurred within 2 wk of onset of the carrier state, and was accompanied by an increase in titer of specific IgG, IgM, and IgA antibodies to meningococci. In early childhood, when few children have antibodies to pathogenic meningococci, active immunization seems to occur as a result of carriage of atypical, nonpathogenic strains. Immunity to systemic meningococcal infection among infants in the neonatal period is associated with the passive transfer of IgG antibodies from mother to fetus. The antigenic determinants which initiate the immune response to meningococci include the group-specific C polysaccharide, cross-reactive antigens, and type-specific antigens.

Adolescent↗

Human immunity to the meningococcus. 3. Preparation and immunochemical properties of the group A, group B, and group C meningococcal polysaccharides.

The group-specific polysaccharides of group A and group C meningococci have been isolated by a new procedure which employs the cationic detergent Cetavlon to precipitate these polysaccharides from the whole culture. The A and C polysaccharide prepared by this method are noteworthy because they are of high molecular weight. The main constituent of the A polysaccharide is N-acetyl, O-acetyl mannosamine phosphate; of the C polysaccharide N-acetyl, O-acetyl neuraminic acid. This purification procedure, when applied to cultures of group B organisms, yields a polysaccharide consisting primarily of N-acetyl neuraminic acid. A passive hemagglutination test developed to measure antibodies to the polysaccharides demonstrated the specificity of these antigens. Using a hemagglutination inhibition test, these antigens were again found to be group-specific, and this test could be used for serogrouping meningococcal isolates.

Amino Acids↗

Human immunity to the meningococcus. IV. Immunogenicity of group A and group C meningococcal polysaccharides in human volunteers.

High molecular weight group A and group C meningococcal polysaccharides had no significant toxicity for mice or guinea pigs. Furthermore, these polysaccharide preparations contained negligible amounts of biologically active endotoxin. The high molecular weight group A and group C meningococcal polysaccharides were excellent immunogens in six human volunteers. Antibodies belonging to the immunoglobulin classes IgG, IgM, and IgA were produced. These antibodies were highly meningococcocidal in the presence of complement.

Adult↗

Human immunity to the meningococcus. V. The effect of immunization with meningococcal group C polysaccharide on the carrier state.

Purified meningococcal polysaccharides were administered to army recruits. No adverse reactions were observed in 145 men who received group C polysaccharide, and in 53 men who were injected with group A polysaccharide. Hemagglutinating and bactericidal activity developed in the sera of all individuals with the exception of two recruits injected with A polysaccharide. During the 6 wk period of observation, the proportion of unvaccinated recruits who acquired group C meningococci in the three companies studied was 38, 42, and 69 per cent. A significantly lower proportion of the individuals vaccinated with group C polysaccharide acquired group C meningococci; 4.6, 24, and 31 per cent respectively.

Adult↗