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Natural Killer Cells

To celebrate the 40th anniversary of the discovery of Natural Killer (NK) cells, this volume focuses on the recent advances in our understanding of NK cell development and differentiation and their acquisition of functional properties, as ...

Author : Eric Vivier

Release : 2016-02-15

Publisher : Springer

ISBN : 3319239163

File Size : 60.37 MB

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To celebrate the 40th anniversary of the discovery of Natural Killer (NK) cells, this volume focuses on the recent advances in our understanding of NK cell development and differentiation and their acquisition of functional properties, as well as the latest models for NK-cell analysis in mice and applications in clinical medicine. NK cells have travelled a circuitous path from their initial description as ‘spontaneous killers’ (for some simply an experimental artifact) to being a bona fide subset of innate lymphoid cells with a complementary mode of action in immune defense and an important mediator of immune reactivity in health and disease. Together, these reviews provide a timely and concise picture of the evolution of NK cells as essential agents in immunity and as potent weapons against disease. This book offers an appealing and insightful resource for scientists and clinicians.

Natural Killer Cells

The book concludes by explaining that natural killer cells are utilized for clinical therapy of malignancies, and that they have led to positive outcomes in the field of biology and medicine.

Author : Michael T. Lotze

Release : 2009-11-12

Publisher : Academic Press

ISBN : 9780080919294

File Size : 43.81 MB

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Natural Killer Cells explains the importance of killer cells and how they are produced. It mentions that the most likely explanation for killer cell production is that they serve as a complementary system for T cells as a primary defense against viruses. However, these cells defend against certain viruses only, such as herpes viruses and influenza viruses. The book also explains the primary functions of killer cells, and it discusses how these cells help recognize damaged tissues, limit further damage to tissues, and regenerate damaged tissues. It discusses how these cells mature and develop, and it covers the different isolation, culture, and propagation methods of these cells. Furthermore, it focuses on the different killer cells that are present in various parts of the human body. The book concludes by explaining that natural killer cells are utilized for clinical therapy of malignancies, and that they have led to positive outcomes in the field of biology and medicine. Provides a broad, detailed coverage of the biology and interactions of NK cells for students, fellows, scientists, and practitioners Includes figures, histologic sections, and illustrations of the ontogeny of NK cells

Macrophages and Natural Killer Cells

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.

Author : Sigurd J. Normann

Release : 2012-12-06

Publisher : Springer Science & Business Media

ISBN : 1468443941

File Size : 80.72 MB

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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.

Natural Killer Cells

Author : Bernard Serrou

Release : 1982

Publisher :

ISBN :

File Size : 63.72 MB

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Natural Killer Cells: the Future of Cancer Immunotherapy

This book focuses on recent advances in NK cell engineering and discusses how NK cells contribute to new immunotherapeutic approaches for treatment against refractory hematological malignancies.

Author : Priyanka Senthil

Release : 2020-04-20

Publisher :

ISBN :

File Size : 26.54 MB

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Cellular therapeutics is an emerging field with significant advances in the engineering of immune effector cells that play a revolutionary role in treatment for cancer. Up until now, most immunomodulatory strategies focus on enhancing T cells, which are lymphocyte immune cells that are important for cell-mediated immunity to fight pathogens and cancer. T cells have proven their ability in successful cellular therapies against leukemia, but may soon face competition. Through several preclinical studies, researchers have discovered new guardian immune cells called chimeric antigen receptor-modified natural killer (CAR NK) cells that have been genetically engineered to produce an artificial T-cell receptor for use in immunotherapy. With chimeric antigen receptors (CARs), CAR NK cells can specifically recognize antigen-expressing tumors and show cytotoxic activity against various solid tumor types. Natural killer (NK) cells target cells that lack expression of major histocompatibility complex (MHC) class I like tumors and virus-infected cells. The preclinical evidence suggests that NK cells have the same cancer-homing receptors as T cells and the ability to effectively recognize and kill targets through genetic modification. However, for the cell to be effective, scientists need to provide antigen specificity, for which they have found strategies to introduce CARs into NK cells and cell lines. If scientists can overcome the challenge of properly manufacturing engineered NK cells, CAR NK cells could be safer, cheaper, easier to produce, and more widely applicable than T cells. This book focuses on recent advances in NK cell engineering and discusses how NK cells contribute to new immunotherapeutic approaches for treatment against refractory hematological malignancies.

