Natural Killer Cells

Natural Killer Cells
Author: Michael T. Lotze,Angus W. Thomson
Publsiher: Academic Press
Total Pages: 660
Release: 2009-11-12
ISBN 10: 9780080919294
ISBN 13: 0080919294
Language: EN, FR, DE, ES & NL

Natural Killer Cells Book Review:

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

Natural Killer Cells

Natural Killer Cells
Author: Eric Vivier,James Di Santo,Alessandro Moretta
Publsiher: Springer
Total Pages: 247
Release: 2016-02-15
ISBN 10: 3319239163
ISBN 13: 9783319239163
Language: EN, FR, DE, ES & NL

Natural Killer Cells Book Review:

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 Cell Protocols

Natural Killer Cell Protocols
Author: Kerry S. Campbell,Marco Colonna
Publsiher: Springer Science & Business Media
Total Pages: 398
Release: 2000
ISBN 10: 1592590446
ISBN 13: 9781592590445
Language: EN, FR, DE, ES & NL

Natural Killer Cell Protocols Book Review:

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.

NK Cell Based Cancer Immunotherapy

NK Cell Based Cancer Immunotherapy
Author: Francisco Borrego,Susana Larrucea,Rafael Solana,Raquel Tarazona
Publsiher: Frontiers Media SA
Total Pages: 329
Release: 2016-09-08
ISBN 10: 2889199347
ISBN 13: 9782889199341
Language: EN, FR, DE, ES & NL

NK Cell Based Cancer Immunotherapy Book Review:

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.

Immunopathogenesis and Immune based Therapy for Selected Autoimmune Disorders

Immunopathogenesis and Immune based Therapy for Selected Autoimmune Disorders
Author: Mourad Aribi
Publsiher: BoD – Books on Demand
Total Pages: 182
Release: 2017-03-22
ISBN 10: 9535130218
ISBN 13: 9789535130215
Language: EN, FR, DE, ES & NL

Immunopathogenesis and Immune based Therapy for Selected Autoimmune Disorders Book Review:

The book Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders is a synthesis work that discusses two main aspects of autoimmunity: Immunopathogenesis and therapeutic approaches essentially based on the immunotherapies. This book deals with different topics on a number of autoimmune disorders, including type 1 diabetes, autoimmune cardiomyopathy, autoimmunity of gastrointestinal tract, systemic sclerosis, and myasthenia gravis. This book will be useful to clinicians, biologists, researchers, teachers, and students who are interested in immunology and immunopathology.

Natural Killer Cells

Natural Killer Cells
Author: Jacques Zimmer
Publsiher: Springer Science & Business Media
Total Pages: 428
Release: 2010-01-12
ISBN 10: 9783642023095
ISBN 13: 3642023096
Language: EN, FR, DE, ES & NL

Natural Killer Cells Book Review:

Natural killer (NK) cells have been at the forefront of immunology for two decades. During that time, a great amount of information about these cells has been obtained. They are important in antiinfectious and antitumoral defense and shape the adaptive immune response. In addition, they can act as immunoregulatory cells. In recent years, the therapeutic potential of NK cells in cancer immunotherapy has become increasingly evident. This book describes in detail current knowledge about NK cells and covers a broad range of NK cell-related topics, including those that are not frequently reviewed, e.g. NK cells and allergy or NK cells and skin diseases.

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

Approaches to Improve the Proliferation and Activity of Natural Killer Cells for Adoptive Cell Therapy
Author: Evelyn Ojo
Publsiher: Anonim
Total Pages: 218
Release: 2019
ISBN 10:
ISBN 13: OCLC:1145643634
Language: EN, FR, DE, ES & NL

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

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.

Immunobiology of Natural Killer Cell Receptors

Immunobiology of Natural Killer Cell Receptors
Author: Eric Vivier,Marco Colonna
Publsiher: Springer Science & Business Media
Total Pages: 284
Release: 2005-12-20
ISBN 10: 3540277439
ISBN 13: 9783540277439
Language: EN, FR, DE, ES & NL

Immunobiology of Natural Killer Cell Receptors Book Review:

Natural Killer (NK) cells are large granular lymphocytes of the innate immune system. They are widespread throughout the body, being present in both lymphoid organs and non-lymphoid peripheral tissues. NK cells are involved in direct innate immune reactions against viruses, bacteria, parasites and other triggers of pathology, such as malignant transformation, all of which cause stress in affected cells. Importantly, NK cells also link the innate and adaptive immune responses, contributing to the initiation of adaptive immune responses and executing adaptive responses using the CD16 FcgRIIIA immunoglobulin Fc receptor. Such responses are mediated through two major effector functions, the direct cytolysis of target cells and the production of cytokines and chemokines. The authors focus here on the nature of recognition events by NK cells and address how these events are integrated to trigger these distinct and graded effector functions.

