Immunoglobulin-containing Cells Research Articles

Characterization of immunoglobulin-containing cells in the submandibular gland of the rat after local immunization.

The large lymphocytes which enter the blood via the thoracic duct lymph have been shown to migrate selectively into the lamina propria of the small intestine (1). These cells are presumably derived from the Peyer’s patches and components of the gut-associated lymphoid tissue (GALT) (2). Recent reports have suggested that cells derived from the GALT may also “home” to other secretory tissues including the mammary (3) and salivary glands (4), It has been demonstrated that lymphocytes, in response to antigens, are recruited from the blood into the local lymph node and during this phase both antibody and nonantibody-secreting precursor cells are recruited into the node (5). Similarly, after migration of IgA precursor cells to the local secretory tissue, differentiation into IgA-synthesizing cells may occur upon contact with antigen. However, quantitative information on the induction of antibody synthesis at the cellular level in exocrine tissues (e.g., salivary glands) is sparse and is usually obtained from examination of fixed tissue sections (6). We have begun a series of studies into aspects of the secretory immune responses in the oral cavity by developing a method for isolation of mononuclear cells from the submandibular gland (SMG) of the rat.KeywordsSalivary GlandCervical Lymph NodeLocal ImmunizationFixed Tissue SectionTotal Mononuclear CellThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

IMMUNOGLOBULIN-CONTAINING CELLS IN MULTIPLE-SCLEROSIS PLAQUES

An immunoperoxidase method has been used to study the content of immunoglobulin-containing cells in 100 multiple sclerosis (M.S.) plaques and 100 adjacent areas of normally myelinated tissue obtained post mortem from ten patients with M.S. Immunoglobulin-containing cells were significantly more numerous in plaques than in non plaques and in recent plaques as compared with old plaques. More of the cells in plaques contained demonstrable light chain than heavy chain, and the x /λ ratio was significantly higher in recent and moderately recent plaques than in normally myelinated tissue. 92% of the demonstrable heavy chain present in cells was IgG, 7·3% was IgA, and 0·7% IgM. It is suggested that each plaque in M.S. may be associated with local proliferation ( a clone or small number of clones of immunoglobulin-producing cells, producing predominantly IgG heavy chains with light chains, and occasionally with λ light chains.

Indirect immunofluorescent identification of 19S immunoglobulin‐containing cells in the intestinal mucosa of Xenopus laevis

The lymphoid structures in the gastrointestinal tract of immunized and non-immunized adult Xenopus laevis were studied by light and fluorescent microscopy. Serial sections stained with May-Grunnwald Giemsa showed that lymphoid aggregations and scattered lymphoid cells are present along the whole digestive tract. The aggregations are few and rather small in the oesophagus and stomach, they are particularly voluminous in the duodenum. An indirect immunofluorescent technique using antisera against Xenopus laevis 19S and 7S immunoglobulins and their heavy polypeptide chains, revealed the presence of immunoglobulin-containing cells in the duodenal region. The oesophagus and stomach were devoid of these. It has been shown that the immunoglobulins produced in the duodenal lamina propria are formed of both heavy and light polypeptide chains, and that the heavy chains are of the 19S H-type.

Immune components in normal and inflamed human dental pulp

Normal and inflamed human pulpal tissues were examined for the presence of humoral immune components. The results indicate that normal pulpal tissue is essentially devoid of components necessary for localized immunoglobulin synthesis as shown by the absence of any immunoglobulin-containing cells (ICC). Tissue fluorescence was observed only in the unwashed samples and mainly with the fluoresceinated IgG reagent. This fluorescence was essentially eliminated by prewashing prior to the application of the fluoresceinated antiserums. On the other hand, inflamed pulpal tissues showed the presence of various ICC. IgG ICC were preponderant, constituting more than 60 per cent of ICC observed. Significant numbers of IgA and IgE ICC were also observed in each sample examined; whereas IgM ICC were present in only 3 of 12 specimens. At the tissue level, fluorescence was observed both in unwashed and prewashed tissues, predominantly with the labelled IgG antiserum. The presence of ICC, as well as extracellular immunoglobulin in inflamed pulpal tissue suggests that the potential exists for immune mechanisms to contribute to the pathological periapical changes seen as sequelae to pulpal inflammation.

Three Immunoglobulin Classes in the Pigeon <i>(Columbia livia)</i>

Three classes of immunoglobulins have been identified in the pigeon. IgG and IgM were purified from pigeon serum whereas IgA was isolated from pigeon hepatic bile. Pigeon IgG and IgM had the same properties and immunohistological distribution as their chicken homologues. Pigeon IgA was identified on the following grounds: (1) it contains the same light chains as pigeon IgM and IgG; (2) it is relatively abundant in exocrine secretions such as bile, egg white, cropmilk and intestinal fluid, whereas it is present only in small amounts in serum; (3) it occurs in the cytoplasm of the majority of the immunocytes from the intestinal mucosa; (4) its electrophoretic mobility and molecular size are similar to those of chicken IgA. Surprisingly, no immunoglobulin-containing cells could be detected in sections of the wall of the cropmilk gland, despite the high IgA content of the cropmilk.

