Immunoglobulin and anti-Escherichia coli antibody in lower respiratory tract secretions from infants weighing less than 1500 g at birth.
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Abstract:
Concentrations of immunoglobulins and anti-Escherichia coli antibody were studied longitudinally in tracheobronchial aspirates from 33 premature intubated neonates, median gestational age 27 weeks. Aspirates collected at birth contained IgG, IgA, and IgM in 100%, 93%, and 79% of samples, respectively. The median IgA concentration at birth was 0.7 micrograms/mg total protein and increased to 5.8 micrograms/mg protein by the sixth week. IgG and IgM antibodies to E coli were present in 90% and 30%, respectively, of tracheobronchial aspirates collected at birth. Samples from three of 28 neonates (11%) contained IgA anti-E coli antibody at birth, and the proportion with IgA antibody rose to 50% during the sixth week. Secretory component associated IgA and IgM were detectable in samples tested at birth and at 4 weeks of age, and secretory component associated anti-E coli antibody was present in aspirates from three of nine neonates studied at 4 weeks of age, but had not been detectable at birth.Keywords:
Immunoglobulin A
Secretory component
Immunoglobulin M
Background. To characterize the potential for adaptive immune protection in cervical mucus plugs with respect to immunoglobulin isotypes and effector cells (phagocytes). Methods. Thirty-one cervical mucus plugs were collected from healthy women in labor at term. The cervical mucus plugs were allocated either to analysis of immunoglobulins by enzyme-linked immunosorbent assay (ELISA), gel chromatography and Western blotting (n = 20) or to microscopical, including immunocytochemical, analyses. The levels of immunoglobulin in the plugs were compared to the levels in 10 samples of ovulatory cervical mucus from nonpregnant women. Results. In the cervical mucus plugs, levels of immunoglobulin G (IgG) [median 3270 µg/mL (100–14 500)] and IgA [540 (22–2820)], but not IgM [30.5 (1.0–160)], were significantly elevated compared to cervical mucus from nonpregnant women (p < 0.02 for IgG and IgA). The IgG : IgA ratio in the plugs was also elevated (p < 0.02). The proportion of secretory immunoglobulin A (SIgA) relative to total IgA in the plugs ranged from 16 to 65% (n = 5). IgA and IgG were largely intact. Microscopically, the vagina-proximal part of the cervical mucus plugs contained bacteria and was rich in cells, mainly phagocytes. Conversely, the uterine part contained few cells. Conclusion. The high immunoglobulin levels in combination with the presence of phagocytes suggest a potential for adaptive immune defense in the cervical mucus plug, which, together with innate immune factors, may act as an immunological gatekeeper protecting the fetomaternal unit against infection from the vagina.
Immunoglobulin A
Cervical mucus
Immunoglobulin M
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Immunoglobulin A
Immunoglobulin M
Helicobacter Infections
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See article in J. Gastroenterol. Hepatol. 2006; 21: 1372–1380. Antibodies present in the external secretions of mucosal surfaces play an important role in the immunological defenses against the environment.1 Secretory antibodies of the immunoglobulin (Ig) A class represent the first line of antigen-specific immune protection against inhaled, ingested and sexually transmitted pathogens and antigens at mucosal surfaces.2 Polymeric immunoglobulins of the A, G, and M classes are transported across mucosal and glandular epithelia by the polymeric immunoglobulin receptor (pIgR).3 The magnitude of pIgR-mediated transport of IgA in the human intestine is impressive, as it has been estimated that 3 g of IgA are transported daily in the average adult. Proteolytic cleavage of pIgR at the apical surface leads to the release of a complex of antibody bound to the soluble external domain of pIgR, known as the secretory component (SC).4,5 At the apical surface, the SC is cleaved and released in free form or as a component of secretory IgA. SC has innate antimicrobial properties and protects secretory IgA from proteolytic degradation. Expression of pIgR is regulated by microbial products through Toll-like receptor signaling6 and by host factors such as cytokines and hormones. Polymeric IgA neutralizes pathogens and antigens within intracellular vesicular compartments during transcytosis. The level of pIgR expression controls the rate of epithelial transcytosis of secretory IgA and IgM. pIgR knockout mice have significantly reduced IgA in external secretions and corresponding elevations in serum IgA and accumulation of IgA in the intestinal lamina propria.7 Accumulation of intestinal intraepithelial lymphocytes is observed in association with lack of pIgR. These mice have a deterioration of their epithelial barrier function; consequently, secretory IgA contributes to the maintenance of mucosal homeostasis. In humans, IgA deficiency has been associated with celiac disease and inflammatory bowel diseases. However, the precise role of IgA in the pathogenesis of these disorders is yet to be fully understood. In their article in this Journal, Murthy et al.8 examined the role of IgA and pIgR during the course of dextran sulfate sodium (DSS) induced model of chronic colitis using mice with a targeted disruption in IgA gene expression (IgA-/- mice) resulting in complete absence of IgA, and animals that lack the polymeric immunoglobulin receptor (pIgR-/- mice), resulting in serum but not secretory IgA. They showed that DSS-treated pIgR-/- mice displayed greater loss of body weight and severe clinical illness compared to similarly treated IgA-/- mice and wild type animals. In addition, colonic tissues from the pIgR-/- mice exhibited progressively and significantly greater inflammation compared to similarly treated IgA-/- mice and wild type animals. These results suggest that pIgR and SC may play an important underappreciated role in modulating inflammatory responses in the mucosa during active colitis. Consequently, secretory immunoglobulins contribute to the protection of the colonic mucosa against DSS, although the isotype of the secretory immunoglobulin (IgA or IgM) may not be a decisive factor in such protection. Thus, pIgR and/or SC are important for the maintenance of epithelial integrity and mucosal homeostasis in the colonic epithelium. This study contributes to the importance of secretory antibodies in the external secretions in physiological as well as pathological conditions and underlines the role of the immune response in inflammatory processes.