NK Cells and Other Natural Effector Cells

NK Cells and Other Natural Effector Cells
Author: Ronald B. Herberman
Publsiher: Elsevier
Total Pages: 1566
Release: 2012-12-02
ISBN 10: 032313971X
ISBN 13: 9780323139717
Language: EN, FR, DE, ES & NL

NK Cells and Other Natural Effector Cells Book Review:

NK Cells and Other Natural Effector Cells reviews the state of knowledge on NK cells and other natural effector mechanisms. The coverage of immune effector systems ranges from basic studies on their nature, regulation, and mechanisms of action to important practical issues such as their role in host resistance, their modulation by therapeutic intervention, and alterations of their activity in disease. The book is organized into 12 parts. Parts I and II examine the characteristics of NK cells and other natural effector cells, respectively. Part III focuses on the cell lineage of NK and related effector cells, providing evidence for or against T cell lineage, for or against macrophage lineage, and for or against other or separate lineage. Part IV deals with the genetics of natural resistance in the mouse and rat. Part V presents studies on the regulation of cytotoxic activity. Part VI examines the specificity of natural effector cells, covering the nature of target cell structures and the nature of recognition receptors in effector cells. Part VII discusses the cytotoxicity by cultured lymphoid cells while Part VIII turns to the mechanisms of cytotoxicity. Part IX deals with natural cell-mediated reactivity against primary tumor cells and against non-tumor targets. Part X examines NK cell tumors or the presence of NK cells at the site of tumor growth. Part XI presents clinical studies with natural effector cells. Part XII provides evidence for in vivo reactivity of natural effector cells.

Lymphocyte Updates

Lymphocyte Updates
Author: Gheorghita Isvoranu
Publsiher: BoD – Books on Demand
Total Pages: 192
Release: 2017-07-12
ISBN 10: 9535133438
ISBN 13: 9789535133438
Language: EN, FR, DE, ES & NL

Lymphocyte Updates Book Review:

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.

In Vivo Mechanisms of Natural Killer Cell Tolerance

In Vivo Mechanisms of Natural Killer Cell Tolerance
Author: Michael David Bern
Publsiher: Anonim
Total Pages: 96
Release: 2020
ISBN 10:
ISBN 13: OCLC:1184039476
Language: EN, FR, DE, ES & NL

In Vivo Mechanisms of Natural Killer Cell Tolerance Book Review:

Natural killer (NK) cells are cytotoxic innate immune cells that provide protection from pathogens and tumors. To carry out these functions, NK cells must distinguish between healthy and unhealthy self-cells. Inability to recognize stressed cells would lead to a failure of NK-cell immunity whereas inability to identify healthy cells could lead to NK-cell autoimmunity. It remains unclear, however, how NK cells are able to distinguish healthy and unhealthy self-cells with a limited repertoire of germline-encoded receptors. The "missing-self" hypothesis proposes that NK cells identify stressed cells by their reduced expression of MHC class I (MHC-I) that is almost ubiquitously expressed as self. NK cells express inhibitory Ly49 receptors that bind to MHC-I and inhibit NK cells from killing healthy cells, and downregulation of MHC-I on stressed cells leads to loss of inhibition and killing by missing-self recognition. The importance of Ly49 receptors and MHC-I for maintaining NK-cell self-tolerance, however, has only been suggested by in vitro experiments and correlative in vivo experiments. Here we generated a mouse with a mutation in the immunoreceptor tyrosine-based inhibitory motif of Ly49A and another mouse with an allele of the gene for beta2-microglobulin containing loxP sites (B2m fl) to directly test the roles of Ly49s and MHC-I in NK cell self-tolerance in vivo. Loss of inhibitory signaling through a mutant Ly49 or global MHC-I downregulation induced changes in NK-cell responsiveness or inhibitory receptor expression that maintained NK-cell self-tolerance. In contrast, downregulation of MHC-I on CD4+ T cells, led to a subtle loss of CD4+ T cells, but NK cells remained tolerant to a substantial population of MHC-I-deficient CD4+ T cells without altering their responsiveness or receptor repertoire. In this setting, infection with murine cytomegalovirus or treatment with a toll-like receptor agonist induced NK cell-mediated rejection of MHC-I-deficient CD4+ T cells. These results show that loss of inhibitory signaling to NK cells in vivo can induce tolerance or rejection of missing-self in different contexts and that inflammation promotes missing-self reactivity.