Natural Killer Cell Protocols

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 ...

Author : Kerry S. Campbell

Release : 2000

Publisher : Springer Science & Business Media

ISBN : 1592590446

File Size : 88.50 MB

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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.

Natural Killer T-cells

Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer (NK) cells.

Author : Nathan V. Fournier

Release : 2008

Publisher : Nova Publishers

ISBN : 9781604562873

File Size : 85.5 MB

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Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer (NK) cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self- and foreign lipids and glycolipids. Upon activation, NK T cells are able to produce large quantities of interferon-gamma, IL-4, and granulocyte-macrophage colony-stimulating factor, as well as multiple other cytokines and chemokines (such as IL-2 and TNF-alpha). NKT cells seem to be essential for several aspects of immunity because their dysfunction or deficiency has been shown to lead to the development of autoimmune diseases (such as diabetes or atherosclerosis) and cancers. NKT cells have recently been implicated in the disease progression of human asthma. The clinical potential of NKT cells lies in the rapid release of cytokines (such as IL-2, IFN-gamma, TNF-alpha, and IL-4) that promote or suppress different immune responses.

Natural Killer Cells

Author : Reinhold E. Schmidt

Release : 1990

Publisher : S Karger Ag

ISBN :

File Size : 62.61 MB

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The Role of Natural Killer Cells in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by itchy, red, scaly rashes.

Author : Madison R. Mack

Release : 2019

Publisher :

ISBN :

File Size : 67.56 MB

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Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by itchy, red, scaly rashes. In the United States alone, AD affects 6-10% of the population and costs $5.3 billion dollars annually in medical treatment. The main pathogenic factors in AD appear to be impaired skin barrier function and inflammation. Specifically, AD-associated inflammation is driven by a type 2 inflammatory module involving T helper type 2 cells, group 2 innate lymphoid cells, and the type 2 cytokines. Therapeutic approaches currently focus directly on barrier restoration and immunosuppression. However, whether some aspect of the immune system might be impaired or required to regulate the aberrant inflammatory response observed in AD is less clear. AD patients do have an enhanced susceptibility to exacerbations of viral skin infections such eczema herpeticum and molluscum contagiosum, though the mechanisms underlying this susceptibility have yet to be fully defined.We demonstrate that AD patients harbor a deficiency in blood natural killer (NK) cells, key cellular mediators of antiviral immunity. Low numbers of blood NK cells have both diagnostic value for AD and improved along with clinical parameters and biomarkers in response to therapy. Over the past decade, NK cells have emerged as a complex and heterogeneous population characterized by a diverse repertoire of receptors and functional capacities. We therefore undertook multidimensional mass cytometry analysis and RNA profiling of blood NK cells, which revealed aberrant activation and susceptibility to cell death that was associated with a loss of mature NK cells from AD patients. Taken together, these findings indicate that NK cell reduction is a central feature of AD that may serve as a diagnostic and treatment-responsive biomarker.In addition to antiviral immunity, we hypothesized that NK cells may provide important inhibitory signals that are lost in the setting of AD-associated inflammation. Previous studies have indicated that NK cells and NK cell-derived cytokines can limit type 2 inflammation in other systems. In agreement with this, we found that NK cell deficiency in a murine model of AD was associated with enhanced type 2 inflammation in the skin, suggesting that NK cells play a critical immunoregulatory role. Based on these findings, we tested an NK cell-boosting cytokine superagonist as an immunotherapy treatment and found marked improvement in AD-like disease in mice. These findings implicate a systemic NK cell reduction in AD pathology and reveal a new treatment paradigm in which NK cells can be enhanced in order to restrain pathogenic type 2 inflammation and improve disease.

Breaking Tolerance to Unresponsiveness to Immunotherapy by Natural Killer Cells

The book is a key reference and go-to resource for researchers and clinicians who want to understand the current limitations associated with bringing natural killer cell-based immunotherapies to the clinic.

