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Characterization Of Nk Cell Subsets Responding To Hiv Infected Cells
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Book Synopsis Characterization of NK Cell Subsets Responding to HIV Infected Cells by : Irene Lisovsky
Download or read book Characterization of NK Cell Subsets Responding to HIV Infected Cells written by Irene Lisovsky and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Globally, over 36 million people are infected with human immunodeficiency virus type 1 (HIV-1). Some individuals exposed to HIV remain persistently seronegative. Among those who become infected a subset of approximately 5% progress to acquired immunodeficiency syndrome (AIDS) slowly, and even fewer, i.e.
Book Synopsis Defining Natural Killer Cell Responses to HIV by : Qi Zhao
Download or read book Defining Natural Killer Cell Responses to HIV written by Qi Zhao and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Human immunodeficiency virus (HIV) remains a major global public health issue, and in the continued absence of a cure or vaccine, novel treatment and prevention strategies are needed to combat the ongoing epidemic. Many lines of evidence have suggested that natural killer (NK) cells, effector cells of the innate immune system that rapidly respond to virus-infected and malignantly transformed cells, can contribute to protection against HIV acquisition and disease progression. Here provide a characterization of methods of NK cell targeting of HIV, encompassing both natural receptor-ligand interactions in the setting of in vitro infection as well as in HIV-infected individuals, as well as via the use of bispecific antibodies to specifically target NK cells to HIV-infected cells. We first optimize an in vitro co-culture system to detect HIV-specific NK cell responses to autologous infected cells. We then use a combination of single cell transcriptomics and mass cytometry to characterize the features of NK cells in these co-cultures. Using single cell RNA-seq, we find a dominant interferon-driven gene signature in NK cells responding to HIV-infected cells. In addition, by mass cytometry profiling of NK cell phenotype and function, paired with profiling of ligand expression on infected CD4 T cells, we identify candidate receptor-ligand interactions (NKG2D/MIC-A/B and ULBP-1/2/5/6, and NKp30-B7-H6) involved in recognition mechanisms, which we then validate using CRISPR knockout of the corresponding ligands on target cells. We thus identify mechanisms of NK cell activation and response against HIV. We then study whether HIV-infected individuals treated with antiretroviral therapy (ART) possess alterations in NK cells that may make them more responsive to a second, in vitro exposure to HIV. We once again use mass cytometry to profile NK cell phenotype and function in both treated, HIV-infected individuals and healthy controls and find that, while there is a shift in the pattern of expression of NK cell receptors including NKp30 and CD2, the overall phenotype and frequency of the subset of cells that respond to in vitro HIV stimulation is not changed. We thus find that while the NK cell repertoire is altered in treated, HIV-infected individuals, it does not become more HIV-specific. Lastly, we develop and test a bispecific antibody that targets HIV gp41 and the NK cell activating receptor CD16. We show that this bispecific antibody has increased affinity and avidity to CD16, and is thus able to robustly enhance NK cell targeting of infected cells. This provides a means for controlled targeting of NK cells to infected cells. Overall, we identify multiple mechanisms that may hold promise to improve NK cell activity against HIV-infected cells. We discuss the extension of these findings in improving NK cell-mediated immunotherapy in HIV infection.
