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S Strobel

Publications and source records attributed to S Strobel.

At least 109 records · Page 6Linked to original sources
PubMed1987

The role of antigen processing and suppressor T cells in immune responses to dietary proteins in mice.

We have examined the role of Ts cels and APC in regulating the tolerance of systemic DTH in mice fed OVA. Oral tolerance to OVA was prevented by eliminating Ts with dGuo and by treating mice with anti-I-J antiserum. In addition, activating the reticuloendothelial system (RES) with oestradiol, muramyl dipeptide (MDP) or GvHR prevented the induction of tolerance. Further studies showed that prevention of oral tolerance correlated with the ability to enhance APC activity and that oestradiol also abrogated the induction of Ts after feeding OVA. Our results show that the tolerance of systemic DTH in mice fed OVA reflects complex interactions between APC and Ts and suggest that defects in these regulatory events may be responsible for clinical food sensitive enteropathy.

Administration, Oral↗
PubMed1987

Irradiated mice lose the capacity to 'process' fed antigen for systemic tolerance of delayed-type hypersensitivity.

'Intestinal antigen processing' is a function of the gastro-intestinal tract whereby shortly after an animal has been fed an immunogenic protein antigen, such as ovalbumin (OVA), a tolerogenic form of the protein is generated and can be detected in the circulation. The effect of damage to the intestinal epithelium on the processing of OVA has been examined in lethally irradiated mice. Irradiated animals were fed 25 mg OVA and their serum collected 1 h later. When this serum was transferred intraperitoneally into naive recipient mice, this did not induce the typical suppression of systemic delayed-type hypersensitivity. Results were similar when the serum donors were at 2 days after irradiation, with crypt hypoplasia, and at 5 days after irradiation when there was reactive crypt hyperplasia. However reconstitution of donors with normal spleen cells immediately after irradiation restored their capacity to generate a tolerogenic form of the antigen. Immunoreactive OVA was detected by ELISA in both tolerizing and non-tolerizing sera, and the immunological properties of these sera were not related to serum levels of OVA after feeding. Thus subtle immunochemical alterations in the nature of a protein antigen are likely to be more important than the quantity of absorbed antigen, in influencing systemic cell-mediated immune responses after feeding. The lack of generation of a tolerogenic form of the protein in irradiated mice, unrelated to the pattern of epithelial cell kinetics, and the restoration of this function by normal spleen cells, suggests that lymphoid cells may be involved in the phenomenon of antigen processing.

Animals↗
PubMed1987

Persistence of oral tolerance in mice fed ovalbumin is different for humoral and cell-mediated immune responses.

The duration of oral tolerance after a single feed of OVA at the age of 6 weeks was studied in BDF1 mice. Significant suppression of systemic antibody responses was present 3 months later, but not at 6.5 months; in contrast, at all times studied from 2 weeks to 17 months after an OVA feed there was suppression of systemic CMI to OVA as measured by an in vivo skin test. This indicates that the two limbs of the immune response differ in the factors responsible for the maintenance of oral tolerance.

Administration, Oral↗
PubMed1986

Modulation of intestinal and systemic immune responses to a fed protein antigen, in mice.

Feeding of a protein antigen to normal adult mice results in systemic immunologic hyporesponsiveness (oral tolerance). Local mucosal cell mediated immunity is not usually elicited. The objectives of these experiments were to abrogate the induction of oral tolerance and concomitantly to induce a local mucosal cell mediated immune response in mice; and thereby to establish which facets of intestinal physiology or immunology are relevant to the induction of normal, mainly suppressor immune responses to a fed antigen. Protein antigen (ovalbumin) was fed to animals in whom immune status had been modulated by intraperitoneal injection of N-acetyl-muramyl dipeptide (MDP), by induction of a graft versus host reaction, or naturally, by virtue of immaturity. The induction of oral tolerance was prevented in all treatment groups. In a second series of experiments mice were orally immunised as before, rested for four weeks, and then challenged with ovalbumin in their drinking water for 10 days. Jejunal architecture was not altered by the antigen challenge, but MDP treated and immature animals which had been sensitised to ovalbumin and later re-exposed to the same antigen had significantly higher intraepithelial lymphocyte counts than appropriate controls. Factors which may lead to abrogation of oral tolerance and induction of intestinal hypersensitivity are discussed in relation to food allergic diseases in man.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Prevention of oral tolerance induction to ovalbumin and enhanced antigen presentation during a graft-versus-host reaction in mice.

