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master's thesis
Fiziološki značaj varijanti gena TLR9 u humanim leukocitima
Zagreb: University of Zagreb, Faculty of Science, 2010. urn:nbn:hr:217:455127
Čorbić, Irena
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Čorbić, I. (2010). Fiziološki značaj varijanti gena TLR9 u humanim leukocitima (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:455127

Čorbić, Irena. "Fiziološki značaj varijanti gena TLR9 u humanim leukocitima." Master's thesis, University of Zagreb, Faculty of Science, 2010. https://urn.nsk.hr/urn:nbn:hr:217:455127

Čorbić, Irena. "Fiziološki značaj varijanti gena TLR9 u humanim leukocitima." Master's thesis, University of Zagreb, Faculty of Science, 2010. https://urn.nsk.hr/urn:nbn:hr:217:455127

Čorbić, I. (2010). 'Fiziološki značaj varijanti gena TLR9 u humanim leukocitima', Master's thesis, University of Zagreb, Faculty of Science, accessed 09 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:455127

Čorbić I. Fiziološki značaj varijanti gena TLR9 u humanim leukocitima [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2010 [cited 2024 November 09] Available at: https://urn.nsk.hr/urn:nbn:hr:217:455127

I. Čorbić, "Fiziološki značaj varijanti gena TLR9 u humanim leukocitima", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2010. Available at: https://urn.nsk.hr/urn:nbn:hr:217:455127

Metadata
TitleFiziološki značaj varijanti gena TLR9 u humanim leukocitima
Title (english)Physiological significance of TRL9 gene variants in human leukocyte
AuthorIrena Čorbić
MentorJelena Knežević (mentor)
Committee memberMaja Matulić (predsjednik povjerenstva)
Committee memberJelena Knežević (član povjerenstva)
Committee memberŽeljka Vidaković-Cifrek (član povjerenstva)
Committee memberGordana Lacković-Venturin (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2010-10-29, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Abstract
TLR9 (Toll like receptor 9) prepoznaje nemetilirane sljedove CpG u dvolančanoj DNA uglavnom bakterijskog i virusnog podrijetla. Njegovom aktivacijom pokreće se složeni imunološki odgovor uključen u oblikovanje prirođene i stečene imunosti domaćina. U ovome radu istražen je fiziološki značaj prethodno pronađenih funkcionalnih varijanti gena TLR9, 111X i R892W, u humanim leukocitima. Metodom ELISA mjerena je koncentracija izlučenih citokina IL-6 i IFNα u supernatantima kultiviranih plazmacitoidnih dendritičkih stanica, te IL-10 u supernatantima kultiviranih stanica limfocita B, nakon stimulacije specifičnim ligandima, CpG-ODN i R848. Rezultati analize pokazuju da istraživane mutacije uzrokuju smanjeni aktivacijski potencijal receptora na proizvodnju IL-10 u stanicama limfocita B. Istraživanjem učestalosti mutacija unutar skupine ispitanika s različitim autoimunim bolestima (550 ispitanika), metodom alelne diskriminacije, putem PCR-analize u stvarnom vremenu, nije potvrđena prisutnost mutacija niti u jednom uzorku, što govori o tome da se radi o iznimno rijetkim mutacijama. Istraživanjem nasljeđivanja varijante 111X analizom uzoraka DNA članova obitelji pokazano je da se mutacija stabilno nasljeđuje u heterozigotnom obliku.
Abstract (english)
Toll like receptor 9 (TLR9) is a sensor for unmethylated DNA stretches with CpG-motifs, usually presented in bacteria and viruses. TLR9 mediated signaling pathway leads to activation of innate immunity but also instructs the development of antigen-specific acquired immunity. In this study we examined the physiological relevance of previously found functional TLR9 gene variants, 111X and R892W, in human leukocyte. We investigated the effects of TLR agonists, CpG-ODN and R848 on the production of cytokines. Using ELISA, we measured the level of secreted IL-6 and IFNα in supernatants of cultivated plasmacytoid dendritic cells and IL-10 in supernatants of cultivated B cells. The results showed that mutations in TLR9 lead to reduced activation potential for IL-10 production in B cells. Using real time PCR (allelic discrimination assay) we investigated the frequency of the two TLR9 polymorphisms in the group of 550 patients suffering from different autoimmune diseases, and showed that these mutations are extremely rare, almost private. Finally, we screened family members for 111X mutation employing real time PCR method and found this mutation to be stably transmitted in the heterozygous form.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:455127
Study programmeTitle: Molecular Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
Type of resourceText
File originBorn digital
Access conditionsAccess restricted to students and staff of home institution
Terms of useLicence In copyright icon
Created on2017-05-03 12:22:48