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Orvosi Hetilap
Authors: Pál Soltész, Zoltán Prohászka, György Füst, Henrietta Dér, György Kerekes, Péter Szodoray, Margit Zeher, and Zoltán Szekanecz

Az atheroscleroticus plakk kialakulásában jelenleg három autoantigént tudunk azonosítani, amelyek patológiai jelentőségét experimentális és klinikai adatok egyaránt bizonyítják. Ezek az antigének a 60 kDa-os hősokk fehérje, a β2-glikoprotein I és az oxidált LDL. Szerepük van az antigénspecifikus T-sejt differenciálódási folyamatokban, valamint ellenük autoantitestes mechanizmusok indulnak be, amelyek prothromboticus hatással bírnak és az atherosclerosis folyamatát felerősítik. Az autoimmun betegségekben ezen tényezők mellett egyéb, betegségenként eltérő mechanizmusok vannak jelen, amelyek összességében az autoimmun vasculopathiák kialakulásához vezetnek. Az összefoglaló közlemény ezen vasculopathiák rövid áttekintését adja.

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Host immune responses are crucial for combating enteropathogenic infections including Campylobacter jejuni. Within 1 week following peroral C. jejuni infection, secondary abiotic IL-10−/− mice develop severe immunopathological sequelae affecting the colon (ulcerative enterocolitis). In the present study, we addressed whether pathogen-induced pro-inflammatory immune responses could also be observed in the small intestines dependent on the innate receptor nucleotide-oligomerization-domain-protein 2 (Nod2). Within 7 days following peroral infection, C. jejuni stably colonized the gastrointestinal tract of both IL-10−/− mice lacking Nod2 (Nod2−/− IL-10−/−) and IL-10−/− controls displaying bloody diarrhea with similar frequencies. Numbers of apoptotic and regenerating epithelial cells increased in the small intestines of C. jejuni-infected mice of either genotype that were accompanied by elevated ileal T and B lymphocyte counts. Notably, ileal T cell numbers were higher in C. jejuni-infected Nod2−/− IL-10−/− as compared to IL-10−/− counterparts. Furthermore, multifold increased concentrations of pro-inflammatory cytokines including IFN-γ, TNF, and MCP-1 could be measured in small intestinal ex vivo biopsies derived from C. jejuni-infected mice of either genotype. In conclusion, C. jejuni-induced pro-inflammatory immune responses affected the small intestines of both Nod2−/− IL-10−/− and IL-10−/− mice, whereas ileal T lymphocyte numbers were even higher in the former.

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Interventional Medicine and Applied Science
Authors: Balázs Nemes, P. Sótonyi, G. Lotz, A. Heratizadeh, F. Gelley, C. Doege, M. Hubay, Zs. Schaff, and B. Nashan

Abstract

In chronic liver rejection lymphocyte mediated processes lead to chronic inflammation, necrosis and repair mechanisms. The aim of the present study was to investigate the expression of apoptosis related proteins (FAS/APO-1, FAS-L, Bcl-2, Bax, TNF-α, and INF-γ). ApopTag reaction and immunohistochemistry were performed on liver samples of chronically rejected allografts and compared with normal donor livers. In chronic rejection, apoptosis was detected in pericentral hepatocytes and in the biliary epithelium. Bcl-2 was strongly expressed on lymphocytes around the bile ducts, but not on the biliary epithelium itself. Bax, FAS, TNF-α and INF-γ were present in pericentral areas. T-cells showed up around bile ducts, whereas macrophages around pericentral areas. In pericentral areas apoptosis seems to be fostered through TNF-α and INF-γ and by the lack of Bcl-2. Based on these results both downregulation and upregulation of apoptotic proteins can be observed in chronic liver allograft rejection: FAS is upregulated in biliary epithelium and zone 2, protein levels of FASL remain unchanged, BAX is upregulated in zone 3, BCL2 is downregulated in both biliary epithelium and zone 1 and both TNFa and IFN are upregulated in zone 3. Our results suggest that the balance between pro- and antiapoptotic patterns was shifted to the proapoptotic side, mainly in the centrilobular area of the hepatic lobule, and in the bile ducts. According to these findings in chronic rejection the predictive sites of apoptosis are the biliary epithelium and the pericentral areas.

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Abstract

Campylobacter jejuni is one of the predominant causes for foodborne bacterial infections worldwide. We investigated whether signaling of C. jejuni-lipoproteins and -lipooligosaccharide via Toll-like-receptor (TLR) -2 and -4, respectively, is inducing intestinal and extra-intestinal immune responses following infection of conventional IL-10-/- mice with chronic colitis. At day 3 following oral infection, IL-10-/- mice lacking TLR-2 or TLR-4 harbored comparable C. jejuni strain ATCC 43431 loads in their colon. Interestingly, infected TLR-4-/- IL-10-/- mice displayed less compromized epithelial barrier function as indicated by lower translocation rates of live gut commensals into mesenteric lymphnodes (MLNs), and exhibited less distinct B lymphocyte responses in their colonic mucosa as compared to naïve IL-10-/- controls. Furthermore, in extra-intestinal compartments such as MLNs and spleens, abundance of myeloid cells was less distinct whereas relative percentages of activated T helper cells and cytotoxic T cells were higher in spleens and dendritic cells more abundant in MLNs of infected IL-10-/- animals lacking TLR-4 as compared to IL-10-/- controls. Taken together, in conventionally colonized IL-10-/- mice, TLR-4, but not TLR-2, is involved in mediating extra-intestinal pro-inflammatory immune responses following C. jejuni infection. Thus, conventional IL-10-/- mice are well suited to further dissect mechanisms underlying Campylobacter infections in vivo.

