Download or read book A Tale of Two Interleukins how Il5 and Il33 Shapes Eosinophil Morphology and Inflammatory Potential written by Joshua Mitchell (Ph.D.) and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Activation of eosinophils by cytokines and chemokines is key step in the transition of eosinophils from the peripheral blood to tissue residency. While required for normal cellular function, increased abundance of activated eosinophils in tissues is a hallmark of eosinophilic diseases and disorders. We sought to elucidate further how two cytokines implicated in eosinophil function, IL5 and IL33, lead to eosinophil activation and how these activated states compare during initial cellular commitment, cellular polarization and migration, and downstream events like degranulation. We utilized proteomics, light microscopy, and cryo-electron microscopy tomography (cryoET) to illuminate mechanisms underlying cytokine activation of eosinophils. To investigate how eosinophils commit to activation when exposed to the cytokines IL5 and IL33 for 10 minutes, we used ten-plex tandem mass tagging to generate proteomic and phosphoproteomic datasets with which to compare effects of the cytokines on eosinophils purified from human peripheral blood. Three different datasets were generated: IL5-activated versus unactivated, IL33-activated versus unactivated, and IL5-activated versus IL33-activated. We found that in the first 10 minutes of exposure to cytokines, no significant proteomic changes are found, but the phosphoproteome changes pervasively. Phosphosites in proteins involved in basic cellular functions like cytoskeletal arrangement, vesicular trafficking, and splicing changed in the same direction comparing either cytokine to no treatment. However, different activation pathways were revealed comparing the two cytokines to each another, with IL5-activated eosinophils processing down a JAK-STAT cascade while IL33-activated eosinophils process through IL1-family signaling through a NFÎðB cascade. The result is positioning of RELA or phosphorylated STAT3 on nuclear speckles to initiate transcription and splicing of eosinophil cytokines/chemokines with the potential to change the phenotype of tissue-resident eosinophils in a cytokine-specific manner. Once activated, eosinophils undergo dramatic morphological changes. The naiÌ8ve unactivated sphere-like eosinophil rapidly morphs into adhesive acorn-like cells when exposed to IL5 and thin pancake-like cells when exposed to IL33. IL5-activated cells are more motile, whereas IL33-activated cells are more stationary. Live imaging shows that a dynamic microtubule network directs migration of the cells, with a stable population of microtubules maintain a stable network spanning across the nucleopod in the rear of the cell to the microtubule organizing center. Activated eosinophils are also substrate sensitive and show greater cellular death when activated on periostin versus fibrinogen. Granules of eosinophils contain high contents of toxic proteins, one of which, major basic protein-1, forms a crystalline core. Prior electron microscopy of eosinophils in tissues indicates that granule content can be released through fusion of the granule with the membrane and wholesale release (exocytosis), in parts (piecemeal degranulation), or deposition of granules after cell death (cytolysis). Lack of a method to address facilely how degranulation occurs within activated eosinophil populations on adhesive substrates has hindered how these mechanisms of release are related and coordinated. We established conditions in which we were able to plunge-frozen IL33-activated eosinophils for cryoET imaging without additional milling or sectioning. We observed numerous double-membrane vesicles that we presume are the same as so-called eosinophil sombrero vesicles noted in previous electron microscopic studies and were surprised to see naked crystalline cores of granules present intracellularly. These initial findings indicate that cryoET will yield important new insights into how activated eosinophils handle their granular content.

