Expression of MHC II genes

Innate and adaptive immunity are connected via antigen processing and presentation (APP), which results in the presentation of antigenic peptides to T cells in the complex with the major histocompatibility (MHC) determinants. MHC class II (MHC II) determinants present antigens to CD4+ T cells, which are the main regulators of the immune response. Their genes are transcribed from compact promoters that form first the MHC II enhanceosome, which contains DNA-bound activators and then the MHC II transcriptosome with the addition of the class II transactivator (CIITA). CIITA is the master regulator of MHC II transcription. It is expressed constitutively in dendritic cells (DC) and mature B cells and is inducible in most other cell types. Three isoforms of CIITA exist, depending on cell type and inducing signals. CIITA is regulated at the levels of transcription and post-translational modifications, which are still not very clear. Inappropriate immune responses are found in several diseases, including cancer and autoimmunity. Since CIITA regulates the expression of MHC II genes, it is involved directly in the regulation of the immune response. The knowledge of CIITA will facilitate the manipulation of the immune response and might contribute to the treatment of these diseases

Implenting a game for learning programing concepts made in Unreal engine 4

Ovaj rad objašnjava razlog kreiranja CodeBreaker igre, te na koji način ona pomaže u učenju osnovnih koncepata programiranja. Uspoređuju se prednosti i mane između klasičnog pisanja koda i vizualnog programiranja, te se prikazuju razlozi odabira klasičnog pisanja koda za igru. Ostatak rada se fokusira na implementaciju same igre, pogotovo na implementaciju koda. U to spadaju Lexer, Parser, semantička analiza te samo pokretanje koda. Nakon toga se pokazuje na kako kod utječe igrin svijet, te kako rade ostali sustavi unutar igre.This paper explains the reason behind the creation of the CodeBreaker game, and how it can help in learning basic programming concepts. It also compares advantages and disadvantages between classic written code and visual scripting, and explains why the classic written code was chosen for the game. The rest of the paper focuses on the implementation of the game, especially on the code implementation. This contains Lexer, Parser, Semantic analysis and the actual code running. After that it explains how the code can affect the game world, as well as explaining the rest of the game systems

Creating a computer game in Unreal Engine 4

U ovom dijelu se prikazuje rad aplikacije QP_Tabletop, ukratko se opisuje Game Engine korišten za njenu kreaciju, odabran po određenim parametrima, te se postepeno opisuje proces kreiranja društvene igre u njoj. Također se detaljno prikazuju osnovne klase, njihove inicijalizacije te međusobne interakcije između tih klasa. Zatim se prikazuje rad unaprijed kreiranih Blueprint klasa, koje se koriste kao komponente druge klase koja predstavlja pravila željene igre. Tada se dio funkcionalnosti premješta u posebnu klasu, kako bi ju korisnik mogao koristiti u budućim društvenim igrama, neovisno o trenutnoj demo igri.This paper shows how QP_Tabletop application works, shortly describes the Game Engine used in its creation, why it was chosen, and presents a step-by-step process of creating a tabletop game. It also describes all the base classes in detail, their initialization, and interactions with each other. Then the pre-made Blueprint classes are described. These pre-made classes act as components for another class that represents the rules of the game. After that, part of the functionality is moved to another special class, which allows the user to use it again in the future

Comparative Analysis of Gingival Tissue Antigen Presentation Pathways in Ageing and Periodontitis

AIM: Gingival tissues of periodontitis lesions contribute to local elevations in mediators, including both specific T cell and antibody immune responses to oral bacterial antigens. Thus, antigen processing and presentation activities must exist in these tissues to link antigen-presenting cells with adaptive immunity. We hypothesized that alterations in the transcriptome of antigen processing and presentation genes occur in ageing gingival tissues and that periodontitis enhances these differences reflecting tissues less capable of immune resistance to oral pathogens. MATERIALS AND METHODS: Rhesus monkeys (n = 34) from 3 to 23 years of age were examined. A buccal gingival sample from healthy or periodontitis sites was obtained, total RNA isolated, and microarray analysis was used to describe the transcriptome. RESULTS: The results demonstrated increased transcription of genes related to the MHC class II and negative regulation of NK cells with ageing in healthy gingival tissues. In contrast, both adult and ageing periodontitis tissues showed decreased transcription of genes for MHC class II antigens, coincident with up-regulation of MHC class I-associated genes. CONCLUSION: These transcriptional changes suggest a response of healthy ageing tissues through the class II pathway (i.e. endocytosed antigens) and altered responses in periodontitis that could reflect host-associated self-antigens or targeting cytosolic intracellular microbial pathogens

Dysregulated Recruitment of the Histone Methyltransferase EZH2 to the Class II Transactivator (CIITA) Promoter IV in Breast Cancer Cells

One mechanism frequently utilized by tumor cells to escape immune system recognition and elimination is suppression of cell surface expression of Major Histocompatibility Class II (MHC II) molecules. Expression of MHC II is regulated primarily at the level of transcription by the Class II Transactivator, CIITA, and decreased CIITA expression is observed in multiple tumor types. We investigate here contributions of epigenetic modifications to transcriptional silencing of CIITA in variants of the human breast cancer cell line MDA MB 435. Significant increases in histone H3 lysine 27 trimethylation upon IFN-γ stimulation correlate with reductions in transcription factor recruitment to the interferon-γ inducible CIITA promoter, CIITApIV, and with significantly increased CIITApIV occupancy by the histone methyltransferase enhancer of zeste homolog 2 (EZH2). Most compelling is evidence that decreased expression of EZH2 in MDA MB 435 variants results in significant increases in CIITA and HLA-DRA mRNA expression, even in the absence of interferon-γ stimulation, as well as increased cell surface expression of MHC II. Together, these data add mechanistic insight to prior observations of increased EZH2 expression and decreased CIITA expression in multiple tumor types

Operons

Operons (clusters of co-regulated genes with related functions) are common features of bacterial genomes. More recently, functional gene clustering has been reported in eukaryotes, from yeasts to filamentous fungi, plants, and animals. Gene clusters can consist of paralogous genes that have most likely arisen by gene duplication. However, there are now many examples of eukaryotic gene clusters that contain functionally related but non-homologous genes and that represent functional gene organizations with operon-like features (physical clustering and co-regulation). These include gene clusters for use of different carbon and nitrogen sources in yeasts, for production of antibiotics, toxins, and virulence determinants in filamentous fungi, for production of defense compounds in plants, and for innate and adaptive immunity in animals (the major histocompatibility locus). The aim of this article is to review features of functional gene clusters in prokaryotes and eukaryotes and the significance of clustering for effective function