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PubMed1997

Quantitative assessment of IgG and IgA subclass producing cells in rectal mucosa during shigellosis.

AIMS: To assess quantitatively both the morphological changes in the rectal mucosa and the changes in the relative frequency of IgA and IgG subclass producing cells found in the rectal mucosa during the acute phase of shigellosis and at convalescence. METHODS: Rectal biopsies from 25 Shigella dysenteriae 1 infected patients, 10 Shigella flexneri infected patients, and 40 uninfected controls were studied. Morphological changes in the mucosa were graded. The frequency of IgA and IgG subclass producing cells was assessed. In addition, immunostaining for secretory component in epithelial cells was analysed. RESULTS: Using morphological grading, 20% of the 35 patients studied had advanced inflammation (grade 3) in the acute phase of the disease. At convalescence, grade 1 inflammation was seen in 37% of the patients and in 10% of the controls. In the acute phase, as well as at convalescence, the number of IgA1, IgA2, and IgG2 positive cells was significantly higher than in the controls. The results were related to the histopathological degree of inflammation. CONCLUSIONS: In shigellosis, there is evidence for a prolonged humoral response residing in the mucosa long after the clinical symptoms have resolved, suggesting that shigellosis induces persisting mucosal humoral immune and inflammatory responses, remaining at least until 30 days after the infection.

Adult↗
PubMed1987

The establishment and characterization of two new cell lines derived from a single human colonic adenocarcinoma.

Two cell lines with different in vitro growth characteristics were established from a single mucinous colonic adenocarcinoma. Epithelial cells of the line 5583-E demonstrated anchorage-dependent growth while those of line 5583-S were anchorage-independent and grew as multicellular floating spheroids. Both cell lines shared common characteristics with respect to the expression of differentiation markers (secretory component, carcinoembryonic antigen), mucins and karyotype (trisomy 12 and 14, marker chromosome) but also showed consistent differences. In nude mice 5583-S cells formed moderately differentiated mucinous adenocarcinomas with high carcinoembryonic antigen and mucin production, whereas 5583-E xenografts were poorly differentiated and almost entirely failed to produce carcinoembryonic antigen and mucins. The plating efficiency of 5583-E cells appeared to be greater and doubling time shorter than those of 5583-S cells. Furthermore, 5583-E cells showed an extra isochromosome, 1q. The cell lines were genotypically and phenotypically stable over a period of 2 years. Our results reemphasize that multiple cell lines with heterogeneous phenotypic and genotypic characteristics can be obtained from a single primary tumor.

Adenocarcinoma, Mucinous↗
PubMed1984

Biosynthesis of the IgA antibody receptor: a model for the transepithelial sorting of a membrane glycoprotein.

Secretory IgA dimer antibodies in exosecretions provide the primary immunological defense for mucosal surfaces. Transmission of IgA2 across the epithelia of mucous and exocrine glands is mediated by a receptor called secretory component (SC). Using three antibodies directed against different domains of SC, we examine its processing in the lactating rabbit mammary gland. SC is synthesized as a core glycosylated transmembrane glycoprotein on the rough endoplasmic reticulum. Pulse-chase experiments reveal the time course of SC maturation in the Golgi, as demonstrated by the acquisition of Endo H resistance (30-60 min). The subsequent routing of SC to the basolateral plasma membrane, where IgA2 binding and endocytosis occurs, the cleavage of the membrane anchoring domain of SC, and the exocytosis from the apical plasma membrane of IgA, bound to the ectoplasmic domain of SC takes place rapidly (30-60 min). Thus maturation in the Golgi may represent the rate limiting step in SC routing. We also demonstrate that SC exists in several conformational states that are processed at different rates.

Animals↗
PubMed1984

Source of IgA in tears of rats.

