Download or read book Regulation of T Cell Migration and the Immune Response by Phosphoinositide 3 kinase Gamma written by Amanda Lorene Martin and published by . This book was released on 2007 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book PI3K signalling written by Klaus Okkenhaug and published by Frontiers Media SA. This book was released on 2015-03-05 with total page 140 pages. Available in PDF, EPUB and Kindle. Book excerpt: The PI3Ks control many key functions in immune cells. PI3Ks phosphorylate PtdIns(4,5)P2 to yield PtdIns(3,4,5)P3. Initially, PI3K inhibitors such as Wortmannin, LY294002 and Rapamycin were used to establish a central role for Pi3K pathway in immune cells. Considerable progress in understanding the role of this pathway in cells of the immune system has been made in recent years, starting with analysis of various PI3K and Pten knockout mice and subsequently mTOR and Foxo knockout mice. Together, these experiments have revealed how PI3Ks control B cell and T cell development, T helper cell differentiation, regulatory T cell development and function, B cell and T cell trafficking, immunoglobulin class switching and much, much more. The PI3Kd inhibitor idelalisib has recently been approved for the treatment of B cell lymphoma. Clinical trials of other PI3K inhibitors in autoimmune and inflammatory diseases are also in progress. This is an opportune time to consider a Research Topic considering when what we have learned about the PI3K signalling module in lymphocyte biology and how this is making an impact on clinical immunology and haematology.
Download or read book PI3K and AKT Isoforms in Immunity written by Margarita Dominguez-Villar and published by Springer Nature. This book was released on 2022-10-15 with total page 462 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides an essential overview of the role of phosphoinositide-3-phosphate kinase (PI3K) isoforms in modulating the function of immune system cells and their involvement in disease. PI3K is a family of kinases involved in basic cellular processes such as proliferation, migration and cell death. Recent work has highlighted the multiple roles of PI3K classes and subunits and their involvement in the immune response to the body’s own and foreign antigens and diseases such as cancer and autoimmunity. This book offers a detailed introduction to the biology of the three PI3K classes, followed by an extensive discussion of the diverse roles of AKT and PI3K isoforms in immune cells. Based on this knowledge, it subsequently explains in more detail how specific isoforms are connected to immune-mediated diseases. The book concludes by highlighting the latest advances in the production of isoform-specific inhibitors and their use in various human diseases. This book is intended as a reference guide for students and researchers interested in the multifaceted aspects of PI3K biology.
Download or read book An Investigation Into the Role of Protein Kinases in T Lymphocyte Migration written by Adam Webb and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The migration of T lymphocytes is a vital component of the immune system, with roles in immunosurveillance and inflammation. The role of Phosphoinositide 3-kinase within T lymphocyte migration is unclear, with some evidence that it may be a disposable signal. Here, using Staphylococcal Enterotoxin B activated peripheral blood mononuclear cells and the T cell line CEM cells, the role of Phosphoinositide 3-kinase and its downstream kinases was investigated. CCL22 mediated CEM cell migration and CXCL12 mediated peripheral blood mononuclear cell migration were shown to be independent of Phosphoinositide 3-kinase using several different broad-spectrum Phosphoinositide 3-kinase inhibitors. However, these cells were Akt-dependent, as demonstrated by incubation with the Akt inhibitor Akti-1/2. Differences in the effect of the inhibitors on Akt activity were discovered, indicating that either Akt can be activated in the absence of Phosphoinositide 3-kinase, or differences exist regarding the relative abundance of each protein within the cell. Th17 cells are a subtype of the T helper cell family and have been shown to be involved in inflammation and immune diseases. Mouse splenocytes were polarised to a Th17 phenotype and analysed for the surface expression of chemokine receptors. CCR2, CCR6 and CCR9 were shown to be expressed on Th17 cells and upregulated under Th17 polarising conditions. However, only CCR2 and CCR6 induced migration of Th17 cells. This migration was sensitive to Phosphoinositide 3-kinase and Akt inhibitors. This data reveals a model for the migration of Th17 cells to areas of inflammation, and sheds light on the role of Phosphoinositide 3-kinase during this process.
