Zlatko Dembic

 Here are some representative articles (-> click her for the complete list and TOP 20 cited articles ):

• Dembic Z, Haas W, Weiss S, McCubrey J, Kiefer H, von Boehmer H and Steinmetz M: 
  Transfer of specificity by murine alpha- and beta-chain T-cell receptor genes. Nature 320, 232-238 (1986).
• Dembic Z, Haas W, Zamoyska R, Parnes J, Steinmetz M and von Boehmer H: 
  Transfection of the CD8 gene enhances T cell recognition. Nature 326, 510-511 (1987).
• Aguet M, Dembic Z and Merlin G: 
  Molecular cloning and expression of human IFN-gamma receptor. Cell 55, 273-276 (1988).
• Vidovic D, Roglic M, McKune K, Guerder S, Mackay C, and Dembic Z: 
  Qa-1 restricted recognition of foreign antigen by a gamma/delta T cell hybridoma. Nature 340, 646-650 (1989).
• Dembic Z, Schenck K, and Bogen B: 
  Dendritic cells purified from myeloma are primed with tumor-specific antigen (idiotype) and activate CD4+ T cells. Proc Natl Acad Sci USA 97, 2697-2702 (2000).
• Dembic Z, Røttingen J-A, Dellacasagrande J, Schenck K and Bogen B. 
  Phagocytic dendritic cells purified from myelomas activate tumor-specific T cells at a single cell level. Blood 97, 2808-14 (2001).
• Dembic Z.. Pharmaco-therapeutic challenges in cancer biology with focus on the immune-system related risk factors. Curr Pharm Des 20(42):6652-9 (2014). 
• Gardar Sveinbjornsson, et al. ... Zlatko Dembic,... Ingileif Jonsdottir, & Kari Stefansson: 
  HLA class II sequence variants influence tuberculosis risk in populations of European ancestry. Nature Genetics 48, 318-322 (2016)
• Dembic, Z., Antitumor Drugs and Their Targets. Molecules (2020), 25, (23).

• Dembic, Z., Cytokines in Innate Immunity. Chapter in Encyclopedia of Infection and Immunity, (2022); pp 170-192.

• Dembic, Z., Defending and integrating an organism by the immune system. Scand J Immunol (2022), 95, (5), e13172.

• Tudor, Karlo; Baranasic, Jurica; Knezevic, Jelena; Serer Vicevic, Marta; Sutic, Maja & Dembic, Zlatko [Vis alle 7 forfattere av denne artikkelen] (2024). Indirect influence of microRNA-146a on the association of IL-6 and TNF-α genetic polymorphisms with the increased risk of hip osteoarthritis. Journal of Orthopaedic Research. ISSN 0736-0266. doi: 10.1002/jor.25804.
• Simunic-Briski, Nina; Vrgoc, Goran; Knjaz, Damir; Jankovic, Sasa; Dembic, Zlatko & Lauc, Gordan (2023). MMP3 single-nucleotide polymorphisms are associated with noncontact ACL injuries in competing high-level athletes. Journal of Orthopaedic Research. ISSN 0736-0266. doi: 10.1002/jor.25663.
• Dembic, Zlatko (2022). Cytokines in Innate Immunity. I Rezaei, Nima (Red.), Encyclopedia of Infection and Immunity. Elsevier. ISSN 978-0-323-90303-5. s. 170–192. doi: 10.1016/B978-0-12-818731-9.00090-2. Vis sammendrag

  The IL-1 family: Members of the IL-1 family of cytokines are similar in structure and function. The functions include agonistic (pro-inflammatory) and antagonistic (anti-inflammatory) activities. The IL-1 family of cytokines can signal damage of tissue integrity, distress, and danger to the organism, ultimately alarming innate and adaptive immunity to fight pathogens. TNF and LT: TNF and LT are trimeric proteins belonging to a structurally related TNF superfamily of cytokines. They are pleiotropic cytokines capable of signaling an array of pro- and anti-inflammatory activities. TNF-α has soluble (sTNF) and membrane (mTNF) forms. Both forms can bind to two TNF receptors (TNF-R1 and TNF-R2), but mTNF can alter the structure of the TNF-R2 such that it binds to sTNF with a lower affinity. Thus, sTNF primarily binds to TNF-R1 and plays an important role in the inflammatory immune response, whereas mTNF-α interacts preferentially with TNF-R2 and promotes cellular proliferation and survival and some other biological effects. IL-6: The IL-6 family of cytokines is structurally characterized by four α-helical bundle structure that signals via the JAK-STAT pathway. IL-6 has a major role in innate and adaptive immunity. IL-6 classic signaling is implicated in acute-phase responses, whereas IL-6 trans-signaling (and trans-presentation/cluster-signaling) characteristically initiates pro-inflammatory pathways with a major impact on adaptive immunity, including plasma cell development and antibody production, and T-cell helper 17 response. Interferons: Interferons are classified into three types. Type I (IFN-α, −β) and type III (IFN-λ) are strong antivirals that can stimulate both innate and adaptive immune responses. Type II interferon (IFN-γ) has a weak antiviral ability, as its major role is in regulating adaptive immunity, particularly in Th1 responses. Cytokine storm and COVID-19: Cytokine storm is a hyperinflammatory state due to overactivity of major pro-inflammatory cytokines like IL-1, IL-6, and TNF. It is a major obstacle for the treatment of severe COVID-19. IL-6 is a potential biomarker for the severity of the disease. Anti-IL-6R (tocilizumab) and anti-virotic “remdesivir” are promising treatments of severe disease. Prevention measures are in place with many auspicious novel vaccines.

• Dembic, Zlatko (2022). Defending and integrating an organism by the immune system. Scandinavian Journal of Immunology. ISSN 0300-9475. 95(5). doi: 10.1111/sji.13172. Fulltekst i vitenarkiv
• Eftedal, Randi Krog; Jotanovic, Zdravko; Balen, Sanja & Dembic, Zlatko (2020). TNFA Genetic Polymorphism is Associated with Risk for Developing Hip but not Knee Osteoarthritis in Croatian Population. EC Gastroenterology and Digestive System. ISSN 2276-1209. Fulltekst i vitenarkiv Vis sammendrag

  Aim: We studied genetic epidemiology of primary large-joint (hip and knee) osteoarthritis (OA), in order to find disease risk factors by a candidate-gene approach. We used TNFA gene SNP rs1800629 in a case-control study in the Croatian Caucasian population. Method: We analyzed 225 hip and 205 knee OA patients (both with total joint replacements), and 554 healthy individuals, majority being blood donors. We genotyped for TNFA SNP rs1800629 (+308, C>T). Allelic and genotypic frequencies were compared between patients and controls. Results: The minor allele (T) of rs1800629 significantly conferred susceptibility only to hip OA (p < 5*10-5, OR = 1.81, CI 95% = 1.34 - 2.44). The major (C) allele was significantly associated with the protection to hip (p < 5*10-5, OR = 0.63, CI 95% = 0.41 - 0.74), but not knee OA. Patients with the homozygous genotype C/C had significantly lower risk of developing hip OA (< 3*10-4, OR = 0.53, CI 95% = 0.38 - 0.76), but had no association with knee OA. The homozygosity of the minor allele (T/T) has been significantly associated with susceptibility to only hip OA (< 2*10-2, OR = 2.56, CI 95% = 1.09 - 5.57). Conclusion. Our findings demonstrate that major and minor alleles of the rs1800629 are associated with lower or higher risk, respectively, to developing hip, but not knee OA in the Croatian population. The data suggest a difference in the etiology of hip OA from that of the knee, perhaps due to an unknown dissimilarity in vulnerability of these joints to the actions of TNFA. Alternatively, other genetic factors including long non-protein coding LOC100287329 and/or miR6832 in vicinity of rs1800629 might be involved in the observed risk. Keywords: Genetic Risk; TNFA; Osteoarthritis; Hip; SNP