Polymeric immunoglobulin receptor
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Transcytosis
J chain
Immunoglobulin A
Lamina propria
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Previously, we reported that smokeless tobacco users have significantly higher levels of immunoglobulin A and J chain in whole saliva than non-tobacco users. Because there was no difference in levels of secretory component between the two groups, the
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J chain
Immunoglobulin A
Polymeric immunoglobulin receptor
Secretory IgA
Immunoglobulin heavy chain
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Mucosal surfaces are protected specifically by secretory immunoglobulin A (SIgA) and SIgM generated through external translocation of locally produced dimeric IgA and pentameric IgM. Their active transport is mediated by the epithelial polymeric Ig receptor (pIgR), also called the transmembrane secretory component. Paracellular passive external transfer of systemic and locally produced antibodies also provides mucosal protection, making the biological importance of secretory immunity difficult to assess. Here we report complete lack of active external IgA and IgM translocation in pIgR knockout mice, indicating no redundancy in epithelial transport mechanisms. The knockout mice were of normal size and fertility but had increased serum IgG levels, including antibodies to Escherichia coli, suggesting undue triggering of systemic immunity. Deterioration of their epithelial barrier function in the absence of SIgA (and SIgM) was further attested to by elevated levels of albumin in their saliva and feces, reflecting leakage of serum proteins. Thus, SIgA did not appear to be essential for health under the antigen exposure conditions of these experimental animals. Nevertheless, our results showed that SIgA contributes to maintenance of mucosal homeostasis. Production of SIgA might therefore be a variable in the initiation of human immunopathology such as inflammatory bowel disease or gluten-sensitive enteropathy.
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Immunoglobulin A
Neonatal Fc receptor
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Biliary transport of rat immunoglobulin was studied by perfusion of isolated rat liver with blood containing radiolabeled immunoglobulin. Transport to bile was selective for polymeric IgA. Between 15 and 27% of polymeric IgA was transported from blood to bile during a 210-min perfusion period, and approximately 60% of the IgA transported to bile bore secretory component. Small quantities of IgM (0.12%) were transported; transport of IgG2 alpha, IgE, or monomeric IgA was not detected. Purification of radiolabeled polymeric IgA by affinity chromatography on human secretory component-Sepharose yielded a fraction that was transported more efficiently (i.e., up to 40% transported). In contrast, secretory IgA (colostral or biliary) was transported 1/25th to 1/12th as well as polymeric IgA myeloma protein. Complexes of 125I-labeled secretory component and polymeric IgA formed in vitro were transported poorly (0.1%) compared to polymeric IgA (26%). It was concluded that biliary transport of polymeric IgA requires combination of it with secretory component in the liver. In support of this hypothesis, rabbit IgG anti-rat secretory component antibodies were also transported to bile but normal rabbit IgG was not.
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J chain
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Background. To characterize the potential for adaptive immune protection in cervical mucus plugs with respect to immunoglobulin isotypes and effector cells (phagocytes). Methods. Thirty‐one cervical mucus plugs were collected from healthy women in labor at term. The cervical mucus plugs were allocated either to analysis of immunoglobulins by enzyme‐linked immunosorbent assay (ELISA), gel chromatography and Western blotting ( n = 20) or to microscopical, including immunocytochemical, analyses. The levels of immunoglobulin in the plugs were compared to the levels in 10 samples of ovulatory cervical mucus from nonpregnant women. Results. In the cervical mucus plugs, levels of immunoglobulin G (IgG) [median 3270 µg/mL (100–14 500)] and IgA [540 (22–2820)], but not IgM [30.5 (1.0–160)], were significantly elevated compared to cervical mucus from nonpregnant women ( p < 0.02 for IgG and IgA). The IgG : IgA ratio in the plugs was also elevated ( p < 0.02). The proportion of secretory immunoglobulin A (SIgA) relative to total IgA in the plugs ranged from 16 to 65% ( n = 5). IgA and IgG were largely intact. Microscopically, the vagina‐proximal part of the cervical mucus plugs contained bacteria and was rich in cells, mainly phagocytes. Conversely, the uterine part contained few cells. Conclusion. The high immunoglobulin levels in combination with the presence of phagocytes suggest a potential for adaptive immune defense in the cervical mucus plug, which, together with innate immune factors, may act as an immunological gatekeeper protecting the fetomaternal unit against infection from the vagina.
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Immunoglobulin M
Cervical mucus
Humoral immunity
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Immunoglobulin A
Immunoglobulin superfamily
J chain
Immunoglobulin M
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Immunoglobulin A
Immunoglobulin M
Rheumatoid factor
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J chain
Immunoglobulin A
Polymeric immunoglobulin receptor
Catabolism
Antigen-Antibody Complex
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