Download or read book Gamma delta T Cells written by Paul R. Bergstresser and published by Karger Medical and Scientific Publishers. This book was released on 2001-01-01 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the last 15 years, since the discovery of the T cell receptor and genes, rapid progress has been made toward the understanding of the biology of T cells. They differ from conventional T cells not only in T cell receptor composition, but also in their development, tissue distribution, and physiological functions. This volume contains seven chapters contributed by experts on different aspects of T cells, including the natural ligands for T cell receptors, IL-7-dependent regulation of T cell development, cytokine-mediated inter-cellular communication of T cells with other cell types, and their physiological functions in innate and adaptive immune responses. The comprehensive review articles collected in this volume will be of interest to basic immunologists who wish to update their knowledge on the biology of T cells. The book also provides a unique opportunity for non-immunologists and clinicians to understand how the immune system is specifically equipped to protect the body against pathogens at the environmental interface.
Download or read book The Importance of G Protein Signaling in Immune Cell Function A Novel Role for Active G i in Cell Adhesion and Migration and the Therapeutic Potential of Targeting G in Inflammation written by Jesi Lee Anne To and published by . This book was released on 2018 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chemotaxis is the directional movement of cells towards a gradient of chemoattractant such as chemokines. Chemokines are small peptides secreted by various cell types and play a role in immune surveillance, inflammation, and development. These molecules bind to their cognate receptors, which belong to the Class A, rhodopsin-like family of G protein-coupled receptors (GPCRs). Downstream effects orchestrated by chemokines include directional migration, reactive oxygen species (ROS) production, proliferation, and survival. Chemokine receptors primarily couple to the Gi/o family of G? proteins. Their activation triggers dissociation of the heterotrimeric G protein, G? and G?? dimer. The role of G?? in chemokine signaling is well established as it regulates multiple downstream effectors critical to cell migration such as phosphoinositide 3-kinase gamma (PI3K?), phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchanger (P-Rex), p21 activated kinase/PAK-interacting exchange factor alpha (PAK/PIX?), and Ras-associating and diluted domain-containing protein (Radil). However, the role of G?i in chemokine signaling is less understood and is thought to only regulate G?? availability and signaling through their association and disassociation cycle. Here we show that both G?i-GTP and G?? signaling are pivotal to cell migration. We also provide evidence for a novel role of G?i-GTP in regulating cell adhesion and migration. Using a small molecule inhibitor of G?? to inhibit migration, we show its anti-inflammatory therapeutic potential against lupus nephritis. Recently, our lab uncovered a novel role for G?i-GTP signaling in neutrophil adhesion through a cAMP-independent pathway. To discover the mechanism for G?i-GTP regulation of adhesion, we used a constitutively active Rap1a(G12V) and its downstream effector Radil to drive adhesion of neutrophil-like HL-60 and HT-1080 fibrosarcoma cells. A G??-Rap1a-Radil complex is known to drive cell adhesion and migration of these cell types. We found that expression of constitutively active G?i1(Q204L) reversed both Rap1a(G12V) and Radil mediated adhesion, suggesting that G?i-GTP regulates adhesion downstream of Rap1a and Radil. Furthermore, Rap1a and Radil reduced migration of HT1080 cells, which is reversed by G?i1(Q204L) expression. These data identify a novel role for G?i-GTP in the regulation of cell adhesion and migration. Multiple chemokines play a role in propagating inflammation and are associated with lupus nephritis pathogenesis by orchestrating immune cell migration toward the kidneys. The chemokine/receptor system has vast and promiscuous properties as one chemokine can bind to multiple receptors and one receptor can bind to more than one ligand. Therefore, valid targeting of individual chemokine receptors associated with a disease may be challenging and display poor efficacy. We used a well-studied G?? inhibitor, gallein, to study its therapeutic potential in alleviating lupus nephritis. Gallein inhibited PI3K?-mediated PIP3 production in neutrophil-like HL-60 cells and inhibited chemotaxis of primary neutrophils and T-cells in response to chemokines. Gallein treatment significantly reduced renal inflammation and proteinuria in NZB/NZW lupus mice. This study illustrates the therapeutic potential of G?? inhibitors against chronic inflammation. Our laboratory has identified a novel small molecule inhibitor of G?? called ellagic acid. Ellagic acid is a naturally occurring polyphenolic compound and that has anti-inflammatory properties. Our evidence showed ellagic acid directly binding to G?? and inhibited downstream G?? signaling. It significantly blocked N-formyl-Met-Leu-Phe (fMLP) chemotactic peptide-induced intracellular calcium release and weakly inhibited G??-mediated phospholipase C ?2 (PLC?2) activation in vitro compared to gallein and peptide SIGKAFKILGYPDYD (SIGK). Ellagic acid also inhibited fMLP-induced PI3K?mediated membrane phosphatidylinositol 3,4,5-triphosphate (PIP3) production, superoxide production, and migration of neutrophil-like HL60 cells. In this study, we identified ellagic acid as a small molecule inhibitor of G?? signaling in neutrophil-like cells and was sufficient to inhibit chemotaxis. This thesis work focuses on the overall importance of G protein signaling in GPCRmediated chemokine signaling and immune cell function. Both G?i and G?? are important mediators of GPCR-mediated chemokine signaling and immune cell function. Furthermore, our studies provide insights into the novel role of G?i in adhesion and migration of both immune cells and cancer cells. Chemokines are not only important during inflammation, but also contribute to the metastatic potential of cancer cells. We illustrate the importance of G?i and G?? in immune cell function such as adhesion and cell migration and we show alleviation of inflammatory lupus nephritis by inhibiting G?? signaling.
