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Biomedical subjects

G D Jackson

Publications and source records attributed to G D Jackson.

At least 109 records · Page 6Linked to original sources

Studies on the origins of biliary immunoglobulins in rats.

This study was designed to investigate the origins of biliary immunoglobulins in rats. Natural antibodies to species of Lactobacillus and Staphylococcus were detected in blood, bile, and lymph, with predominant activity being associated with immunoglobulin A in lymph and bile and with immunoglobulins M and G in blood. Six hours after thoracic duct cannulation, serum immunoglobulins G, M, and A had fallen to 60%, 65%, and 40%, respectively, of the preoperative levels, whereas the level of total and specific immunoglobulin A in bile was reduced to 25% with no significant decline of immunoglobulin G. Thoracic duct occlusion caused a similar selective reduction in biliary immunoglobulin A. It is calculated that 50% of thoracic duct lymph immunoglobulin A entering the blood is secreted in bile. Synthesis of immunoglobulins M, G, and A in the liver was established by the detection of antibody-secreting cells. It is proposed that the major part of biliary immunoglobulin A is derived from intestinal lymphoid tissues and that a portion of the remainder, as well as part of biliary immunoglobulins M and G, results from local synthesis.

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The transient appearance of IgM antibodies in the bile of rats injected with Salmonella enteritidis.

Following the intravenous injection of 2 X 10(8) killed Salmonella enteritidis into rats, high levels of specific antibodies were detected in the serum and bile after 4 days. The level in serum persisted while that in bile had virtually disappeared by day 7. On the basis of gel filtration on Ultrogel AcA22 the activity in bile was found to be associated with the IgM fraction. The transient nature of the biliary response was further evidenced by the association of the agglutinating activity with a four-fold increase in the concentration of IgM and the presence of complement-fixing bactericidal antibody. Initial evidence suggests that the source of the biliary IgM is from cells within the liver rather than transport of IgM from blood to bile. It is proposed that immune stimulation by blood-borne microorganisms can lead to a pulse of IgM in the bile, providing rapid augmentation of other local immune processes in the gastrointestinal tract.

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Enzyme-linked immunoassays for antibodies against Vibrio cholerae.

Glutaraldehyde-treated V. cholerae organisms bind firmly to the surfaces of plastic microELISA plates, thus providing a stable immobilized antigen for use in enzyme-linked immunosorbent assays (ELISA). Serum absorption and ELISA-inhibition experiments indicate that, in addition to detecting natural antibodies in normal rat serum, the immobilized antigen may be used to quantitate specific anti-V. cholerae antibodies induced in rats by injection of live organisms. Apart from serotypically specific anti-lipopolysaccharide (LPS) antibodies, the reaction with immobilized organisms seems to involve antibodies common to Inaba and Ogawa serotypes; it is suggested that these antibodies are primarily directed against antigens of the outer membrane protein complex of V. cholerae cells. These findings have led to the development of an indirect ELISA method which quantitates levels of antibodies that react with heat-sensitive surface antigens of V. cholerae without involvement of anti-LPS antibodies. When used in conjunction with the indirect LPS-ELISA, the test has been found to provide a more detailed description of the serum antibody responses of rats to parenteral injections of live V. cholerae than has been reported previously.

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The role of serum and biliary antibodies and cell-mediated immunity in the clearance of S-typhimurium from chickens.

The development of three parameters of immunity in response to a non-lethal infection of Salmonella typhimurium in adult chickens has been examined. Intravenous inoculation of 1 X 10(6) organisms established infection in the liver, spleen and intestinal tract of all birds; the organism persisted in these sites until day 9 of the infection, after which it was cleared rapidly from all sites. High levels of agglutinating and haemagglutinating antibodies were found in serum and bile 5 days after infection; they peaked at days 7 to 10, and detectable antibody was still present in both fluids 6 weeks after infection. The presence of this antibody did not appear to cause a significant reduction in organism numbers in any of the sites examined. Cell mediated immunity was detected at day 14. It is suggested that cells mediated immunity is responsible for clearance of the organisms from the tissues.

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Immune responses of rats to live Vibrio cholerae: antibodies in serum and intestinal secretions.

Following injection of live Vibrio cholerae into the small intestine of rats, antibodies appear in the serum and mucus secretions associated with the intestinal surfaces. In contrast to oral immunization, single pulses given by this route cause primary and secondary agglutinating and vibriocidal antibody responses; they are slower to develop but similar to those induced by intravenous injection of 10-fold lower doses of the organisms. However, the intestinal route of injection appears to favour local formation of agglutinating antibodies that are directly transferred to the mucus secretions; it is likely that these are of the sIgA class. Evidence has also been presented which suggests that intestinal injection causes formation of antibodies which inhibit agglutination of V. cholerae by type-specific antiserum; these inhibitory effects are eliminated if the reaction is carried out in the presence of diluted normal rabbit serum rather than saline.

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Immune responses of rats to live Vibrio cholerae: secretion of antibodies in bile.

Agglutinating and vibriocidal antibodies appear in the bile of rats within a few days of intravenous or intraintestinal injection of live Vibrio cholerae. Whereas the presence of IgM and IgG antibodies area accounted for by passive exudation from serum., those of the IgA class are selectively (actively) transferred from serum to bile. Bile duct ligation causes a 10-fold increase in serum IgA levels over a 48-h period; a similar increase in agglutinating antibody titre occurs only in rats injected intraintestinally, thus providing further evidence for the predominance of IgA-antibody formation when antigen is taken up from the intestinal lumen. Biliary antibodies do not appear to augment the antibody levels in mucus secretions that adhere to the small intestine surfaces. However, when the bile flow is interrupted by bile duct occlusion or cannulation, the antibody levels in these secretions increase in parenterally-immunized animals. It is unlikely, therefore, that bile duct ligation will provide a satisfactory approach to determining the protective function of biliary V. cholerae antibody.

