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Biomedical subjects

A M Svennerholm

Publications and source records attributed to A M Svennerholm.

7 recordsLinked to original sources

Evaluation of a ganglioside immunosorbent assay for detection of Escherichia coli heat-labile enterotoxin.

The GM1 ganglioside enzyme-linked immunosorbent assay (GM1-ELISA), an immunological method for detection of Escherichia coli heat-labile enterotoxin (LT), was quantitatively and qualitatively compared with the conventional adrenal cell test for the identification of LT-producing strains. A micromodification model of the assay was developed. Enterotoxin preparations from 120 E. coli isolates from individuals with diarrhea, which had been previously shown to be enterotoxigenic by the adrenal cell test, and from 44 control strains of E. coli were compared in parallel by the two methods. Quantitatively the covariation of the enterotoxin titers was highly significant (RS = 0.98, P less than 0.001), the GM1-ELISA being somewhat more sensitive than the adrenal cell test. The methodological error was less than 5% in both tests. Qualitatively the overall agreement for positive and negative reactions for the two methods was 89%. The GM1-ELISA is practical for routine use in the diagnosis of enterotoxigenic E. coli, especially in laboratories without facilities for cell culture.

Adrenal Glands

Secretory IgA antibodies to enterobacterial virulence antigens: their induction and possible relevance.

1) Milk and salivary s-IgA antibodies are via the homing of IgA producing cells from the Peyer's patches closely connected with antigenic stimuli in the intestine. This explains the presence in human milk of s-IgA antibodies against E. coli O and K antigens, V. cholerae and Shigella O antigens, E. coli and V. cholerae enterotoxins. These secretory antibodies can be induced by intestinal exposure and boosted by parenteral vaccination. 2) Preliminary data suggest that the IgA response in the urinary tract and possibly in the lung may be involved in the homing mechanism as well. 3) The protective role of the milk s-IgA antibodies to enterobacterial virulence antigens is strongly suggested, as is the protection mediated by urinary antibodies against urinary tract infections.

Animals

Secretory immunoglobulin A and G antibodies prevent adhesion of Escherichia coli to human urinary tract epithelial cells.

The adhesion of Escherichia coli to human urinary tract epithelial cells was inhibited by commercial gamma globulin, the total immunoglobulin fraction of human breast milk and urine, as well as the isolated immunoglobulin G and secretory immunoglobulin A fractions of urine from patients with acute pyelonephritis. Urinary anti-O6 antibodies reduced the adhesion of several O6 strains. Absorption of antibodies to the lipopolysaccharide of the adhering strain markedly decreased the antiadhesive capacity of all the immunoglobulin preparations, whereas elimination of antibodies to the capsular polysaccharide antigen consistently had a small but not significant effect. When urine was absorbed with whole, live bacteria of the patients' infecting strains, the antiadhesive effect completely disappeared. Absorption with bacteria lacking pili only partially reduced this effect.

Antibodies, Bacterial

Mechanisms of disease and immunity in cholera: a review.

The adenyl cyclase-activating enterotoxin of Vibrio cholerae was shown to contain two types of subunit: six smaller units (L) that are responsible for the binding to cell membrane receptors and a larger unit (H) that mediates the toxic action. The receptor was identified as the ganglioside GM1 (galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide), and the results suggested that penetration of the toxin molecule into the membrane follows the rapid binding to GM1. The relationship of these findings to the mechanism of protective immunity, which is mediated by antibodies to the enterotoxin as well as those to the cell wall lipopolysaccharide of V. cholerae, was investigated. The antitoxic antibodies were directed mainly against the L subunit and protected by preventing binding of toxin; the antibacterial antibodies probably interfered with adhesion of V. cholerae to the intestine. The finding that the immune responses to toxin and bacteria act synergistically in protection against experimental cholera indicates that an improved cholera vaccine should contain both toxoid and lipopolysaccharide as antigens. In the rabbit, either subcutaneous or enteral immunization gave rise to intestinal synthesis of specific antibodies to V. cholerae.

Adenylyl Cyclases

Enterotoxin antibodies in relation to diarrhoea in Swedish soldiers in Cyprus.

The development of antibodies to Escherichia coli heat-labile enterotoxin (LT) and its relationship to diarrhoea was studied in two Swedish battalions (one in the winter, WB, and one in the summer, SB) of the United Nations Peace-keeping Force in Cyprus. Whereas only 6-15% of the soldiers had detectable levels of anti-LT antibodies in their sera before leaving Sweden, as many as 69% of the SB and 43% of the WB soldiers who developed diarrhoea in Cyprus acquired significant titres of enterotoxin antibodies in their sera (acute phase serum). During the summer, many soldiers without diarrhoea also obtained anti-LT antibodies, whereas no such response was observed in healthy soldiers during the winter. Civilian Turkish Cypriots had positive sera in high frequency (60-66%) during both study periods. Parallel titration of positive sera against E. coli LT and cholera toxin indicated that the enterotoxin-neutralizing antibodies registered were induced by bacteria producing enterotoxin identical or closely related to LT.

Antibodies, Bacterial

Antitoxic immunity in experimental cholera: protection, and serum and local antibody responses in rabbits after enteral and parenteral immunization.

The protective effect of enternal and parenteral immunization with cholera toxin antigen against experimental cholera in rabbits was studied by using the small-bowel loop technique. Subcutaneous injection of crude toxin as well as purified toxin or toxoids gave rise to significant protection against toxin challenge. The enhanced resistance to toxin was found to correspond to a many-fold higher magnitude of protection against challenge with live vibrios. In the primary response the protection increased during the first month. Booster immunization gave rise to a further increased immunity which, however, declined rapidly. Multiple oral or repeated intraintestinal antigen administrations also induced protective antitoxic immunity although of less magnitude than that obtained by parenteral immunization. Enteral and, to a lesser extent, parenteral immunization gave rise to increased antitoxic antibody titers and immunoglobulin levels in intestinal washings and mucosa scraping. Immunoglobulin G (IgG) and IgG antitoxins predominated, but after enteral immunization total IgA and specific IgA antibodies occasionally reached levels similar to those for IgG. In serum, significantly increased antibody levels (IgG) were only recorded after parenteral immunization. Both the primary binding and the neutralizing antitoxin titers showed a stayistically significant correlation with the degree of protection against toxin challenge; however, for the neutralizing antibodies this correlation was not without exceptions. No relation to protection was found for intestinal antibodies. The results of the present study indicate that enternal as well as parenteral immunization with toxin antigen can give rise to effective cholera immunity. After enternal immunization, the protection appears to be medicated by locally synthesized antibodies. After parenteral vaccination both serum-derived and locally produced antibodies seem to be effective.

Administration, Oral