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At least 523 records · Page 29Linked to original sources
PubMed1990

Jejunal immunoglobulin and antigliadin antibody secretion in adult coeliac disease.

We compared the local intestinal immunoglobulin (Ig) secretion in six adult patients with coeliac disease and nine control subjects by perfusion of a small bowel segment under an occluding balloon and analysis of the perfusion fluid for the content of Ig and secretory component. The results were compared to the number of Ig-containing plasma cells in the test segment. There was, respectively, a two-fold and a fivefold increase in jejunal secretion rates of IgA (both monomeric and polymeric) and IgM in patients with coeliac disease compared with control subjects. The high IgA and IgM secretion rates parallel the increase of Ig-containing plasma cells in the lamina propria. In contrast, the IgG plasma cell density increase was barely significant in patients with coeliac disease and did not result in a high IgG secretion rate. The jejunal secretion rate of secretory component was significantly increased in patients with coeliac disease and no free dimeric IgA was present in the jejunal fluid. Antigliadin-IgA was detected in the serum and jejunal fluid of the six patients with coeliac disease. Antigliadin-IgA, however, was almost entirely polymeric IgA linked to secretory component in jejunal fluid, whereas 61% was dimeric IgA not linked to secretory component in serum. This result, combined with a raised secretory component secretion rate with no evidence of secretory component saturation, suggests that serum and intestinal antigliadin IgA might be of different origins in coeliac disease.

Adolescent↗
PubMed1993

Gene transfer into respiratory epithelial cells by targeting the polymeric immunoglobulin receptor.

A system for targeting foreign DNA to epithelial cells in vitro has been developed by exploiting receptor-mediated endocytosis. The polymeric immunoglobulin receptor transports dimeric immunoglobulin A and immunoglobulin M through epithelial cells, including those of the respiratory tract, by binding the immunoglobulins at the basolateral surface and transporting them across the cell. Fab fragments of antibodies directed against the extracellular portion of the receptor, secretory component, are similarly transported. Anti-human secretory component Fab fragments were covalently linked to a polycation, and complexed to various expression plasmids. When bound to an expression plasmid containing the Escherichia coli lacZ gene ligated to the Rous sarcoma virus promoter, the complexes transfected HT29.74 human colon carcinoma cells induced to express polymeric immunoglobulin receptor, but not those lacking the receptor. Primary cultures of human tracheal epithelial cells grown on collagen gels, which induce the expression of polymeric immunoglobulin receptor, were also transfected with the complexes. From 5 to 66% of the respiratory epithelial cells had beta-galactosidase activity after treatment, comparable to the percentage of cultured human tracheal epithelial cells that express polymeric immunoglobulin receptor (8-35%). The addition of excess human secretory component (Fab ligand) to the culture medium at the time of transfection blocked the delivery of DNA. The expression plasmid, either alone, complexed to the polycation, or complexed to a carrier based on an irrelevant Fab fragment, was not effective in transfecting either cell type. This DNA carrier system introduces DNA specifically into epithelial cells that contain pIgR in vitro.

Biological Transport↗
PubMed2001

Chewing stimulates secretion of human salivary secretory immunoglobulin A.

Immunoglobulin A (IgA) is the most abundant immunoglobulin in saliva and other mucosal secretions and plays an important role in mucosal immunity. The present study examined whether secretion of IgA, like other salivary proteins, is increased by reflex stimulation. Parotid saliva was collected from subjects into separate vials under resting conditions and during chewing-stimulated secretion over 45 min. Enzyme-linked immunosorbent assay (ELISA) indicated that chewing increased IgA secretion. The extent and pattern of the increase were similar to those of total protein and acinar cell amylase. SDS gel electrophoresis and Western blotting showed that high-molecular-weight forms of IgA-containing secretory component predominated in all saliva samples. Secretory component, the cleaved epithelial receptor for polymeric IgA, was secreted in a pattern very similar to that of IgA. It is concluded that chewing stimulates epithelial cell transcytosis of IgA and increases secretion of secretory IgA into saliva.

Adult↗
PubMed1975

The secretory immune system and renal disease.