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Induction of IgM immunological memory to lipoteichoic acids in rabbits. Part I.

Intravenous immunisation of rabbits with 10(9) lactobacillus fermentum cells elicited a response, specific for lipoteichoic acid (LTA), detectable as IgM plaque-forming cells (PFC) in the spleen by day 2 and as thiol-sensitive 19s antibodies in sera by day 3. Direct PFC responses peaked at day 6, with no indirect PFC demonstrable at the time. Specific IgG PFC appeared after 14 days. A second intravenous injection 5 weeks later induced a 10-fold higher IgM PFC response to LTA which reached a maximum on day 4. An enhanced specific IgG PFC response was also observed. Serum analysis showed further evidence of the anamnestic IgM response to LTA. The results are discussed in terms of the T-dependence of the LTA immunogen.

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Immune responses to lipoteichoic acid: comparison of antibody responses in rabbits and mice. Part II.

Humoral immune responses to lipoteichoic acid (LTA) as a surface antigen of Lactobacillus fermentum were assessed in rabbits and mice. Intravenous injection of rabbits with whole bacteria was effective, over a wide range of doses (10(4) to 10(10) cells), in eliciting antibodies to LTA. In mice, significant levels of anti-LTA antibodies were induced only following intraperitoneal injection of 10(8) to 10(9) L. fermentum cells. Rabbit antibodies to LTA were predominantly of the IgM class and were specific for the polyglycerol phosphate and carbohydrate moieties of the LTA. In contrast, both IgM and IgG anti-LTA antibodies were produced in the mouse, and antibody specificity was restricted to the polyglycerol phosphate sequence.

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Induction of hypersensitivity reactions to Lactobacillus fermentum and lipoteichoic acid in rabbits. Part II.

Regimens of intravenous injections of saline-washed Lactobacillus fermentum elicited hypersensitivity reactions in rabbits. Pathological investigation revealed evidence consistent with induction of aggregate anaphylaxis, characterised by acute cor pulmonale. Additional evidence of similar tissue injury was observed in livers of rabbits which had received several intravenous injections of L. fermentum. Deposition of immune complexes in kidney glomeruli was demonstrated in only 1 out of 11 animals. Skin testing experiments revealed that lipoteichoic acid was involved in type I and type II antibody-mediated hypersensitive states. The involvement of bacterial cell surface components and extracellular products in such reactions implies a potential role in host tissue injury.

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High levels of secretory IgA and free secretory component in the serum of rats with bile duct obstruction.

In the rat , ligation of the bile duct induces a rapid and progressive elevation of the IgA levels in serum. The increase is about 4-fold at 1 h, 15-fold at 1 day, and 30-fold at 1 wk after ligation. The additional IgA is of the secretory type. Free secretory component also appears in serum after bile duct obstruction; it does not continue to increase and occasionally disappears from serum after prolonged ligation. The increase in serum IgA levels is selective. These changes are totally reversible if the bile duct is reopened at 1 day after ligature. These findings confirm the role of the rat liver in the transfer of circulating IgA into the bile.

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Rapid disappearance from serum of intravenously injected rat myeloma IgA and its secretion into bile.

Intravenously injected monoclonal rat IgA is first removed from rat serum at a very fast rate (93% in 4 h), then at a much slower rate (t/2 = 24 h). The rapid initial disappearance is thought to be due in part to secretion into rat bile. This was demonstrated by rat liver perfusions with semisynthetic medium containing diluted (1:200) IgA myeloma serum. During perfusion, the cannulated bile displayed increasingly high levels of this IgA, with a bile to medium ratio of 38 after 1 h of perfusion; at the same time, there was a 40% drop of the rat monoclonal IgA concentration in the medium, which was not observed for rat IgG2a and albumin. All of the monoclonal biliary IgA was bound to secretory component. The rat liver is thus able to actively secrete a monoclonal IgA from the circulation into bile against a strong concentration gradient.

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Role of the liver in the rat intestinal s-IgA system.

Rat bile is an important source of s-IgA and FSC about 10 mg of s-IgA are poured daily in the duodenum via the bile. The normal rat liver is capable of actively transferring IgA from the circulation into bile against a strong concentration gradient. Circulating IgA transferred in bile was bound to SC. Ligature of the rat bile duct induces a large and selective increase of the IgA level in serum. All this additional IgA is s-IgA and even FSC appears in serum after bile duct obstruction. The liver appears to have an important reinforcing role in the intestinal s-IgA system of the rat.

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Relevance of biliary IgA antibodies in rat intestinal immunity.

Two intraperitoneal administrations of foreign red cells in Freund's complete adjuvant, or two intragastric intubations of erythrocytes, given to rats at 15 days interval, both elicit the appearance of specific antibodies in bile and serum. When bile was compared to serum, the selective predominance of IgA antibodies in this secretion was observed for both the intraperitoneally and intragastrically immunized groups, being more pronounced for the orally immunized group when related to IgG or IgM antibodies. The IgA content of upper intestinal washings was roughly ten-fold smaller in rats with bile duct cannulation than in sham-operated controls. Altogether, the data demonstrate that bile IgA may significantly contribute to the secretory IgA system of the gut.

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Rat bile as a convenient source of secretory IgA and free secretory component.

Rat hepatic bile contains three proteins as major constituents: secretory IgA (SIgA), free secretory component (FSC) and albumin. Traces of alpha-macroglobulin, transferrin, IgG and IgM are also detectable. The bile duct daily pours between 5-12 mg each of SIgA and FSC into the rat duodenum. The origin and function of these proteins in bile may represent important clues in the understanding of the SIgA system.

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