Idiopathic inflammatory bowel diseases: immunological hypothesis.
Circumstantial evidence indicates that immunological mechanisms are important in the pathogenesis of inflammatory bowel diseases. In Crohn's disease lesions the naive T cells are reduced and memory T cells are increased in number. Colonocytes of normal mucosa do not express MHC class II molecules but aberrant HLA-DR expression is induced in inflammatory conditions. Also in ileal epithelial cells there is increased MHC class II molecules expression suggesting augmented antigen presentation. Once the initiating event (environmental, dietary, infectious or enterobacterial products) has activated inflammatory cells, an auto-amplifying inflammatory immune cascade is induced by numerous agents such as cytokines, transforming growth factors, leukotrienes, prostaglandins and other mediators. Tissue injury may be caused by oxygen free radicals generated by neutrophils and macrophages. The inflammatory process can be perpetuated by a persistent antigenic stimulus or alternatively, by abnormal regulation of immune and inflammatory responses. This can mean exaggerated activation of inflammatory responses to "normal" stimuli or defective feedback mechanisms of down-regulation. The early lesions of inflammatory bowel disease are patchy necrosis of the surface epithelium, focal accumulations of leukocytes adjacent to crypts and an increased number of intraepithelial lymphocytes. In Crohn's disease the earliest lesions are aphthoid ulcers overlying lymphoid follicles in the terminal ileum. In patients with spondylarthropathy and asymptomatic intestinal inflammation we demonstrated lesions in the top of the follicle associated epithelium. The changes consist of increase in number of membranous (M) epithelial cells, ruptures, fissures and perforations of M cells. Aphthoid ulcers that may occur in the entire gastrointestinal tract are typically found at the M cell level.(ABSTRACT TRUNCATED AT 250 WORDS)
Cuvelier
C
C
Dept of Pathology, University Hospital Ghent, Belgium.
Mielants
H
H
De Vos
M
M
Quatacker
J
J
Veys
E
E
D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000648:ultrastructure; D008285:Major Histocompatibility Complex / Q000276:immunology*
D006684:HLA-DR Antigens