Author : Sandro Matosevic

Release : 2020-12-01

Publisher : Academic Press

ISBN : 0128208805

File Size : 69.66 MB

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Breaking Tolerance to Unresponsiveness to Immunotherapy by Natural Killer Cells presents chapters by leaders in translational natural killer cell research and bridges the gap between clinical need and basic science by presenting state-of-the-art knowledge on innate immunity and the challenges associated with translating it to practical adoptive immunotherapies. New approaches, such as the genetic engineering of NK cells and their combination with checkpoint blockade therapies are discussed among other potential interventions to improve natural killer cell functionality against targets. In addition, challenges, such as the difficulty in genetically modifying NK cells or a poor understanding of their effect on checkpoint inhibition are included. The book is a key reference and go-to resource for researchers and clinicians who want to understand the current limitations associated with bringing natural killer cell-based immunotherapies to the clinic. Discusses translational aspects from leaders in the field to facilitate readers’ understanding of clinical challenges Addresses important events that occur in patient tumor microenvironments as they pertain to NK cells and how they are, or can be, tackled to overcome immunosuppression of NK cells Focuses on immunometabolism by discussing the metabolic reprogramming that NK cells undergo in solid tumors, including hypoxia, adenosine and other metabolites

Immunobiology of Natural Killer Cells

First published in 1986: This book contributes to the advancing knowledge of reads in the field of NK cells, and will be helpful as a teaching device.

Author : Eva Lotzova

Release : 2019-06-05

Publisher : CRC Press

ISBN : 9780367255541

File Size : 90.98 MB

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First published in 1986: This book contributes to the advancing knowledge of reads in the field of NK cells, and will be helpful as a teaching device.

Approaches to Improve the Proliferation and Activity of Natural Killer Cells for Adoptive Cell Therapy

In conclusion, this work has evaluated the NKF expansion system and demonstrated its ability to robustly expand NK cells.

Author : Evelyn Ojo

Release : 2019

Publisher :

ISBN :

File Size : 50.97 MB

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Cancer is the second-leading cause of death in the United States and worldwide leading to 8.8 million deaths in 2015. Despite major advancements in science and health, patients at advanced stages of particular cancer types experience significant mortality. Cancer patients often relapse following treatment with conventional therapeutic modalities such as chemotherapy and radiation therapy. Conventional treatment approaches do not successfully address the heterogeneity present in most solid tumors, result in severe off-target effects resulting in severe side effects, and fail to kill dormant cancer cells. Immunotherapy is the use of immune cells as tools to combat diseases. Natural killer (NK) cells are lymphocytes that lyse tumor cells and virally-infected cells through diverse mechanisms including release of cytotoxic granules. NK cell therapy has shown much promise in preclinical studies however it fails to demonstrate efficacy in various cancer populations. This body of work tackles two crucial barriers to NK cell therapy in patients with solid tumors. NK cell numbers in the tumor has been correlated with good prognosis in cancer patients. Obtaining clinically efficacious numbers of NK cells is limited by the relatively small proportion of NK cells in peripheral blood. We, therefore, designed and engineered a novel IL-21-based NK cell expansion platform consisting of OCI-AML3 cells transduced with membrane-bound IL-21 (NKF cells). We demonstrated that NKF cells are effective at expanding NK cells. The NK cells expanded using NKF cells were able to lyse a wide array of tumor types and demonstrated a favorable metabolic signature as compared to non-expanded NK cells. Additionally, NKF-expanded NK cells significantly reduced the tumor burden in sarcoma cell-infected mice. Cancer cells have developed mechanisms to evade anti-tumor activities of NK cells, dampening the efficacy of NK cell-mediated lysis of cancer cells. Transforming growth factor-ß (TGF-ß) is an immunosuppressive cytokine abundantly secreted by cancer cells to modify the cancer landscape to support the growth and development of the tumor. We demonstrated that inhibition of TGF-ß using the clinical grade TGF-ß inhibitor, galunisertib, resulted in rescue of NK cell cytokine secretion and cytotoxic function. In conclusion, this work has evaluated the NKF expansion system and demonstrated its ability to robustly expand NK cells. NKF-expanded NK cells have increased glycolytic and oxidative phosphorylation rates and continue to expand beyond 5 weeks of expansion. Feeder cell-expanded NK cells demonstrate superior cytotoxic function following inhibition of TGF-ß signaling. Infusion of NKF-expanded NK cells coupled with TGF-ß inhibition has the potential to result in decreased tumor burden in cancer patients.