• Oršolić, Ines; Bursać, Slađana; Jurada, Deana; Drmić Hofman, Irena; Dembic, Zlatko & Bartek, Jiri [Vis alle 8 forfattere av denne artikkelen] (2020). Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint. Oncogene. ISSN 0950-9232. 39(17), s. 3443–3457. doi: 10.1038/s41388-020-1231-6. Vis sammendrag

  Perturbations in ribosome biogenesis have been associated with cancer. Such aberrations activate p53 through the RPL5/ RPL11/5S rRNA complex-mediated inhibition of HDM2. Studies using animal models have suggested that this signaling pathway might constitute an important anticancer barrier. To gain a deeper insight into this issue in humans, here we analyze somatic mutations in RPL5 and RPL11 coding regions, reported in The Cancer Genome Atlas and International Cancer Genome Consortium databases. Using a combined computational and statistical approach, complemented by a range of biochemical and functional analyses in human cancer cell models, we demonstrate the existence of several mechanisms by which RPL5 mutations may impair wild-type p53 upregulation and ribosome biogenesis. Unexpectedly, the same approach provides only modest evidence for a similar role of RPL11, suggesting that RPL5 represents a preferred target during human tumorigenesis in cancers with wild-type p53. Furthermore, we find that several functional cancer-associated RPL5 somatic mutations occur as rare germline variants in general population. Our results shed light on the so-far enigmatic role of cancer- associated mutations in genes encoding ribosomal proteins, with implications for our understanding of the tumor suppressive role of the RPL5/RPL11/5S rRNA complex in human malignancies.

• Dembic, Zlatko (2020). Antitumor Drugs and Their Targets. Molecules. ISSN 1431-5157. 25(23). doi: 10.3390/molecules25235776. Fulltekst i vitenarkiv Vis sammendrag

  Through novel methodologies, including both basic and clinical research, progress has been made in the therapy of solid cancer. Recent innovations in anticancer therapies, including immune checkpoint inhibitor biologics, therapeutic vaccines, small drugs, and CAR-T cell injections, mark a new epoch in cancer research, already known for faster (epi-)genomics, transcriptomics, and proteomics. As the long-sought after personalization of cancer therapies comes to fruition, the need to evaluate all current therapeutic possibilities and select the best for each patient is of paramount importance. This is a novel task for medical care that deserves prominence in therapeutic considerations in the future. This is because cancer is a complex genetic disease. In its deadly form, metastatic cancer, it includes altered genes (and their regulators) that encode ten hallmarks of cancer-independent growth, dodging apoptosis, immortalization, multidrug resistance, neovascularization, invasiveness, genome instability, inflammation, deregulation of metabolism, and avoidance of destruction by the immune system. These factors have been known targets for many anticancer drugs and treatments, and their modulation is a therapeutic goal, with the hope of rendering solid cancer a chronic rather than deadly disease. In this article, the current therapeutic arsenal against cancers is reviewed with a focus on immunotherapies.

• Dembic, Zlatko (2019). On integrity in immunity during ontogeny or how thymic regulatory T cells work. Scandinavian Journal of Immunology. ISSN 0300-9475. s. 1–12. doi: 10.1111/sji.12806. Fulltekst i vitenarkiv Vis sammendrag

  The Standard model of T cell recognition asserts that T cell receptor (TCR) specificities are positively and negatively selected during ontogeny in the thymus and that periph- eral T cell repertoire has mild self‐major histocompatibility complex (MHC) reactiv- ity, known as MHC restriction of foreign antigen. Thus, the TCR must bind both a restrictive molecule (MHC allele) and a peptide reclining in its groove (pMHC ligand) in order to transmit signal into a T cell. The Standard and Cohn's Tritope models sug- gest contradictory roles for complementarity‐determining regions (CDRs) of the TCRs. Here, I discuss both concepts and propose a different solution to ontogenetic mecha- nism for TCR‐MHC–conserved interaction. I suggest that double (CD4+CD8+)‐posi- tive (DP) developing thymocytes compete with their αβTCRs for binding to self‐pMHC on cortical thymic epithelial cells (cTECs) that present a selected set of tissue‐restricted antigens. The competition between DPs involves TCR editing and secondary rearrange- ments, similar to germinal‐centre B cell somatic hypermutation. These processes would generate cells with higher TCR affinity for self‐pMHC, facilitating sufficiently long binding to cTECs to become thymic T regulatory cells (tTregs). Furthermore, CD4+ Foxp3+ tTregs can be generated by mTECs via Aire‐dependent and Aire‐independent pathways, and additionally on thymic bone marrow–derived APCs including thymic Aire‐expressing B cells. Thymic Tregs differ from the induced peripheral Tregs, which comprise the negative feedback loop to restrain immune responses. The implication of thymocytes’ competition for the highest binding to self‐pMHC is the co‐evolution of species‐specific αβTCR V regions with MHC alleles.

• Cohn, Melvin; Anderson, Colin C. & Dembic, Zlatko (2019). The case for allele-specific recognition by the TCR. Scandinavian Journal of Immunology. ISSN 0300-9475. 90(2). doi: 10.1111/sji.12790. Fulltekst i vitenarkiv Vis sammendrag

  There is a sharp difference in how one views TCR structure-function behavior dependent on whether its recognition of MHC-encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele-specific. The establishing of allele-specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here the case for allele-specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.

• Eftedal, Randi Krog; Vrgoc, Goran; Jotanovic, Zdravko & Dembic, Zlatko (2019). Alternative Interleukin 17A/F Locus Haplotypes Are Associated With Increased Risk to Hip and Knee Osteoarthritis. Journal of Orthopaedic Research. ISSN 0736-0266. 37(9), s. 1972–1978. doi: 10.1002/jor.24334. Fulltekst i vitenarkiv Vis sammendrag

  We studied the genetic epidemiology of primary large‐joint (hip and knee) osteoarthritis (OA), in order to find disease risk factors by a candidate‐gene approach. We used case–control study in the Croatian Caucasian population. We genotyped 500 OA patients (260 hip, 240 knee; both with total joint replacements) and 597 healthy individuals for single‐nucleotide polymorphisms (SNPs) in interleukin 17A (IL17A) (rs2275913) and IL17F (rs763780 and rs1889570) genes. On the basis of our population and allelic and genotypic frequencies haplotypes were predicted by PHASE software and compared between patients and controls. The three‐SNP haplotype (rs2275913–rs763780–rs1889570) G–C–A confers predisposition to hip (p < 0.005) but not knee OA. The three‐SNP haplotype having opposed nucleotides A–T–G was found significantly associated with 2.6 times higher risk for developing knee (p < 0.02) but not hip OA. The haplotype G–T (IL17A–IL17F; rs2275913–rs763780) is associated with protection to the disease in hip OA (p < 0.01). Our analyses show that two disparate haplotypes within the IL17A‐F gene locus are associated with higher risk to developing hip and knee OA in the Croatian population. The data might suggest a difference in the etiology of hip OA from that of the knee OA, perhaps due to an unknown dissimilarity in vulnerability of these joints to the actions of IL17. Alternatively, other differences in genetic factors like the long non‐ protein coding region LINCMD1 and/or microRNA species like miR133b and miR206 found in the vicinity of the IL17 locus might be involved in the observed risk.

