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Human gastrointestinal mucosal secretory immunity : investigation and regulation

Current ideas of human gut immunity are derived heavily from animal studies; the few human studies have mainly addressed cellular aspects, and those on immunoglobulins and antibodies have used serum (or rarely jejunal aspirate) to investigate immune events at the gut level, assuming that these fluids are representative of the gut. The aims of this thesis were to develop, evaluate, and apply protocols for the study of gut secretions in man. Saliva was examined as a secretion in its own right, to investigate the relationship between systemic (serum) and mucosal antibodies, and as a potential mirror of immune events occurring more distally in the gut. Methods for the collection and processing of jejunal fluid, and intestinal fluid obtained via whole gut irrigation were then developed. Enzyme linked immunosorbent assay techniques were used to measure total immunoglobulin concentrations and antibody levels to three representative dietary protein antigens, in saliva, intestinal fluid, jejunal aspirate, and serum. Healthy subjects and groups of patients with a variety of gut diseases likely to have increased immunity were examined. There was great physiological variation in immunoglobulin concentrations and antibody levels in saliva, which were universally decreased by eating. In patients on a gluten-free or elemental diet, salivary antibody levels were maintained despite a lack of antigen stimulation. Neither saliva nor serum reflected immunity in gut lavage fluid, the only regularly observed relationship being a positive correlation between serum and saliva, especially after gut mucosal damage has occurred. Differences between control subjects and patients with coeliac disease were insufficient to allow the use of saliva as a diagnostic or clinical tool. Smoking strikingly influenced immunoglobulin concentrations, with a dose-dependent and reversible decrease in salivry IgA, and an increase in IgM. These alterations were not due to changes in the numbers of immunoglobulin-producing cells in the parotid gland. Smoking may also decrease IgA in lavage fluid.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:641354
Date January 1992
CreatorsBarton, John Roger
PublisherUniversity of Edinburgh
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://hdl.handle.net/1842/19960

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