Showing papers by "Fergus Shanahan published in 1987"

Immunologic mechanisms in intestinal diseases

Abstract: The intestine is a unique immunologic organ that comprises an afferent and efferent compartment and provides the host with the ability to respond through several different effector mechanisms against environmental factors. We discuss mechanisms in three intestinal diseases in this overview of the mucosal immune system. Genetic and immunologic factors are important in the pathogenesis of celiac disease, which is characterized by damage to the mucosa of the small intestine with resultant malabsorption. Pathogenic microbes are important environmental agents that interact with the intestinal mucosa and initiate local immune responses. Advances in the understanding of the mucosal immune response to these pathogenic microbes have produced a clear picture of the way in which this specialized immune system works in concert with systemic immunity. As to the autoimmune nature of inflammatory bowel disease, no specific antigen has been shown to incite the inflammatory reactions and neither the target cells nor the effector mechanism involved have been identified. Several factors exist, however, to suggest an autoimmune mechanism and the role of mucosal immunologic factors in this disease.

Human Lung Mast Cells: Distribution and Abundance of Histochemically Distinct Subpopulations

Abstract: Methods originally employed to demonstrate the heterogeneity of mast cells in the rat and more recently in the human intestine were used to study mast cell heterogeneity in the human bronchial mucosa and lung parenchyma. Thus, a quantitative survey of pulmonary mast cells using different fixation and staining procedures indicated that two distinct mast cell subpopulations (formalin-sensitive and formalin-resistant) are present and have distinct patterns of distribution and abundance. The findings are of potential clinical importance because histochemical heterogeneity may be a marker of functional mast cell differences in humans including differences in responsiveness to antiallergic drugs, as occurs in rats. The findings also indicate that conventional methods of fixation are likely to lead to a gross underestimation of total mast cell numbers.

Defective memory B cell formation in patients with inflammatory bowel disease following tetanus toxoid booster immunization.

Abstract: Inflammatory bowel disease patients with mild to inactive disease were studied for their ability to generate pokeweed mitogen responsive anti-tetanus toxoid IgG producing B cells in the peripheral blood 21 days following in vivo tetanus toxoid booster immunization. Compared to normals and disease controls, patients with inflammatory bowel disease had significantly impaired in vitro production of anti-tetanus toxoid antibody during an 8 day pokeweed mitogen stimulated culture period. There was poor correlation between the ratio of helper to suppressor T cells in the peripheral blood and pokeweed mitogen stimulated antibody production. Likewise, there was little correlation between in vitro antibody production and peripheral blood natural killer cell cytotoxic activity. Culture of the patients B cells with normal T cells failed to improve antibody production in vitro. These results indicate that many inflammatory bowel disease patients have an impaired humoral immune response to tetanus toxoid booster immunization. This impaired immune response may be due to an inability to generate B cell precursors of anti-tetanus toxoid IgG producing B cells rather than to abnormal circulating helper or suppressor T cell activity or natural killer cell regulatory activity.

Cytotoxic Lymphocytes in Human Intestinal Mucosa

Abstract: Although cytotoxic lymphocytes have been well studied and characterized in the peripheral blood, the nature and function of these effector cells in human gut mucosa is still unclear. Previous studies have suggested that human intestinal lamina propria lymphocytes (LPL) exhibit mitogen induced cellular cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) but that freshly isolated mucosal cells do not exhibit NK activity or exhibit it at very low levels (1–7). This is surprising since the intestinal mucosa is frequently affected by neoplastic, infectious and inflammatory diseases and is in apparent contrast with studies of the mucosal immune system in rodents where spontaneously cytotoxic cells are well represented (8,9). However, when isolated human colonic cells are cultured in the presence of interleukin-2 (IL-2) significant lytic activity is observed (lymphokine activated killers [LAK]) (10, 11).