• Vrgoc, Goran; Vrbanec, Jurica; Eftedal, Randi Krog; Dembic, Petra L.; Balen, Sanja & Dembic, Zlatko [Vis alle 7 forfattere av denne artikkelen] (2018). Interleukin-17 and Toll-like Receptor 10 genetic polymorphisms and susceptibility to large joint osteoarthritis. Journal of Orthopaedic Research. ISSN 0736-0266. 36(6), s. 1684–1693. doi: 10.1002/jor.23823.
• Bretscher, Peter; Corthay, Alexandre; Anderson, Colin C.; Dembic, Zlatko; Havele, Calliopi & Nagy, Zoltan A. [Vis alle 7 forfattere av denne artikkelen] (2017). Immune Class Regulation and Its Medical Significance Part II of a Report of a Workshop on Foundational Concepts of Immune Regulation. Scandinavian Journal of Immunology. ISSN 0300-9475. 85(4), s. 242–250. doi: 10.1111/sji.12525. Vis sammendrag

  We discussed different proposals for how the nature of the Th1/Th2 phenotype of an immune response is determined, and favoured one, the Threshold Hypothesis, as plausible and so useful as the basis for further discussions. The activation of a target CD4 T cell can be facilitated by helper CD4 T cells when the CD4 T cells interact via an antigen-presenting cell. The Threshold Hypothesis states that tentative and robust antigen-mediated CD4 T cell cooperation results in the target CD4 T cell, respectively giving rise, upon activation, to Th1 and Th2 cells. We primarily discussed four topics. We briefly discussed in the background section certain limitations of the Th1/Th2 paradigm in understanding immune class regulation, and the remarkable anti-inflammatory properties of human IgG4 antibody. Secondly, we assessed the role of class II MHC molecules in determining the number of mature CD4 T cells and so affecting the Th1/Th2 phenotype of immune responses. We also discussed the controversial role of CD8 T cells in affecting the Th1/Th2 phenotype of responses to MHC and other antigens, and the potential role of their relative scarcity in neonates in biasing responses towards an antibody, Th2 mode. Lastly, we examined the regulation of the Th1/Th2 phenotype of both primary and ongoing immune responses in the context of the intriguing proposal that antigen initially generates different classes/subclasses of immunity and then selects, by a feedback mechanism, the most effective class. We found this interesting idea difficult to reconcile with various observations.

• Teofilović, Natalija Knežević; Bihi, Mahjoub; Stojković, Marijana Radić; Tumir, Lidija M.; Ester, Katja & Kralj, Marijeta [Vis alle 17 forfattere av denne artikkelen] (2017). 1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro. Bioorganic & Medicinal Chemistry Letters. ISSN 0960-894X. 27(7), s. 1530–1537. doi: 10.1016/j.bmcl.2017.02.048.
• Anderson, Colin C.; Bretscher, Peter; Corthay, Alexandre; Dembic, Zlatko; Havele, Calliopi & Nagy, Zoltan A. [Vis alle 7 forfattere av denne artikkelen] (2017). Immunological Tolerance. Part I of a Report of a Workshop on Foundational Concepts of Immune Regulation. Scandinavian Journal of Immunology. ISSN 0300-9475. 85(2), s. 84–94. doi: 10.1111/sji.12500.
• Vrbanec, Jurica; Lederer-Dembic, Petra; Bulat-Kardum, Ljiljana; Balen, Sanja; Eftedal, Randi Krog & Dembic, Zlatko (2016). Genetic Risk of Tuberculosis is Spread within the Hallmarks of the Disease. Immunotherapy: Open Access. ISSN 2471-9552. 2(2), s. 117–122. doi: 10.4172/2471-9552.1000117. Fulltekst i vitenarkiv
• Sveinbjornsson, Gardar; Gudbjartsson, Daniel F.; Halldorsson, Bjarni V.; Kristinsson, Karl G.; Gottfredsson, Magnus & Barrett, Jeffrey C. [Vis alle 30 forfattere av denne artikkelen] (2016). HLA class II sequence variants influence tuberculosis risk in populations of European ancestry. Nature Genetics. ISSN 1061-4036. 48(3), s. 318–322. doi: 10.1038/ng.3498.
• Armingohar, Zahra; Jørgensen, Jørgen J.; Kristoffersen, Anne Karin; Schenck, Karl & Dembic, Zlatko (2015). Polymorphisms in the interleukin-10 gene and chronic periodontitis in patients with atherosclerotic and aortic aneurysmal vascular diseases. Journal of Oral Microbiology. ISSN 2000-2297. 7(1), s. 1–8. doi: 10.3402/jom.v7.26051. Fulltekst i vitenarkiv
• Jotanovic, Zdravko; Mihelic, Radovan; Gulan, Gordan; Sestan, Branko & Dembic, Zlatko (2015). Osteoarthritis of the hip: An overview. Periodicum biologorum. ISSN 0031-5362. 117(1), s. 95–108.
• Bulat-Kardum, Ljiljana; Etokebe, Godfrey; Lederer, Petra; Balen, S & Dembic, Zlatko (2015). Genetic Polymorphisms in the Toll-like Receptor 10, Interleukin (IL)17A and IL17F Genes Differently Affect the Risk for Tuberculosis in Croatian Population. Scandinavian Journal of Immunology. ISSN 0300-9475. 82(1), s. 63–69. doi: 10.1111/sji.12300.
• Etokebe, Godfrey; Jotanovic, Zdravko; Mihelic, Radovan; Mulac-Jericevic, Biserka; Nikolic, Tamara & Balen, Sanja [Vis alle 8 forfattere av denne artikkelen] (2015). Susceptibility to Large-Joint Osteoarthritis (Hip and Knee) is Associated with BAG6 rs3117582 SNP and the VNTR Polymorphism in the Second Exon of the FAM46A Gene on Chromosome 6. Journal of Orthopaedic Research. ISSN 0736-0266. 33(1), s. 56–62. doi: 10.1002/jor.22738.
• Etokebe, Godfrey; Zienolddiny, Shanbeh; Kupanovac, Zeljko; Enersen, Morten; Balen, Sanja & Flego, Velkjo [Vis alle 12 forfattere av denne artikkelen] (2015). Association of the FAM46A gene VNTRs and BAG6 rs3117582 SNP with non small cell lung cancer (NSCLC) in Croatian and Norwegian populations. PLOS ONE. ISSN 1932-6203. 10(4). doi: 10.1371/journal.pone.0122651. Fulltekst i vitenarkiv Vis sammendrag