An immunopathological analysis of renal tissue from 105 patients was undertaken: (1) to clarify the relationship of the secretory immune system to renal diseases in which glomerular deposits of immunoglobulin A, (alpha chain), occurred; (2) to determine the lower nephron localization of secretory component and alpha chain in renal disease. This study, which included twenty-four patients with glomerular deposits of alpha chain, failed to reveal glomerular localization of secretory IgA. Secretory component was not found in renal tubular cells in kidneys with normal or minimally abnormal renal histology. In contradistinction to these findings, significant amounts of secretory component were found in tubular epithelial cells and casts in tissue from fifty-one patients with morphological evidence of significant renal damage; this localization had no correlation with glomerular deposits of IgA, IgM or other immunoreactants. Alpha Chain was rarely found in the tubular epithelium or in interstitial round cells; fifteen patients had alpha chain in casts. We conclude that the glomerular localization of immunoglobulin in glomerulonephritis is not derived from the secretory immune system, and the IgA present in glomeruli is not secretory IgA. The finding of secretory component in tubular cells in diseased kidneys without alpha chain may support an hypothesis for an independent role for secretory component in renal disease, apart from its function in the transport and stabilization of secretory IgA.

Adolescent↗
PubMed1982

Immunoperoxidase study of the secretory immunoglobulin system and lysozyme in normal and diseased gastric mucosa.

Using an immunoperoxidase technique the distribution of secretory component, IgA, and lysozyme has been investigated in normal, inflamed, dysplastic, and carcinomatous gastric mucosa. Apart from pyloric glands which contain lysozyme, normal gastric mucosa stains negatively for all three antigens. In gastric mucosa neck cells appear to adapt by synthesising secretory component and lysozyme and transporting IgA. Intense staining for the three antigens is seen in dysplastic gastric epithelium and in well-differentiated intestinal type carcinomas. With progressive de-differentiation the tumours lose the ability to synthesise secretory component and lysozyme. Carcinomas of the diffuse type stain positively for secretory component and lysozyme and individual cells appear to take up IgA even in the absence of surrounding IgA containing plasma cells. These functional properties are retained in lymph node metastases. It is suggested that secretory component synthesising malignant cells might take up circulating dimeric IgA and that this could be a reflection of an important physiological mechanism.

Gastric Mucosa↗
PubMed1992

Analysis of epithelial and lymphoid phenotypic markers in relation to growth pattern of colorectal adenomas.

The relationship of villous to tubular adenomas is poorly understood and often difficult to characterize morphologically. A villous growth pattern in colorectal adenomas has been associated with a higher frequency of high-grade dysplasia. We compared phenotypic markers using immunoperoxidase techniques in paired samples of villous (75% to 100% villous) and pure tubular adenomas matched for size and degree of dysplasia, which were selected by review of 1,000 polyps from our files. The following monoclonal antibodies were used: CAM 5.2 and AE1/AE3 to cytokeratins; B18, D14, B7.1, and B7.8 to four distinct carcinoembryonic antigen epitopes; Leu-M1 and LN3 to HLA-DR antigen; LN2 to invariant chain class II major histocompatibility complex; LN1 and MB2 to B-cell markers; UCHL1 and MT1 to T-cell markers; Leu-7 to natural killer cells; Mac 387 to macrophages; S-100 to Langerhans-type cells; and a polyclonal antibody to secretory component. LN3 reactivity correlated with villous morphology and secretory component correlated with tubular morphology. Combined HLA-DR and secretory component expression discriminated between tubular and villous growth patterns in 12 of 15 pairs of adenomas (P less than .001). LN2 was expressed more frequently than LN3, but did not correlate with growth pattern. Neuroendocrine cells (Leu-7) were more frequent in tubular adenomas. Carcinoembryonic antigen epitopes did not relate to growth pattern. We did not confirm previously reported differences in cytokeratin expression. We concluded that among the markers tested, HLA-DR expression, which may have an immunologic basis, is most characteristic of colorectal adenomas that exhibit a villous growth pattern.

Adenoma↗
PubMed1986

Functional expression of the polymeric immunoglobulin receptor from cloned cDNA in fibroblasts.

The polymeric immunoglobulin receptor, a transmembrane protein, is made by a variety of polarized epithelial cells. After synthesis, the receptor is sent to the basolateral surface where it binds polymeric IgA and IgM. The receptor-ligand complex is endocytosed, transported across the cell in vesicles, and re-exocytosed at the apical surface. At some point the receptor is proteolytically cleaved so that its extracellular ligand binding portion (known as secretory component) is severed from the membrane and released together with the polymeric immunoglobulin at the apical surface. We have used a cDNA clone coding for the rabbit receptor and a retroviral expression system to express the receptor in a nonpolarized mouse fibroblast cell line, psi 2, that normally does not synthesize the receptor. The receptor is glycosylated and sent to the cell surface. The cell cleaves the receptor to a group of polypeptides that are released into the medium and co-migrate with authentic rabbit secretory component. Cleavage and release of secretory component do not depend on the presence of ligand. The cells express on their surface 9,600 binding sites for the ligand, dimeric IgA. The ligand can be rapidly endocytosed and then re-exocytosed, all within approximately 10 min. Very little ligand is degraded. At least some of the ligand that is released from the cells is bound to secretory component. The results presented indicate that we have established a powerful new system for analyzing the complex steps in the transport of poly-Ig and the general problem of membrane protein sorting.

