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PubMed1978

Relationships between immunoglobulins and the intestinal epithelium.

The intestinal epithelium is intimately associated with immunoglobulins. This association may begin in neonatal life with the ingestion of large quantities of immunoglobulins in breast fluids. These ingested immunoglobulins probably have a local protective action in the intestinal lumen. In some mammalian species a large portion of the maternal immunoglobulins is translocated intact across the intestinal epithelium into the circulation, providing additional immunological protection. In rodents, the transepithelial translocation of IgG from breast fluids is initiated and critically dependent upon receptors on enterocyte surface membranes for the Fc region of IgG. Close epithelial-immunoglobulin relationships continue throughout life with the transfer of various classes of immunoglobulins across the epithelium into the intestinal fluids. In man and other mammalian species, IgA and IgM are selectively transported through enterocytes, principally in the crypts of intestinal glands. This transfer may involve binding of polymeric forms of these immunoglobulins to receptors on the abluminal surfaces of the enterocytes. The secretory component, a glycoprotein synthesized by enterocytes, may be such a receptor. IgE and IgG enter the gut lumen by mechanisms that are not defined but seem to be distinct from those involved in the translocation of IgA and IgM. Secreted antibodies in intestinal fluids and mucus bathe the luminal surfaces of intestinal epithelial cells but appear not to be firmly bound to their apical plasma membranes or glycocalyces. The intimate association of immunoglobulins with intestinal epithelial cells illustrates the close relationships that exist between the gut and lymphoid cells and their products. These relationships suggest the possibility that the gut epithelium is affected by a large variety of immunological reactions in health and disease; these possibilities, which have been explored only minimally, warrant much attention in the future. Studies on the binding, uptake, and intracellular transport of immunoglobulins by enterocytes could contribute much to the understanding of receptors for immunoglobulins on many other types of cells, such as lymphocytes, macrophages, mast cells, and the lining cells of placental or yolk sac membranes.

Animals↗
PubMed1985

[Serum and secretory immunoglobulins in allergic diseases].

A total of 158 patients with pollinosis, bronchial asthma, urticaria and Quincke's edema were examined. The immunoglobulin and C3 levels in sera and the immunoglobulin and albumin levels in saliva were determined by the method of single radial immunodiffusion with the corresponding monospecific antisera. In all the groups of patients subjected to examination the presence of polyclonal hypergammaglobulinemia was detected, which was manifested by a rise in the levels of IgG, IgA and especially IgM; the level of IgD was low. A decrease in the level of C3 was detected in pollinosis patients in the absence of the exacerbation of the disease. No circulating immune complexes were detected. An essential increase in the level of IgG in saliva was revealed, which was due to the local synthesis of this immunoglobulin. In winter the level of salivary IgA in pollinosis patients was found to be essentially below normal, but at the period of exacerbation it increased twofold, probably in response to local stimulation with antigen-allergen. Patients with bronchial asthma and pollinosis were found to have a high level of free secretory component (SC); in pollinosis the level of free SC sharply increased during the stage of exacerbation, which was due to the increase of its synthesis and secretion by the epithelial cells of the mucous membranes. The importance of these data for the pathogenesis of allergic diseases are discussed.

Adolescent↗
PubMed1975

[Preparation of porcine IgA and its detection using the fluorescent antibody technic].

The preparation of immunoglobulin A (IgA) from porcine colostrum, intestinal content and serum is described. The best results were achieved with colostrum, from which an antigen of satisfactory purity was prepared by purification on Sephadex G-200, on DEAE cellulose and subsequent filtration on Sephadex G-200. The serum to this antigen raised in rabbits was adsorbed to an immunoadsorbent from porcine serum (PS) or porcine IgG. The adsorbtion of the serum against secretory IgA (SIgA) to PS removed its undesirable heterologous and nonspecific reactivity. The anti-SIgA serum adsorbed in this way still reacted with IgA from porcine serum. In the direct and indirect immunofluorescent staining we detected the main antigenic determinants of the SIgA molecule, i. e. the heavy chains and the secretory component.

Animals↗
PubMed1976

In vitro synthesis of immunoglobulins and other proteins by dysplastic and neoplastic human mammary tissues.