Natural Killer Cells

Natural Killer Cells
Author: Srinivas S. Somanchi
Publsiher: Humana Press
Total Pages: 365
Release: 2016-05-13
ISBN 10: 9781493936823
ISBN 13: 1493936824
Language: EN, FR, DE, ES & NL

Natural Killer Cells Book Review:

This volume contains collection of Natural Killer Cell methodologies relevant for both basic and translational research. These methodologies present new developments in the natural killer (NK) cell field, such as understanding the influence of NK cells metabolism on its function, identifying complexity of NK cell subsets through mass cytometry, and determining the emergence of memory NK cells in murine model of MCMV infection. Methods that study NK cell migration and cytotoxicity through endpoint analysis or live single cell imaging are also discussed. Chapters also describe methods pertaining to translational application of NK cells, such as ex vivo expansion of NK cells on K562 cell lines genetically modified to express either membrane bound IL-15 or membrane bound IL-21, large scale NK cell culture, current techniques for engineering NK cells to express chimeric antigen receptors or chemokine receptors using retroviral vectors, electroporation of mRNA, and the natural phenomenon of trogocytosis. Written in the highly successful Methods in Molecular Biology series format, these chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting edge and thorough, Natural Killer Cells: Methods and Protocols is a valuable resource for researchers who not only want to understand mechanisms that govern NK cell behavior and diversity, but also for those who want to understand how to systematically evaluate NK cells for adoptive immunotherapy applications.

Defining Natural Killer Cell Responses to HIV

Defining Natural Killer Cell Responses to HIV
Author: Qi Zhao
Publsiher: Anonim
Total Pages: 329
Release: 2020
ISBN 10:
ISBN 13: OCLC:1183855761
Language: EN, FR, DE, ES & NL

Defining Natural Killer Cell Responses to HIV Book Review:

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.

Current Topics in Microbiology and Immunology

Current Topics in Microbiology and Immunology
Author: Klas Kärre
Publsiher: Anonim
Total Pages: 248
Release: 1967
ISBN 10:
ISBN 13: CORNELL:31924073523940
Language: EN, FR, DE, ES & NL

Current Topics in Microbiology and Immunology Book Review:

Immunobiology of Natural Killer Cell Receptors

Immunobiology of Natural Killer Cell Receptors
Author: Eric Vivier,Marco Colonna
Publsiher: Springer Science & Business Media
Total Pages: 284
Release: 2005-12-20
ISBN 10: 3540277439
ISBN 13: 9783540277439
Language: EN, FR, DE, ES & NL

Immunobiology of Natural Killer Cell Receptors Book Review:

Natural Killer (NK) cells are large granular lymphocytes of the innate immune system. They are widespread throughout the body, being present in both lymphoid organs and non-lymphoid peripheral tissues. NK cells are involved in direct innate immune reactions against viruses, bacteria, parasites and other triggers of pathology, such as malignant transformation, all of which cause stress in affected cells. Importantly, NK cells also link the innate and adaptive immune responses, contributing to the initiation of adaptive immune responses and executing adaptive responses using the CD16 FcgRIIIA immunoglobulin Fc receptor. Such responses are mediated through two major effector functions, the direct cytolysis of target cells and the production of cytokines and chemokines. The authors focus here on the nature of recognition events by NK cells and address how these events are integrated to trigger these distinct and graded effector functions.