Gastric Mucosal Cell Proliferation and Immunoglobulin-Containing Cells in Ménétrier’s Disease

The amount of immunoglobulin-containing cells in gastric mucosa from 6 patients with Ménétriér's disease was estimated. Furthermore, the rate of gastric epithelial cell proliferation was sutdied in 4 of the patients. Fluorescent antisera specifically reacting with IgA, IgG and IgM were applied, and accordingly the cells were differentiated and quantitated. Other biopsies were labelled in vitro with 3H-thymidine and autoradiographs were prepared. The percentage of DNA-synthesising cells in the progenitor cell region was estimated. The number of IgM-containing cells in the gastric fundic mucosa was markedly increased, while the rate of epithelial cell proliferation was increased in 2 cases and within normal range in the remaining 2 patients.

Immunological phenomena in the jejunum and serum after reintroduction of dietary gluten in children with treated coeliac disease.

Jejunal mucosal immunoglobulin-containing cells of all three major classes (IgA, IgM, IgG) were increased in coeliac children on gluten-containing diets but only IgM cell numbers were raised in those on gluten-free diets. Patients with subtotal villous atrophy had greater numbers of immunoglobulin-containing cells than patients with normal mucosa. In previously treated patients studied before and after three months on a gluten-containing diet ther was an increase in all three classes of cell, IgM containing cells showing the greatest proportional rise. Basement membrane staining with anti-IgA serum occurred in coeliacs and was most intense in untreated patients. Apart from one patient with very low levels of serum IgA, serum immunoglobulins did not differ from normal. However, after reintroduction of gluten to the diet a significant fall in serum IgM concentrations occurred compared with levels in the same patients while on gluten-free diets. It seems probable that both IgA and IgM systems are important in the immunopathogenesis of the small intestinal lesion of childhood coeliac disease.

Humoral immunity in the pig.

The newborn pig relies on colostrum as its sole source for serum antibody and milk for its intestinal antibody during most of the post natal period. Colostrum and milk are well adapted to perform their very different immune functions--immunoglobulin in colostrum being derived from serum, whereas milk antibodies are locally produced in the mammary gland and mirror the immunoglobulin profile of adult intestinal juice. Intramammary vaccination is far superior to intramuscular vaccination because it produces not only a local but a systemic response. Oral vaccination is similarly effective. Vaccination of one mammary gland results in antibody activity in the secretion of all glands. Irrespective of the route of vaccination, antibody activity is found in all immunoglobulin classes. The main site of immunoglobulin-containing cells is the lamina propria of the intestinal tract, suggesting that the gut is a major site of immunoglobulin formation. In the piglet, immunoglobulin producing cells first appear in the gut at the end of the first week of life and reach a mature profile after a month. During this period the piglet is likely to be capable of responding to orally presented antigens.

Synthesis and secretion of secretory immunoglobulins: with special reference to dental diseases.

The distribution of immunoglobulin-containing cells in human tonsils, salivary glands, and inflamed gingiva is described. The cellular localization of J chain indicates that this peptide is a basic gene product of B cells that is expressed only in the early phase of clonal differentiation. Gland-associated immunocytes apparently are derived from this phase, which may be relevant to their local homing mechanism. The selective glandular transport of dimeric or polymeric IgA and 19S IgM may be determined by the content of J chain in these immunoglobulins. A J-chain-dependent configuration seems to be responsible for their noncovalent affinity for SC, and this may explain their specific reception at the epithelial cell membranes. Subsequent stabilization of the Ig-SC complexes takes place during their external transport, probably because of disulfide exchange. The latter process is more efficient for secretory IgA than for secretory IgM. The secretory dynamics of parotid IgA differs from that of other parotid proteins and is highly dependent on the degree of secretory stimulation. The secretion rate (mug/min/gland) seems to be a better measure of an individual's parotid IgA output than the absolute concentration of IgA in the secretion. A low parotid IgA secretion rate is associated with high susceptibility to dental caries, perhaps reflecting inferior resistance to dental plaque formation. It is not known whether such resistance, in part, is determined by specific antibodies to certain bacterial antigens. A potential candidate for an efficient preventive action of salivary antibodies could be the GTF enzyme system of S mutans. However, we were able to demonstrate only extremely rare immunocytes producing antibodies to GTF in human tonsils and gingiva, and none at all in salivary glands.