Animals↗
PubMedDate not supplied

[Humoral response of the immunologic secretory system of the small intestine in children infected with Giardia intestinalis].

Local humoral response of the intestinal mucosa was determined with secretory IgA levels and secretory component activity in enterocytes and duodenal content of 15 children infected with G. intestinalis. The obtained results were compared to those in 5 children with coeliac disease and 12 children with diarrhoea without lambliasis. Secretory IgA was increased in about 50% of children with lambliasis (in the remaining groups in 25% of children) to the values higher than that in the comparative groups. Secretory component activity was relatively high in the intestinal epithelium. Secretory component activity in the duodenal content was high in about 40% of children independently of the examined group. No correlation between the said variables was noted except positive correlation of secretory IgA levels and secretory component activity in the bile.

Adolescent↗
PubMed2005

The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces.

Secretory antibodies of the immunoglobulin A (IgA) class form the first line of antigen-specific immune protection against inhaled, ingested, and sexually transmitted pathogens and antigens at mucosal surfaces. Epithelial transcytosis of polymeric IgA (pIgA) is mediated by the polymeric immunoglobulin receptor (pIgR). At the apical surface, the extracellular ligand-binding region of pIgR, known as secretory component (SC), is cleaved and released in free form or as a component of secretory IgA (SIgA). SC has innate anti-microbial properties, and it protects SIgA from proteolytic degradation. Expression of pIgR is regulated by microbial products through Toll-like receptor signaling and by host factors such as cytokines and hormones. Recent studies of the structure of the extracellular ligand-binding domain of pIgR have revealed mechanisms by which it binds pIgA and other ligands. During transcytosis, pIgA has been shown to neutralize pathogens and antigens within intracellular vesicular compartments. The recent identification of disease-associated polymorphisms in human pIgR near the cleavage site may help to unravel the mystery of how pIgR is cleaved to SC. The identification of novel functions for SC and SIgA has expanded our view of the immunobiology of pIgR, a key component of the mucosal immune system that bridges innate and adaptive immune defense.

Animals↗
PubMed1989

The immune function of the endometrium.

The endometrial mucosa is unique amongst mucosal sites in that it must mount an immune response against micro-organisms and resist tumour growth whilst tolerating sperm and the allogeneic fetus. Bacterial and viral infection in the uterus leads to local endometrial mucosal immune responses evidenced by the secretion of secretory component (SC), secretory IgA (sIgA) and IgG. The secretion of these molecules is under hormonal control. Trafficking of locally sensitized lymphocytes to other mucosae does not appear to occur, whereas priming at other mucosal surfaces leads to memory responses to antigen in the uterus. Proclivity to local immune function is related to sparse lymphatic supply to the endometrium together with a local distribution of antigen-presenting dendritic cells. During pregnancy, particularly in the region of the decidua and embryo, the number of Ia+ cells and the lymphatic supply become diminished. The antigenic status of sperm may lead to certain types of maternal sensitization. However, immunosuppressive factors in seminal plasma protect the sperm on its passage up the female genital tract and diminish subsequent immunogenicity. On fertilization of the oocyte, an allogenic fetus develops, that potentially could stimulate production of maternal immune effectors. Endometrial cells of various types (macrophage, decidual, NK, T cells) interact via soluble factors leading to a local immunoprotection of the fetus. Similar factors appear to operate in resisting tumour growth in the uterus.

Endometrium↗
PubMed1992

Humoral immune response patterns of human mucosae: induction and relation to bacterial respiratory tract infections.