The synthesis of several proteins in human mammary carcinomas and in dysplastic breast tissues was studied by tissue culture and by immunofluorescence. The synthesis of immunoglobulins showed marked quantitative and qualitative variations from one specimen to another, and a preferential synthesis of immunoglobulin G and C'3 in the carcinomas with lymphocytic infiltration. Fixation of immunoglobulins G and M on the surface of neoplastic cells was noted in some carcinomas. Secretory component was detectable in some cases by immunofluorescence, but no synthesis could be found in vitro, presumably because of unfavorable culture conditions. The synthesis of lactoferrin, casein, and some serum alpha- and beta-globulins was significantly greater in noncancerous tissues than in carcinomas. Synthesis of lactoferrin was also more frequent in the well differentiated carcinomas than in the poorly differentiated carcinomas. The tissue culture technique used in this study, although in need of better adaptation to the requirements in vitro of human mammary tissues, proved to be a useful tool for investigating the synthesis of several protein components by the epithelial cells of cancerous and dysplastic tissues of the human breast. Whether a preferential synthesis of 1 class of immunoglobulins or of other proteins might influence the evolution of a mammary lesion could not be determined in this material but it should be studied further.

Alpha-Globulins↗
PubMed1984

[Motility of the small intestine: organization, regulation and functions. 15 years' research on migrating complexes].

The motility pattern of the small intestine has been widely studied over the past fifteen years since a cyclically recurring and distally migrating sequence of myoelectric and motor events was first discovered. Myoelectric or motor migrating complexes (MMC) are composed of 3 main consecutive phases: quiescence, irregular spiking activity and regular spiking activity. Though specific characteristics have been recorded, this sequence seems to be a common pattern in several species of mammals, despite wide differences in digestive anatomy and physiology and very different food habits. Moreover, the basic pattern has been observed to be able to adapt to the mode of feeding and the food composition. Usually, MMC are initiated on the duodenum, but they may be initiated at any level from wandering sources. The anatomical integrity of the intestinal wall is necessary to regular proximodistal migration of the full sequence. Through the cholinergic network of the plexuses, the intrinsic nervous system plays a determinant role in controlling both the initiation and the migration of MMC. The cyclic recurrence of the full sequence, which seems to be a property of the intrinsic plexuses, can be explained by analogy with relaxation oscillators. Nevertheless, the extrinsic nervous system also plays a role, mainly by modulating the duration and intensity of the irregular spiking activity phase. Such a modulation supports the adaptive changes of MMC to feeding. The significance of several hormones and regulatory peptides has also been considered, as some of them cyclically vary in phase with MMC and, as exogenous peptides, they may affect MMC. However, none of these substances plays any determinant role; they rather serve as feedback regulations coordinating small intestine motility with gastric function and pancreatic and biliary secretion, thus giving rise to the so-called secretory component of MMC. The secretions show a cyclic pattern parallel to the MMC pattern, resulting in a cyclic variation of the pH of the duodenal contents. Moreover, it now appears that nervous and humoral controls of MMC should not be distinguished. An overall view of the whole control system is even more complicated due to the possible role of the central nervous system and to the ubiquity of several peptides of the brain-gut axis. In spite of extensive data on these mechanisms, there are still several gaps in our knowledge. But the MMC pattern and its related functions obviously support the coordination of the sequential events involved in digestion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Systemic and local intestinal antibody response in dogs given both infective and inactivated canine parvovirus.

Systemic and local immune responses were evaluated in dogs given infective canine parvovirus (CPV) and 2 administrations of inactivated CPV 6 months later. Before the inactivated CPV was given, a jejunal cannulation was performed on the animals. During infective CPV administration, concentrations of class-specific copro- and sero-immunoglobulin (Ig)G, IgA, and IgM were determined by enzyme-linked immunosorbent assay. High concentrations of both copro- and sero-IgM, as well as a moderate increase in the concentrations of sero-IgG and copro-IgA, were detected within 3 days after experimental challenge. Hemagglutination inhibition titers correlated with both serum anti-CPV IgG and IgM early and serum anti-CPV IgG in the later states of infection. After 2 oral administrations of inactivated CPV, class-specific jejuno-, copro-, and sero-IgG, IgM, and IgA anti-CPV antibodies also were determined by enzyme-linked immunosorbent assay. High concentrations of jejuno-IgM and moderate levels of jejuno-IgG and IgA were found. Copro-IgM was not detected in the feces; however copro-IgG and IgA were. Also, no correlations were found to exist when sero-IgM and IgG were compared with jejuno- and coproantibody concentrations throughout the experimental period. Thus, it appears that the immune responses to CPV include both a secretory component of the intestinal mucosa and a systemic component of peripheral lymphoid tissues. Application of the modified Witzel's enterostomy to this study of local intestinal immunity proved beneficial. The technique was well tolerated by experimental animals and allowed for simple, multiple sample collections of intestinal contents for virus and antibody determinations with apparently minimal alterations in the luminal environment.