  We analyzed for associations between a variable number of tandem repeat (VNTR) polymorphism in the Family with sequence similarity 46, member A (FAM46A) gene and a single nucleotide polymorphism (rs3117582) in the BCL2-Associated Athanogene 6 (BAG6) with non small cell lung cancer in Croatian and Norwegian subjects. A total of 503 (262 Croatian and 241Norwegian) non small cell lung cancer patients and 897 controls (568 Croatian and 329 Norwegian) were analyzed. We found that the frequency of allele b (three VNTR repeats) of FAM46A gene was significantly increased in the patients compared to the healthy controls in the Croatian and the combined Croatian and Norwegian subjects. Genotype frequencies of cd (four and five VNTR repeats) and cc (four VNTR repeats homozygote) of the FAM46A gene were significantly decreased in the patients compared to the healthy controls in the Croatian and Norwegian subjects, respectively. Logistic regression analyses revealed FAM46A genotype cc to be an independent predictive factor for non small cell lung cancer risk in the Norwegian subjects after adjustment for age, gender and smoking status. This is the first study to suggest an association between the FAM46A gene VNTR polymorphisms and non small cell lung cancer. We found also that BAG6 rs3117582 SNP was associated with non small cell lung cancer in the Norwegian subjects and the combined Croatian-Norwegian subjects corroborating the earlier finding that BAG6 rs3117582 SNP was associated with lung cancer in Europeans. Logistic regression analyses revealed that genotypes and alleles of BAG6 were independent predictive factor for non small cell lung cancer risk in the Norwegian and combined Croatian-Norwegian subjects, after adjustment for age and gender.

• Etokebe, Godfrey; Bulat-Kardum, Ljiljana; Munthe, Ludvig Andre; Balen, Sanja & Dembic, Zlatko (2014). Association of variable number of tandem repeats in the coding region of the FAM46A gene, FAM46A rs11040 SNP and BAG6 rs3117582 SNP with susceptibility to tuberculosis. PLOS ONE. ISSN 1932-6203. 9(3). doi: 10.1371/journal.pone.0091385. Fulltekst i vitenarkiv
• Dembic, Zlatko (2014). Pharmaco-therapeutic challenges in cancer biology with focus on the immune- system related risk factors. Current pharmaceutical design. ISSN 1381-6128. 20(42), s. 6652–6659. doi: 10.2174/1381612820666140826154147.
• Haabeth, Ole Audun; Tveita, Anders; Fauskanger, Marte Hotvedt; Schjesvold, Fredrik Hellem; Lorvik, Kristina Berg & Hofgaard, Peter Olaf [Vis alle 11 forfattere av denne artikkelen] (2014). How do CD4+ T cells detect and eliminate tumor cells that either lack or express MHC class II molecules? Frontiers in Immunology. ISSN 1664-3224. 5:174. doi: 10.3389/fimmu.2014.00174. Fulltekst i vitenarkiv
• Jotanovic, Zdravko; Mihelic, Radovan; Sestan, Branko & Dembic, Zlatko (2014). Emerging pathways and promising agents with possible disease modifying effect in osteoarthritis treatment. Current Drug Targets. ISSN 1389-4501. 15(6), s. 635–661. doi: 10.2174/1389450115666140306153115.
• Armingohar, Zahra; Jørgensen, Jørgen J.; Kristoffersen, Anne Karin; Schenck, Karl & Dembic, Zlatko (2014). Polymorphisms in the interleukin-1 gene locus and chronic periodontitis in patients with atherosclerotic and aortic aneurysmal vascular diseases. Scandinavian Journal of Immunology. ISSN 0300-9475. 79(5), s. 338–345. doi: 10.1111/sji.12166. Vis sammendrag

  Chronic periodontitis (CP) and atherosclerotic and aortic aneurysmal vascular diseases (VD) are inflammatory conditions that share a number of predisposing factors. They have a complex genetic heritability and may share genetic risk factors, but a well-defined relationship is still not determined. In addition, distinct genetic patterns of predisposition have been associated with these diseases. Here, we investigated the association of polymorphisms in the IL-1 gene locus with CP in a case-case study analysing VD patients with or without CP. Seventy-four patients with VD of whom 36 had CP were genotyped for single nucleotide polymorphisms in the IL1A -889 (rs1800587), IL1B +3954 (rs1143634) and IL1B at -511 (rs16944) genes and for VNTR polymorphisms in the IL1RN gene. A significantly higher frequency (17%) for allele 1 (four repeats) of the IL1RN VNTR gene was found among the VD patients with CP compared to those without CP. In addition, the frequency of the IL1RN VNTR genotypes 1/1 (4/4 repeats) and 2/2 (2/2 repeats) were significantly higher and lower, respectively, in VD patients with CP. These findings suggest an association of genetic polymorphisms in the IL1-gene locus with risk for CP in patients with VD. The carriage of the risk genotypes, the development and the subsequent influence of CP on systemic health may constitute an additional burden in the pathogenesis of VD. This emphasizes the importance of effective periodontal treatment in patients with VD.

• Dembic, Zlatko (2013). On recognizing 'shades-of-gray' (Self-nonself discrimination) or 'colour' (Integrity model) by the immune system. Scandinavian Journal of Immunology. ISSN 0300-9475. 78(4), s. 325–338. doi: 10.1111/sji.12090. Vis sammendrag

  The aim is to discuss Cohn's T-cell receptor (TCR) Tritope model of recognition, propose a novel suggestion for prior-to-positive selection of thymocytes contributing to inherent major histocompatibility complex (MHC) reactivity of a T-cell repertoire and clarify the Integrity model about the function of the immune system. If we compare the perception of light with the recognition of nonself, we could imagine that the opacity might be a measure of docking interaction between specific receptors for antigen on T or B cells (TCR/peptide-MHC or BCR/antigen). From this viewpoint, the self-nonself discrimination (S-NS) metaphor would be perception of black (self) versus white (nonself). However, whereas detection of shades-of-gray suffices to describe S-NS discrimination principle, colour vision of the antigenic world portrays best the Integrity model. In concert with recognition of opacity, the Integrity model proposes detection of at least three colours (signals): red (harmful), blue (useful) and yellow (the rest, including homoeostatic ones). As a result, recognition of nonself is transferred into communication within self while deciding on type of the immune response. Hence, the S-NS discrimination model seems to be an oversimplification, because it fails to see colours and consequently lacks the need for suppressor/regulatory function. Similarly, the Danger model stops short of detecting being useful signals that confer immune asylum to helpful micro-organisms like commensals. I suggest that the immune system's repertoire for recognition, in general, has evolved by a novel drive called 'natural integrity' alongside natural selection, thus facilitating communication between cells of the immune system.