Book Synopsis Deep Profiling of Natural Killer Cells in Health and Disease by : Geoffrey T Ivison
Download or read book Deep Profiling of Natural Killer Cells in Health and Disease written by Geoffrey T Ivison and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Natural killer (NK) cells are innate immune cells with a crucial role in the early anti- viral and anti-cancer immune responses. In this thesis, I present two distinct projects in which the phenotype and function of NK cells are deeply profiled--the first in healthy individuals, and the second in individuals chronically infected with HIV-1. Understanding the intracellular signaling pathways that govern NK cell responses to target cells is crucial for designing optimal NK cell based therapeutics. NK cells are a highly diverse cell type, with many identified functional subsets. Studying this diversity requires the use of high-parameter, single cell approaches. Many previous studies of NK cell signaling with defined receptor stimulation rely on antibody crosslinking of the targeted receptors. This approach is limited in its ability to re-create the stimuli encountered by NK cells in vivo. The latent HIV-1 reservoir represents a major barrier to achieving a long-term antiretroviral therapy (ART)-free remission or cure for HIV-1. NK cells have been shown to be involved in preventing HIV-1 infection and, in those who are infected, delaying time to progression to AIDS. However, their role in limiting HIV-1 persistence on long term ART is still uncharacterized. In Chapter 1, I provide relevant background information and summarize relevant literature for these two projects. In Chapter 2, I provide a proof of concept and application of a system we developed to simultaneously profile the phenotype and signaling response of NK cells to defined target cells. I show that I can measure the breadth of the NK cell signaling response in bulk NK cells. I also identify a memory-like phenotype of NK cells that has lower signaling responses across the board. In Chapter 3, I present a study in which we deeply profiled the NK cell receptor and ligand repertoire in patients chronically infected with HIV-1. We found that the NK cell receptor and ligand repertoires did not change across three longitudinal samples over one year--a median of 25 weeks and 50 weeks after the initial sampling. To determine the features of the receptor-ligand repertoire that associate with markers of HIV-1 persistence, we performed a LASSO normalized regression. This analysis revealed that the NK cell ligands CD58, HLA-B, and CRACC, as well as the killer cell immunoglobulin-like receptors (KIRs) KIR2DL1, KIR2DL3, and KIR2DS4 were robustly predictive of markers of HIV-1 persistence, as measured by total HIV-1 cell-associated DNA, HIV-1 cell-associated RNA, and single copy HIV-RNA assays. To characterize the roles of cell populations defined by multiple markers, we augmented the LASSO analysis with FlowSOM clustering. This analysis found that an immature NK cell phenotype (CD16+CD56dimCD57-LILRB1-NKG2C-) was associated with lower HIV-1 cell associated DNA. Finally, we found that surface expression of HLA-Bw6 measured by CyTOF was associated with lower HIV-1 persistence. Genetic analysis revealed that this was driven by lower HIV-1 persistence in HLA-Bw4/6 heterozygotes. In Chapter 4, I discuss the impact of these studies on their respective fields, and how these results may most effectively be followed up in future studies. Deep profiling of NK cell biology has yielded unprecedented understanding of how NK cells are involved in maintaining health and responding to disease. In this thesis, I lay out two studies that demonstrate the value of this approach to understanding basic NK cell biology and to mapping out the relationship of NK cells to the persistence of HIV on therapy. These studies advance our understanding of the role NK cells play in responding to dangerous cells and putting a check on infectious disease.
Book Synopsis Macrophages and Natural Killer Cells by : Sigurd J. Normann
Download or read book Macrophages and Natural Killer Cells written by Sigurd J. Normann and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 814 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is the outcome of a meeting held in Davos, Switzerland, February 7-12, 1982 focused primarily on mononuclear phagocytes and on natural killer (NK) cells. This IX International RES Congress was attended by 489 scientists from 31 countries and there were 340 scientific presentations in oral or poster session. The essential purpose of the Congress was to bring together scientists representing various aspects of mononuclear phagocyte biology to review and examine cri~ically the effects and mechanisms of macrophage growth control as well as the participatio~ of these cells in the afferent and efferent limbs of the immune response. Additional topics included the production and distribution of mono nuclear phagocytes; the intrinsic and extrinsic regulation of these cells; and the origin, nature, function and regulation of NK cells. The ultimate goal of the Congress was to enhance communication between scientists in various countries and disciplines so that new research directives could be defined with which to explore basic aspects of macrophage and NK cell participation in the control of cancer and infection.
Book Synopsis Handbook on Immunosenescence by : Tamas Fulop
Download or read book Handbook on Immunosenescence written by Tamas Fulop and published by Springer Science & Business Media. This book was released on 2009-02-27 with total page 1693 pages. Available in PDF, EPUB and Kindle. Book excerpt: This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.
Book Synopsis Molecular Biology of The Cell by : Bruce Alberts
Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Natural Killer Cell Protocols by : Kerry S. Campbell
Download or read book Natural Killer Cell Protocols written by Kerry S. Campbell and published by Springer Science & Business Media. This book was released on 2008-02-03 with total page 394 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Natural Killer Cell Protocols: Cellular and Molecular Methods, Kerry S. Campbell and Marco Colonna have assembled a comprehensive collection of readily reproducible methods designed to study natural killer (NK) cells from the broadest variety of viewpoints. These include not only classic techniques, but also new approaches to standard methods, newly evolved techniques that have become valuable for specific applications, and unique models for manipulating and studying NK cells. Among the advanced methods covered are those for in vitro transendothelial migration, in vivo detection of cells migrating into tumors, immunofluorescence staining of intracellular cytokines, and in vitro NK cell development. Valuable techniques for specific applications include vaccinia virus protein expression, soluble KIR-Fc fusions for HLA class I binding assays, calcium mobilization in cell conjugates, and identification of heterodimeric receptor complexes using cDNA library expression cloning. No less important are accounts of such classic methods as hybrid resistance, ADCC, viral defense, target cell cytotoxicity assays, cloning and culturing, tumor immunotherapy, and generation of HLA class I transfected target cells. Natural Killer Cell Protocols: Cellular and Molecular Methods offers immunologists, cancer researchers, virologists, and cell biologists today's most comprehensive collection of both established and cutting-edge techniques, methods that will contribute significantly to advancing our understanding of this fascinating and critically important class of cells.
