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Biomedical subjects

D L Kasper

Publications and source records attributed to D L Kasper.

At least 127 records · Page 7Linked to original sources
PubMed1986

The role of complement and antibody in opsonophagocytosis of type II group B streptococci.

The role of complement and antibody in the opsonophagocytosis of type II group B streptococci (type II GBS) was defined with sera from healthy adults and two populations with theoretical susceptibility to type II GBS infection--neonates and insulin-dependent diabetics. Significant opsonophagocytosis (bactericidal index, greater than or equal to 90%) of five clinical isolates of type II GBS lacking components of protein antigen c was demonstrated by each of 12 adult sera, as well as by agammaglobulinemic serum, a result indicating that opsonophagocytosis can proceed by antibody-independent activation of the classic complement pathway. Strains containing components of protein antigen c were somewhat more resistant to opsonin-binding activity. Four of 10 neonatal sera and nine of 15 diabetic sera exhibited inefficient opsonophagocytosis. Some of the adult sera with either high or low concentrations of specific antibody to type II GBS promoted opsonophagocytosis via the alternative complement pathway, but this response was not observed with neonatal sera. The addition of sufficient amounts of specific antibody to type II GBS to neonatal and adult diabetic sera in vitro, however, promoted efficient opsonophagocytosis via the alternative pathway.

Adult↗
PubMed1985

Antibody-independent and -dependent opsonization of group B Streptococcus requires the first component of complement C1.

The role of the classical complement pathway and specifically the first component, C1 in antibody-independent opsonization of type Ia group B Streptococcus (GBS) was investigated. For these studies a radiolabeled bacterial uptake assay was developed that was dependent on time and bacterial concentration and that required an intact classical complement pathway. To directly investigate the role of C1 in opsonization of type Ia GBS, C1 was isolated by chromatography on an immunoglobulin G (IgG) affinity column and further purified by molecular sieve chromatography on an Ultrogel AcA 22 column. When normal human serum was absorbed with 10(9) CFU of type Ia or III GBS, the serum opsonic capacity diminished (33 to 34%) for type Ia GBS compared with unadsorbed serum. Preincubation of the bacteria with purified C1 (10(4)U of C1 per ml) restored the opsonizing capacity of the adsorbed serum. A C1-depleted serum was prepared from the nonadherent fractions of the CH-sepharose 4B IgG column which only contained 5 U of C1 per ml. Substitution of C1-depleted reagent for normal serum in the uptake assay resulted in dramatic decreases in the opsonization of type Ia GBS, but opsonization could be restored by preincubation of the bacteria with purified C1. Heat-inactivated C1 depleted serum did not support opsonization of type Ia GBS, even with the addition of C1. Preincubation of type Ia GBS with heat-inactivated hyperimmune sera did not result in opsonization of type Ia GBS in the presence of C1-depleted serum. However, opsonization could be restored by the addition of C1, and the effects of C1 and antibody were additive. These results indicate the critical role of C1 in direct activation of the classical complement pathway by type Ia GBS and in antibody-mediated opsonization of the bacteria.

Adult↗
PubMed1985

A soluble suppressor T cell factor protects against experimental intraabdominal abscesses.

This paper describes a suppressor T cell factor which protects mice against intraabdominal abscesses caused by Bacteroides fragilis. This soluble cell-free factor (ITF) is derived from splenic T cells from mice immunized with capsular polysaccharide (CP) of B. fragilis. Mice receiving ITF are protected from developing abscesses caused by B. fragilis to the same degree as animals receiving intact immune splenic T cells. The factor appears to be small in molecular size as protective activity is dialyzable through a 12,000-mol wt exclusion dialysis membrane and is present in fractions intermediate between the bed and void volumes of a P2 Biogel column. The protective effect of ITF is antigen-specific to B. fragilis alone. Mice given a complex inoculum of B. fragilis, enterococcus, and another anaerobe develop abscesses even after receiving column-purified ITF. The activity of ITF also is eliminated after adsorption with B. fragilis CP coupled to sheep erythrocytes but not with an unrelated CP coupled to sheep erythrocytes. ITF, therefore, appears to have a binding site for B. fragilis CP. ITF is heat-labile and loses efficacy after protease digestion, suggesting that the active material is a protein. These studies define a suppressor cell factor with activity in a model system resembling human disease and offer promise for increased understanding of the diversity of cell-mediated immune systems.

Abdomen↗
PubMed1985

Immunochemical analysis of the types Ia and Ib group B streptococcal polysaccharides.