Immunoglobulin-producing cells in mucosal tissues, quantitatively the body's most important humoral immune system, synthesize mainly dimers and larger polymers of IgA (poly-IgA) with incorporated J (joining) chain. Poly-IgA is actively transported to exocrine secretions by a transmembrane epithelial glycoprotein called secretory component. Enhancing secretory immunity by oral vaccination is an interesting possibility, but mucosal antigen uptake and local immune regulation are complex and only partly understood. Immunoglobulin isotype response patterns in the upper respiratory mucosa and distal gut are strikingly different. The preferential production of IgA1 in nasal and bronchial mucosae is intriguing in view of the frequent synthesis of IgA1-specific proteases by Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. A relationship of proneness to produce invasive disease and enzymatically induced deterioration of secretory immunity has been proposed. Differences in mucosal immune response patterns among patients with selective IgA deficiency or IgG subclass deficiencies also suggest that local humoral immunity is an important variable in resistance to infections.

Antibodies, Bacterial↗
PubMed1982

Selective excretion of IgA in rat bronchial secretions: lack of significant contribution from plasma IgA.

Concentrated rat bronchial washings (BW) were analyzed by gel-filtration and immunochemical methods. BW contained mainly albumin, transferrin and IgG. Free secretory component and secretory IgA were identified in BW; the BW-IgA had the same three sedimentation coefficients, i.e. +/- 11 S, 13 S, 15 S by sucrose density gradient ultracentrifugation, as rat milk and rat bile IgA; the three peaks were secretory IgA. Compared to serum, and relatively to albumin, BW were significantly enriched in IgA, although much less than rat bile. Purified polyclonal rat polymeric 125I-IgA was injected intravenously into normal rats, and into rats with bile duct ligation or partial hepatectomy, which decrease the liver plasma-to-bile transfer of IgA. BW were then collected, one or four hours later, to assess the recovery of the 125I-IgA in BW and to estimate the contribution of serum IgA to BW-IgA. Very little 125I-IgA (less than 0.2%) was recovered in all BW. The specific activity, measured only in the rat with the highest recovery in BW, was 20 times lower in BW than in serum. The data demonstrate that rat serum IgA does not contribute significantly to IgA in BW.

Albumins↗
PubMed1992

Ontogeny of the receptor for polymeric immunoglobulins in rat hepatocytes.

Based on in vitro experiments measuring daily secretion rates in the culture media of rat hepatocytes and in vivo experiments using pulse labeling of intracellular precursors, the present study examines the ontogenic expression of the polymeric immunoglobulin receptor and secretory component by hepatocytes during growth. Our data indicate that hepatocytes from infant and suckling rats (day 5, 15) cultured in serum-free and hormone-free conditions only secreted trace amounts of secretory component. Beginning on day 20, basal secretion rate showed a marked upsurge with a 10-fold increase by day 35. The addition of dexamethasone (10(-7) mol/L) to the culture media enhanced by 2.5-fold the basal secretion of secretory component by hepatocytes from 20-, 25-, and 35-day-old rats, while addition of insulin to the media had no effect. The response to dexamethasone was dose-dependent (10(-5), 10(-6), 10(-7) mol/L) and specific. In vivo pulse labeling of receptor precursors in hepatocytes from 40-day-old rats allowed the identification of three intracellular forms: a 105-kilodalton peptide and a 116-120-kilodalton mature doublet. In 13-day-old rats, three immature precursors were detected: a 105-kilodalton peptide and a high molecular weight doublet of 185-190 kilodaltons. Sucklings (13 days) treated with corticosterone showed a pattern of precursors similar to controls. These findings support the following conclusions: (a) hepatocytes from infant and suckling rats synthesize and process immature receptor precursors whose expression is unaffected by corticosterone treatment, and (b) active secretion of secretory component is initiated at weaning independently from humoral and hormonal factors while the magnitude of its production by the liver is under the control of glucocorticoids.

Aging↗
PubMed1995

Biliary IgA secretion in obstructive jaundice: the effects of endoscopic drainage.