Animals↗
PubMed1983

The immunochemical characterization of mesangial IgA deposits.

Mesangial deposits of IgA are found in IgA nephropathy, Schönlein-Henoch purpura (SHP) and in some patients with alcoholic cirrhosis and systemic lupus erythematosus (SLE). In this study the authors characterized the mesangial IgA deposits in patients with the above diseases using antiserums or monoclonal antibodies to A1, A2, J-chain and secretory component (SC), and examined SC binding in vitro. SC was not present, J-chain was ubiquitous, and A2 was found (with the use of monoclonal antibodies) rarely but with equal frequency in all groups. The SC binding capacity of the deposits differed between the groups and was found in 13 of 16 patients with alcoholic liver disease, 3 of 4 with SLE, 1 of 10 with primary IgA nephropathy, and none of 6 with SHP.

Antibodies, Monoclonal↗
PubMed1983

The occurrence of secretory IgM in the bile of rats.

The concentration of IgM in the bile of normal rats is extremely small, too low to be detected by conventional immunodiffusion methods. However, IgM is easily detected in bile samples from rats bearing the IgM secreting IR202 plasmacytoma, at concentrations ranging from 0.07 to 1.2 mg/ml. The IgA concentration in the same bile samples is about half the normal level, whereas in corresponding samples of serum, IgA concentrations are elevated by a factor of three. Most of the IgM in the bile is complexed with secretory component. Thus, when IgM concentrations in the blood are sufficiently high relative to those of IgA, IgM in rats is capable of undergoing transhepatic transport by the same route as polymeric IgA. This situation probably corresponds to that in IgA deficient humans where IgM replaces polymeric IgA in the secretions.

Animals↗
PubMed1984

Tumor immunotherapy in the mouse with the use of 131I-labeled monoclonal antibodies.

This report describes the use of 131I-labeled monoclonal antibodies in two experimental models for tumor immunotherapy. In vitro treatment of the radiation-induced murine thymoma ITT-1-75NS with radiolabeled anti-Ly-2.1 significantly impaired subsequent tumor growth in vivo. However, in vivo treatment of this tumor, which previously had been injected into C57BL/6 mice, was unsuccessful. By contrast, in vitro treatment of a human colorectal tumor cell line (COLO 205) with 131I-labeled 250-30.6--a monoclonal antibody directed against a secretory component of normal and malignant gastrointestinal epithelium--completely inhibited subsequent tumor growth in BALB/c nude (nu/nu) mice. Furthermore, in vivo treatment of preexisting human colorectal tumor xenografts significantly impaired progressive tumor growth. Although some tumor inhibition was also produced by unlabeled 250-30.6 antibody, this response was considerably amplified by treatment with [131I]-labeled 250-30.6 (P less than .05), suggesting that in vivo treatment of human tumors with the use of 131I-labeled monoclonal antibodies may be clinically beneficial. The antithyroid drug propylthiouracil was used to reduce dehalogenation of the radiolabeled immunoglobulins in an attempt to improve their therapeutic efficacy.

Animals↗
PubMed1983

[Neural control of saliva secretion. Review of questions on special neurosecretory functions of the facial nerve].

Fifty years ago, anatomists and physiologists still held the opinion that the N. facialis had a purely motor fuction without any sensory or secretory components. With respect to the previously only occasionally mentioned possibility of an additional neurosecretory function of the N. facialis, clinical and experimental, especially neurophysiological research and experiences of the last five decades have however led to results which are being discussed under particular consideration of the neural control of salivary secretion. In this connection, side-functions are discussed that are just appearing in outlines and have not yet been fully cleared up, for example questions regarding an internal secretion of certain parts of the facial nerve, especially related to the patotid gland. In connection with this question, the author considered it necessary to refer to some medical-historical findings of earlier times.