The purpose of the present study was to determine whether IgA in rat tears originates from serum and/or local synthesis. To examine the first possibility, we compared the IgA levels in serum and tears of rats with a portacaval anastomosis. This operation induced a chronic and progressive elevation of polymeric IgA concentrations in serum. By 8 weeks after surgery, serum IgA levels in 'portacaval' rats were 20-fold higher than those of sham-operated or intact controls. In contrast, IgA levels in tears of 'portacaval' rats did not increase after surgery, despite the availability of free secretory component (SC) in tears. The lack of correlation between tear and serum IgA concentrations resulted in a significant decrease in the tear IgA/serum IgA ratio after anastomosis surgery. To assess whether tear IgA might be derived from local synthesis, we cultured various ocular tissues from male rats in the presence or absence of cycloheximide, an inhibitor of protein synthesis. Incubation of exorbital (lacrimal) glands resulted in the accumulation of substantial quantities of IgA in the culture medium. This accumulation was significantly reduced by the presence of cycloheximide. In contrast, cycloheximide had no effect on the amounts of IgA in cultures of 'lids', Harder's glands and globes. These results indicate that IgA in rat tears originates from local synthesis and not from serum transfer. Furthermore, our findings suggest that the rat exorbital gland is responsible for the synthesis and secretion of tear IgA.

Animals↗
PubMed1996

Serum secretory immunoglobulins in ankylosing spondylitis.

Humoral mucosal immunity may be implicated in pathophysiology of ankylosing spondylitis (AS). The aim of the study was to evaluate serum levels of IgA, IgM and secretory IgA (sIgA), secretory IgM (sIgM) as well as free secretory component (FSC) in patients with AS compared to controls and rheumatoid arthritis (RA) patients. Levels of sIgA, sIgM and FSC were measured with a specific ELISA in 37 AS patients, 45 controls and 27 RA. The results were as follows: Serum levels of IgA were higher in AS vs controls and in RA vs controls (p = 0.01). Levels of sIgA were higher in AS vs controls (p = 0.01), but higher in RA vs AS (p = 10(-4)). There was no difference of sIgM in AS vs controls, FSC levels were higher in AS vs controls, and higher in AS patients with elevated CRP. In view of elevated FSC, this increase of sIgA in AS may have been due to excessive production of mucosal IgA after bacterial stimulation according to the current hypothesis of the disease.

Adult↗
PubMed1992

Mucosal immune defence mechanisms in enterocolitis complicating Hirschsprung's disease.

Enterocolitis remains an important cause of morbidity and mortality in Hirschsprung's disease. The aetiology of enterocolitis is uncertain-ischaemic and bacterial causes and recently, rotavirus infections, have been suggested. Bowel tissue from 12 patients with Hirschsprung's disease who underwent Swenson's operation (five of whom had clinical evidence of enterocolitis) and colon from six controls subjects were examined to investigate possible immunopathological mechanisms associated with the disease. IgA, IgM, and J chain (but not IgG) containing plasma cells were significantly increased in the lamina propria along the entire length of resected bowel in enterocolitis patients, compared with non-enterocolitis patients and controls (p less than 0.01). Luminal secretory component staining of the anganglionic segment of colon from enterocolitis patients was considerably reduced. Lamina propria CD68 positive monocyte/macrophages and CD45RO positive leukocytes were increased in enterocolitis patients compared with non-enterocolitis patients (p less than 0.01). CD57 positive natural killer (NK) cells showed a unique distribution pattern compared with other cell types. Patients with enterocolitis showed a significant increase in CD57 positive NK cells in the lamina propria of ganglionic bowel only (p less than 0.05). NK cell values in ganglionic bowel of non-enterocolitis patients and in aganglionic bowel in all patients were similar to controls. The diversity of altered local immune response seen in this study may reflect a multifactorial microbial aetiology in enterocolitis associated with Hirschsprung's disease.

Antigens, CD↗
PubMed1989

Localization of epithelial markers and defence proteins in minor and major salivary glands.