• Kårvatn, Marikken; Jotanovic, Zdravko; Mihelic, Radovan; Etokebe, Godfrey; Mulac-Jericevic, Biserka & Tijanic, Tamara [Vis alle 9 forfattere av denne artikkelen] (2013). Associations of the Interleukin-1 Gene Locus Polymorphisms with Risk to Hip and Knee Osteoarthritis: Gender and Subpopulation Differences. Scandinavian Journal of Immunology. ISSN 0300-9475. 77(2), s. 151–161. doi: 10.1111/sji.12016. Vis sammendrag

  Genetic predisposition to the complex hereditary disease like osteoarthritis (OA) of the large joints (hip and knee) includes the interleukin-1 gene (IL-1) cluster on chromosome 2. Using a case–control study with 500 OA patients (240 knee and 260 hip OA patients, all with joint replacement), we analysed frequencies of IL-1 gene cluster polymorphisms in Croatian Caucasian population. The control samples came from 531 healthy individuals including blood donors. We genotyped two single nucleotide polymorphisms in the IL-1 gene locus at IL-1A (−889, C>T, rs1800587) and IL-1B (+3594, C>T, rs1143634) and compared their frequencies between patients and controls. We predicted haplotypes by combining current data with our previous results on gene polymorphisms (IL-1B, rs16944 and the IL-1 receptor antagonist gene [IL-1RN] variable number tandem repeat [VNTR]) for the same population. Haplotype analyses revealed gender disparities and showed that women carriers of the 1-2-1-1 haplotype [IL-1A(rs1800587) – IL-1B(rs1143634) – IL-1B(rs16944) – IL-1RN(VNTR)] had sixfold lower risk to develop knee OA. However, carriers of the 1-1-1-2 haplotype of both sexes had over twofold higher predisposition to hip OA. Our results differ from some earlier studies in Caucasian subpopulations, which may be due to the fact that this is the first study to separate genders in assessing the IL-1-locus genetic risk of OA. The results suggest that inflammatory mediators like IL-1 might be implicated in the pathogenesis of primary OA in large joints and that as yet unidentified gender-specific factors exist in a Croatian Caucasian population

• Jotanovic, Zdravko; Etokebe, Godfrey; Mihelic, Radovan; Kårvatn, Marikken; Mulac-Jericevic, Biserka & Tijanic, Tamara [Vis alle 9 forfattere av denne artikkelen] (2012). IL1B-511(G > A) and IL1RN (VNTR) allelic polymorphisms and susceptibility to knee osteoarthritis in Croatian population. Rheumatology International. ISSN 0172-8172. 32(7), s. 2135–2141. doi: 10.1007/s00296-011-1946-3.
• Knezevic, Jelena; Pavlinic, Dinko; Rose II, William A.; Leifer, Cynthia A; Bendelja, Kreso & Gabrilovac, Jelka [Vis alle 16 forfattere av denne artikkelen] (2012). Heterozygous Carriage of a Dysfunctional Toll-like Receptor 9 Allele Affects CpG Oligonucleotide Responses in B Cells. Journal of Biological Chemistry. ISSN 0021-9258. 287(29), s. 24544–24553. doi: 10.1074/jbc.M111.337477. Vis sammendrag

  Toll-like receptors (TLR) are employed by the innate immune system to detect microbial pathogens based on conserved microbial pathogen molecules. For example, TLR9 is a receptor for CpG-containing microbial DNA, and its activation results in the production of cytokines and type I interferons from human B cells and plasmacytoid dendritic cells, respectively. Both are required for mounting an efficient antibacterial or antiviral immune response. These effects are mimicked by synthetic CpG oligodeoxynucleotides (ODN). Although several hyporesponsive TLR9 variants have been reported, their functional relevance in human primary cells has not been addressed. Here we report a novel TLR9 allele, R892W, which is hyporesponsive to CpG ODN and acts as a dominant-negative in a cellular model system. The R892W variant is characterized by increased MyD88 binding and defective co-localization with CpG ODN. Whereas primary plasmacytoid dendritic cells isolated from a heterozygous R892W carrier responded normally to CpG by interferon-α production, carrier B cells showed impaired IL-6 and IL-10 production. This suggests that heterozygous carriage of a hyporesponsive TLR9 allele is not associated with complete loss of TLR9 function but that TLR9 signals elicited in different cell types are regulated differently in human primary cells.

• Kårvatn, Marikken; Vrbanec, Jurica; Kulic, Ana; Knezević, Jelena; Petricevic, Branka & Balen, Sanja [Vis alle 8 forfattere av denne artikkelen] (2012). Single Nucleotide Polymorphism in the Interleukin 12B Gene is Associated with Risk for Breast Cancer Development. Scandinavian Journal of Immunology. ISSN 0300-9475. 76(3), s. 329–335. doi: 10.1111/j.1365-3083.2012.02736.x.
• Jotanovic, Zdravko; Mihelic, Radovan; Sestan, Branko & Dembic, Zlatko (2012). Role of Interleukin-1 Inhibitors in Osteoarthritis An Evidence-Based Review. Drugs & Aging. ISSN 1170-229X. 29(5), s. 343–358. doi: 10.2165/11599350-000000000-00000.
• Dzumhur, A; Zibar, L; Wagner, J; Simundic, T; Dembic, Zlatko & Barbic, J (2012). Association Studies of Gene Polymorphisms in Toll-Like Receptors 2 and 4 in Croatian Patients with Acute Myocardial Infarction. Scandinavian Journal of Immunology. ISSN 0300-9475. 75(5), s. 517–523. doi: 10.1111/j.1365-3083.2012.02681.x.
• Kaarvatn, Marikken Heiland; Eftedal, Randi Krog; Vrbanec, Jurica; Jotanovic, Zdravko; Etokebe, Godfrey & Sanja, Balen [Vis alle 8 forfattere av denne artikkelen] (2012). Interleukin-1 Gene Locus Polymorphisms are Associated with Risk to Breast Cancer in Croatian Population. Periodicum biologorum. ISSN 0031-5362. 114(4), s. 497–503. Fulltekst i vitenarkiv Vis sammendrag

  Breast cancer has a complex genetic susceptibility. Innate and adaptive immunity can additionally increase the genetic risk to breast cancer development. We typed polymorphisms in the genes of the interleukin(IL)-1 and IL-17 proinflammatory cytokines in a case-control study in Caucasian population from Croatia. We compared the allelic and genotypic frequencies between patients (n=194), healthy women (n=188) and general population (n=531). The risk for breast cancer has been significantly different at both allelic and genotypic levels for two polymorphisms: the IL1B gene single nucleotide polymorphism (SNP) at -511 (G>A; rs16944) and the IL1 Receptor antagonist gene (IL1RN) variable number of tandem repeats (VNTR). Themajor allele (G) of the IL1B rs16944 SNPwas associated with susceptibility to breast cancer (P<0.01) in general populationwith odds ratio (OR) of 1.42 and 95 % confidence interval (CI) at 1.09–1.85. The IL1RN VNTR allele 3 (5 repeats) was correlated with predisposition to disease (P<0.01,OR: 9.71, 95%CI: 1.34–198.51) inwomen. At the genotype level, G/G homozygosity at IL1B rs16944 was significantly associated with predisposition to disease (P<0.02, OR: 1.68, 95 % CI: 1.10–2.57), whereas the heterozygosity (G/A) was correlatedwith protection to disease (P<0.01, OR: 0.57, 95 % CI: 0.37–0.89) in women. The IL1RN VNTR genotype 1/3 was significantly associated with susceptibility to breast cancer (P<0.01, OR: 10.01, 95 % CI: 1.37–207.55). Genotypic differences were also significantly different in comparison with general population for IL1B SNP (P<0.001) and IL1RN VNTR (P<0.01). These results corroborate a premise that inflammatory factors play a role in pathogenesis to breast cancer.