Afferent Pathways↗
PubMedDate not supplied

[A case of Behçet's disease in a child: clinical, genetic, and immunologic characteristics].

Behçet's disease, which is rarely observed in infancy, is a systemic inflammatory disease of unknown etiology, whose clinical feature consist in the triad of mouth ulcers, genital ulcers and iritis. A 14 years old girl has been studied in whom classical findings of Behøcet's disease were associated with neurological symptoms miming a neuro-Behøcet's syndrome, but which were caused by previous abuse in corticosteroid therapy. Interestingly some features (arthritis, gastrointestinal manifestations), which can be connected with Behøcet's disease, resulted to be present since the very first years of life. Partial features of the disease (arthritis or mouth ulcers) were present in three members of the patient's family on the father's side. Extensive immunological studies have been carried out. T and B lymphocyte number and function were normal. T-cell subsets (defined by monoclonal antibodies) and natural killer activity (both never examined in patients with Behøcet's disease) resulted to be within normal range. Secretory Component, which has been claimed to be absent in these patients, was normally present in saliva. A defect in neutrophil chemotaxis has been found which promptly improved by levamisole therapy. Authors discuss clinical, genetic and immunological findings of the patient, on the basis of a review of literature.

Adolescent↗
PubMed1983

Early gastric cancer superimposed on infestation of an Anisakis-like larva: a case report.

This report describes a 73-year-old male with early gastric cancer (type IIc) superimposed on infestation of a parasitic larva. Eosinophilic granulomas surrounding a dead worm were seen in the submucosa just beneath the intramucosal tubular adenocarcinomatous lesion measuring 1 X 1cm at the anterior wall in the acid-secreting area. The cancer cells showed lowered and altered mucin production in comparison with the surrounding non-cancerous fundic mucosa. The parasite was identified as an Anisakis-like larva by the presence of typical lateral chords. An immunohistochemical examination revealed that the cancer cells were more strongly positive for IgA and secretory component than the surrounding non-cancerous mucosa, and that IgG, IgA and IgM were detected in plasma cells around the granulomas but IgE and IgD were not. The possibility that the Anisakis-like larva preferentially infested the cancerous mucosa because of the change in mucin, local defect in acid secretion and/or other structural alterations in the area is discussed.

Adenocarcinoma↗
PubMed1984

Effects of p-aminohippurate and pyrazinoate on urate excretion in Cebus monkeys.

Changes in the fractional excretion of urate (FEurate) induced by various concentrations of p-aminohippurate (PAH) and pyrazinoate in plasma were evaluated in anesthetized Cebus monkeys using the standard clearance technique. PAH at concentrations between 2 and 40 micrograms/ml produced modest uricosuria (delta FEurate, ca 50%). At higher concentrations of PAH (up to 1200 micrograms/ml) the values of FEurate were not different from controls. Pyrazinoate at concentrations between 1 and 700 micrograms/ml reduced FEurate. The depressant effect of pyrazinoate was not influenced by the presence of PAH. These results are consistent with the idea that the secretory component for urate is distinct from that for PAH in this monkey.

Aminohippuric Acids↗
PubMed1984

An individualized plastic intraoral device for the collection of human parotid saliva.

A new individualized, non-invasive device for the collection of parotid saliva is described which offers the following advantages: automatic placement in the proper position for saliva collection by patients without the help of a technician, lack of deadspace, lack of salivary leakage around the device, elimination of cross contamination between patients, and unlimited re-use. Because of its simplicity, it is an ideal device for routine collection of parotid saliva samples in therapeutic drug monitoring, biochemical monitoring of exposure to toxic materials, and detection of secretory component deficiencies of immune system disorders.

Adult↗
PubMed1982

[Features of inflammation of the mucosa of the large intestine in nonspecific ulcerative colitis and Crohn's disease].

