Ontogeny of the mucosal immune response.
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Biomedical subjects
Publications and source records attributed to J Spencer.
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Vagotomy and omeprazole effectively inhibited 2-deoxy-D-glucose (-91%) and pentagastrin (-72%) stimulated acid production in mice, respectively. Both vagotomy and omeprazole treatment were accompanied by massive increases in histamine secretion (8-fold or more, during both basal and stimulated states). Mucosal stores of histamine, however, were not depleted. Similar rises in luminal histamine have been observed in patients treated in these ways. The mouse model may thus be suitable to elucidate the kinetics of histamine release in patients.
The rate of crypt epithelial cell proliferation and mucosal morphology have been studied in vitro in explants of fetal human small intestine in organ culture in which a cell-mediated immune response has been elicited by stimulating lamina propria T cells with pokeweed mitogen or monoclonal anti-CD3 antibodies. Twelve hours after the addition of anti-CD3 or pokeweed mitogen, most lamina propria T cells expressed CD25. By 18 and 24 h after the addition of anti-CD3, there were significantly more crypt cells in the cell cycle than in controls, although villus height and crypt depth are the same in both groups. After 3 days, by dissecting microscopy, the villi appeared shorter in cultures in which the T cells were stimulated than in control cultures, and the mucosal surface was obscured by a layer of extruded enterocytes. Villus atrophy was confirmed by direct measurement of Feulgen-stained, microdissected villi. Crypts were longer in T-cell-stimulated cultures, and the rate of crypt epithelial cell proliferation measured by metaphase arrest was increased 10-fold. By electron microscopy, the microvilli and cellular morphology of the surface enterocytes were normal in T-cell-stimulated cultures. These experiments clearly show that a profound immune-mediated crypt epithelial cell hyperplasia can occur in the absence of damage to surface enterocytes.
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A patient presenting with upper gastrointestinal bleeding had two visceral angiograms, the second of which demonstrated the hepatic veins in the late phase of the hepatic arterial injection. This observation led to the correct diagnosis of hepatic telangiectasia with arteriovenous shunting and the suspicion, subsequently confirmed at endoscopy, of similar-lesions in the gastrointestinal tract. Visualisation of hepatic veins in visceral arteriography is unusual but may, as discussed, be normal.
Two major global problems face mankind in the forthcoming decades. The rapidly increasing populations, especially in developing countries, are already causing social and economic strain in many areas, and the escalating demand for energy at both the individual and collective levels are matters requiring serious global attention. The product of increasing population and increasing energy demand compounds both problems. The origins of both population increase and escalating demand for energy originate behaviourally. That is to say that, theoretically, if the human behaviour underlying these problems could be modified, either voluntarily on an individual basis, or by educational, legislative or correctional means, then these worrying trends could be brought under control. This paper is concerned principally with the underlying behaviours and dynamics of energy usage by human beings as the present trend of ever-increasing consumption which seems to be directionless and illogical is very similar to another group of existing behavioural disorder known as addiction behaviours or dependency. These behaviours have recently received much attention and research and some of the strategies for dealing with them may be of considerable use in modifying and controlling both the per caput and collective use of energy.
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Chylous ascites remains rare as a complication of surgical intervention. Although therapeutic manoeuvres to control chylous ascites have been developed over the past 20 years, its pathophysiology is poorly understood. Conservative approaches involving dietary restriction of long-chain triglycerides and salt, together with multiple paracenteses, are still the therapies of choice. Persistent chylous ascites may be treated surgically by ligation of leaking lymphatics or implantation of a peritoneovenous shunt once the lymphatic anatomy has been defined by preoperative investigations. We report a case of chylous ascites developing after laparotomy and duodenotomy for obscure gastrointestinal bleeding, which did not respond adequately to medical therapy and was successfully managed by the insertion of a peritoneovenous shunt.
The effect of tripotassium dicitrato bismuthate (De-Nol) on the breakdown of the gastric mucus barrier was investigated by measuring the output of mucus glycoprotein in pentagastrin-stimulated secretion from 13 patients before and after treatment for peptic ulcer, and by examining the accumulation of dialysable peptides and amino acids (DPAA) in stimulated secretion from ten of these patients. The accumulation of DPAA was significantly reduced after De-Nol (by 54%) and to a greater extent than was the output of mucus glycoprotein (by 27%). These observations are consistent with a decrease in the rate of breakdown of the mucus barrier as a result of De-Nol treatment. De-Nol significantly reduced pepsin output (by 32%) in the same group of patients. Comparison of the change in pepsin output with the change in accumulation of DPAA in stimulated juice indicated that De-Nol increases the resistance of the mucus barrier to acid-pepsin proteolysis and/or inhibits the secretion of amino acids and peptides from gastric mucosa.
Two new monoclonal antibodies (MoAbs), UCL3D3 and UCL4D12 were obtained following immunization with follicular lymphoma (UCL3D3) or low-grade primary B cell gastric lymphoma cells (UCL4D12). In normal splenic white pulp, tonsil and small intestinal Peyer's patches, UCL4D12 recognizes marginal zone B cells and a subpopulation of follicle centre cells, whereas mantle zone B cells are UCL4D12 negative. In contrast, UCL3D3 recognizes mantle zone B cells and follicular dendritic cells, but not marginal zone B cells or follicle centre B cells. Double-immunofluorescence studies showed that in the splenic white pulp, these antibodies stain reciprocally. The majority of UCL3D3+ cells are sIgM+ and sIgD+ whereas a higher proportion of UCL4D12+ cells express surface IgM (sIgM) but not surface IgD (sIgD). Less than 10% of splenic B cells express both 3D3 and 4D12 antigens. None of the cell lines tested expressed either antigen. Functional studies showed that both antigens play a role in B cell activation as the MoAbs increase the mitogenic effect of Staphylococcus aureus Cowan I on tonsil B cells. This effect was maximal at 72 h in culture. TPA activation was reduced, and no effect was observed with anti-immunoglobulin (anti mu) or CDw40 (G28.5). UCL3D3 and UCL4D12 did not show any stimulatory effect on their own. Biochemical studies show that both MoAbs recognize proteins of 80-90 kD under reducing conditions. These two MoAbs appear to recognize new B cell surface antigens which may be useful for identifying subpopulations of B cells.