Immunotherapy

Immunotherapy
Author: Krassimir Metodiev
Publsiher: BoD – Books on Demand
Total Pages: 414
Release: 2017-04-26
ISBN 10: 9535131052
ISBN 13: 9789535131052
Language: EN, FR, DE, ES & NL

Immunotherapy Book Review:

This is another attempt of InTechOpen to continue the dissemination of international knowledge and experience in the field of immunology. The present book includes a number of modern concepts of specialists and experts in the field of immunotherapy, covering the major topics and analyzing the history, current stage, and future ideas of application of modern immunomodulation. It is always a benefit, but also a compliment, to gather a team of internationally distinguished authors and to motivate them to reveal their expertise for the benefit of medical science and health practice. On behalf of all readers, immunologists, immunogeneticists, biologists, oncologists, microbiologists, virologists, hematologists, chemotherapists, health-care experts, as well as students and medical specialists, also on my personal behalf, I would like to extend my gratitude and highest appreciation to InTechOpen for giving me the unique chance to be the editor of this exclusive book.

Immunobiology of Natural Killer Cells

Immunobiology of Natural Killer Cells
Author: Eva Lotzova,Ronald B. Herberman
Publsiher: CRC Press
Total Pages: 239
Release: 2019-06-05
ISBN 10: 9780367255541
ISBN 13: 0367255545
Language: EN, FR, DE, ES & NL

Immunobiology of Natural Killer Cells Book Review:

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.

A Gnl1 dependent Natural Killer Cell Deficiency is Associated with Altered Cell Cycle and Ribosomal Protein Gene Expression and is Overcome by P53 Ablation

A Gnl1 dependent Natural Killer Cell Deficiency is Associated with Altered Cell Cycle and Ribosomal Protein Gene Expression and is Overcome by P53 Ablation
Author: Natasha Barone
Publsiher: Anonim
Total Pages: 329
Release: 2019
ISBN 10:
ISBN 13: OCLC:1190697450
Language: EN, FR, DE, ES & NL

A Gnl1 dependent Natural Killer Cell Deficiency is Associated with Altered Cell Cycle and Ribosomal Protein Gene Expression and is Overcome by P53 Ablation Book Review:

"Natural Killer (NK) cells are the founding members of the innate lymphoid cell family. They are bone marrow derived effector lymphocytes that have cytotoxic and regulatory capacities which provide protection against viral infection and tumor formation. Following an N-ethyl-N-nitrosourea (ENU) induced mutagenesis screen in mice, we identified a pedigree with severe susceptibility to murine cytomegalovirus (MCMV) infection due to a loss-of-function mutation in the gene, Guanine nucleotide-binding protein-like 1 (Gnl1). The mutation introduces a premature stop codon at amino acid position 365 (mutant = Gnl1C365X), resulting in an NK cell deficiency. The overall objective of this study is to understand the mechanism by which mutation of GNL1 leads to NK cell deficiency. Based on the close sequence homology of GNL1 to other YRG family proteins and reports on the function of human GNL1, we hypothesize that the Gnl1C365X mutation perturbs ribosomal protein and cell cycle gene expression, p53 activation and cell survival in NK cells. In order to address the hypothesis, we performed RNA-sequencing to identify differentially expressed genes (DEGs) between Gnl1+/+ and Gnl1C365X NK cells. A total of 143 DEGs were identified. Gene ontology highlighted terms associated with cell cycle, and cell cycle checkpoints. A gene set enrichment analysis (GSEA) using immunological or KEGG gene sets demonstrated a positive enrichment in cell cycle and a negative enrichment in ribosome signatures in Gnl1C365X NK cells. Bub1, Bub1b and Plk1 were three cell cycle genes among the 143 DEGs leading the enrichment of the KEGG cell cycle pathway. Bub1, Bub1b and Plk1 contain p53 responsive elements and have been shown to interact with p53. Ribosomal transcripts were reduced in the Gnl1C365X NK cells which could be inducing ribosomal stress to activate p53 pathways. By knocking out the cell fate gate keeper p53, we were able to rescue the MCMV susceptibility observed in Gnl1C365X mice. Moreover, the Gnl1C365X NK cell deficiency, caspase 3 levels, and receptor expression (KLRG1, NKG2D, Ly49H, Ly49G2 and CD122) were restored to wild-type levels. In this study, we highlight that Gnl1C365X NK cells are undergoing p53-dependent apoptotic cell death and the NK cell deficiency is underlying the susceptibility to MCMV infection. Furthermore, our data suggests that a downregulation in ribosomal protein transcription induces p53 activation resulting in abnormal NK cell cycle, proliferation and survival"--