• Jotanovic, Zdravko; Etokebe, Godfrey; Mihelic, Radovan; Kårvatn, Marikken; Mulac-Jericevic, Biserka & Tijanic, Tamara [Vis alle 9 forfattere av denne artikkelen] (2011). Hip Osteoarthritis Susceptibility Is Associated with IL1B-511(G &gt; A) and IL1 RN (VNTR) Genotypic Polymorphisms in Croatian Caucasian Population. Journal of Orthopaedic Research. ISSN 0736-0266. 29(8), s. 1137–1144. doi: 10.1002/jor.21378.
• Etokebe, GE; Skjeldal, F; Nilsen, Nadra; Rodionov, Dmitrii; Knezevic, Jelena & Bulat-Kardum, Ljiljana [Vis alle 9 forfattere av denne artikkelen] (2010). Toll-Like Receptor 2 (P631H) Mutant Impairs Membrane Internalization and is a Dominant Negative Allele. Scandinavian Journal of Immunology. ISSN 0300-9475. 71(5), s. 369–381. doi: 10.1111/j.1365-3083.2010.02379.x. Fulltekst i vitenarkiv
• Etokebe, Godfrey; Kuchler, Axel Matthias; Haraldsen, Guttorm; Landin, Maria Augusta Dos S Silva; Osmundsen, Harald & Dembic, Zlatko (2009). Family-with-sequence-similarity-46, member A (Fam46a) gene is expressed in developing tooth buds. Archives of Oral Biology. ISSN 0003-9969. 54(11), s. 1002–1007. doi: 10.1016/j.archoralbio.2009.08.005.
• Etokebe, Godfrey; Knezević, Jelena; Petricević, Branka; Pavelić, Jasminka; Vrbanec, Damir & Dembic, Zlatko (2009). Single-nucleotide polymorphisms in genes encoding toll-like receptor -2, -3, -4, and -9 in case-control study with breast cancer. Genetic Testing and Molecular Biomarkers. ISSN 1945-0265. 13(6), s. 729–734. doi: 10.1089/gtmb.2009.0045.
• Etokebe, Godfrey; Axellson, Stefan; Svaerd, Niels Henrik; Storhaug, Kari & Dembic, Zlatko (2008). Detection of Hemizygous Chromosomal Copy Number Variants in Williams-Beuren Syndrome (WBS) by Duplex Quantitative PCR Array: An Unusual Type of WBS Genetic Defect. International Journal of Biomedical Science. ISSN 1550-9702. 4(3), s. 161–170. Fulltekst i vitenarkiv Vis sammendrag

  We have developed a dual probe quantitative PCR (qPCR ) mini array enabling a more accurate analysis of the relationship between copy number variants (CNVs) and other genomic features in specific areas. We used it to map hemizygous microdeletion on human chromosome 7 around the elastin gene (ELN), which is the molecular basis of the Williams-Beuren syndrome (WBS). In two WBS patients, the haploid content of the elastin gene was ascertained previously by the fluorescence in-situ hybridization (FISH). Our dual-color qPCR assay used this information to normalize for DNA content in all tests. We mapped the extent of the deleted area using 10 loci spanning over 4 Mb. A border region containing the GTF2I gene, usually deleted in most cases, was found about 10 times amplified in both patients, suggesting an unusual type of the WBS genetic defect. This 10-WBS-loci-specific qPCR assay could be an affirmative diagnostic tool alternative to FISH. Due to low cost, it could be used as a screening test that would not only facilitate research on CNVs, but also allow early diagnosis of the disease, as well-timed diagnosis would benefit WBS children with earlier proper health-care measures.

• Etokebe, Godfrey; Bulat-Kardum, L; Johansen, MS; Knezevic, J; Balen, S & Matakovic-Mileusnic, N [Vis alle 11 forfattere av denne artikkelen] (2006). Interferon-gamma gene (T874A and G2109A) polymorphisms are associated with microscopy-positive tuberculosis. Scandinavian Journal of Immunology. ISSN 0300-9475. 63, s. 136–141.
• Bulat-Kardum, L; Etokebe, Godfrey; Knezevic, J; Balen, S; Matakovic-Mileusnic, N & Zaputovic, L [Vis alle 9 forfattere av denne artikkelen] (2006). Interferon-gamma receptor-1 gene promoter polymorphisms (G-611A; T-56C) and susceptibility to tuberculosis. Scandinavian Journal of Immunology. ISSN 0300-9475. 63.
• Dembic, Zlatko (2005). The Function of Toll-like Receptors. I Rich, Tina (Red.), Toll and Toll-Like Receptors: An Immunologic Perspective. Landes Bioscience / Eurekah.com and Kluwer Academic / Plenum Publishers. s. 18–55.
• Corthay, Alexandre; Lundin, Katrin; Munthe, Ludvig Andre; Frøyland, Marianne; Gedde-Dahl, Thobias & Dembic, Zlatko [Vis alle 7 forfattere av denne artikkelen] (2004). Immunotherapy in multiple myeloma: Id-specific strategies suggested by studies in animal models. Cancer Immunology and Immunotherapy. ISSN 0340-7004. 53, s. 759–769.
• Dai, Kezheng; Johansen, Finn Eirik; Kolltveit, Kristin Melkevik; Aasheim, Hans-Christian; Dembic, Zlatko & Vartdal, Frode [Vis alle 7 forfattere av denne artikkelen] (2004). Transcriptional activation of the SH2D2A gene is dependent on a cyclic adenosine 5'-monophosphate-responsive element in the proximal SH2D2A promoter. Journal of Immunology. ISSN 0022-1767. 172, s. 6144–6151. Vis sammendrag

  The SH2D2A gene, encoding the T cell-specific adapter protein (TSAd), is rapidly induced in activated T cells. In this study we investigate the regulation of the SH2D2A gene in Jurkat T cells and in primary T cells. Reporter gene assays demonstrated that the proximal 1-kb SH2D2A promoter was constitutively active in Jurkat TAg T cells and, to a lesser extent, in K562 myeloid cells, Reh B cells, and 293T fibroblast cells. The minimal SH2D2A promoter was located between position -236 and -93 bp from the first coding ATG, and transcriptional activity in primary T cells depended on a cAMP response element (CRE) centered around position -117. Nuclear extracts from Jurkat TAg cells and activated primary T cells contained binding activity to this CRE, as observed in an EMSA. Consistent with this observation, we found that a cAMP analog was a very potent inducer of SH2D2A mRNA expression in primary T cells as measured by real-time RT-PCR. Furthermore, activation of SH2D2A expression by CD3 stimulation required cAMP-dependent protein kinase activity. Thus, transcriptional regulation of the SH2D2A gene in activated T cells is critically dependent on a CRE in the proximal promoter region.

