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Specific and nonspe...
Specific and nonspecific immune mechanisms in human gut : a comparative study of normal and ulcerative colitis intestine
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- Yeung, Moorix Mo-Wai (författare)
- Umeå universitet,Immunologi/immunkemi
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- Hammarström, Sten, Professor (preses)
- Umeå universitet,Immunologi/immunkemi
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- Hammarström, Marie-Louise, Docent (preses)
- Umeå universitet,Immunologi/immunkemi
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visa fler...
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- Troye-Blomberg, Marita, Docent (opponent)
- Stockholm
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visa färre...
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(creator_code:org_t)
- ISBN 9171912355
- Umeå : Umeå universitet, 1996
- Engelska 95 s.
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Serie: Umeå University medical dissertations, 0346-6612 ; 485
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- The intestine, with its large mucosal surface area, digests and absorbs food nutrients and maintains a beneficial microbial flora in the colon. Local protective immune responses against intestinal pathogens ensure the survival of the individual. These immune reactions are both specific and non-specific in nature. The intestinal epithelium is single-layered and constantly renewed with differentiating epithelial cells moving from the crypt to the luminal surface. Intraepithelial lymphocytes (IEL) are interspersed between the epithelial cells. Ulcerative colitis (UC) is a life-threatening chronic inflammation affecting colon.In this study three molecules belonging to the carcinoembryonic antigen (CEA) family, namely CEA proper, nonspecific cross-reacting antigen 50/90 (NCA 50/90) and biliary glycoprotein (BGP), were found to be specifically localized to the apical surface of colonic epithelial cells. Full expression of these molecules occurs when the cells reach the upper 1/3 of the crypts and are maintained on the mature cells at the luminal surface. Ultrastructurally, CEA, NCA50/90 and BGP are localized to microvesicles and microfilaments of the fuzzy coat/glycocalyx as well as to the microvilli of the epithelial cells. Their unique localization and documented bacterial binding capacities suggest that they have a role in innate immunity.Functional analysis of IEL in normal jejunum, ileum and colon revealed that IEL are in vivo activated T-lymphocytes expressing mRNA for the cytokines IL-1β, IL-2, IL-8, IFNγ and TNFα and that jejunal IEL have T-cell receptor (TCR)/CD3 dependent cytolytic capacity. As many as 10% of IEL actively produce IFNγ. CD4+TCRαβ+IEL, CD8+TCRαβ+IEL and CD4-CD8-TCRαβ+IEL all had a TH1/cytotoxic cytokine profile. IEL could be further stimulated in vitro to express IL-10, TNFβ and TGFβ1, to proliferate and to secrete IFNγ. Thus, active protection and/or regulation of the epithelium via cell-mediated immune reactions are prominent in the gut.UC colon was characterized by a marked lymphocyte infiltration in the lamina propria, 10-50 times the normal level. Most lymphocytes were present in follicle-like cell aggregates containing both T- and B-cells. An unexpected finding was that γδT-cells constituted about 15% of the cells in the aggregates. Such cells are only found intraepithelially in normal gut. γδT-cells of both the intestinal- (TCR-Vδ1/Vγ8) and blood type (TCR-Vδ2/Vγ9) were seen. T-cells in UC colon were activated but nonproliferating and had a down-regulated TCR/CD3 complex. RT-PCR and quantitative immunohistochemistry for cytokine mRNA (n=11) and protein respectively, revealed that the T-cells in UC colon did not produce IL-2, in marked contrast to T-cells in normal colon and to ileal T-cells from UC patients. This was a selective defect since TNFα, IFNγ, IL-1β, IL-8 and TGFβ1 were similarly expressed in normal colon. No TH2 cytokines were seen. Lamina propria leukocytes in UC colon expressed IL-6, a cytokine not found in normal colon. The epithelial cells of UC colon were activated expressing MHC class II antigens, heat shock proteins and the co-stimulatory molecule B7.1/CD80.Our study demonstrates that UC is an immunological disease. The immunopathological picture seen in UC colon probably reflects an inappropriate down-regulation of local immune responses perhaps due to a selective loss of the key cytokine IL-2 in a situation of extreme antigenic stress.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Nyckelord
- human intestine
- ulcerative colitis
- lymphoid aggregates
- intraepithelial lymphocytes
- lamina propria lymphocytes
- γδT-cells
- cytokines
- IL-2
- carcinoembryonic antigen
- biliary glycoprotein
- epithelial cells
- glycocalyx
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- vet (ämneskategori)
- dok (ämneskategori)
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