Biomedical subjects

T T MacDonald

Publications and source records attributed to T T MacDonald.

185 records · Page 11Linked to original sources

PubMed1977

Hypersensitivity reactions in the small intestine. III. The effects of allograft rejection and of graft-versus-host disease on epithelial cell kinetics.

Allograft rejection of fetal intestine and graft-versus-host (GvH) disease have been used to study the effects of cell-mediated immune reactions on epithelial cell kinetics in mouse small intestine. In heterotopically transplanted isografts the cell production rate per crypt was similar to that in normally sited small intestine of the same age. However there was a six-fold increase in the rate of cell production per crypt during allograft rejection and a three-fold increase during GvH disease. Furthermore animals with GvH disease developed villous atrophy and had fewer crypts per villus that littermate controls. At the age of 19 days cell production per villus per hour was 97-5 in animals with GvH disease compared with 54-6 in controls. These results indicate that the pathological entity of 'partial villous atrophy' evolves in two distinct phases. Phase 1, a state of increased cell turnover with crypt hyperplasia but villi of normal length precedes the development of Phase 2, true villous atrophy.

Animals↗

PubMed1976

Hypersensitivity reactions in the small intestine. 2. Effects of allograft rejection on mucosal architecture and lymphoid cell infiltrate.

Small intestinal mucosa contains both thymus dependent and thymus independent lymphoid cells and thus has the capacity to act via humoral and cellular mechanisms as a site of local immunity and local hypersensitivity. Allograft rejection of mouse small intestine is a model of a local cell mediated reaction. The effects of this clearly defined, immunologically mediated damage villi, crypts, enterocytes, and lymphoid cell infiltrate have been assessed by comparing the morphology of rejecting allografts with that of isografts and normal small intestine of the same age. In rejection there is infiltration of the lamina propria with lymphocytes, hyperplasia of the crypts of Lieberkuhn, and an eventual sloughing off of the mucosa. Usually, but not always, there is villous atrophy and increased numbers of intraepithelial lymphocytes. However, the morphology of individual enterocytes remains normal throughout rejection and neither plasma cells nor polymorphonuclear leucocytes infiltrate the lamina propria before mucosal ulceration. These results show unequivocally that a local T cell mediated immune response causes villous atrophy and crypt hyperplasia in this animal model, and since there is no evidence of local enterocyte cytotoxicity, a lymphokine may be the link between the activated T cell and the effects on mucosal architecture. We suggest that a local CMI reaction may be the cause of villous atrophy, crypt hyperplasia, and malabsorption in many clinical and experimental conditions, including coeliac disease, food allergy, and intestinal infections.

Animals↗

PubMed1975

Cell-mediated immunity to gliadin within the small-intestinal mucosa in coeliac disease.

In an attempt to demonstrate local cell-mediated immunity (C.M.I.) to gliadin in patients with coeliac disease, fragments of jejunal-biopsy specimens were cultured in the presence and absence of alpha-gliadin and the culture-medium was assayed for its capacity to inhibit migration of normal human peripheral-blood leucocytes (i.e., for a migration-inhibition factor [M.I.F.]). No M.I.F. activity was detected in the culture-medium when biopsy specimens from patients with coeliac disease or controls were cultured without added antigen. However, an M.I.F. was secreted into the culture-medium when biopsy specimens from patients with coeliac disease were cultured with alpha-gliadin. These findings suggest that there is a population of lymphocytes which are sensitised to gliadin in the intestinal mucosa of patients with untreated coeliac disease. They support the theory that a local C.M.I. reaction to gliadin may be the cause of villous atrophy and crypt hyperplasia in coeliac disease.

Adult↗

PubMedDate not supplied

Effects of local delayed hypersensitivity on the small intestine.

There are many T and B cells in the small intestinal mucosa and local T cell immunity could have a role both in protective immunity and as a cause of disease (i.e. hypersensitivity). This latter aspect has been investigated by using several animal models to assess the effects of local delayed hypersensitivity on the structure and function of the small intestine. Heterotopically transplanted grafts of fetal small intestine in mice (isografts and allografts) have been examined by conventional histology, scanning and transmission electron microscopy, by making direct measurements of villi, crypts, and lymphoid cell infiltrate, and by counting the number of mitoses per crypt. This cell-mediated immune reaction causes lymphocyte infiltration which is most marked in the lamina propria, hyperplasia of the crypts of Lieberkühn, increased cell loss with villous atrophy and a flat surface, but the individual enterocytes appear fairly normal. Graft-versus-host disease cause exactly the same changes in structure and in cell kinetics as does rejection. However, crypt hyperplasia has been found to precede villous atrophy by several days. Preliminary experiments on local contact hypersensitivity suggest that intraluminal injection of oxazolone in the gut of sensitized mice also produces villous atrophy and crypt hyperplasia. It is postulated that these effects are likely to be produced via lymphokines: by an 'enteropathic' factor which damages the lamina propria and basement membrane, and a factor which is mitogenic for crypt stem cells. In mice infected with Giardia lamblia, crypt hyperplasia and lymphocyte infiltration of the epithelium are present and there is accelerated epithelial cell turnover. In rats infected with Nippostrongylus brasiliensis, the flat mucosa has been shown to be due to the thymus-dependent immune response and not directly to the damage produced by the parasite itself. A common factor in the variety of conditions associated with villous atrophy and crypt hyperplasia may well be a local cell-mediated immune reaction to food, microbial, parasite or other antigens which causes changes in enterocyte turnover rate and malabsorption.

Animals↗

PubMedDate not supplied

Immunoepidemiology of intestinal helminthic infections. 3. Mucosal macrophages and cytokine production in the colon of children with Trichuris trichiura dysentery.

Mucosal macrophages and accessory cells have been studied by immunohistochemistry in the lamina propria of the colon of children with Trichuris trichiura dysentery syndrome (TDS). No difference was found in the numbers of cells recognized by the monoclonal antibodies CD11c, CD68, or RFD7 between TDS children and local controls. However, large numbers of cells were recognized by an antibody against calprotectin (an anti-bacterial glycoprotein found in tissue infiltrating-monocytes) in TDS colonic mucosa, but few in control colon. Large numbers of cells containing tumour necrosis factor alpha (TNF alpha) were also seen in TDS mucosa; cells isolated from TDS mucosa secreted more TNF alpha than cells from control mucosa; and children with TDS had high levels of circulating TNF alpha. Non-specific macrophage-mediated inflammation and local cytokine production may therefore play a role in the pathogenesis of TDS.

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