Systemic hyporesponsiveness after ingestion of a protein antigen (oral tolerance) depends on antigen processing by the gut and the actions of immunoregulatory T cells. We have examined the effects of a graft-versus-host reaction (GvHR) on oral tolerance, since both immune status and intestinal function are altered in GvHR. The GvHR was induced in unirradiated (CBA X BALB/c)F1 mice by intraperitoneal injection of CBA spleen cells. The tolerance of systemic humoral immunity and of delayed-type hypersensitivity normally found in mice fed 25 mg ovalbumin (OVA) was partially abrogated from 1 to 3 weeks after induction of the GvHR. In addition, mice with GvHR had a persistent enhancement of systemic immunity to OVA, and this was associated with an augmented ability of spleen cells to present OVA to primed T cells. The phagocytic activity of the reticuloendothelial system, as established by carbon clearance tests, was not altered by the GvHR. These findings suggest that enhanced antigen-presenting cell activity interferes with the induction of oral tolerance, and may be another pathogenetic mechanism of intestinal hypersensitivity disease.

Administration, Oral↗
PubMed1984

Cellobiose/mannitol sugar permeability test complements biopsy histopathology in clinical investigation of the jejunum.

Intestinal permeability to probe molecules has been shown to correlate closely with the presence or absence of villous atrophy in a jejunal biopsy. The purpose of this study was to establish if there exist groups of patients with functional derangement of intestinal permeability but normal histopathology of the small bowel mucosa. In 135 patients a cellobiose/mannitol permeability test was performed at the same time as jejunal biopsy. Diagnosis included coeliac disease, Crohn's disease, irritable bowel syndrome, idiopathic diarrhoea, self diagnosed food allergy, atopic eczema and postinfectious malabsorption. The value of the cellobiose/mannitol test in identifying patients with abnormal jejunal biopsy histopathology was confirmed. The permeability test was abnormal in all 28 patients with partial or subtotal villous atrophy, and also in all 10 in whom there was a high intraepithelial lymphocyte count despite normal villi and crypts. Functional abnormality of the small intestine has not previously been reported in patients with this jejunal biopsy abnormality. Abnormalities of permeability were also found in patients with idiopathic diarrhoea, folate deficiency, postinfectious or traveller's diarrhoea, small bowel Crohn's disease, and atopic eczema. These results show that sugar permeability tests have more potential in clinical investigation than merely serving as screening tests before jejunal biopsy. There are groups of patients without morphological changes in the small bowel in whom intestinal permeability is abnormal.

Adolescent↗
PubMed1984

Immune responses to fed protein antigens in mice. 3. Systemic tolerance or priming is related to age at which antigen is first encountered.

The normal effect of feeding an antigen, such as ovalbumin (hens' egg albumin), to adult animals is the induction of a state of specific nonreactivity of the lymphoid tissues when the same antigen is presented again (oral tolerance). We have carried out feeding experiments in neonatal mice to investigate subsequent immune responses after physiologic antigen exposure and to examine the role of the neonatal intestine. We demonstrate for the first time that feeding a weight related dose of ovalbumin within the first week of life results in priming for both humoral and cell-mediated immune responses, despite the profound tolerance found in adult animals when treated in the same way. When the time scale of antigen exposure was extended into the prenatal period, the enhancement of the immune response was even more pronounced. These effects are long lasting and effects on cell-mediated immune responses are still demonstrable 14 wk after the initial priming feed. We postulate that after an antigen feed in the neonatal period, immunologic and digestive immaturity lead to a net gain in T help which prevents the induction of systemic hyporesponsiveness (oral tolerance).

Aging↗
PubMed1984

Gluten intolerance (coeliac disease).

Coeliac disease is a permanent condition of gluten intolerance associated with characteristic gluten-sensitive changes in the jejunal mucosa. In Edinburgh and the Lothians Region of Scotland, the prevalence of the disease is one in 1637 (61/100,000) with considerable variation in age, and sex-specific prevalence and incidence. Several lines of evidence indicate an immunologic basis for the gluten-sensitive enteropathy in coeliac disease. Animal models of intestinal T cell-mediated reactions in the gut have shown pathologic features similar to those of coeliac disease. These include changes in villus and crypt architecture with crypt hyperplasia, and increased numbers of intraepithelial lymphocytes and of intraepithelial lymphocyte mitosis. Experimental CMI reactions also influence differentiation of goblet cells and expression of Ia antigen on epithelial cells, but these factors have not yet been reported for the coeliac mucosa. In addition to this circumstantial evidence, based on animal work, other factors which suggest that CMI reactions rather than antibodies are relevant to coeliac disease include the findings of antigliadin antibodies in a proportion of normal individuals, patients without gastrointestinal disease (seen in hospital), and patients with jejunal Crohn's disease. In addition, there is a well documented patient with adult onset primary hypogammaglobulinaemia and coeliac disease. The underlying pathogenesis in coeliac disease can be envisaged as failure of the normal inhibition of immune responses to this particular food antigen in the gut. Manipulation of immunoregulatory mechanisms would provide a new approach to treatment or cure of this disease and of other food protein-sensitive enteropathies.

Adult↗
PubMed1983

Human intestinal mucosal mast cells: expanded population in untreated coeliac disease.

