Regulation of T Cell Migration and the Immune Response by Phosphoinositide 3-kinase Gamma

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ISBN 13 :
Total Pages : 256 pages
Book Rating : 4.:/5 (319 download)

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Book Synopsis Regulation of T Cell Migration and the Immune Response by Phosphoinositide 3-kinase Gamma by : Amanda Lorene Martin

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:

PI3K and AKT Isoforms in Immunity

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Publisher : Springer Nature
ISBN 13 : 3031065662
Total Pages : 462 pages
Book Rating : 4.0/5 (31 download)

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Book Synopsis PI3K and AKT Isoforms in Immunity by : Margarita Dominguez-Villar

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.

PI3K signalling

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Publisher : Frontiers Media SA
ISBN 13 : 2889194191
Total Pages : 140 pages
Book Rating : 4.8/5 (891 download)

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Book Synopsis PI3K signalling by : Klaus Okkenhaug

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.

An Investigation Into the Role of Protein Kinases in T Lymphocyte Migration

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ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (757 download)

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Book Synopsis An Investigation Into the Role of Protein Kinases in T Lymphocyte Migration by : Adam Webb

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.

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

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Publisher :
ISBN 13 :
Total Pages : 128 pages
Book Rating : 4.:/5 (123 download)

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Book Synopsis 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 by : Jesi Lee Anne To

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.

The Role of Phosphoinositide 3-kinase Gamma in the Host Immune Response Against Cutaneous Leishmaniasis Caused by Leishmania Mexicana

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ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (747 download)

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Book Synopsis The Role of Phosphoinositide 3-kinase Gamma in the Host Immune Response Against Cutaneous Leishmaniasis Caused by Leishmania Mexicana by : Hannah Elizabeth Cummings

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.

Arrest chemokines

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Publisher : Frontiers Media SA
ISBN 13 : 2889194302
Total Pages : 109 pages
Book Rating : 4.8/5 (891 download)

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Book Synopsis Arrest chemokines by : Klaus Ley

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.

Immunopharmacology

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Publisher : Springer Science & Business Media
ISBN 13 : 0387779760
Total Pages : 275 pages
Book Rating : 4.3/5 (877 download)

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Book Synopsis Immunopharmacology by : Manzoor M. Khan

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.

Signaling Mechanisms Regulating T Cell Diversity and Function

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Publisher : CRC Press
ISBN 13 : 149870509X
Total Pages : 258 pages
Book Rating : 4.4/5 (987 download)

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Book Synopsis Signaling Mechanisms Regulating T Cell Diversity and Function by : Jonathan Soboloff

Download or read book Signaling Mechanisms Regulating T Cell Diversity and Function written by Jonathan Soboloff and published by CRC Press. This book was released on 2017-03-27 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.

The Cytoskeleton in T Cell Migration and Activation

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Publisher : Frontiers Media SA
ISBN 13 : 2832506259
Total Pages : 140 pages
Book Rating : 4.8/5 (325 download)

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Book Synopsis The Cytoskeleton in T Cell Migration and Activation by : Jerome Delon

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:

T Cell Hybridomas

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Publisher : Springer
ISBN 13 :
Total Pages : 304 pages
Book Rating : 4.:/5 (44 download)

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Book Synopsis T Cell Hybridomas by : Michael J. Taussig

Download or read book T Cell Hybridomas written by Michael J. Taussig and published by Springer. This book was released on 1985 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Visualizing Immunity

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Publisher : Springer Science & Business Media
ISBN 13 : 3540938648
Total Pages : 299 pages
Book Rating : 4.5/5 (49 download)

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Book Synopsis Visualizing Immunity by : Dorian McGavern

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.

Phosphoinositide 3-kinase in Health and Disease

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Publisher : Springer Science & Business Media
ISBN 13 : 3642148166
Total Pages : 308 pages
Book Rating : 4.6/5 (421 download)

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Book Synopsis Phosphoinositide 3-kinase in Health and Disease by : Christian Rommel

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 308 pages. Available in PDF, EPUB and Kindle. Book excerpt: PI3K has become a very intense area of research, with over 2000 publications on PI3K in PubMed for 2009 alone. The expectations for a therapeutic impact of intervention with PI3K activity are high, and progress in the clinical arena is being monitored by many. However, targeted therapies almost invariably encounter roadblocks, often exposing unresolved questions in the basic understanding of the target

Encyclopedia of Signaling Molecules

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Publisher : Springer
ISBN 13 : 9781493968008
Total Pages : 6330 pages
Book Rating : 4.9/5 (68 download)

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Book Synopsis Encyclopedia of Signaling Molecules by : Sangdun Choi

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.

Cytoskeletal Regulation of Immune Response

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Publisher : Frontiers Media SA
ISBN 13 : 2889719405
Total Pages : 267 pages
Book Rating : 4.8/5 (897 download)

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Book Synopsis Cytoskeletal Regulation of Immune Response by : Sudha Kumari

Download or read book Cytoskeletal Regulation of Immune Response written by Sudha Kumari and published by Frontiers Media SA. This book was released on 2022-01-04 with total page 267 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Chemokine Biology - Basic Research and Clinical Application

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Publisher : Springer Science & Business Media
ISBN 13 : 3764374373
Total Pages : 171 pages
Book Rating : 4.7/5 (643 download)

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Book Synopsis Chemokine Biology - Basic Research and Clinical Application by : Kuldeep Neote

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.

T-Cell Motility

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Publisher : Humana
ISBN 13 : 9781493990351
Total Pages : 0 pages
Book Rating : 4.9/5 (93 download)

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Book Synopsis T-Cell Motility by : Navin Kumar Verma

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.