The types Ia and Ib group B streptococcal type-specific polysaccharides have remarkable immunologic differences despite a great deal of structural similarity. Although these two complex polysaccharides differ only by a single glycosidic linkage, they are antigenically distinct. Furthermore, terminal sialic acid residues appear to be critical to the immunodeterminant on the type Ia polysaccharide, whereas the antigenicity of the type Ib polysaccharide does not show this dependence on sialic acid. In the current investigation we defined better the immunodeterminant of these polysaccharides. With homologous rabbit antiserum, the type Ia native and core polysaccharides demonstrated partial serologic identity, whereas the type Ib native and core polysaccharides demonstrated complete serologic identity. Surprisingly, the type I degalactosylated polysaccharide, degraded structure, was capable of reacting with a population of antibodies present in type Ia antiserum similar to the complete type Ia native polysaccharide, although demonstrating a reduced level of immunodeterminant expression. Unlike the reactions of the type Ia polysaccharides with homologous rabbit antiserum, the Ib native and core polysaccharides were able to react with identical populations of antibodies in type Ib-specific antiserum. A minor population of antibodies was demonstrated in the type Ib antiserum, which was reactive with the degalactosylated polysaccharide. That a population of antibodies reactive toward the degalactosylated polysaccharide is present in both type Ia and type Ib antisera suggests that the Iabc cross-reacting determinant is due to the presence of serum antibodies reactive with this trisaccharide repeating unit, which is shared by both the type Ia and the type Ib native and core polysaccharides.

Animals↗
PubMed1984

Potentiation of virulence by group B streptococcal polysaccharides.

The ability of group B streptococcal (GBS) capsular polysaccharides to potentiate virulence was examined. Incubation of soluble type Ia or III polysaccharide in hypogammaglobulinemic human serum inhibited classical complement-dependent opsonophagocytic killing of type Ia strain 515. When functional complement components were measured, C1 activity increased in sera with added polysaccharide whereas C4 activity decreased 80%-90%. Incubation of purified C1 with type Ia polysaccharide inhibited lysis of EAC4 cells in a C1 transfer assay. In a mouse lethality model, tail-vein injection of 50 micrograms of type Ia or III polysaccharide decreased the 50% lethal dose (LD50) from 3.2 X 10(6) to 2.2 X 10(5). Total hemolytic complement levels in mice immediately after polysaccharide injection were increased over levels in control mice, but this difference was not seen 30 min later. The LD50 in mice depleted of C3 (with cobra venom factor) was 6 X 10(5) and simultaneous injection of polysaccharide did not further lower the LD50.

Animals↗
PubMed1984

Two unlinked genetic loci interact to control the human immune response to type III group B streptococcal antigen.

Serum samples were collected from 30 healthy adult Caucasian volunteers before and after immunization with native type III polysaccharide of group B streptococcus. Serum antibody to this polysaccharide was measured and sera were typed for several Gm and Km(1) allotypes. A significant interactive effect of Gm(23) and Km(1) was found on immune responsiveness to native type III group B streptococcus polysaccharide antigen.

Antigens, Bacterial↗
PubMed1984

Class specificity of naturally acquired and vaccine-induced antibody to type III group B streptococcal capsular polysaccharide: determination with a radioimmunoprecipitin assay.

A radioimmunoprecipitin test was developed to determine the immunoglobulin class distribution of naturally acquired and vaccine-induced antibody to the native capsular polysaccharide of type III group B streptococci (III-GBS). In sera from adults and pregnant women with naturally acquired antibody, the mean percentage of antigen bound by immunoglobulin G (IgG) was 74.9 and 78.6, respectively, whereas antigen bound by IgM comprised less than 10% of the total. In contrast, early-convalescent-phase sera (mean, 16.3 days) from neonates responding to III-GBS infection with an increase in specific antibody had significantly more IgM (mean, 36%; P less than 0.001, unpaired t test). However, in late convalescence, the immunoglobulin class distribution in sera from these neonates was similar to that of naturally immune adults. Four weeks after immunization with III-GBS polysaccharide vaccine, sera from adults with low (less than 2 micrograms/ml) preimmunization antibody levels in their sera and from those with moderate (mean, 5.5 micrograms/ml) preimmunization levels contained specific antibody predominantly of the IgG class. Although the percentage of IgG-specific antibody was greater in sera from naturally immune adults than in that from vaccinees with a presumed primary immune response, the major portion of antigen bound by sera at 4 weeks postimmunization (62.5%) was associated with IgG. These observations support the opinion that immunization of pregnant women with III-GBS capsular polysaccharide could be efficacious for the prevention of invasive neonatal III-GBS disease.