Natural Killer Cell Response During Acute Toxoplasmosis Development of an Antibody dependent Phagocytosis Assay for the Assessment of HIV specific Antibodies

Natural Killer Cell Response During Acute Toxoplasmosis   Development of an Antibody dependent Phagocytosis Assay for the Assessment of HIV specific Antibodies
Author: Kevin D. Fettel
Publsiher: Anonim
Total Pages: 111
Release: 2019
ISBN 10: 9781085587709
ISBN 13: 1085587703
Language: EN, FR, DE, ES & NL

Natural Killer Cell Response During Acute Toxoplasmosis Development of an Antibody dependent Phagocytosis Assay for the Assessment of HIV specific Antibodies Book Review:

Part I. NATURAL KILLER CELL RESPONSE DURING ACUTE TOXOPLASMOSIS: Natural Killer (NK) cells, members of group 1 innate lymphoid cells, play a crucial role in innate host defense against the ubiquitous parasite Toxoplasma gondii. To better understand the acute response by NK cells during the early phases of infection, we sought to measure parasite-induced alterations and trends in the phenotype of the NK cell population during the course of acute infection to Type II ME49 T. gondii in the peritoneum (PEC) and spleen. Few NK cells exist within the naïve PEC environment. However, NK cells respond immediately following infection, undergoing rapid and sustained increases in the NK cell population, before undergoing a rapid contraction phase by 7-dpi. Proliferation, as measured by Ki67, trended toward optimal proliferation by 5-dpi. While splenic NK cells respond following an infection, the increases in the absolute number of NK cells do not appear to be sustained in the manner found at the local site of primary infection within the peritoneal cavity. Further, disparate trends in maturation were observed between the PEC and spleen. The frequency of terminally mature NK cells was found to increase within the PEC while decreasing at the spleen. Developmental transcription factors T-Bet and Eomes did not appear to be impaired by infection, showing elevated absolute numbers of NK cells expressing these transcription factors throughout the acute kinetic. Absolute number and frequency of KLRG1 expression of NK cells for both the PEC and spleen trended upward throughout the kinetic, irrespective of maturation status. Part II. DEVELOPMENT OF AN ANTIBODY-DEPENDENT PHAGOCYTOSIS ASSAY FOR THE ASSESSMENT OF HIV-SPECIFIC ANTIBODIES: Antibody-dependent phagocytosis and cytotoxicity are actuated by the temporal and spatial engagement of both inhibitory and activating Fc receptors on professional phagocytes. While the variable domains of antibodies are critical for antigen specificity, growing clinical attention is being placed on the ability of antibodies to both recruit innate immune cells and their ability to modulate effector immune responses via the subclass and glycosylation profile of the Fc domains. Fc-mediated immune effector activity has been implicated as a clinical correlate of protection against varying disease states ranging from microbial infections, autoimmunity to cancerous malignancies. To study the functional differences of antibody glycosylation that may enable selective augmentation of antibody-dependent phagocytosis, cytotoxicity, and other immune effector functions, we modified an Antibody-Dependent Phagocytosis assay that utilizes a Specific Hybridization Internalization Probe (SHIP) developed by Batiz et al based on earlier work done by Ackerman et al and Liu et al. The method herein describes a high-throughput and high-resolution assay that allows for discrimination of surface-bound or phagocytosed gp120-coated fluorescent beads by confocal microscopy that may be coupled with differing glycosylated antibodies to evaluated antibody-dependent immune effector response.

Mechanisms of Lymphocyte Activation and Immune Regulation X

Mechanisms of Lymphocyte Activation and Immune Regulation X
Author: Sudhir Gupta,William E. Paul,Ralph Steinman
Publsiher: Springer Science & Business Media
Total Pages: 163
Release: 2007-03-20
ISBN 10: 0387241809
ISBN 13: 9780387241807
Language: EN, FR, DE, ES & NL

Mechanisms of Lymphocyte Activation and Immune Regulation X Book Review:

This volume is edited by Dr. Sudhir Gupta, internationally recognized expert in Immunology, Professor of Medicine, Pathology, Microbiology and Molecular Genetics. Topics include toll receptors, dendritic cells, NK cells, and complement receptors.