Download or read book A Tale of Two Interleukins how Il5 and Il33 Shapes Eosinophil Morphology and Inflammatory Potential written by Joshua Mitchell (Ph.D.) and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Activation of eosinophils by cytokines and chemokines is key step in the transition of eosinophils from the peripheral blood to tissue residency. While required for normal cellular function, increased abundance of activated eosinophils in tissues is a hallmark of eosinophilic diseases and disorders. We sought to elucidate further how two cytokines implicated in eosinophil function, IL5 and IL33, lead to eosinophil activation and how these activated states compare during initial cellular commitment, cellular polarization and migration, and downstream events like degranulation. We utilized proteomics, light microscopy, and cryo-electron microscopy tomography (cryoET) to illuminate mechanisms underlying cytokine activation of eosinophils. To investigate how eosinophils commit to activation when exposed to the cytokines IL5 and IL33 for 10 minutes, we used ten-plex tandem mass tagging to generate proteomic and phosphoproteomic datasets with which to compare effects of the cytokines on eosinophils purified from human peripheral blood. Three different datasets were generated: IL5-activated versus unactivated, IL33-activated versus unactivated, and IL5-activated versus IL33-activated. We found that in the first 10 minutes of exposure to cytokines, no significant proteomic changes are found, but the phosphoproteome changes pervasively. Phosphosites in proteins involved in basic cellular functions like cytoskeletal arrangement, vesicular trafficking, and splicing changed in the same direction comparing either cytokine to no treatment. However, different activation pathways were revealed comparing the two cytokines to each another, with IL5-activated eosinophils processing down a JAK-STAT cascade while IL33-activated eosinophils process through IL1-family signaling through a NFÎðB cascade. The result is positioning of RELA or phosphorylated STAT3 on nuclear speckles to initiate transcription and splicing of eosinophil cytokines/chemokines with the potential to change the phenotype of tissue-resident eosinophils in a cytokine-specific manner. Once activated, eosinophils undergo dramatic morphological changes. The naiÌ8ve unactivated sphere-like eosinophil rapidly morphs into adhesive acorn-like cells when exposed to IL5 and thin pancake-like cells when exposed to IL33. IL5-activated cells are more motile, whereas IL33-activated cells are more stationary. Live imaging shows that a dynamic microtubule network directs migration of the cells, with a stable population of microtubules maintain a stable network spanning across the nucleopod in the rear of the cell to the microtubule organizing center. Activated eosinophils are also substrate sensitive and show greater cellular death when activated on periostin versus fibrinogen. Granules of eosinophils contain high contents of toxic proteins, one of which, major basic protein-1, forms a crystalline core. Prior electron microscopy of eosinophils in tissues indicates that granule content can be released through fusion of the granule with the membrane and wholesale release (exocytosis), in parts (piecemeal degranulation), or deposition of granules after cell death (cytolysis). Lack of a method to address facilely how degranulation occurs within activated eosinophil populations on adhesive substrates has hindered how these mechanisms of release are related and coordinated. We established conditions in which we were able to plunge-frozen IL33-activated eosinophils for cryoET imaging without additional milling or sectioning. We observed numerous double-membrane vesicles that we presume are the same as so-called eosinophil sombrero vesicles noted in previous electron microscopic studies and were surprised to see naked crystalline cores of granules present intracellularly. These initial findings indicate that cryoET will yield important new insights into how activated eosinophils handle their granular content.

Download or read book Mast Cells and Basophils written by Gianni Marone and published by Academic Press. This book was released on 2000-05-25 with total page 738 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mast Cells and Basophils will be essential reading for immunologists, biochemists and medical researchers. Detailed chapters cover all aspects of mast cell and basophil research, from cell development, proteases, histamine, cysteinyl leukotrienes, physiology and pathology to the role of these cells in health and disease. Chapters also discuss the clinical implications of histamine receptor antagonists.

Download or read book Principles of Cancer Biotherapy written by Robert K. Oldham and published by Springer Science & Business Media. This book was released on 2009-08-29 with total page 743 pages. Available in PDF, EPUB and Kindle. Book excerpt: At the time of the first edition of Principles of Cancer Biotherapy in 1987, this book represented the first comprehensive textbook on biological therapy. In 1991, when the second edition was published, there was still some doubt on the part of many oncologists and cancer researchers as to the therapeutic value of these new approaches. By 2003 and the fourth edition, it was generally agreed that biopharmaceuticals were producing major opportunities for new cancer therapies. Cancer biotherapy has now truly matured into the fourth modality of cancer treatment. This fifth revised edition describes the tremendous progress that has been made in recent years using biologicals in cancer treatment. This book summarizes an evolving science and a rapidly changing medical practice in biotherapy. In this new millennium, it is now possible to envision a much more diversified system of cancer research and treatment that will afford greater opportunities for a patient’s personalized cancer treatment. This was first envisioned in the 1987 initial edition of this textbook and is now a “new” and popular approach to cancer treatment. Some forms of cancer biotherapy use the strategy of tumor stabilization and control through continued biological therapy, akin to the use of insulin in the treatment of diabetes. This textbook illustrates new methods of thinking and new strategies for control of cancer. It is always difficult to move from past dogma to future opportunity, but this fifth edition of Principles of Cancer Biotherapy illustrates why it is so important to the patients for researchers and clinicians to explore and quickly apply these new opportunities in cancer biotherapy.