Book Synopsis NK Cell Subsets in Health and Disease: New Developments by :
Download or read book NK Cell Subsets in Health and Disease: New Developments written by and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Natural Killer (NK) cells were discovered ca 1975, as the first group of lymphoid cells that were neither T cells nor B cells. Since then, the dissection of the biology of NK cells has been growing exponentially with many seminal discoveries from the identification of MHC class I-specific inhibitory receptors to the discovery of receptor-ligand pairs involved in NK cell activation and to the manipulation of NK cells in cancer. In this research topic, we asked a group of thought leaders in NK cell biology to review recent advances in their origins and biology, and their roles in cancer, infection and inflammation. Together, these 25 articles provide a timely survey of NK cells as critical immunologic components of health and disease. They will hopefully prompt further dialogue and developments in basic and translational immunology.
Book Synopsis Innate Immunity in Health and Disease by : Shailendra K. Saxena
Download or read book Innate Immunity in Health and Disease written by Shailendra K. Saxena and published by BoD – Books on Demand. This book was released on 2021-08-25 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book focuses on various aspects and properties of innate immunity, whose deep understanding is integral for safeguarding the human race from further loss of resources and economies due to innate immune response-mediated diseases. Throughout this book, we examine the individual mechanisms by which the innate immune response acts to protect the host from pathogenic infectious agents and other non-communicable diseases. Written by experts in the field, the volume discusses the significance of macrophages in infectious disease, tumor metabolism, and muscular disorders. Chapters cover such topics as the fate of differentiated macrophages and the molecular pathways that are important for the pathologic role of macrophages.
Book Synopsis Chronic Viral Hepatitis by : Kirti Shetty
Download or read book Chronic Viral Hepatitis written by Kirti Shetty and published by Springer Science & Business Media. This book was released on 2009-06-13 with total page 501 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chronic viral hepatitis affect hundreds of millions of people worldwide, and each year millions more people become infected. In Chronic Viral Hepatitis, Second Edition, a panel of distinguished clinicians and clinical investigators build upon the first edition by comprehensively reviewing all the relevant new information regarding resistance, side effects, and therapies for chronic viral hepatitis. The text covers recent advances in the understanding of pathogenesis of viral hepatitis while discussing promising agents in development for its treatment. The authors devote special attention to reactivation of hepatitis B with chemotherapy and immunosuppression, herbal and non-traditional therapies, chronic viral hepatitis in the pediatric population, and immunology and immunotherapy of HCV and provide relative costs for all diagnostic and therapeutic options. Authoritative and up-to-date, Chronic Viral Hepatitis, Second Edition offers today's gastroenterologists, internists, hepatologists, and infectious disease specialists a practical guide to the recognition, diagnosis and treatment of chronic viral hepatitis from a multidisciplinary approach.
Download or read book HIV-1 Latency written by Guido Silvestri and published by Springer. This book was released on 2018-10-11 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume summarizes recent advances in understanding the mechanisms of HIV-1 latency, in characterizing residual viral reservoirs, and in developing targeted interventions to reduce HIV-1 persistence during antiretroviral therapy. Specific chapters address the molecular mechanisms that govern and regulate HIV-1 transcription and latency; assays and technical approaches to quantify viral reservoirs in humans and animal models; the complex interchange between viral reservoirs and the host immune system; computational strategies to model viral reservoir dynamics; and the development of therapeutic approaches that target viral reservoir cells. With contributions from an interdisciplinary group of investigators that cover a broad spectrum of subjects, from molecular virology to proof-of-principle clinical trials, this book is a valuable resource for basic scientists, translational investigators, infectious-disease physicians, individuals living with HIV/AIDS and the general public.