The respiratory tract immune system in the pig. II. associated lymphoid tissues.

The distribution of immunoglobulins A, G and M were assessed in the bronchial lymph node and palantine tonsil of pigs from birth to maturity, using the immunoperoxidase technique. Immunoglobulin-containing cells appeared earlier in the tonsil than in the lymph node; this probably reflects the exposure of the tonsil to environmental antigens. IgG-containing cells predominated after the first 3 weeks of life, but the IgA:IgG ratio was much higher in the tonsil than in the lymph node. Extracellular, reticular staining was visible in the central region of some follicles in addition to a few immunoglobulin-containing cells that resembled large lymphocytes or blast cells.

The respiratory tract immune system in the pig. I. Distribution of immunoglobulin-containing cells in the respiratory tract mucosa.

The number of cells containing immunoglobulins A, G and M in the respiratory tract mucosa of pigs from birth to maturity was assessed using the immunoperoxidase technique. Immunoglobulin-containing cells first appeared at 6-7 days of age and rose rapidly to reach levels at 3-4 weeks similar to those in the adult. IgA-containing cells predominated at all sites in all age groups, although there were significant proportions of cells containing IgM and IgG. Our findings suggest that IgA is transported into secretions via the mixed mucoserous glands of the nasal and tracheobronchial mucosa, and that this route is also operative for colostral IgA absorbed from the gut in the baby pig.

DICHOTOMY BETWEEN IMMUNOGLOBULIN SYNTHESIS BY CELLS IN GUT AND BLOOD OF PATIENTS WITH HYPOGAMMAGLOBULINÆMIA

Eleven of fifteen patients with late-onset hypogammaglobulinæmia were found to have significant numbers of immunoglobulin-containing cells in the lamina propria of the gut. In six of them typical plasma cells were detected. In contrast the blood lymphocytes of only two of these patients could be induced to synthesise immunoglobulin by stimulation with pokeweed mitogen in vitro. Moreover, one patient in whom immunoglobulin-containing cells and plasma cells were detected in the rectum and jejunum failed to show similar cells in a peripheral lymph-node even after immunisation with pneumococcal polysaccharide type-III antigen in the drainage area of the node. It is possible, therefore, that the gut is a privileged site for the differentiation of B cells in these patients.

Repopulation with IgA-Containing Cells of Bronchial and Intestinal Lamina Propria after Transfer of Homologous Peyer's Patch and Bronchial Lymphocytes

Transfer of 50 million rabbit allogeneic lymphocytes from either bronchus-associated lymphoid tissue (BALT) or Peyer's patches into 1000 R x-irradiated recipients results, 6 days later, in predominant repopulation of gut and bronchial lamina propria, as well as spleen with IgA-containing cells. After repopulation with BALT or Peyer's patch cells, lymphoid follicles in both gut and lung showed peripheral cellular membrane type of fluorescence with fluorescein-conjugated anti-IgA antisera only. Six days after x-irradiation alone, little evidence of repopulation was seen and immunofluorescent qualitative observations of gut and lung, and quantitative data in the spleen, confirmed these findings. After transfer of 50 million lymph node cells, very few immunoglobulin-containing cells were seen in the gut or bronchial lamina propria. These results suggest that there may be a common mucosal immunologic system, and that repopulation of gut and lung lamina propria may be through the organized lymphoid tissue therein.

Monoclonal immunoglobulinaemia associated with glomerulopathy.

Four patients with benign monoclonal immunoglobulinaemia and associated glomerulopathy are described. Immunohistochemical investigations of the immunoglobulin-containing cells in the bone marrow revealed an unexpectedly pronounced predominance of monoclonal over polyclonal cells as typically seen in macroglobulinaemia and multiple myeloma, but in contrast to the malignant plasma cell proliferations the percentage of immunoglobulin-containing cells only constitued 6-12% of the nucleated cells. The possible pathogenetic mechanisms relating monoclonal immunoglobulinaemia and glomerulopathy are unknown. The sera did not contain antibodies to glomerular basement membrane, cryoglobulins, antinuclear factors or antiglobulins. The immunohistochemical technique certainly offers a clear advantage over conventional bone marrow cytology in the study of patients with monoclonal immunoglobulinaemia.

Immunoglobulin-containing cells in the intestinal mucosa in ulcerative colitis

Nine patients with ulcerative colitis who received thymectomy were selected for the immunological study. The study on the distribution of immunoglobulin—containing cells in the colonie mucosa revealed practically no significant trend in IgG—or IgM—containing cell distribution in any of 7 cases of ulcerative colitis, compared with normal controls, whereas an evidence was noted for increased population of IgA-containing cells in 2 of these 7 cases However, a tendency to restore to normal levels in the serum immunoglobulins but IgM was noted after thymectomy.