Immunohistochemical demonstration of cytokeratin (CK), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), lactoferrin (Lf), lysozyme (Ly) and secretory component (SC) was performed in major salivary glands (MaSG), labial and palatal salivary glands (LSG, PSG). CK and TPA were demonstrated in ductal cells of all SGs. In addition, binding of anti-CK (Mw-56 Kd) antibody (AB) KL I was seen in all serious acini of MaSG, basophilic acini and demilunes of LSG and in some mucous acini of PSG. Binding of anti-CK (Mw 44-54 Kd) AB-PKK I, another polyclonal anti-CK (Mw 55-67 Kd) AB-PCK and anti-TPA AB was demonstrated in all basophilic acini of LSG, basophilic portions of mucous acini in PSG and not in acini of MaSG. Significant differences were observed in the expression of CEA, Ly, Lf and SC between acini of MaSG and MiSG which probably reflects different functions of these glands.

Antibodies, Monoclonal↗
PubMed1984

Breast-milk antimicrobial factors of rural Gambian mothers. II. Influence of season and prevalence of infection.

The effects of season and variations in the prevalence of infectious disease on the concentrations and daily production of breast-milk immunoproteins were studied in 152 rural Gambian mothers and their children up to 26 months post-partum. IgA, IgG, IgM, C3, C4, lactoferrin, lysozyme and secretory component concentrations and breast-milk volumes were measured longitudinally over a six month period which encompassed dry and rainy seasons. No increase in the production of any immunoprotein was observed at the time of maximum prevalence of serious infectious diseases, especially diarrhoea, in the children. Enhanced secretion of certain immunoproteins was noted in mothers of children aged 9-18 months at the beginning of the rainy season. There was some evidence that this may have been associated with skin sepsis, particularly impetigo, in the children. The production of most immunoproteins fell during the rainy season. This was not the result of declining maternal food intakes as similar decreases were seen for women receiving a dietary supplement.

Bacterial Infections↗
PubMed1987

Comparison of phenotypic and genotypic features in human primary large bowel carcinomas and lymph node metastases.

In order to test the contention that metastasis is a selective process and that therefore metastases might show a more restricted pattern of phenotypic and genotypic characteristics than primary tumors, we compared the expression of carcinoembryonic antigen, Ca 19-9, secretory component, serotonin, and mucin production as well as flow cytometric data on DNA content and percentage of S-phase cells in 87 primary large bowel carcinomas and their lymph node metastases. In a majority of the cases primary tumors and their metastases were largely identical with regard to the examined phenotypic features. In discrepant cases, however, metastases did not invariably show a more restricted pattern than primary tumors, indicating high differentiational plasticity of primary and metastatic colorectal cancer cells. In contrast, in a number of cases genotypic discrepancies were observed. We conclude that phenotypic characteristics of colorectal cancer cells cannot be used to study the pathogenesis of lymph node metastasis. Genotypic studies, however, suggest that lymphogenic metastasis may be a selective event.

Antigens, Neoplasm↗
PubMed1985

The human gastrointestinal secretory immune system in health and disease.

The main function of secretory IgA is to exert immune exclusion; that is, by intimate cooperation with innate non-specific defence mechanisms, it dampens down penetration of soluble antigens and inhibits epithelial colonisation of bacteria and viruses. Secretory IgM may exert a similar protective function in the gut as its local synthesis sometimes is markedly increased, especially in selective IgA deficiency. IgG should not be considered a secretory immunoglobulin because its external translocation depends on passive intercellular diffusion. By activating complement, antibodies of this isotype may cause increased mucosal permeability and tissue damage. IgG may thus contribute to persistent immunopathology in mucosal lesions. The same is true for IgE antibodies which, in atopic individuals, may be carried into the gut mucosa by mast cells and cause their degranulation with histamine release. Secretory IgA and secretory IgM are the products of two cell types: plasma cells synthesise IgA dimers and IgM pentamers which, by non-covalent association, become complexed with the secretory component (SC) which is synthesized by serous-type glandular cells. The adsorption of the Ig polymers to the SC-expressing epithelial cells depends on J chain-determined binding sites. This fact gives biological significance to the striking J chain expression shown by mucosal immunocytes regardless of the Ig class they produce. The immunocytes populating the gut mucosa apparently belong to relatively early memory B cell clones. The obvious functional goal of J chain expression at this stage of clonal differentiation is local generation of SC-binding IgA and IgM polymers. In various gut diseases, altered immune regulation results in a disproportionately increased number of J chain-negative IgG-producing cells in the mucosa. Such altered immunological homeostasis may contribute to perpetuation of inflammatory bowel diseases.