Download or read book Modulation of T Cell Activation and Function by PI3K controlled Transcriptional Regulators Foxo1 and Id3 written by Jenna Marie Sullivan and published by . This book was released on 2018 with total page 67 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Role of Phosphoinositide 3 kinase Gamma in the Host Immune Response Against Cutaneous Leishmaniasis Caused by Leishmania Mexicana written by Hannah Elizabeth Cummings and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: The leishmaniasis are a group of diseases resulting from infection with protozoan parasites of the genus Leishmania. Cutaneous leishmaniasis, caused by species such as Leishmania mexicana, is the most widespread form of disease and is common throughout Central and South America, Africa, India, and Southwest Asia. Cutaneous infection results in the formation of well defined, localized lesions that generally self-resolve without need for treatment. However, some patients experience progressive disease and develop non-healing chronic infections. Problems associated with enhanced drug resistance by parasites and increased patient-unresponsiveness towards standard chemotherapeutics has become a significant concern for health officials worldwide. With 350 million people currently living in areas of active parasite transmission, the need for effective therapeutics to treat infection is considered a primary goal of The World Health Organization and health officials worldwide. The Phosphoinositide 3-kinases (PI3Ks) are a large family of evolutionarily conserved protein kinases involved in intracellular signal transduction. PI3Ks are grouped into three classes and include Class IA and IB, Class II, and Class III PI3Ks. Studies using broad-spectrum PI3K inhibitors such as wortmannin and LY294002 have shown that Class I PI3Ks are involved in phagocytosis and in mediating entry of parasites such as Trypanosoma cruzi into host cells however, the precise role of each isoform remains unclear. Class IB PI3K[gamma] is expressed primarily by immune cells and has been shown to play a critical role in chemo-attractant induced cell migration by controlling actin cytoskeletal reorganization. In this document, we have characterized a role for PI3K[gamma] in cutaneous leishmaniasis caused by Leishmania mexicana. Using a PI3K[gamma]-selective inhibitor, AS- 605240, and PI3K[gamma]-deficient mice, we demonstrate that PI3K[gamma] contributes to the pathogenesis of cutaneous leishmaniasis by mediating recruitment of phagocytes and regulatory T cells to the site of infection and by facilitating parasite entry into phagocytes. Furthermore, we demonstrate that AS-605240 is as effective as standard anti-leishmanial chemotherapy with sodium stibogluconate in limiting parasite growth after infection. These findings reveal a novel role for PI3K[gamma] in Leishmania mexicana invasion and establishment of chronic infection, and demonstrate that therapeutic targeting of host pathways involved in establishment of infection is a viable treatment strategy for treating cutaneous leishmaniasis caused by Leishmania mexicana and possibly other intracellular pathogens of phagocytes.