Adult↗
PubMed1983

Antibody to type III group B Streptococcus in the rhesus monkey.

Susceptibility to infection due to intra-amniotic type III group B streptococcal infection was studied in 27 rhesus monkeys. Sera from mothers and their offspring were tested to determine the concentration of antibody to the native type III group B Streptococcus antigen. Among 17 controls there was a statistically significant association between the concentration of maternal antibody prior to infection and both the neonatal survival rate and survival time (P less than 0.05). Neonatal survival was decreased to less than or equal to 6 hours (P = 0.005) if the maternal antibody concentration was less than 0.5 micrograms/ml. Modified immune serum globulin was given intravenously to the mothers prior to intra-amniotic infection with (five animals) or without (five animals) neonatal modified immune serum globulin. Neither of the modified immune serum globulin groups demonstrated a significant reduction in the neonatal mortality rate; however, the addition of the modified immune serum globulin provided protection against rapid neonatal death among those animals born to mothers which had low or no detectable antibody. All maternal groups developed a significant increase in the concentration of antibody in postpartum sera. These results indicate that both naturally acquired and passive (modified immune serum globulin) antibodies to type III group B Streptococcus antigen are partially protective against intra-amniotic infection.

Animals↗
PubMed1983

Demonstration of a saturable binding site for thyrotropin in Yersinia enterocolitica.

Several lines of evidence suggest that there might be immunologic cross-reactivity between the thyroid plasma membrane in humans and antigenic determinants in the enteric pathogen Yersinia enterocolitica. Studies were therefore performed to determine whether Y. enterocolitica, like the thyroid membrane, contains a thyrotropin binding site. A saturable binding site for bovine thyrotropin was indeed demonstrable, particularly in preparations of the organism that have been treated with ethylenediaminetetraacetate and lysozyme. Hormonal specificity of the binding site, as judged from the inhibition of binding of 125I-labeled bovine thyrotropin, was similar to that of the thyrotropin receptor in human thyroid tissue.

Binding Sites↗
PubMed1983

Interactions of Bacteroides fragilis and phagocytes: studies with whole organisms, purified capsular polysaccharide and clindamycin-treated bacteria.

Bacteroides fragilis plays a key role in the pathogenesis of anaerobic infections and is often found mixed with aerobic organisms. We explored the interactions of this organism with phagocytes in an attempt to discern additional information about its virulence factors. We confirm an earlier report that killing of aerobic organisms by polymorphonuclear leukocytes (PMN) is decreased in the presence of high numbers of Bact. fragilis but this effect could also be demonstrated with Bact. distasonis or Staphylococcus aureus. Our data support the concept that this phenomenon may be due to competition for opsonins. Virulence of Bact. fragilis has been associated with a polysaccharide capsule. We were unable to demonstrate any deleterious effect of the purified capsular polysaccharide of Bact. fragilis on phagocytosis, killing, or chemotaxis by PMN. We were not able to demonstrate any effect of subinhibitory levels of clindamycin on the interactions of neutrophils and Bact. fragilis.

Bacteroides↗
PubMed1983

Capsular polysaccharides and lipopolysaccharides from two Bacteroides fragilis reference strains: chemical and immunochemical characterization.

Fermentor growth of Bacteroides fragilis under controlled conditions in a complex medium containing 1% glucose and 10% fetal calf serum resulted in high yields of bacteria. After hot phenol-water extraction of the organisms, capsular polysaccharide was isolated from the aqueous phase and purified by Sephacryl S-300 chromatography in a buffer with 3% sodium deoxycholate. Lipopolysaccharide was isolated by phenol-chloroform-light petroleum ether extraction. The capsular polysaccharide from B. fragilis strain NCTC 9343 contained six sugars: L-fucose, D-galactose, D- and L-quinovosamine, D-glucosamine, and galacturonic acid. The capsule of strain ATCC 23745 also contained D-glucose, L-fucosamine, L-rhamnosamine, and a 3-amino-3,6-dideoxyhexose but lacked D-quinovosamine. The latter capsule also contained alanine (4%). The capsular polysaccharides were different immunochemically by ELISA inhibition. The lipopolysaccharide of both strains contained the same sugars (L-rhamnose, D-glucose, D-galactose, and D-glucosamine) and fatty acids (13-methyl-tetradecanoic and 3-hydroxy-hexadecanoic and 3-hydroxy-15 methyl-hexadecanoic as major constituents) and were identical by ELISA inhibition.

Amino Acids↗