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Ultrastructural examination of biopsies showing Helicobacter pylori associated chronic gastritis reveals close attachment between gastric surface epithelial cells and the organism. The finding of 'adhesion pedestals', which represents a cellular response to the presence of the organism, is analogous to the response of intestinal cells to enteropathogenic E coli. Thus the development of bacterial attachment sites in H pylori associated gastritis might be an indication of pathogenicity. We have therefore explored the relationship between the proportion of organisms forming attachment sites and histological indices of disease 'activity'. Antral biopsies from 40 patients with H pylori positive gastritis were examined histologically and ultrastructurally, and the percentage of attached organisms compared with subjective assessments of epithelial degeneration, mucin depletion, polymorphonuclear and chronic inflammatory cell infiltration. We found a significant increase in the proportion of attached bacteria in cases showing histological epithelial degeneration, and a significant decrease in cases showing intraepithelial polymorph infiltration. The direct relationship between bacterial attachment and cellular degeneration lends further support to a pathogenic effect. Reduced attachment in the face of polymorph infiltration might indirectly reflect aspects of the immune response--namely, blocking of adhesion by IgA, with complement activation and generation of leucotactic factors.
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The histology, microenvironment and migratory pathways of low grade B cell lymphomas (LGBL) are thought to reflect those of normal lymphoid tissue of similar lineage. Striking clinical differences between LGBL of peripheral lymph nodes and those of the gastrointestinal tract serve to emphasize the lineage differences between mucosal and non-mucosal B cells and suggest that LGBL of gut-associated lymphoid tissue (GALT) could serve as a natural experimental model for the investigation of the properties of normal human GALT. The histology of LGBL of GALT parallels that of normal GALT and draws particular attention to the previously undescribed GALT marginal zone B cells which show close lineage homology with LGBL of GALT. These cells known as centrocyte-like (CCL) cells surround follicles, infiltrate the epithelium and frequently show plasma cell differentiation possibly in response to stimulation from the gut lumen. In LGBL of GALT the CCL cells have an intimate relationship with reactive follicles similar to that described for rat splenic marginal zone cells. LGBL of GALT are slow to disseminate to the periphery and can often be cured by local eradication. This suggests CCL cells do not enter the peripheral blood. However, the gastrointestinal tract remote from the primary tumour is occasionally selectively involved, a finding which supports circulation and homing as described in animals. Using a murine monoclonal anti-idiotypic antibody in one case of LGBL of GALT we have shown that CCL cells appear to enter the circulation and, in the absence of evident tumour, can be identified in the mucosae as well as the marginal zone of the spleen where they undergo plasma cell differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Activated T cells can be identified immunohistochemically in the intestinal lamina propria in a number of gastrointestinal diseases including food sensitive enteropathy (coeliac disease) and intractable diarrhoea of infancy. Experimental studies have shown that T cell activation in human intestinal lamina propria in vitro produces an increase in crypt cell proliferation, villous atrophy, increased HLA-DR expression on enterocytes, increased intraepithelial lymphocyte numbers, and, phenotypically, macrophage activation. All of these features are seen in food sensitive enteropathy and it is proposed that lamina propria T cell activation to food antigens plays the primary role in the pathogenesis of these disorders by altering mucosal morphology and the rate of epithelial cell proliferation.
Mice were exposed to a single dose of 9 or 15 Gy of X rays directed to the stomach. Histamine and histamine formation capacity (HFC) in the oxyntic region of the stomach were assayed at regular intervals for 7 weeks. After 9 Gy, mean gastric mural histamine fell to 61% of the control value (p less than 0.01) 7 days after irradiation while HFC rose to 172% (p less than 0.05). Both histamine and HFC returned to control values within 2 weeks after irradiation. With 15 Gy, on Day 7, histamine fell to 46% (p less than 0.01) and HFC rose to 260% (p less than 0.05). Histamine concentration remained low (less than half of the control value) while HFC returned to normal. These dose-dependent changes in histamine were observed neither elsewhere in the gut nor in the circulating blood. Further groups of mice were exposed to 3, 6, 9 or 15 Gy to the stomach, with gastric histamine and HFC assayed on Day 7. Histamine concentration was inversely related to dose (r = -0.59, p less than 0.001) and HFC was directly dose dependent (r = 0.52, p less than 0.001). These results suggest that irradiation of the stomach may reduce gastric histamine without inducing a general histamine release. The depletion of the gastric histamine store may explain the inhibitory effect of irradiation of the stomach on gastric acid secretion.
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Von Recklinghausen's disease (congenital neurofibromatosis) is rarely associated with spontaneous haemorrhage. When such bleeding occurs, it is usually from the gastrointestinal tract and due to mucosal hypervascular plexiform neurofibromata. The upper small bowel is most commonly involved. Very rarely intracoelomic haemorrhage occurs and is usually fatal. We report the case of a patient with von Recklinghausen's disease who suffered three spontaneous, near-fatal haemorrhages (two retroperitoneal and one intrathoracic) following a routine hysterectomy. The patient underwent immediate surgery on each occasion and has survived.