Download or read book Arrest chemokines written by Klaus Ley and published by Frontiers Media SA. This book was released on 2015-05-20 with total page 109 pages. Available in PDF, EPUB and Kindle. Book excerpt: Arrest chemokines are a small group of chemokines that promote leukocyte arrest from rolling by triggering rapid integrin activation. Arrest chemokines have been described for neutrophils, monocytes, eosinophils, naïve lymphocytes and effector memory T cells. Most arrest chemokines are immobilized on the endothelial surface by binding to heparin sulfate proteoglycans. Whether soluble chemokines can promote integrin activation and arrest is controversial (Alon-Gerszten). Many aspects of the signaling pathway from the GPCR chemokine receptor to integrin activation are the subject of active investigation. Leukocyte adhesion deficiency III is a human disease in which chemokine-triggered integrin activation is defective because of a mutation in the cytoskeletal protein kindlin-3. About 10 different such mutations have been described. The defects seen in patients with LAD-III elucidate the importance of rapid integrin activation for host defense in humans. We welcome reports that help clarifying this crucial first step in the process of leukocyte transendothelial migration.
Download or read book The Cytoskeleton in T Cell Migration and Activation written by Jerome Delon and published by Frontiers Media SA. This book was released on 2022-11-16 with total page 140 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Encyclopedia of Signaling Molecules written by Sangdun Choi and published by Springer. This book was released on 2017-12-15 with total page 6330 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.
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 Visualizing Immunity written by Dorian McGavern and published by Springer Science & Business Media. This book was released on 2009-06-12 with total page 299 pages. Available in PDF, EPUB and Kindle. Book excerpt: Researchers have used a variety of techniques over the past century to gain fun- mental insights in the field of immunology and, as technology has advanced, so too has the ability of researchers to delve deeper into the biological mechanics of immunity. The immune system is exceedingly complex and must patrol the entire body to protect us from foreign invaders. This requires the immune system to be highly mobile and adaptable - able to respond to diverse microbial challenges while maintaining the ability to distinguish self from a foreign invader. This latter feature is of great importance because the immune system is equipped with toxic mediators, and a failure in self/non-self discrimination can result in serious diseases. Fortunately, in most cases, the immune system operates within the framework of its elegant design and protects us from diverse microbial challenges without initiating disease. Because the immune system is not confined to a single tissue, a comprehensive understanding of immunity requires that research be conducted at the molecular, cellular, and systems level. Immune cells often find customized solutions to h- dling microbial insults that depend on the tissue(s) in which the pathogen is found.
Download or read book Phosphoinositide 3 kinase in Health and Disease written by Christian Rommel and published by Springer Science & Business Media. This book was released on 2010-10-17 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt: From humble beginnings over 25 years ago as a lipid kinase activity associated with certain oncoproteins, PI3K (phosphoinositide 3-kinase) has been catapulted to the forefront of drug development in cancer, immunity and thrombosis, with the first clinical trials of PI3K pathway inhibitors now in progress. Here we give a brief overview of some key discoveries in the PI3K area and their impact, and include thoughts on the current state of the field, and where it could go from here
Download or read book T Cell Motility written by Navin Kumar Verma and published by Humana. This book was released on 2019-01-05 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume discusses the latest developments in cellular, molecular, biochemical, and imaging assays to study the biology and functions of T-cells. The chapters in this book cover topics such as LFA-1/ICAM-1 interactions in T-cell motility; using 3D-SIM to dissect signaling cross-talks in motile T-cells; GapmeR-mediated gene silencing in motile T-cells; activity of cellular kinases in migrating T-cells; and computational analysis of protein-protein interactions in motile T-cells. Written in the highly successful Methods in Molecular Biology series format, 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 comprehensive, T-Cell Motility: Methods and Protocols is an essential resource for graduate students, postdoctoral fellows, and principal investigators working in the fields of immunology, T-cell biology, biochemistry, molecular biology, and imaging.
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.
Download or read book Chemokine Biology Basic Research and Clinical Application written by Kuldeep Neote and published by Springer Science & Business Media. This book was released on 2007-08-08 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chemokines play an important role in recruiting inflammatory cells into tissues in response to infection and inflammation. They also play an important role in coordinating the movement of T-cells, B-cells and dentritic cells, necessary to generate an immune response (response to injury, allergens, antigens, invading microorganisms). They selectively attract leukocytes to inflammatory foci, inducing both cell migration and activation. They are involved in various diseases, like atherosclerosis, lung and skin inflammation, multiple sclerosis, or HIV. Volume 2 of this two-volume set discusses the pathophysiology of chemokines. It is divided into two parts: a) chemokines in animal disease models, and b) chemokines as drug targets. Together with volume 1, which discusses the immunobiology of chemokines, both volumes give a comprehensive overview of chemokine biology.
