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S V Hetherington

Publications and source records attributed to S V Hetherington.

27 records · Page 2Linked to original sources
PubMed1990

Antibody affinity in infants after immunization with conjugated capsular polysaccharide from Haemophilus influenzae type b.

The affinities of IgG antibodies to Haemophilus influenzae b capsular polysaccharide (polyribosyl ribitol phosphate [PRP]) elicited 1 month after immunization of 47 infants 2-greater than 18 months of age with a PRP-outer membrane protein conjugate (PRP-OMP) were measured by ELISA. Thirty-four sera had affinities distributed normally about a logarithmic mean of 3.2 x 10(5) l/mol, but 13 samples had undetectable affinities (less than 10(4) l/mol). Median affinities of sera from children 2-6 (1.5 x 10(5) l/mol) and 7-11 months of age (1.6 x 10(5) l/mol) were significantly greater than the median affinities of sera from infants 12-18 (1.8 x 10(4) l/mol) or greater than 18 months of age (4.2 x 10(4) l/mol). Sera from children greater than 18 months of age vaccinated with PRP conjugated to diphtheria toxoid had a median affinity of 6.1 x 10(4) l/mol, equivalent to that of the same age group vaccinated with PRP-OMP. Children vaccinated with PRP conjugate vaccines may produce antibodies of very low affinity, a finding that may have significance for protection from invasive disease.

Adult↗
PubMed1989

Antibody to the outer membrane proteins is the dominant opsonic antibody in normal human serum against H. influenzae type b.

We hypothesized that the predominant opsonic antibody of normal serum is directed against outer membrane proteins (OMP). Sera from 10 normal adults were tested for their opsonic capacity against Haemophilus influenzae b (Eagan strain) by the luminol-enhanced neutrophil chemiluminescence elicited on incubation with serum-opsonized bacteria, and the ability to deposit C3 on the bacterial surface. Peak chemiluminescence correlated with the amount of C3 on the bacterial surface (r = 0.71, P less than 0.025) and this, in turn, correlated with the concentration of IgG directed against outer membrane proteins, (r = 0.75, P less than 0.01), but not with the concentration of anticapsular polysaccharide antibody. Two groups of sera were easily distinguished based on the chemiluminescence experiments: a high opsonic group (greater than 50,000 peak counts per second; c.p.s.) and a low opsonic group (less than 10,000 c.p.s.). The IgG fraction from the high opsonic sera could augment C3 deposition when added to a low opsonic serum, but could not after absorption of the anti-OMP antibody by affinity chromatography. We conclude that the predominant opsonin of normal serum is antibody to outer membrane proteins, a finding which could be significant for the development of future vaccines against H. influenzae b.

Antibodies, Bacterial↗
PubMed1988

The intrinsic affinity constant (K) of anticapsular antibody to oligosaccharides of Haemophilus influenzae type b.

Antibody to the polyribosylribitol phosphate (PRP) capsular polysaccharide of Haemophilus influenzae type b is crucial to host defense. Affinities of antibody elicited by vaccination with PRP and PRP-diphtheria toxoid conjugate were determined using oligosaccharides (OS) from PRP. The affinities of antibody induced by vaccination with PRP to OS of three and four repeat units were similar but greater than the affinity to the two-unit OS. NaBH4 reduction of the three-unit OS did not alter the binding affinity, indicating that the reducing end of the OS did not participate in antibody binding. Over the range of OS concentrations tested, antibody affinity appeared to be homogeneous. Antibody concentration could be determined from binding experiments independently from affinity. Whole serum had 8- to 40-fold less antibody detected by binding analysis than by RIA, but the antibody concentration of an IgG fraction measured by the two methods agreed within a factor of two. We could not account for the discrepancy in concentrations found with whole serum by the presence of IgM or IgA antibody. The average affinity of antibodies of 10 adults vaccinated with PRP was similar to that of antibodies elicited in 14 adults vaccinated with a PRP-diphtheria toxoid conjugate (10.7 x 10(5) vs 7.6 x 10(5) liter/mol, respectively, p greater than 0.05). We conclude that the intrinsic affinity of antibody after vaccination with PRP is low and is not different from that of antibody elicited by PRP diphtheria toxoid conjugate.

Adult↗
PubMed1985

Human polymorphonuclear leukocytes of the bone marrow, circulation, and marginated pool: function and granule protein content.

