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Immune mechanisms of induction and expression of contact hypersensitivity reaction in rats

dc.contributor.advisorMirkov, Ivana
dc.contributor.otherKataranovski, Milena V.
dc.contributor.otherMedenica, Ljiljana
dc.contributor.otherVučević, Dragana
dc.creatorPopov Aleksandrov, Aleksandra D.
dc.date.accessioned2016-01-05T11:47:31Z
dc.date.available2016-01-05T11:47:31Z
dc.date.available2020-07-03T08:07:19Z
dc.date.issued2013-12-06
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=809
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/2108
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:7142/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024629938
dc.description.abstractAlergijski kontaktni dermatitis (AKD) je česta zapaljenska bolest kože kod ljudi, koja pogađa 15-20% svetske populacije. Velika zastupljenost hemijskih agenasa (haptena) koji izazivaju AKD, uz odsustvo adekvatne konvencionalne imunosupresivne terapije, čine ovu bolest velikim izazovom za javno zdravlje, i savremenu imunologiju. Razvoj životinjskog modela AKD, reakcije kontaktne preosetljivosti, omogućio je napredak u razumevanju njene patogeneze. Iako je reakcija kontaktne preosetljivosti (KP) dosta ispitivana, pretežno na mišjem modelu, mehanizmi u osnovi razvoja bolesti nisu dovoljno poznati. Takođe, mali je broj podataka o reakciji KP kod drugih eksperimentalnih životinja, osim miševa, koji bi mogli da unaprede znanje o imunobiologiji kontaktnih alergija. U svetlu toga, u ovom radu su ispitane karakteristike reakcije KP kod pacova, korišćenjem dva soja pacova, Dark Agouti (DA) i Albino Oxford (AO), za koje je pokazano da se razlikuju u reaktivnosti na pojedine zapaljenske stimuluse. Indukcija (senzibilizacija) i izazivanje (elicitacija) reakcije KP vršene su sa haptenom dinitrohlorobenzenom (DNCB), koji je primenjen u dve različite koncentracije (režim senzibilizacije/elicitacije 0.4%/0.13% i 4%/1.3% DNCB). Mehanizmi KP kod pacova ispitani su u fazi senzibilizacije i elicitacije reakcije, praćenjem dinamike promena aktivnosti ćelija drenirajućih limfnih čvorova (dLČ) u fazi senzibilizacije, i ispitivanjem produkcije inflamatornih/ anti-inflamatornih medijatora u kondicioniranom medijumu organokulture uha, i promena aktivnosti ćelija dLČ u fazi elicitacije reakcije (24 časa nakon elicitacije). Rezultati su pokazali povećanje in vivo (otok uha) i ex vivo (patohistološka analiza isečaka kože uha) parametara reakcije KP kod oba soja pacova nakon tretmana sa višom dozom haptena, ali je reakcija bila intenzivnija kod DA u odnosu AO soj. Nakon senzibilizacije dolazi do: povećanja broja ćelija u dLČ kod oba soja (izraženije kod DA jedinki), promene zastupljenosti CD4+ i CD8+ ćelija i njihovog odnosa (povećanja odnosa CD4+/CD8+ ćelija kod DA soja, zbog povećanja zastupljenosti CD4+ ćelija a pada zastupljenosti CD8+ ćelija, i smanjenja odnosa CD4+/CD8+ kod AO soja, zbog pada zastupljenosti CD4+ ćelija a povećanja CD8+ ćelija), povećanja ex vivo proliferacije izolovanih ćelija i povećanja spontane i specifične (nakon in vitro stimulacije ćelija sa haptenom) produkcije inflamatornih citokina IFN-γ i IL-17, i Th2/anti-inflamatornog citokina IL-10 (izraženije kod DA soja)...sr
dc.description.abstractAllergic contact dermatitis (ACD) is a common skin inflammatory disease in humans, affecting 15-20% of the general population. Large number of chemical agents that induce ACD (called haptens), together with lack of adequate conventional immunosuppressive therapy, make this disease a major challenge for public health and modern immunology. Pathophysiology of ACD is studied on animal models referred as contact hypersensitivity. Although the reaction of contact hypersensitivity (CHS) has been much studied, mostly in mice, the knowledge of its mechanisms is still far from complete. In addition, there is paucity of data about CHS in other experimental animals, beside mice, which might increase our understanding of the immunobiology of contact allergy. In light of this, in the present study the characteristics of CHS were analyzed in rats, using two strains, Dark Agouti (DA) i Albino Oxford (AO), which have been shown to differ in reactivity to certain inflammatory stimuli. CHS to hapten dinitrochlorobenzene (DNCB) was induced by applying two different hapten concentrations in sensitization and elicitation phases (sensitization/elicitation regime 0.4%/0.13% and 4%/1.3% DNCB). Mechanisms of CHS were studied in induction (sensitization) and expression (elicitation) phases, by evaluating dynamics in activity changes of draining lymph node (dLN) cells in sensitization phase and by evaluating production of inflammatory/anti-inflammatory mediators in conditioned medium of ear skin organ culture and activity changes of dLN cells in elicitation phase (24 hours after elicitation). The results showed increased in vivo (ear thickness) and ex vivo (patohistology analysis of ear skin) parameters of CHS reaction, in both rat strains following the treatment with high DNCB dose, but the reaction was more intensive in DA compared to AO rats. In sensitization phase it was showed: increased dLN cell number in both strains (higher in DA rats), changes in ratio of CD4+ and CD8+ subsets (increased ratio of CD4+/CD8+ cells in DA rats, because of increased relative number of CD4+ and decreased relative number of CD8+ cells and decreased CD4+/CD8+ ratio in AO rats, because of decreased relative number of CD4+ cells and increased CD8+ cells relative number), increased ex vivo proliferation of dLN cells and increased spontaneous and specific (induced by in vitro cell stimulation with hapten) production of inflammatory cytokines IFN-γ and IL-17 and Th2/anti-inflammatory cytokine IL-10 (more pronounced in DA rats)...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173039/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectReakcija kontaktne preosetljivostisr
dc.subjectContact hypersensitivity reactionen
dc.subjectDNCBsr
dc.subjectFaza senzibilizacijesr
dc.subjectFaza elicitacije reakcijesr
dc.subjectDA i AO pacovisr
dc.subjectDrenirajući limfni čvorovisr
dc.subjectOrganokultura eksplantata kože uha.sr
dc.subjectDNCBen
dc.subjectSensitization phaseen
dc.subjectElicitation phaseen
dc.subjectDA and AO ratsen
dc.subjectDraining lymph nodesen
dc.subjectEar skin organ culture.en
dc.titleImunski mehanizmi indukcije i ekspresije reakcije kontaktne preosetljivosti kod pacovasr
dc.titleImmune mechanisms of induction and expression of contact hypersensitivity reaction in ratsen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dcterms.abstractМирков, Ивана; Меденица, Љиљана; Катарановски, Милена В.; Вучевић, Драгана; Попов Aлександров, Aлександра Д.; Имунски механизми индукције и експресије реакције контактне преосетљивости код пацова; Имунски механизми индукције и експресије реакције контактне преосетљивости код пацова;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/1566/Disertacija.pdf


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