• Dembic, Zlatko; Hofgaard, Peter Olaf; Omholt, Hilde & Bogen, Bjarne (2004). Anti-class II antibodies, but not cytotoxic T-lymphocyte antigen 4-immunoglobulin hybrid molecules, prevent rejection of major histocompatibility complex class II-negative myeloma in T-cell receptor-transgenic mice. Scandinavian Journal of Immunology. ISSN 0300-9475. 60, s. 143–152.
• Dellacasagrande, Jerome; Schreurs, Olav Joseph F; Hofgaard, Peter Olaf; Omholt, Hilde; Steinsvoll, Svein E B & Schenck, Karl [Vis alle 8 forfattere av denne artikkelen] (2003). Liver metastasis of cancer facilitated by chemokine receptor CCR6. Scandinavian Journal of Immunology. ISSN 0300-9475. 57(6), s. 534–544.
• Fraser, D. A.; Loos, Bruno G.; Boman, U; Winkelhoff, Arie J Van; Velden, U van der & Schenck, Karl [Vis alle 7 forfattere av denne artikkelen] (2003). Polymorphisms in an interferon-gamma receptor-1 gene marker and susceptibility to periodontitits. Acta Odontologica Scandinavica. ISSN 0001-6357. 61(5), s. 297–302.
• Dembic, Zlatko (2003). Critical elements in case-control studies in predisposition to tuberculosis. Scandinavian Journal of Immunology. ISSN 0300-9475. 58.
• Fraser, D. A.; Bulat-Kardum, L; Knezevic, J; Babarovic, Z; Matakovic-Mileusnic, N.* & Dellacasagrande, Jerome [Vis alle 10 forfattere av denne artikkelen] (2003). Interferon-gamma receptor-1 gene polymorphism in tuberculosis patients from Croatia. Scandinavian Journal of Immunology. ISSN 0300-9475. 57(5), s. 480–484.
• Fraser, DA; Loos, BG; Boman, U; van Winkelhoff, AJ; van der Velden, U & Schenck, Karl [Vis alle 7 forfattere av denne artikkelen] (2003). Polymorphisms in an interferon-gamma receptor-1 gene marker and susceptibility to periodontitis. Acta Odontologica Scandinavica. ISSN 0001-6357. 61, s. 297–302.
• Dembic, Zlatko; Rottingen, John-Arne; Dellacasagrande, Jerome; Schenck, Karl & Bogen, Bjarne (2001). Phagocytic dendritic cells from myelomas activate tumor-specific T cells at a single cell level. Blood. ISSN 0006-4971. 97(9), s. 2808–14. Vis sammendrag

  Antigen-presenting cells (APCs) from subcutaneous mouse MOPC315 plasmacytoma phagocytosed immunoglobulin G-coated magnetic beads, enabling efficient isolation within 2 hours by magnetic separation (APC-MB). Cell morphology was heterogeneous, with some of the cells having dendrites. The surface phenotype of purified tumor APCs-MB was CD11b(+), CD11c(+), CD40(+), CD80(+), CD86(+), and MHC class II(+). Tumor APCs-MB expressed messenger RNA for fractalkine and ABCD-1 chemokines, and for CC-type chemokine receptors CCR5 and CCR7, indicating the presence of mature dendritic cells (DCs). Visualized at a single cell level within 4 hours after disruption of the tumor, APCs-MB induced rapid Ca(++) mobilization in MHC class II-restricted tumor idiotype (Id)-specific cloned CD4(+) T cells. In long-term assays, tumor APCs-MB induced proliferation of naive T cells from Id-specific T-cell receptor transgenic mice. The results suggest that tumor APCs-MB represent a heterogeneous cell population that includes myeloid-derived DCs of various stages of maturation. A considerable fraction (> or = 15%) of DCs is spontaneously primed with tumor-specific antigen.

• Dembic, Zlatko; Schenck, Karl & Bogen, Bjarne (2000). Dendritic cells purified from myeoloma are spontaneously primed with tumor-specific antigen (idiotype) and activate CD4+ T cells. Proceedings of the National Academy of Sciences of the United States of America. ISSN 0027-8424. 97, s. 2697–2702.
• Bogen, Bjarne; Schenck, Karl; Munthe, Ludvig Andre & Dembic, Zlatko (2000). Deletion of Idiotype(Id)-specific T cells in multiple myeloma. Acta Oncologica. ISSN 0284-186X. 39, s. 783–788.
• Dembic, Zlatko; Munthe, Ludvig Andre; Schenck, Karl; Mueller, C. & Bogen, Bjarne (1998). Transient overexpression of CD4 enhances allelic exclusion of T-cell receptor (TCR) a chains and promotes positive selection of class II-restricted TCR-transgenetic thymocytes. Molecular Immunology. ISSN 0161-5890. s. 23–38.
• Bogen, Bjarne; Weiss, S. & Dembic, Zlatko (1997). Idiotypes and T cell selection. In Handbook of Immune Modulating Agents. I Kresina, T. (Red.), Marcel Decker. New York.
• Schreurs, Olav Joseph F; Halstensen, Trond Sundby; Dembic, Zlatko; Bogen, Bjarne & Schenck, Karl (1997). TUNEL combined with staining for epithelial cellmarker permits unambiguous localization of apoptic cells in murine thymus. Biochemica. ISSN 0946-1310. 4, s. 19–21.
• Merlin, G.; Leede, B. J. M. van der ; McKune, K.; Bannwarth, W.; Romquin, N. & Viegas-Pequignot, E. [Vis alle 8 forfattere av denne artikkelen] (1997). The gene for the ligand binding chain of the human interferon gamma receptor. Immunogenetics. ISSN 0093-7711. 45, s. 413–421.
• Munthe, Ludvig Andre; Blichfeldt, E.; Sollien, Anders; Dembic, Zlatko & Bogen, Bjarne (1996). T cells with two TCR_b chains and reactivity to both MHC/idiotypic peptide and superantigen. Cellular Immunology. ISSN 0008-8749. 170, s. 283–290. Vis sammendrag

  T lymphocytes, MHC, idiotypes, peptides, superantigens

• Magyar, JP; Martini, R; Ruelicke, T; Aguzzi, A; Adlkofer, K & Dembic, Zlatko [Vis alle 8 forfattere av denne artikkelen] (1996). Impaired differentiation of Schwann cells in transgenic mice with increased PMP22 gene dosage. Journal of Neuroscience. ISSN 0270-6474. 16, s. 5351–5360. Vis sammendrag

  Schwann cells, differentiation, transgenic mice, genes

• Ebensperger, C; Muthukumaran, G; Lembo, D; Donnely, RJ; Pestka, S & Dembic, Zlatko (1996). Genomic organization and promotor analysis of the gene ifngr2 encoding the second chain of the mouse interferon-g-receptor. Scandinavian Journal of Immunology. ISSN 0300-9475. 44, s. 599–606. Vis sammendrag

  genomic organization, promotor analysis, genes, interferon gamma receptor

• Rhee, S; Ebensperger, C; Dembic, Zlatko & Pestka, S (1996). The structure of the gene for the second chain of the human interferon gamma receptor. Journal of Biological Chemistry. ISSN 0021-9258. 271, s. 28947–28952. Vis sammendrag

  interferon, receptors, interferon gamma receptor, genes

• Muthukumaran, G; Donnely, RJ; Ebensperger, C; Mariano, TM; Garotta, G & Dembic, Zlatko [Vis alle 8 forfattere av denne artikkelen] (1996). The intracellular domain of the second chain of the interferon-gamma-receptor is interchangeable between species. Journal of Interferon and Cytokine Research. ISSN 1079-9907. 16, s. 1039–1045. Vis sammendrag

  genes, domains, interferon gamma receptor

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• Dembic, Zlatko (2015). The Cytokines of the Immune System. Academic Press. ISBN 978-0-12-419998-9. 310 s. Vis sammendrag

  Cytokines of the immune system include IFN alphas, beta, and gamma, Interleukins (IL) 1 to 38, Chemokines; TNF, TGF, TSLP, and others that are involved in the innate and adaptive immunity. Each cytokine has been described with relation to its structure, function, its receptors, their signal transduction and their relationship with diseases. The organization of the immune system has been described, as well as the theories about its function.