Histological, morphometric, and immunohistochemical studies (with detection of the local production of IgA, IgM, IgG, IgE, and IgD, secretory component of IgA, and deposition of the third complement component, C3) were carried out on biopsies of the colon mucosa from 66 patients with recurrent and continuous forms of nonspecific ulcerative colitis and 16 patients with Crohn's disease. Inflammation in the colon mucosa in the diseases under study was found to be accompanied by marked activation of the local immune system, increased local production of IgA and IgM as well as IgG, particularly in those parts of the mucosa which had no glands. Local synthesis of IgE and IgD also increases indicating allergic reaction in the mucosa alongside with tissue eosinophilia. The basal membrane of the surface epithelium was found to have C3 depositions. A typical feature was the lack of correlation between infiltration of the layer proper of the mucosa and epithelium which is regarded to be a manifestation of deficiency of T-lymphocytes (subpopulation of suppressors or lymphocytes taking part in regulation of epithelium regeneration).

Biopsy↗
PubMed1980

IgA glomerulonephritis (Berger's disease): evidence of high serum levels of polymeric IgA.

Eleven out of 15 patients with IgA mesangial glomerulonephritis (Berger's disease) had an increased proportion of serum IgA in 9-21S fractions on 5-40% sucrose density-gradient ultracentrifugation; the heavier fractions decreased at acid pH. Serum IgA purified by starch electrophoresis was subjected to reduction-alkylation yielding fragments of lower molecular weight. J chain was detected on urea alkaline polyacrylamide electrophoresis and the high-molecular weight IgA bound the human secretory component. In six patients treated with phenytoin for 1 year there was a decrease in polymeric IgA and an increase in monomeric IgA adopting a pattern similar to that of the controls. Our results show the presence of a large amount of true IgA polymers, partially as immune complexes, in the serum of patients with Berger's disease. These data together with their normalization after phenytoin treatment may open a new pathogenic and therapeutic approach to this entity.

Antigen-Antibody Complex↗
PubMed1980

Immunohistochemical studies of the immunoglobulin-producing cell systems of the human intestinal mucosa.

Since the reliability of immunohistochemical observations is highly dependent on the quality of the immunological reagents, the importance of purification, characterization and performances testing of the fluorochrome conjugates is discussed. The methods of tissue processing, immunohistochemical staining and differential enumeration of fluorescing cells used in our laboratory are described. The normal intestinal mucosa shows a striking preponderance (80-90%) of IgA immunocytes, and these cells produce J chains which are incorporated into dimeric IgA. The dimers are taken up by the columnar epithelial cells which produce "secretory component" (SC). Complexing of dimeric IgA with SC seems to explain the selective transport of IgA through the crypt epithelium. A similar transport mechanism operates for J-chain-containing pentameric IgM. Marked alterations of the intestinal immunocyte populations are seen associated with various bowel diseases. In coeliac disease and dermatitis herpetiformis, a numerical increase takes place for all Ig-producing cell classes--in relative terms most prominent for IgG and IgM cells. In ulcerative colitis and Crohn's disease, the IgG-cell response is very striking, In alpha-chain disease, the lamina propria is infiltrated with IgA cells that lack light-chain-producing capacity but show some ability to synthesize J chains; dimers of alpha chain are hence transported to the intestinal lumen but cannot function as antibodies. In patients with a complete and selective lack of IgA in serum, IgA-producing cells are absent from the intestinal mucosa, and there is a numerical increase of local IgG- and specially IgM-producing cells. Conversely, patients with a partial deficiency of serum IgA may show a fairly normal intestinal IgA-cell population, although the proportion of IgM-producing cells is often increased. The intestinal mucosa of patients with a generalized hypogrammaglobulinaemia is sometimes devoid of plasma cells, but rare Ig-producing immunocytes, especially of the IgM class, are often seen. Supported in part by the Norwegian Research Council for Science and the Humanities, Anders Jahres Fond, and Helga Sembs fond. We thank Ms. Evy Eriksen and Ms. Gummvor Oijordbakken for technical assistance, and Ms. Liv Støottum for typing the manuscript.

Adolescent↗
PubMed1980

A possible common pathogenesis of the mesangial IgA glomerulonephritis in patients with Berger's disease and Schönlein-Henoch syndrome.

High serum levels of polymeric IgA, partially as immune complexes, have been found in patients with Berger's disease and Schönlein-Henoch syndrome. Polymeric IgA was also found in the renal mesangium in both entities as judged by its affinity for the human secretory component. These data reinforce the clinical and morphological suspicion that both entities may represent variations of the spectrum of the same disease.

Fluorescent Antibody Technique↗