A Search for Escherichia coli Antigens in Kidneys from Children with Urinary Tract Infection by Means of Immunofluorescence

Extract: Kidneys from 14 children with diagnosis of recurrent pyelonephritis were studied for deposits of Escherichia coli, antigen, complement component C3, and immunoglobulincontaining cells using immunofluorescence. E. coli O antigen was found in a scarred region in the kidney from only one patient. This was also confirmed by indirect hemagglutination inhibition using eluted antigen from the kidney. In 10 of the 14 patients immunoglobulin G- as well as A-containing plasma cells were seen, while immunoglobulin M-containing cells were found in 6 kidneys. No deposits of complement were observed in any of the kidneys. Speculation: The deposition of E. coli antigen in kidneys after pyelonephritis might be of significance for the development of kidney scarring. Local antibody synthesis in the infected kidney might occur as a protection against the invading organisms.

The plasma cells in inflammatory disease of the colon: a quantitative study.

Immunoglobulin-containing cells have been counted in the mucosa of colectomy specimens from patients with ulcerative colitis and Crohn's disease. An increase in IgA cells occurs in both when compared with normal. In Crohn's colitis the increase is significantly higher than in ulcerative colitis. The importance of these findings in relation to pathogenesis is discussed.

Jejunal mucosal immunoglobulin-containing cells and jejunal fluid immunoglobulins in adult coeliac disease and dermatitis herpetiformis

Immunoglobulin-containing plasma cell densities in the jejunal mucosa and serum and jejunal fluid immunoglobulins have been measured in patients with adult coeliac disease and dermatitis herpetiformis with and without jejunal mucosal abnormality. Studies were performed in patients before and after treatment of the jejunal lesion.Total immunofluorescent plasma cells were increased in untreated adult coeliac disease and dermatitis herpetiformis patients with jejunal lesions, but in general the normal predominance of IgA > IgM > IgG was found. There was no difference from controls in IgA-containing cells in the two conditions before or after treatment. The numbers of IgM-containing cells were significantly increased both before and after treatment in groups of patients with adult coeliac disease and dermatitis herpetiformis who had jejunal lesions. IgG-containing cells were significantly raised in only the before-treatment groups. Patients with dermatitis herpetiformis without jejunal lesions, even whilst on gluten-containing diets, had normal numbers of immunoglobulin-containing cells. IgA and IgM jejunal fluid immunoglobulins were significantly raised in dermatitis herpetiformis and adult coeliac disease.It is concluded that patients with dermatitis herpetiformis with jejunal morphological abnormality have a comparable immunological disturbance of the jejunal mucosa to that found in adult coeliac disease.

Heligmosomoides polygyrus (= Nematospiroides dubius): Humoral and intestinal immunologic responses to infection in mice

Measurements of serum IgG 1, IgG 2a, IgM, and IgA levels and antibody titers in these immunoglobulin classes were made at intervals after initial infection and challenge infection of mice immunized by two or three previous infections. Identical measurements were made on the content of the small intestine in mice which had been exposed to the same infection schedule. Sections of small intestine taken after initial infection and challenge infection were examined by the fluorescent antibody technique for changes in populations of immunoglobulin-containing cells and by routine histologic procedures for histopathologic changes. In serum, only IgG 1 was consistently increased after initial infection, and antibody in IgG 1 was detected within the first 2 wk of infection. In immunized animals, only IgG 1 and antibody of this class always responded to challenge infection, although antibody in other immunoglobulin classes was detected. IgA concentration of the intestinal content did not differ significantly after initial infection or challenge infection of immunized mice. Immunized mice had about twice the IgG 1 concentration in intestinal content as singly infected animals. No intestinal antibody was detected after initial infection; only IgG 1 antibody was detected in the intestinal content of immunized and challenged mice. Cell infiltrates in the intestinal mucosa and submucosa of immunized animals contained numerous IgG 1-containing cells. Mast cells and globular leukocytes were observed in the intestine of immunized animals.

Ontogeny of Peyer's Patches and Immunoglobulin-Containing Cells in Pigs

Abstract The embryonic development of intestinal lymphoid tissue and immunoglobulin-containing cells (µ-, γ- and light chain determinants) was examined in 55 porcine fetuses. Lymphoid cells in a characteristic follicular distribution were found in Peyer's patches as early as 50 days of gestation, but detection of Peyer's patches from 50 to beyond 70 days of gestation required microscopic examination of serial sections of the intestines. The size of the intestinal lymphoid follicles steadily increased during gestation, but cortico-medullary division was not observed until after birth. IgM-containing cells were first seen in 55-day spleens and were followed by IgG-containing cells in the thymus 10 to 15 days later. These observations are interpreted as support for the hypothesis that the lymphoid follicles in Peyer's patches are mammalian bursa-equivalent sites.