Download or read book Human Eosinophils written by Gianni Marone and published by Karger Medical Scientific. This book was released on 2000 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Eosinophils represent approximately 1% of peripheral blood leukocytes and play a central proinflammatory and immunoregulatory role in various immune disorders. This volume provides the reader with a comprehensive survey of the major aspects of human eosinophilic biology and immunology as well as the most clinically relevant aspects of eosinophil-related disorders. Expert contributions cover the ultrastructural and phenotypic characteristics of human eosinophils, and their fundamental biochemical features including receptors for IgE and chemokines. The production of cytokines and their role in the activation of eosinophils are reviewed. Furthermore, the classic eosinophil-related disorders such as hypereosinophilia, drug reactions, allergic disorders and some cardiovascular diseases are described. Each of the chapters is written by an investigator actively engaged in research on the topic under consideration. The well-edited and stimulating material compiled in this volume will be of interest to all those working in allergology, immunology, biochemistry and pulmonary medicine.

Download or read book Immunopharmacology written by Manzoor M. Khan and published by Springer Science & Business Media. This book was released on 2008-12-19 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: During the past decades, with the introduction of the recombinant DNA, hybridoma and transgenic technologies there has been an exponential evolution in understanding the pathogenesis, diagnosis and treatment of a large number of human diseases. The technologies are evident with the development of cytokines and monoclonal antibodies as therapeutic agents and the techniques used in gene therapy. Immunopharmacology is that area of biomedical sciences where immunology, pharmacology and pathology overlap. It concerns the pharmacological approach to the immune response in physiological as well as pathological events. This goals and objectives of this textbook are to emphasize the developments in immunology and pharmacology as they relate to the modulation of immune response. The information includes the pharmacology of cytokines, monoclonal antibodies, mechanism of action of immune-suppressive agents and their relevance in tissue transplantation, therapeutic strategies for the treatment of AIDS and the techniques employed in gene therapy. The book is intended for health care professional students and graduate students in pharmacology and immunology.

Download or read book Mast Cell Biology written by Alasdair M. Gilfillan and published by Springer Science & Business Media. This book was released on 2011-06-28 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: The editors of Mast Cell Biology, Drs. Gilfillan and Metcalfe, have enlisted an outstanding group of investigators to discuss the emerging concepts in mast cell biology with respect to development of these cells, their homeostasis, their activation, as well as their roles in maintaining health on the one hand and on the other, their participation in disease.

Download or read book Damage Associated Molecular Patterns in Human Diseases written by Walter Gottlieb Land and published by Springer. This book was released on 2018-10-09 with total page 870 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents current understanding of the importance of modern immunology in the etiopathogenesis of human diseases and explores how this understanding is impacting on diagnosis, prognosis, treatment, and prophylaxis. As the core of modern immunology, the “danger/injury model” is introduced and addressed throughout the book. Volume I of the book describes the network of damage-associated molecular pattern molecules (DAMPs) and examines the central role of DAMPs in cellular stress responses and associated regulated cell death, the promotion and resolution of inflammation, the activation of innate lymphoid cells and unconventional T cells, the stimulation of adaptive immunity, and tissue repair. The significance of DAMPs in a wide range of human diseases will then be explored in Volume II of the book, with discussion of the implications of injury-induced innate immunity for present and future treatments. This book is written for professionals from all medical and paramedical disciplines who are interested in the introduction of innovative data from immunity and inflammation research into clinical practice. The readership will include practitioners and clinicians such as hematologists, rheumatologists, traumatologists, oncologists, intensive care anesthetists, endocrinologists such as diabetologists, psychiatrists, neurologists, pharmacists, and transplantologists.

Download or read book Practical Insights into Atopic Dermatitis written by Kwang Hoon Lee and published by Springer Nature. This book was released on 2021-04-30 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a comprehensive, practical guide to the latest developments in the understanding and management of atopic dermatitis. Detailed information is provided on age-specific clinical symptoms, features, and diagnostic methods. Current theories on the pathogenesis of atopic dermatitis are closely examined, with attention to the roles played by genetic, allergic, immunologic, and skin barrier dysfunctions. In the second half of the book, the scientific background to and the practical use of the full range of treatment methods are described, covering topical agents, systemic agents, phototherapy, allergen-specific immunotherapy, and the most recently developed biologics and small molecules. This textbook will be an excellent guide to diagnosis and treatment for not only dermatologists but also practitioners in allergy and general medicine, including pediatricians, allergists, and primary care physicians. In addition, it will be of value for all scientists interested in developing new drugs for atopic dermatitis.