Previous retrospective studies of intestinal mucosal mast cells in coeliac disease have given divergent results, and we have recently reported that inappropriate methodology could account for these discrepancies. In this prospective study, mucosal mast cell counts were performed in Carnoy fixed, peroral jejunal biopsy specimens from patients with coeliac disease, both untreated and treated with a gluten-free diet; and from controls (mainly irritable bowel syndrome). Mean mucosal mast cell count in 27 control subjects was 146/mm2, SD 29. Significantly higher values were obtained in untreated coeliac disease (mean 243, SD 41, p less than 0.001) returning to the normal range in coeliacs treated with a gluten-free diet with normal jejunal biopsy morphology. In seven patients mucosal mast cell counts were performed in multiple jejunal biopsies, and these showed that mucosal mast cell distribution was not patchy. There was no evidence of degranulation of intestinal mucosal mast cells under the conditions of routine biopsy (overnight fast). An increase in mucosal mast cells in untreated coeliac disease may be one explanation for the high number of IgE positive stained cells in the intestinal mucosa that has been reported by some authors.

Celiac Disease↗
PubMed1983

T-cell mediated immunity in food allergy.

There are many T-cells within the intestinal mucosa, and histopathology, applied to biopsies of intestinal mucosa taken before and after food reintroduction, provides information on possible cell-mediated immunity to foods within the gut. Food sensitive enteropathies occur in man and in domestic animals, particularly in the young. Our hypothesis is that these are related to a relative deficiency of suppressor T-cells. There is no evidence that T-cell-mediated immunity to foods plays a part in severe atopic eczema, even in patients with clinical evidence of associated food allergy and high titres of IgE antibodies to foods.

Adult↗
PubMed1983

Immunological responses to fed protein antigens in mice. II. Oral tolerance for CMI is due to activation of cyclophosphamide-sensitive cells by gut-processed antigen.

Mice fed ovalbumin develop specific systemic hyporesponsiveness. This oral tolerance is abrogated by cyclophosphamide pretreatment, and the mechanism of abrogation could be either via T suppressor cells or via damage to the gut epithelium. A serum transfer protocol was used to examine the site of action of cyclophosphamide in this system. Serum was collected from ovalbumin-fed mice and transferred into recipients which were then parenterally immunized with ovalbumin in Freund's complete adjuvant. Serum transfer suppressed the delayed-type hypersensitivity (DTH) responses but not the antibody responses of the recipients. Cyclophosphamide pretreatment (100 mg/kg) of recipients (but not of donors) abrogated this suppressor effect. Parenteral administration of ovalbumin in a range of doses did not induce immunological hyporesponsiveness. It is suggested that absorption across the gut mucosa leads to generation of fragments of ovalbumin that induce suppressor cells selective for DTH.

Administration, Oral↗
PubMed1982

Immunogenicity of foods and food additives--in vivo testing of gums arabic, karaya and tragacanth.

An inexpensive animal model is described, for investigation of the immunogenicity of substances such as food additives. Inbred mice were immunised with antigen emulsified in complete Freund's adjuvant, and specific cell-mediated immunity subsequently measured by a footpad swelling test. This method has been applied in an investigation of the immunogenicity of the exudate gums, gum arabic, gum karaya and gum tragacanth. These substances are capable of eliciting an immune response which is comparable to the specific immune responses elicited by a protein antigen, e.g. hens' egg ovalbumin. Purification of commercially available gum preparations led to a significant (P less than 0.005) reduction of the immune response under in vivo test conditions.

Allergens↗
PubMed1982

Immunological responses to fed protein antigens in mice. I. Reversal of oral tolerance to ovalbumin by cyclophosphamide.

Feeding ovalbumin over a wide range of doses is known to reduce subsequent systemic immune responses to parenteral immunization. In the present study, we have fed mice 2 mg and 25 mg ovalbumin (OVA) 2 weeks before systemic immunization and followed the resulting humoral antibody and cell-mediated immune (CMI) responses. The results indicate that while 25 mg OVA will reduce subsequent IgM, IgG and CMI responses to OVA, feeding 2 mg OVA will only suppress CMI responses and to a lesser extent the IgM response. Furthermore, the tolerant state induced by feeding 25 mg OVA was only partially prevented by 100 mg/kg cyclophosphamide (CY) while the suppressed CMI after feeding 2 mg OVA was completely blocked by CY pretreatment. These findings suggest that the humoral and cell-mediated limbs of the immune response may be controlled by different regulatory systems after feeding antigen, and that activation of these systems is dependent on the dose of oral antigen use. In addition, the results are in agreement with our previous finding that CY pretreatment will allow the development of CMI in the gut and gut-associated lymphoid tissue (GALT) after oral OVA and suggest that this phenomenon is related to breakdown of oral tolerance induction.

Administration, Oral↗