Adult↗
PubMed1988

The effect of aging on the secretory immune system of the eye.

The objective of the present study was to examine the influence of aging on the ocular secretory immune system of the eye. Levels of IgA and free secretory component (FSC) were measured in lacrimal glands and/or tears of 0.6, 1.3, 3, 8 and 17-month-old male and female rats. In addition, the FSC output of lacrimal tissue cultured in vitro was evaluated. During the period from 0.6 to 1.3 months of age, the content of tear IgA increased nine- and 13-fold in females and males, respectively. This rise was paralleled by changes in the concentration of tear FSC. Prior to the onset of puberty, FSC could be detected in only 7% of tear samples, whereas after pubertal maturation, tear FSC levels had attained adult concentrations. This tear FSC profile was similar to the age-related pattern of FSC output by lacrimal tissue incubated in vitro. Following puberty, tear IgA content continued to increase in both sexes until adulthood (3 months of age) and then plateaued in females from 8 to 17 months of age. In contrast, tear IgA in males appeared to stabilize from 3 to 8 months and then rose significantly to the highest levels at 17 months of age. This increase in males was also reflected in their lacrimal tissue: IgA content underwent a six-fold elevation from 3 to 17 months. Of interest is that the differential kinetics involved in tear IgA and FSC expression resulted in an age-associated decline in the FSC/IgA ratio from post-puberty to senescence. A striking finding in these studies was the persistence of a sexual dimorphism in the secretory immune system of the eye. After pubertal development, IgA and FSC levels were significantly higher in tears of males, compared to those of females, at all ages tested up to 17 months. These gender- and age-related variations in tear IgA and FSC amounts could not be accounted for by changes in either the volume of, or total protein content in, tears.

Aging↗
PubMed1989

Gastric carcinoma with lymphoid stroma. Analysis using mucin histochemistry and immunohistochemistry.

A total of 626 surgically resected gastric carcinomas were reviewed, and 24 cases (3.8%) of "gastric carcinoma with lymphoid stroma" were identified. The tumour cells were consistently arranged in an anastomosing trabecular or alveolar pattern and were densely infiltrated by lymphoid cells. The specimens were studied using mucin histochemistry and the indirect immunoperoxidase method to determine the histochemical properties of this form of gastric carcinoma. The tumour cells were consistently positive for concanavalin A paradoxical staining, class III and almost devoid of acidic mucins, features demonstrating preferential differentiation toward pyloric glands or pseudopyloric glands. Immunohistochemically, positive reactions for Leu M1 and lysozyme, marker substances of (pseudo)pyloric gland cells, were often observed. Carcinoembryonic antigen was positive in focal areas without (pseudo)pyloric glandular patterns. Secretory component was focally positive. HLA-DR was strongly expressed in most cancer cells and 17 tumours (71%) showed positivity for interleukin 1 (IL-1). The lymphoid stroma contained a high percentage of UCHL1-reactive T cells both within and around the cancer cell nests, while SL26-reactive B cells clustered in lymphoid follicles. A considerable number of T-lymphoid cells were also reactive for IL-1. A number of plasma cells with a predominance of IgG-type were distributed around the cancer cell nests. S-100 protein-positive dendritic cells were not identified. We speculate that the prominent lymphoid stroma including intraepithelial lymphocyte-like T cells with IL-1 receptors is possibly induced by IL-1 related mediators released from the HLA-DR-positive gastric cancer cells of the (pseudo)pyloric gland-type.