Download or read book Eosinophils in Health and Disease written by James J. Lee and published by Academic Press. This book was released on 2012-11-02 with total page 679 pages. Available in PDF, EPUB and Kindle. Book excerpt: Eosinophils in Health and Disease provides immunology researchers and students with a comprehensive overview of current thought and cutting-edge eosinophil research, providing chapters on basic science, disease-specific issues, therapeutics, models for study and areas of emerging importance.

Download or read book Immunopathology in Toxicology and Drug Development written by George A. Parker and published by Springer. This book was released on 2017-03-28 with total page 682 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a fundamental understanding of immunopathology and immunopathologic processes, with particular attention to nonclinical toxicology studies. Chapters provide an overview of general immunobiology, cells of the immune system, signaling and effector molecules, and immunopathology assays. A companion volume, Immunopathology in Toxicology and Drug Development: Volume 2, Organ Systems, offers summaries of organ-specific immunobiology and immunopathology as well as common responses to xenobiotics. These informative and strategic books were created in response to the large segment of drug development that focuses on chronic diseases, many of which involve alterations to the immune system. Therapies that target these diseases commonly involve some form of immunomodulation. As a result, the two volumes of Immunopathology in Toxicology and Drug Development are critical texts for individuals involved in diverse aspects of drug development. Readers will acquire a thorough understanding of immunopathology for detection and accurate interpretation of pathologic effects of xenobiotics on the immune system.

Download or read book Evolution of Atopic Dermatitis in the 21st Century written by Ichiro Katayama and published by Springer. This book was released on 2017-12-06 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive guide offers a state-of-the-art overview of basic and clinical aspects of atopic dermatitis (AD). The name "atopic dermatitis" was first used in 1933, and Drs. Lewis Webb Hill and Marion B. Sulzberger presented their report "Evolution of atopic dermatitis" in 1935. Their observations accurately forecasted the contemporary issues in the management of the condition, such as the conclusions that should be drawn from our understanding of the pathogenesis of AD, and the use of steroids as the main treatment. Several aggravating factors have recently been identified, and these also need to be addressed. In this context, the expert contributors to this book describe and discuss the evolution of atopic dermatology from Sulzberger’s era to the present day, including clinical manifestations, etiopathology and treatment. In addition, it explores skin care intervention, the role of microbiom and GWAS studies, and presents unique, previously unpublished cohort studies. It provides insights into the dynamic changes in AD since Sulzberger introduced topical steroids for its treatment. It is a valuable resource for dermatologists, medical practitioners and researchers who are interested in atopic dermatology.

Download or read book Mechanical Stretch and Cytokines written by Andre Kamkin and published by Springer Science & Business Media. This book was released on 2011-09-06 with total page 247 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents the latest findings in the field of investigation of molecular mechanisms of mechanical stretch and the role of cytokines in response of different tissues to it. On the one hand this Volume demonstrates how mechanical stretch enhances cytokines production. It describes how cytokines influence tissues and cells on a background of a mechanical stretching. It provides a description of how cells in different tissues are activated by stretch and cytokines via various signaling pathways, and how they change their gene expression. The book is a unique collection of reviews outlining current knowledge and future developments in this rapidly growing field. Knowledge of biomechanics, and mechanisms which underlie it on molecular, cellular and tissue, is necessary for understanding of the normal functioning of living organisms and allows to predict changes, which arise due to alterations of their environment.

Download or read book Tumor Microenvironments in Organs written by Alexander Birbrair and published by Springer Nature. This book was released on 2020-02-06 with total page 155 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on the tumor microenvironment in over thirty human organs, including the parathyroid gland, heart, intestine, testicles, and more. Taken alongside its companion volumes, these books update us on what we know about the different aspects of the tumor microenvironments in distinct organs as well as future directions. Tumor Microenvironments in Organs: From the Brain to the Skin – Part A is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.