Se alle arbeider i Cristin

• Dembic, Zlatko (2012). The Immune System Maintains Integrity of an Organism. Fulltekst i vitenarkiv Vis sammendrag

  The workings of the immune system, in philosophical terms, follow integrity principle, which I regard as a sum of homeostatic (integrity preservation) and analytic (integration) functions of tissues within an organism. It states that damage of particular tissue is followed by restitution of integrity by interplay of positive and negative feedback loops. Such principle is seen as a driving force for evolution of the immune system from primordial integrity-repair mechanism. The most common disruption of integrity in vertebrates is caused by microorganisms, which can initiate the immune response. Natural selection favored the host/commensal rather than host/pathogen relationship, and consequently tolerance towards commensals co-evolved with the initiation of the immune response against pathogens (including host tolerance). However, the necessity of developing commensal tolerance by the immune system dissociated (evolutionarily) its analytic part (the afferent arm; started by disruption of tissue integrity) from its restorative part (the efferent arm) in ‘space’ and ‘time’. The renewal process includes bio-destruction of an intruder and restoration of integrity. The analysis - renewal separation in space and time further necessitated evolution of characteristics such as immune specificities, chemotaxis and multicellular crosstalk. Due to various selective pressures, the immune systems of vertebrates exhibit diverse communications between cells of the afferent and efferent arms of the immune response. Diversification of the immune repertoire, in turn, facilitated the establishment of long-term memory. These mechanisms work to protect commensals (potential symbionts), reject harmful pathogens and neglect the rest of microbiota. Therefore, the role of the immune system is to dynamically maintain the integrity of a being, in a common effort with other tissues and with a little help from our tiny friends (commensals).

• Jodal, Henriette Cecilie; Hofgaard, Peter Olaf; Dembic, Zlatko & Bogen, Bjarne (2011). A New Mouse Model for Multiple Myeloma. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), s. 388–388.
• Kårvatn, Marikken; Jotanovic, Zdravko; Etokebe, Godfrey; Mihelic, Radovan; Mulac-Jericevic, Biserka & Tijanic, Tamara [Vis alle 9 forfattere av denne artikkelen] (2011). Interleukin-1(IL-1)A, IL-1B and IL-1 Receptor Antagonist Gene Polymorphisms in Predisposition to Hip and Knee Osteoarthritis in Croatian Population. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), s. 370–371.
• Kaarvatn, MH; Jotanovic, Z; Etokebe, Godfrey; Mihelic, NN; Mulac-Jericevic, NN & Tijanic, T [Vis alle 9 forfattere av denne artikkelen] (2010). Polymorphisms in the Interleukin-1B And IL-1 Receptor Antagonist Genes in Predisposition to Hip and Knee Osteoarthritis in Croatian Population. Scandinavian Journal of Immunology. ISSN 0300-9475. 71(6), s. 482–482.
• Dembic, Zlatko (2008). Beginning of the end of (understanding) the immune response. Scandinavian Journal of Immunology. ISSN 0300-9475. 68(4), s. 381–382. doi: 10.1111/j.1365-3083.2008.02159.x. Vis sammendrag

  The algorithm about the workings of the immune system should incorporate in its basic form the ability to explain several basic features: the ability to reject pathogens, to respond differently to invasions by class switching, to retain memory of rejecting past infections, the regulatory T-cell formation and the acquisition of a life-long antigen tolerance in adults. The Danger and the two self–non-self theories – Pathogenicity (Janeway) and the Associated Antigen Recognition (Langman and Cohn) – cannot explain satisfactorily one or more of these issues. By failing to find appropriate solutions to help their corresponding basic algorithms to be operative, these theories negate, instead of finding explanations (no matter how complicated) for interpretations of certain results, one of them being the existence of a regulatory cell as a physiological component of the immune system. On the other hand, the integrity model can incorporate regulatory T cells in a basic algorithm of the workings of the immune system, explaining it as a downregulation of the immune response provided advantageous commensalism prevails over disadvantages of parasitism.

• Dembic, Zlatko (2004). Response to Cohn: The immune system rejects the harmful, protects the useful and neglects the rest of microorganisms. Scandinavian Journal of Immunology. ISSN 0300-9475. 60, s. 3–5.
• Dembic, Zlatko; Fraser, David; Loos, Bruno G.; Velden, Ubele van der & Schenck, Karl (2004). Genetic Polymorphism in Periodontal Disease.
• Dembic, Zlatko (2004). Immunosurveillance of malign tumors.
• Dai, Ke-Zheng; Johansen, Finn-Eirik; Kolltveit, Kristin Melkevik; Aasheim, Hans-Christian; Dembic, Zlatko & Vartdal, Frode [Vis alle 7 forfattere av denne artikkelen] (2003). Transcriptional activation of the SH2D2A gene is dependent on a cyclic adenosine 5� monophosphate responsive element in the proximal SH2D2A promoter.
• Loos, Bruno G.; Schreiber, S.; Scholtz, C.; Jebsen, S.; Groessner-Schreiber, B. & Dembic, Zlatko [Vis alle 7 forfattere av denne artikkelen] (2003). CARD4 and CARD15 gene polymorphysms in relation to aggressive periodontitis.
• Dembic, Zlatko; Røttingen, John-Arne; Dellacasagrande, Jerome & Schenck, Karl (2001). Isolated phagocytic dendritic cells from myeloma activate tumor-specific T cells at a single cell level.
• Dembic, Zlatko; Røttingen, John-Arne; Dellacasagrande, Jerome; Schenck, Karl & Bogen, Bjarne (2001). Phagocytic dendritic cells from myelomas activate tumor-specific T cells at a single cell level.
• Bogen, Bjarne; Dembic, Zlatko; Røttingen, John-Arne & Schenck, Karl (1999). Professional APC in plasmacytomas are primed with myeloma protein idiotype (Id) and are able to introduce activation of class II restricted Id-specific CD4+ cells.
• Dembic, Zlatko (1996). Do we need integrity? Scandinavian Journal of Immunology. ISSN 0300-9475. 44, s. 549–550. Vis sammendrag

  Tolerance, immunology, T lymphocytes

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