Adult↗
PubMed1984

Adenocarcinoma in situ and invasive adenocarcinoma of the uterine cervix. An immunohistologic study with antibodies specific for several epithelial markers.

The distribution of carcinoembryonic antigen (CEA), secretory component (SC), fat globule membrane antigens ( FGMA ), and keratin was determined immunohistochemically in 22 invasive adenocarcinomas of various types and in 9 adenocarcinomas in situ of the uterine cervix. In the invasive adenocarcinomas 77% were positive for CEA, 47% for SC, 89% for keratin, and 77% for FGMA . In adenocarcinomas in situ 67% were positive for CEA, 11% for SC, and 44% for keratin. The location of the markers was variable in the cells, and the cells in a tumor were irregularly positive. For a given histologic type there were several phenotypes. No correlation was found between histologic types of invasive adenocarcinomas and the various phenotypes. It remains to be shown whether a particular phenotype has a particular biological behavior. The detection in the serum of the markers shown in histologic preparations could be useful in the postsurgical monitoring.

Adenocarcinoma↗
PubMed1992

A novel IgA receptor expressed on a murine B cell lymphoma.

The specificity and properties of a novel IgA receptor expressed on the surface of a tissue culture-adapted B cell lymphoma, T560, that originated in murine gut-associated lymphoid tissue, have been explored. Like the IgA receptors of murine T and splenic B cells studied by others, the T560 IgA receptor is trypsin sensitive and neuraminidase resistant and is up-regulated on T560 cells by exposing them overnight to high concentrations of polymeric IgA. Unlike them, the T560 IgA receptor is inhibited by low concentrations of IgM and high concentrations of IgG2a and IgG2b, binds at pH 4.0 but not at pH 8.0, is down-regulated by activation of protein kinase C and is sensitive to phosphatidylinositol-specific phospholipase C, indicating that it is glycosyl phosphatidylinositol-linked to the cell membrane. It is not a cell-bound form of galactosyl transferase, does not appear to bind to Ig through carbohydrate residues and does not react specifically with antibody to secretory component. It may be a completely new, cross-reactive receptor, perhaps related in some way to the polymeric Ig receptor or to the receptor for IgA expressed on the apical surface of Peyer's patch M cells, which is known to cross-react with IgG. Alternatively, it may be homologous to the highly IgA-specific Fc alpha R of T cells but, perhaps because of its glycosyl phosphatidylinositol linker, may have an ability to move and interact with other Ig receptors on the cell surface such that Ig bound to them are cross-inhibitory.

Alkaloids↗
PubMed1977

Immunologic studies on the cystic effusions of ovarian epithelial neoplasms.

Cystic effusions from 12 epithelial tumors of the ovary and pooled normal ovarian tissue were studied by immunodiffusion for the presence of immunoglobulins G (IgG), M (IgM), and A (IgA) and free secretory component (FSC). In pooled normal ovarian tissue, IgG was the only immunoglobulin detected. In the neoplastic samples studied, IgG was detected in each of the 12 samples (100%), IgM was found in 10 of the 12 samples (83%), and IgA was detected in 11 of the 12 samples (92%). There was no discernible correlation between the immunoglobulins detected and the composition of the effusions or the pathologic classification of the tumors. FSC was detected in all mucinous samples studied, malignant as well as benign. This substance was not detected in any of the nonmucinous samples or in pooled normal ovarian tissue. The data suggest a correlation between the presence of FSC and the mucinous composition of the tumor effusion. Possible use of FSC assays in the study of mucinous tumors of the ovary is discussed.

Adolescent↗
PubMed1986

Antibody response in serum and intestine in children up to six months after a naturally acquired rotavirus gastroenteritis.