Download or read book Pharmacology of Immunotherapeutic Drugs written by Clinton B. Mathias and published by Springer Nature. This book was released on 2019-10-18 with total page 399 pages. Available in PDF, EPUB and Kindle. Book excerpt: Medicine has entered a golden age in which therapeutic agents are becoming widely available due to advances in basic science and technology. As such, many drugs have been developed that target inflammatory processes and/or the immune system. This book is intended for health professionals examining the modulation of inflammation by immunotherapeutic drugs. The immune system fills the primordial role of host defense and resistance to infections with pathogenic microorganisms. Several hematopoietic-derived cells constituting the innate and adaptive immune systems cooperate to provide barriers for microbial colonization and/or promote pathogen destruction within the host. Conversely, many immune cells are also involved in the pathogenesis and propagation of chronic inflammatory diseases. The beginning of this book details various components of the immune system including the cell types, lymphoid tissues, soluble cytokines and surface molecules that are essential for host defense. Breakdowns in immune tolerance, or dysregulated immune responses to antigens derived from self tissues or innocuous sources, can lead to the development of autoimmunity or chronic inflammatory diseases. Pathophysiologic roles for the immune system are detailed in corresponding chapters on autoimmunity, epithelial surfaces (lungs, skin, intestine), and transplantation, with special emphasis placed on immunotherapeutic drug targets. The last section of the book focuses on treatments that stimulate our immune system to specifically target and fight infectious diseases and cancer. In each chapter, the medications used to treat various diseases/conditions in terms of their mechanism of action and other pharmacologic properties are detailed. Chapters begin with a table showing drug names and classifications. The importance of basic science and clinical trials cannot be understated in the context of drug development. As such, the discovery of certain medications that had a lasting impact in medicine and pharmacy are highlighted in chapter subsections named “Bench to Bedside.” Several clinical applications of immunotherapeutic drugs are described within end-of -chapter case studies including practice questions. The Pharmacology of Immunotherapeutic Drugs is a reference for immunologists and clinicians (medical doctors, pharmacists, nurses) examining the modulation of inflammatory processes by a variety of medications targeting the cells and mediators of our immune system.​

Download or read book Eukaryome Impact on Human Intestine Homeostasis and Mucosal Immunology written by Nancy Guillen and published by Springer Nature. This book was released on 2020-06-01 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple demographic or economic parameters contribute to the origin of emerging infections, for example: poverty, urbanization, climate change, conflicts and population migrations. All these factors are a challenge to assess the impact (present and future) of parasitic diseases on public health. The intestine is a major target of these infections; it is a nutrient-rich environment harbouring a complex and dynamic population of 100 trillion microbes: the microbiome. Most researches on the microbiome focus on bacteria, which share the gut ecosystem with a population of uni- and multi cellular eukaryotic organisms that may prey on them. Our interest focuses on the families of eukaryotic microbes inhabiting the intestine, called “intestinal eukaryome”, that include fungi, protists and helminths. Knowledge on the reciprocal influence between the microbiome and the eukaryome, and on their combined impact on homeostasis and intestinal diseases is scanty and can be considered as an important emerging field. Furthermore, the factors that differentiate pathogenic eukaryotes from commensals are still unknown. This book presents an overview of the science presented and discussed in the First Eukaryome Congress held from October 16th to 18th, 2019 at the Pasteur Institute in Paris. This book covers the following topics: Phylogenetic, prevalence, and diversity of intestinal eukaryotic microbes; and their (still enigmatic) historical evolution and potential contributions to mucosal immune homeostasis. Integrative biology to study the molecular cell biology of parasite-host interactions and the multiple parameters underlining the infectious process. The exploitation of tissue engineering and microfluidics to establish three-dimensional (3D) systems that help to understand homeostasis and pathological processes in the human intestine.

Download or read book From Basic to Clinical Immunology written by Vladimir V. Klimov and published by Springer. This book was released on 2019-03-06 with total page 377 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book fills a gap at the interface of fundamental and clinical immunology, and allergy. For many years, experts in fundamental immunology and physicians involved in clinical immunology and allergy worked separately – but the fundamental immunologists did not have medical qualifications and the physicians were not involved in the field of fundamental research. Written by a teacher and an expert in both fields, this book combines current knowledge on basic immunology and immunopathology with clinical comments that complete the whole picture. Immunology is a complex science, which requires a simplified approach in order to be taught and understood effectively. This book is based on the authors’ long experience in teaching undergraduate, postgraduate students and interns both basic and clinical immunology. Reviewing a variety of important components related to the immune system, it is clearly and logically structured, and enriched by figures, tables and boxes with important immunology definitions. Each chapter has its own bibliography, and most units include links to electronic quizzes and audio files to accompany readers step by step. This easy-to-follow volume concludes with suggestions for future study. It is a valuable resource for undergraduate and postgraduate students, as well as medical practitioners.