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.: Combined administration of a mutant TGF-beta1/Fc and rapamycin promotes induction of regulatory T cells and islet allograft tolerance. J. Immunol., 2010, 185 , 4750–4759. Shen M

Open access
European Journal of Microbiology and Immunology
Authors: Andreas Erich Zautner, Annina Hage, Katja Schneider, Karolin Schlösser, Ortrud Zimmermann, Else Hornecker, Rainer F. Mausberg, Hagen Frickmann, Uwe Groß, and Dirk Ziebolz

Abstract

It is well known that dental caries and periodontitis are the consequence of bacterial colonization and biofilm formation on the enamel surface. The continuous presence of bacterial biofilms on the tooth surface results in demineralization of the tooth enamel and induces an inflammatory reaction of the surrounding gums (gingivitis). The retention and survival of microorganisms on toothbrushes pose a threat of recontamination especially for certain patients at risk for systemic infections originating from the oral cavity, e.g., after T-cell depleted bone marrow transplantation. Thus, the effects of different decolonization schemes on bacterial colonization of toothbrushes were analyzed, in order to demonstrate their applicability to reduce the likelihood of (auto-)reinfections.

Toothbrushes were intentionally contaminated with standardized suspensions of Streptococcus mutans or Staphylococcus aureus. Afterwards, the toothbrushes were exposed to rinsing under distilled water, rinsing and drying for 24 h, 0.2% chlorhexidine-based decolonization, or ultraviolet (UV) radiation. The remaining colony forming units were compared with freshly contaminated positive controls. Each experiment was nine-fold repeated. Bi-factorial variance analysis was performed; significance was accepted at P < 0.05.

All tested procedures led to a significant reduction of bacteral colonization irrespective of the toothbrush model, the brush head type, or the acitivity state. Chlorhexidine-based decolonization was shown to be superior to rinsing and slightly superior to rinsing and drying for 24 h, while UV radiation was similarly effective as chlorhexidine. UV radiation was slightly less prone to species-dependent limitations of its decolonizing effects by bristle thickness of toothbrushes than chlorhexidin.

Reduction of bacterial colonization of toothbrushes might reduce the risk of maintaining bacterial infections of the upper respiratory tract. Accordingly, respective procedures are advisable, particularly as they are cheap and easy to perform.

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Orvosi Hetilap
Authors: Leonóra Méhes, Béla Telek, Miklós Udvardy, Ágota Schlammadinger, and László Rejtő

A köpenysejtes lymphoma (MCL) mérsékelten agresszív betegség, amely kemoimmunoterápiával nem gyógyítható. A medián túlélés rövid, mintegy három év. Többnyire előrehaladott stádiumban ismerik fel. A csontvelő a betegek felében, a gastrointestinalis traktus a negyedükben érintett, leukémiás transzformáció 25%-ban fordul elő. A malignus sejtek B-sejt-eredetűek és CD5-pozitívak, jellemző a ciklin-D1-expresszió. A kezelésben kombinált kemoterápia, kemoimmunoterápia, valamint autológ perifériás őssejt- (és allogén) transzplantáció jöhet szóba. A bemutatott két beteg esetében, az optimális kezdeti terápia hiánya ellenére, tartós túlélés volt elérhető. Az alkalmazott komplex kezelés (kemoimmunoterápia, sugárkezelés, sebészi beavatkozás, autológ őssejt-transzplantáció) ugyanis 80, illetve 90 hónapig tartó túlélést eredményezett. A két beteg kórtörténetének ismertetése mellett a szerzők áttekintik a köpenysejtes lymphoma korszerű kezelésének mai lehetőségeit.

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A coeliakia, lisztérzékenység a vékonybél leggyakoribb malabszorpcióhoz vezető immunmediált bélbetegsége, amelyet a gabonafélék gluténfrakciója indít el genetikailag arra hajlamos egyénekben. A gluténexpozíciót követően T-sejt-mediált immunológiai folyamatok indulnak el, amelyek jellemző intestinalis és extraintestinalis tünetekhez vezetnek. Diagnosztikája jelenleg is a jejunalis biopsziára, endomysium és szöveti transzglutaminázellenes antitestek meglétére épül. Genetikai szempontból HLA DQ2/DQ8 asszociáció ismert a bélbetegség hátterében. Gluténmentes étrend szigorú betartása mellett, a klinikai tünetek terén, szövettanilag és szerológiailag is javulás következik be, kedvezően változik a társuló betegségek lefolyása. Az alapbetegség etiopatogenezisében, a genetikai és immunológiai tényezők tekintetében számos új információ vált ismertté az elmúlt években. A társbetegségek körében a mozgásszervi megnyilvánulások közül a csontmetabolikus eltérésekről több, a gyulladásos kórformákkal kapcsolatban kevesebb közlemény jelent meg. Az összefoglaló tanulmány fő célja a genetikai és immunológiai szempontból közös háttér áttekintése az elmúlt évek irodalmi adatainak segítségével.

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Vecino, W. H. et al.: Mucosal DNA vaccination with highly attenuated Shigella is superior to attenuated Salmonella and comparable to intramuscular DNA vaccination for T cells against HIV. Immunol. Lett. 82

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References [1] Tiegs , G. , Hentschel , J. , Wendel , A. 1992 A T cell-dependent experimental liver injury in mice inducible by concanavalin A J. Clin. Invest. 90 196 – 203 . [2] Mizuhara , H. , O’Neill , E. , Seki , N

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