Polymorphonuclear leukocytes (PMN) demonstrate altered function during acute infections and after administration of corticosteroids. We questioned whether or not such changes are due to population shifts from functionally different compartments of the granulocyte pool. Volunteers were given epinephrine to induce demargination or hydrocortisone (HC) to promote egress of PMN from the bone marrow. PMN obtained before and after drug administration were compared for adherence, chemotaxis, luminol-enhanced chemiluminescence, and total content and release of lactoferrin (LF), myeloperoxidase (MPO), and beta-glucuronidase (beta-glu). Epinephrine induced a significant neutrophilia of mature PMN (segmented neutrophils), but there were no changes in function or granule protein content. HC induced a significant neutrophilia with segmented neutrophils and immature PMN (bands). Circulating PMN obtained 4 hr after HC administration demonstrated less adherence, increased chemiluminescence, increased MPO release, and decreased MPO content. Band neutrophils, however, were more adherent than segmented PMN and showed a similar decrease in adherence following HC in vivo. Thus alteration of PMN adherence following intravenous corticosteroids is not due to an influx of immature neutrophils. On the other hand, it is possible that MPO content and release and capacity for oxidative metabolism change as PMN mature.

Blood Circulation↗
PubMed1984

Opsonic activity of immunoglobulin prepared for intravenous use.

The opsonic activity of two immunoglobulin preparations modified for intravenous infusion was tested against Streptococcus pneumoniae types 3, 7F, and 14 and two strains of Staphylococcus aureus by polymorphonuclear leukocyte uptake of 3H-thymidine-labeled bacteria. Reduced and alkylated immunoglobulin (Chem-IgG) and immunoglobulin prepared by chromatography with diethylaminoethyl-Sephadex (DEAE-IgG) were evaluated with and without complement and compared with the opsonic activity of immune serum globulin and heated pooled human serum. Opsonic activity of DEAE-IgG was greater than that of Chem-IgG and equivalent to the activity of immune serum globulin and pooled human serum against S. aureus 502A and type 3 pneumococcus. Both intravenous immunoglobulins had lower opsonic activity than either pooled human serum or immune serum globulin against type 14 pneumococcus. There were no differences in antibody avidity for pneumococcal antigen among the immunoglobulins tested. All four opsonins had similar opsonic activity against the protein A-deficient S. aureus Wood 46. Modification of immunoglobulin for intravenous infusion by chemical alteration may adversely affect opsonic activity by changing the Fc portion of the antibody molecule.

Antigens, Bacterial↗
PubMed1983

An enzyme-linked immunoassay (ELISA) for measurement of lactoferrin.

An enzyme-linked immunosorbent assay has been developed for quantitation of lactoferrin (LF) in body fluids. An indirect double-sandwich method was used which allows a sensitivity of 3 ng LF/ml in samples of polymorphonuclear cell lysates and serum. Mean LF content of serum was 0.307 +/- 0.066 micrograms/ml (n = 18). Mean LF content of polymorphonuclear cells was 4.90 +/- 1.48 micrograms/10(6) PMN. Concentrations of LF were similar in serum and in plasma of EDTA anticoagulated blood. Advantages of this method include its rapidity, and radioactivity is not required.

Animals↗
PubMedDate not supplied

Bacterial and polymorphonuclear leukocyte contribution to middle ear inflammation in chronic otitis media with effusion.

Bacteria can be cultured from approximately one third of chronic middle ear effusions, yet the contribution of these bacteria to the pathogenesis of chronic otitis media with effusion (OME) is not clear due to the absence of signs and symptoms of acute infection in most children with this disease. To explore the role of bacteria in chronic OME, lysozyme, lactoferrin, serum complement factors C3 and C5a, and polymorphonuclear leukocyte (PMNL) chemotaxin content was measured in 21 chronic middle ear effusion samples. Concentrations of lysozyme, lactoferrin, and chemotaxin were significantly higher in culture-positive than in sterile effusions. Lysozyme appeared to be contributed by both PMNL and non-PMNL sources in the middle ear space. These non-PMNL sources, presumably middle ear epithelial cells, accounted for 50% to 80% of the lysozyme variation in middle ear effusion. Although C3 and C5a were present in effusion, chemotaxin content correlated poorly with the C3 and C5a content, suggesting that chemotaxins were derived from bacterial peptides rather than from complement activation products. These results suggest that bacteria contribute to chronic middle ear inflammation with effusion. The eradication of bacteria from chronic middle ear effusion might disrupt the host responses which maintain chronic OME.

Bacterial Physiological Phenomena↗