Book Synopsis Immunopathogenesis of HIV Infection by : Anthony S. Fauci
Download or read book Immunopathogenesis of HIV Infection written by Anthony S. Fauci and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt: During the last 5 years, major advances have been made in our understanding of the pathogenesis of human immunodeficiency virus (HIV) disease and in the development of new potent antiviral agents. With regard to HIV pathogenesis, several recent observations have not only changed our perspectives of HIV disease, but have been critical for the design of therapeutic strategies.
Book Synopsis Liver Immunology by : M. Eric Gershwin
Download or read book Liver Immunology written by M. Eric Gershwin and published by Springer Science & Business Media. This book was released on 2013-11-19 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: Liver Immunology: Principles and Practice, Second Edition begins with important information about the epidemiology and mortality of liver disease worldwide. This information is followed by chapters related to basic immunology, application of liver immunology for diagnosis, and several excellent chapters that provide a solid foundation for understanding immune-mediated liver disease, including those associated with the biliary tree. A chapter on non-hepatic manifestations of immune mediated liver disease helps provide context for how these diseases affect the patient overall. In addition, chapters discuss various discrete immunologically-mediated infectious liver disorders including those related to bacteria, parasites, and all of the classic viruses. Chapters on the traditional autoimmune liver diseases -- primary biliary cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis as well as overlap syndrome – are also included. The breadth of this comprehensive second edition is highlighted by chapters on alcoholic liver disease, non-alcoholic fatty liver disease, and drug-induced liver disease, among others. This invaluable new edition ends with a forward-looking view of future directions and how the field might meet the challenge of refractory patients. Developed by a renowned group of authors, Liver Immunology: Principles and Practice, Second Edition will again serve as a comprehensive textbook by providing an excellent overview for this rapidly evolving field. It greatly adds to the understanding of the pathogenesis of these diseases, while also providing novel insights that can be harnessed into helping improve the care of patients afflicted with various immune-mediated diseases. This volume will again be a must-read for clinicians at all levels, investigators and students.
Book Synopsis Current Perspectives in HIV Infection by : Shailendra K. Saxena
Download or read book Current Perspectives in HIV Infection written by Shailendra K. Saxena and published by BoD – Books on Demand. This book was released on 2013-04-10 with total page 484 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book gives a comprehensive overview of HIV and AIDS including NeuroAIDS, as well as general concepts of pathology, immunity and immunopathology, diagnosis, treatment, epidemiology and etiology to current clinical recommendations in management of HIV/AIDS including NeuroAIDS, highlighting the ongoing issues, recent advances and future directions in diagnostic approaches and therapeutic strategies.
Book Synopsis Lymphocyte Updates by : Gheorghita Isvoranu
Download or read book Lymphocyte Updates written by Gheorghita Isvoranu and published by BoD – Books on Demand. This book was released on 2017-07-12 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book represents a synergic effort of an international team of specialists in immunology to expand the scientific achievements in the field of lymphocytes. It offers important and specific updated information to researchers, students, teachers, and medical professionals. Moreover, considering the remarkable dynamics of immunology and immunotherapy, this book "Lymphocyte Updates - Cancer, Autoimmunity, and Infection" aims to represent a significant source of concise scientific data and advancement of knowledge in this field. The chapters offer new insights into the latest scientific progress on lymphocyte roles in protective immunity, as well as their involvement in pathogenesis of various disorders.
Book Synopsis Persistent Viral Infections by : R. Ahmed
Download or read book Persistent Viral Infections written by R. Ahmed and published by Wiley-Blackwell. This book was released on 1999 with total page 754 pages. Available in PDF, EPUB and Kindle. Book excerpt: Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.
Book Synopsis Flow Cytometry and Cell Sorting by : Andreas Radbruch
Download or read book Flow Cytometry and Cell Sorting written by Andreas Radbruch and published by Springer Science & Business Media. This book was released on 2013-03-14 with total page 365 pages. Available in PDF, EPUB and Kindle. Book excerpt: The analysis and sorting of large numbers of cells with a fluorescence-activated cell sorter (FACS) was first achieved some 30 years ago. Since then, this technology has been rapidly developed and is used today in many laboratories. A Springer Lab Manual Review of the First Edition: "This is a most useful volume which will be a welcome addition for personal use and also for laboratories in a wide range of disciplines. Highly recommended." CYTOBIOS