The aim of this study was to provide detailed information about the local and systemic antibody response and their relationship following a rotavirus gastroenteritis. Rotavirus-specific immunoglobulins were analyzed by enzyme-linked immunosorbent assay (ELISA). The study included 49 children referred to hospital with rotavirus gastroenteritis and 16 children with nonrotavirus gastroenteritis. The concentrations of rotavirus immunoglobulin A (IgA) in serum increased within the first 2 weeks and those of rotavirus IgG within the first month after the onset of diarrhea. Thereafter, they remained unchanged during the 6-month observation period. Rotavirus ScIg (i.e., antirotavirus immunoglobulin-containing secretory component) appeared in serum almost exclusively within 7-14 days after onset (i.e., 85% of the samples). After the first 2 weeks, rotavirus IgA could be detected in the majority of fecal samples, even up to 6 months after the disease. However, rotavirus ScIg was absent in the majority of fecal samples. The severity of illness correlated only with the increase of rotavirus IgG in serum. Conclusively, there is a longstanding immune response after a naturally acquired rotavirus gastroenteritis. Moreover, with the present methods, measurements of rotavirus IgA and IgG in serum can be safely used for serodiagnosis, even when samples are taken with 6-month interval. It is suggested that trials with rotavirus vaccines include measurements of rotavirus IgA and ScIg in serum and rotavirus IgA in feces.

Adolescent↗
PubMed1996

Immunocytochemistry of mucosal changes in patients infected with the intestinal nematode Strongyloides stercoralis.

AIM: To investigate the immunopathological changes in duodenal tissues induced by strongyloidiasis and to relate these to degrees of clinical severity. METHODS: Tissues taken from 21 patients showing mild, moderate or severe symptoms of strongyloidiasis, and from non-infected controls, were sectioned and stained immunocytochemically for IgA, secretory component (SC) and HLA-DR. Immunopathology was assessed by changes in numbers, intensity and distribution of stained cells. RESULTS: Parasitised individuals showed villous atrophy and crypt hyperplasia. There was notable infiltration of the lamina propria by IgA positive plasma cells and of the epithelium by intraepithelial lymphocytes. Infection was also associated with increased expression of SC and decreased expression of HLA-DR in epithelial cells. Changes in all parameters correlated with degree of clinical severity. CONCLUSIONS: Profound mucosal changes are induced by strongyloidiasis. Some are analogous to those seen in coeliac disease, but others seem quite unusual. It is likely that these changes are functionally related to the immunopathophysiological consequences of infection seen in patients with severe disease.

Adult↗
PubMed1985

Large cell carcinoma of the lung--ultrastructural and immunohistochemical studies.

Twenty-seven cases of surgically resected large cell carcinoma of the lung including nine cases of giant cell carcinoma were examined ultrastructurally and immunohistochemically. Ultrastructurally, of 18 large cell carcinomas other than giant cell carcinoma eight showed characteristic differentiation toward adenocarcinoma, four toward adenosquamous carcinoma, and one each toward squamous cell carcinoma and neuroendocrine cell carcinoma, but the remaining four were undifferentiated. Six of the nine giant cell carcinomas also showed features of adenocarcinoma, two showed features of squamous cell carcinoma, and one was undifferentiated carcinoma. Immunohistochemically, secretory component (SC) was observed in seven of 14 cases with features of adenocarcinoma and two of four cases with features of adenosquamous carcinoma. Carcinomas with only squamous cell differentiation did not stain for SC. Keratin staining was positive in five of the 14 with features of adenocarcinoma, three of the four cases with features of adenosquamous carcinoma and two of the three cases with features of squamous cell carcinoma. The numbers of tumor cells positive for keratin and/or SC were small. One carcinoma with neurosecretory type granules was stained positively for calcitonin. These findings indicate that many large cell carcinomas showed differentiation toward glandular cells and/or squamous cells, and some did not show any differentiation ultrastructurally or immunohistochemically, indicating that the majority of large cell carcinomas are poorly differentiated form of either adenocarcinomas or squamous cell carcinomas.

Adenocarcinoma↗