NK Cell-Based Cancer Immunotherapy

In addition, NK cells express Fc?RIIIA or CD16, the receptor that exerts antibody-dependent cell mediated cytotoxicity (ADCC). NK cells also express the death ligands FasL and TRAIL.

Author : Francisco Borrego

Release : 2016-09-08

Publisher : Frontiers Media SA

ISBN : 2889199347

File Size : 60.3 MB

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Natural killer (NK) cells are innate lymphoid cells that have a significant role in regulating the defenses against cancer development and certain viral infections. They are equipped with an array of activating and inhibitory receptors that stimulate or diminish NK cell activity, respectively. Inhibitory receptors include, among others, the MHC class I ligands killer cell immunoglobulin-like receptors (KIR) in humans, and members of the Ly49 family of receptors in mice, and CD94/NKG2A. Activating receptors include cytokine and chemokine receptors, and those that interact with ligands expressed on target cells, such as the natural cytotoxicity receptors or NCRs (NKp30, NKp44 and NKp46), NKG2D, CD244 and DNAM-1. In addition, NK cells express Fc?RIIIA or CD16, the receptor that exerts antibody-dependent cell mediated cytotoxicity (ADCC). NK cells also express the death ligands FasL and TRAIL. The killing or sparing of target cells depends on the integration of distinct signals that originate from NK cell receptors. NK cells spare healthy cells that express normal levels of MHC class I molecules and low amounts of stress-induced self-molecules, whereas they kill target cells that down-regulate MHC class I molecules and/or up-regulate stress-induced self-molecules. The latter are common signatures of virus-infected cells and tumors. All the accumulated knowledge on NK cell biology, along with many clinical observations, is driving multiple efforts to improve the arsenal of NK cell-based therapeutic tools in the fight against malignant diseases. Indeed, NK cell-based immunotherapy is becoming a promising approach for the treatment of many cancers. It is well known that NK cells have a significant role in the anti-tumor effect of therapeutic antibodies that use ADCC as a mechanism of action. In addition to this, administration of autologous and allogeneic NK cells after activation and expansion ex vivo is used in the treatment of cancer. Moreover, adoptive transfer of NK cell lines has been tested in humans, and genetically modified NK cells expressing chimeric antigen receptors are being studied in preclinical models for potential use in the clinic.

Natural Killer Cells Interaction with Carbon Nanoparticles

The increased use of nanomaterials for biomedical purposes has warranted the need to introspect their toxicological properties and assess their utility to human health, particularly the immune system.

Author : A. Alam

Release : 2017

Publisher :

ISBN :

File Size : 20.65 MB

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The increased use of nanomaterials for biomedical purposes has warranted the need to introspect their toxicological properties and assess their utility to human health, particularly the immune system. Natural killer (NK) cells hold a pivotal position in innate immunity and serve as first line of defense against foreign bodies. Acid functionalized Carbon nanotubes (CNTs) that easily polydisperse in aqueous solution and could be coupled with fluorescent molecules were used to study the effect of carbon nanoparticles on NK cells in vitro and in vivo. Flow cytometry-based assays were used to study the effect of CNTs on various physiological parameters of NK cells, such as cell recovery, apoptosis, cell cycle, and generation of reactive oxygen species. A downregulation of the cytotoxicity of IL-2-activated murine NK cells was observed in the presence of acid-functionalized CNTs. The mechanistic basis of this downregulation was studied by assessing markers of NK cell activation (CD69), generation (NLK1.1), degranulation (CD107a) and apoptosis (annexin V assay). This chapter provides a blueprint for assessing the effect of carbon nanoparticles on NK cells. The assays mentioned in this chapter can be extrapolated to study the effect of other nanoparticles on different cell types as well.