primary prevention of coeliac disease - Associazione Italiana ...

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66 MECHANISMS OF ORAL TOLERANCE Epithelial cells IELs Anatomical structure Antigen structure Lamina propria T cells Environment (cytokines) Antigen presenting cells Fig. 2. Components involved in control of mucosal immune response. IELs =intraepithelial lymphocytes. cells. However, there is little evidence that conventional antigen stimulation takes 29 place and it may be that epithelial cells interact with T lymphocytes using non- 30 classical MHC molecules such as CD1d . Since epithelial cells do not express the costimulatory molecules CD80 and CD86, it might be expected that these cells play a role 31-32 in inducing anergy of T cells rather than an active T cell response . The importance of the epithelial cell barrier is emphasised by what happens when barrier function is disrupted. This may occur during the course of local inflammation in 33 which tight junction function is impeded . This in turn would allow ready access of antigens to immunocompetent cells in the lamina propria. This may explain the presence of high levels of antibodies to dietary antigens (including gliadin) in Crohn's 34 and peptic ulcer disease . A further demonstration of the importance of the epithelial cell barrier is found in certain gene knockout mouse models in which epithelial cell adherence or their cytoskeletal structure is disrupted: in these models, genes for either E-cadherin or keratin 8 (respectively) are knocked out, with the spontaneous 35-36 development of inflammatory bowel disease as a consequence . Antigen factors The size, structure and nature of antigens affects the response of the mucosal immune system. Thus in health, soluble dietary antigens induce a limited, local immune response and often a barely discernible response in the systemic circulation. Likewise, the gut flora induces a local immune response only. In contrast, particulate antigen is 37 absorbed by specialised epithelial cells called microfold or M cells . M cells are found
MECHANISMS OF ORAL TOLERANCE 67 interposed between the lining epithelial cells and following uptake of antigen, particulate antigen is processed and presented to local T helper cells. This in turn results in a systemic immune response to the antigen. As discussed earlier, in contrast to other food antigens, gluten appears to have an unique capacity to stimulate a local T cell mediated immune response in CD patients, leading to damage of the local mucosa. The chemical properties of gluten involved in eliciting such a response are unknown, since no essential structural difference is 10 thought to exist between self-antigens and foreign antigens . Intraepithelial lymphocytes Intraepithelial lymphocytes (IELs) are T cells located within the surface epithelium of the mucosa. Despite intense research of these cells over the past two decades, their 38 principal function remains enigmatic . The majority of IELs express the CD8 molecule and employ the abT cell receptor (TCR). It is well established that increased numbers of IELs are found in certain intestinal inflammatory states such as coeliac disease. Moreover, in coeliac disease the number of IELs expressing the gdTCR 39 increases, with as many as 30% belonging to this phenotype . According to recent evidence, IELs may include heterogeneous populations of T cells, natural killer T cells 40 and also natural killer cells . It has been speculated that IELs play a role in oral tolerance and there is some experimental evidence to support a role for gdT cells in 41 tolerance induction . Lamina propria T cells The major population of lamina propria T cells express the CD4 molecule and employ the abTCR. These T helper cells are thought to have initially encountered mucosal antigen in organised lymphoid structures such as Peyer's patches and after passage through the systemic circulation have specifically homed back to the intestine. In this location, lamina propria T cells play a major role in orchestrating other cells of 12 the immune system and act as conductors of this orchestra . These T cells possess a full range of surface molecules to allow productive interaction with many other cell types. Moreover, individual populations manufacture the variety of cytokines required to influence B cell production of specific antibody isotypes, to induce specific populations 13 of antigen presenting cells and to activate other populations of T cells . Thus, regulation of immune events in the intestine is largely a function of these cells, and hence maintenance of “oral tolerance” or mucosal immune homeostasis is likely to be achieved by these cells. Dendritic and other antigen presenting cells The activation of intestinal T cells requires the presentation of antigen by local populations of antigen presenting cells (APCs). This task may be performed by a variety of APCs including dendritic cells, macrophages, B cells and, as discussed 12-13 earlier, possibly by enterocytes . Populations of all these cell types have been identified in the mucosal tissue. In individual situations, it is likely that the presentation of antigen is principally performed by specific cell types. Dendritic cells, in particular, may play a central role in presenting antigen and influencing the evolution of specific
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Perspectives on Coeliac Disease Vol
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The AIC Meeting was held in the Aul
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Italian Coeliac Society, Via Picott
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Preface Coeliac disease (CD) is a u
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Contents Current understanding of t
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2 THE BASIS OF COELIAC DISEASE hapl
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4 THE BASIS OF COELIAC DISEASE 1 pr
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6 THE BASIS OF COELIAC DISEASE spre
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8 THE BASIS OF COELIAC DISEASE Ackn
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10 THE BASIS OF COELIAC DISEASE glu
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Catassi C, Fasano A, Corazza GR (ed
Page 29: T CELL RESPONSES TO GLUTEN PEPTIDES
Page 32 and 33: 18 A DOMINANT EPITOPE IN GLUTEN PEP
Page 42 and 43: 28 ROLE OF A-GLIADIN 31-49 PEPTIDE
Page 45 and 46: Catassi C, Fasano A, Corazza GR (ed
Page 47 and 48: COELIAC DISEASE IN THE SAHARAWI 33
Page 55: COELIAC DISEASE IN THE SAHARAWI 41
Page 58 and 59: 44 INFANT FEEDING PRACTICES AND COE
Page 66 and 67: Age (years) 52 INFANT FEEDING PRACT
Page 76 and 77: 62 MECHANISMS OF ORAL TOLERANCE the
Page 78 and 79: 64 MECHANISMS OF ORAL TOLERANCE pot
Page 82 and 83: 68 MECHANISMS OF ORAL TOLERANCE typ
Page 84 and 85: 70 MECHANISMS OF ORAL TOLERANCE 51
Page 86 and 87: 72 MECHANISMS OF ORAL TOLERANCE 23.
Page 91 and 92: GENETICALLY DETOXIFIED GRAINS 77 to
Page 93 and 94: • • GENETICALLY DETOXIFIED GRAI
Page 95 and 96: GENETICALLY DETOXIFIED GRAINS 81 3.
Page 99 and 100: IMMUNOTHERAPY OF COELIAC DISEASE 85
Page 101 and 102: IMMUNOTHERAPY OF COELIAC DISEASE 87
Page 105 and 106: RECENT ADVANCES ON GLUTEN TOXICITY
Page 107 and 108: Index A Antiendomysium antibodies (
Page 109: INDEX 95 W Wheat, 7, 23, 27, 31, 53
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