BACKGROUND: Immunoglobulin A is the predominant immunoglobulin in the bile. Data on the effects of biliary obstruction on IgA secretion are few. METHODS: The serum and bile IgA levels in patients with common duct stones (n = 27) or with malignant obstructive jaundice (n = 20) were collected by insertion of nasobiliary catheters. Single samples of common duct bile from patients with gallstones (n = 24) were collected as controls. Bile samples collected were measured for total IgA, secretory IgA, and free secretory component levels by sandwich enzyme-linked immunosorbent assays. RESULTS: Bile total IgA, secretory IgA, and free secretory component in the common duct stones group (82.7 +/- 11.4 microgram/ml, 18.4 +/- 1.7 microgram/ml, 0.74 +/- 0.15 microgram/ml) and the malignant obstructive jaundice group (81.6 +/- 10.7 microgram/ml, 18.2 +/- 2.4 microgram/ml, 0.57 +2- 0.12 microgram/ml) were found to be significantly lower than those of the control gallstone patients (104.8 +/- 3.4 microgram/ml, 33.2 +/- 2.9 microgram/ml, 1.03 +/- 0.12 microgram/ml) (P < 0.05). Serum secretory IgA levels in the common duct stones (26.53 +/- 1.75 microgram/ml) and malignant obstructive jaundice groups (26.03 +/- 3.48 microgram/ml) were significantly higher than the gallstone group (18.45 +/- 4.56 microgram/ml). The bile-to-serum concentration ratio of total IgA, secretory IgA, and free secretory component levels rose significantly within 48 hours after relief of obstruction. CONCLUSIONS: Biliary obstruction secondary to both calculus or malignancy of the hepatobiliary system causes suppression of bile IgA secretion and elevated serum level of secretory IgA. Bile secretory IgA secretion recovers with endoscopic drainage of the obstructed system.

Aged↗
PubMed1991

Effect of smokeless tobacco use in humans on mucosal immune factors.

To assess the effects of smokeless tobacco on the secretory immune system and dental caries, we examined users of smokeless tobacco and non-tobacco users. There were no significant differences in the prevalence of DMFS between users and non-users. There was significantly more salivary IgA, IgA2 and J-chain in users. Levels of salivary lysozyme and lactoferrin were significantly lower in users than controls. Because there was no difference in levels of secretory component in relation to the increased IgA levels of smokeless tobacco users, this suggests an effect of smokeless tobacco on secretory epithelial cells responsible for synthesis of secretory component, lysozyme and lactoferrin, and for the packaging of secretory component on IgA. There were only slight differences in salivary or serum antibody levels to Streptococcus mutans. These findings indicate that although smokeless tobacco has a significant influence on the synthesis of secretory IgA, the numbers of DMFS were similar between smokeless tobacco users and controls.

Adolescent↗
PubMed1976

Secretory immunoglobulins in colonic neoplasms.

Secretory immunoglobulins are found in nongoblet columnar cells of normal intestinal epithelium. These molecules consist of a secretory component portion, which is synthesized in the columnar cells, and an immunoglobulin portion which enters the columnar cells from plasma cells in the adjacent lamina propria. In the present work, the synthesis and transport of these various subunits have been studied by immunofluorescence in benign polyps and cancers of the colon. In both the epithelium and plasma cells of benign and malignant tumors, as well as in normal tissue, IgA is the principal immunoglobulin, followed by IgM. However, when compared to normal tissue, neoplastic epithelium contains less immunoglobulin and also less secretory component; the decrement usually inversely parallels the degree of differentiation. Thus, benign polyps closely resemble normal colonic mucosa in so far as the secretory immunoglobulin system is concerned. In contrast, atypical areas of benign polyps and carcinomas exhibit greatly decreased or absent synthesis and transport of secretory IgA. Plasma cells tend to be markedly decreased in the stroma of carcinomas, suggestive of an alteration in the normal mechanism for attracting the circulating precursors of local IgA plasma cells. Whenever neoplastic epithelium contained IgA, plasma cells with IgA could be observed in the vicinity; this is in keeping with the concept of local synthesis of secretory IgA. In some instances in which local plasma cells were plentiful, neoplastic cells were deficient in secretory component and IgA, which suggested impairment of the mechanisms for transporting IgA across epithelium. The possible role of secretory component in such transport and in attracting lymphoblasts to mucous membranes is dicussed.

Colonic Neoplasms↗
PubMed1987

Local production of rotavirus specific IgA in breast tissue and transfer to neonates.

Rotavirus specific IgA, secretory component, and IgG were measured by enzyme linked immunosorbent assay in 20 pairs of mothers and babies to estimate antibody transfer from the mother, particularly from breast milk to neonatal faeces. Colostrum contained high titres of specific IgA and secretory component, which decreased gradually. Faeces after breast feeding for three days showed detectable titres of IgA and secretory component, with further increases by seven days. There was a positive correlation between titres of secretory component in breast milk and in faeces. To clarify the mechanism of high anti-rotavirus activity in breast milk, ratios of rotavirus specific IgA in maternal serum samples to breast milk were calculated and compared with those that were herpes simplex virus specific. Significantly higher concentrations were obtained for the herpes simplex virus specific samples, indicating that anti-rotavirus IgA is selectively produced in breast tissue.

Antibodies, Viral↗