Immune-related Lectin-like Receptors in Zebrafish Innate Immunity

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Title: Immune-related Lectin-like Receptors in Zebrafish Innate Immunity
Author: Yang, Jibing
Advisors: Mac Law, Committee Member
Nanette Nascone-Yoder, Committee Member
Susan Tonkonogy, Committee Co-Chair
Jeffrey Yoder, Committee Chair
Abstract: The superfamily of lectin receptors is composed of proteins that recognize diverse ligands including carbohydrates present on bacteria and fungi or stress-related and viral proteins. Natural killer (NK) cells are a subset of lymphocytes that can recognize and directly kill virally infected or transformed cells. This recognition is mediated through their cell surface receptors including the Group V C-type lectin-like domain (CTLD) receptors (also known as NK cell receptors or NKRs). NKRs in different mammalian species have been widely studied in the past two decades. However, in lower vertebrates, the knowledge of NKRs is limited to genomic sequence or computational structure analysis in few bony fish species. It would be valuable to identify orthologs of NKRs in non-mammalian vertebrates and explore the evolutionary function of these receptors. In this regard, our lab has characterized a family of immune-related, lectin-like receptors (ILLRs) in zebrafish that are structurally similar to Group II CTLD receptor yet contain intracellular signaling domains similar to Group V NKRs. In order to better understand the role of ILLRs in zebrafish innate immunity, it is necessary to develop a way to enable identification, purification, characterization and function of ILLR expressing cells. Chapter I is an introduction to discuss C-type lectin receptors and zebrafish innate immunity providing an ideal background for these studies. Chapter II investigates the expression patterns of ILLRs at the cellular level. RNA in situ hybridization from wild type zebrafish and flow cytometric analysis of cells from transgenic fish did not successfully detect ILLR expressing cells due to low levels of expression. Therefore, the goal of Chapter III was to develop a method to boost ILLR expression in vivo and facilitate the identification and purification of ILLR expressing cells. Chapter IV applied the immune-challenged model developed in Chapter III to transgenic fish to identify ILLR expressing cells. Chapter V explores additional ILLR genes in zebrafish Chromosome 19. Current results indicate that illrL gene expression increases dramatically upon pathogen infection, suggesting that C-type lectin receptors in zebrafish may conserve the host-pathogen interaction function as shown in mammals and may play a critical role in zebrafish innate immunity.
Date: 2009-12-03
Degree: PhD
Discipline: Immunology

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