Download or read book Early Signaling Events in T Cell Activation written by Nancy Chiu and published by . This book was released on 1997 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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.
Download or read book Study of Early Signaling Events in T Cell Activation Enabled Through a Modular and Multi time Point Microfluidic Device written by Catherine Aurelie Rivet and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Binding of the antigen receptor on T cells initiates a rapid series of signaling events leading to an immune response. To fully understand T cell mediated immunity, underlying regulatory properties of the receptor network must be understood. Monitoring dynamic protein signaling events allows for network analysis. Unfortunately, dynamic data acquisition is often extremely time-consuming and expensive with conventional methods; the number of proteins monitored at the same time on the same sample is limited. Furthermore, with conventional, multi-well plate assays it is difficult to achieve adequate resolution at sub-minute timescales. Microfluidics is a capable alternative, providing uniformity in sample handling to reduce error between experiments and precision in timing, an important factor in monitoring phosphorylation events that occur within minutes of stimulation. We used a two-module microfluidic platform for simultaneous multi-time point stimulation and lysis of T cells to investigate early signaling events with a resolution down to 20 seconds using only small amounts of cells and reagents. The device did not elicit adverse cellular stress in Jurkat cells. The activation of 6 important proteins in the signaling cascade upon stimulation with a soluble form of Î"--CD3 in the device was quantified and compared under a variety of conditions. First, in comparison to manual pipetting, the microdevice exhibits significantly less error between experiments. Secondly, a comparison between Jurkat cells and primary T cells shows similar dynamic trends across the 6 proteins. Finally, we have used the device to compare properties of long-term vs, short-term cultured primary T cells. As expected, older cells present a much weakened response to antigenic cues, as measured with TCR response markers. This modular microdevice provides a flexible format for investigating cell signaling properties through the use of soluble cue stimuli.
Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Imaging Initial Events in T cell Activation written by Lawrence Otto Klein and published by Stanford University. This book was released on 2010 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis is organized in four chapters. Chapter I is intended to give a general introduction to [alpha][beta] T cells, their role in the immune system, their T cell receptor (TCR), and the specific TCR transgenic system used in this work. In chapter II the TCR signaling pathway is introduced, and a photoactivation method we developed for interrogating proximal events in this pathway is described. We describe experiments using this method that defined delay times between TCR-pMHC binding and initiation of various TCR proximal signaling events. We found delays much shorter than previous measurements suggested, and propose that they may represent a feature of the pathway predicted by the kinetic-proofreading model of TCR signaling. In this chapter we also describe experiments that took advantage of the ability to precisely define a sub-cellular region of TCR stimulation to interrogate the spatial dynamics of TCR signaling. We found that the T cell membrane was compartmentalized such that even rapidly diffusible second-messengers were confined to the local region of stimulation. By stimulating distinct regions of T cells sequentially, we showed that desensitization occurred rapidly in some branches of the TCR signaling pathway but not at all in others. In chapter III we introduce previous research that sought to define properties of the TCR-pMHC interaction that determine stimulatory potency, and explain how these studies have led to interest in measuring kinetic parameters of the TCR-pMHC interaction in a native two-dimensional environment. We describe development of a new method to measure two-dimensional kinetics using a combination of our photoactivation system and direct detection of receptor-ligand binding via FRET. Using this method we showed that the rate of pMHC binding in a T cell contact interface was not influenced by a variety of cellular factors, but was defined by the kinetics of TCR-pMHC binding measured in vitro. We developed a quantitative method for analyzing our data and found that it fit very well to a simple bimolecular binding model, yielding kinetic parameters in clear agreement with 3D in vitro measurements. Our technique allowed direct, bulk measurement of 2D receptor-ligand binding and has the potential to measure kinetics too fast to measure by previous methods. Finally, in chapter IV we discuss earlier work describing molecular movements that occur during formation of the T cell-APC contact, called the immunological synapse. We describe the results of a series of experiments using our combined FRET and photoactivation assay that revealed the dynamics of TCR-pMHC interactions during immunological synapse formation. Our experiments showed that ligand binding was initiated in small clusters that were stable for tens of seconds while being actively transported toward the center of the cell. We describe the interesting observations that TCR-pMHC binding occurred in a distribution more heterogeneous than either the receptor or ligand distribution, and was regulated by cytoskeletal activity. We showed that in naïve cells this distribution was markedly different than in antigen-experienced cells, indicating that these two cell types may search for antigen in different ways. The results in this chapter indicate that molecular interactions in the synapse are actively regulated by cellular processes and are much more complex than would be expected from measurements of molecular distributions.
Download or read book Visualising Early Signaling Events During TCR Activation written by J. G. Borger and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: T cell activation, differentiation and expansion are induced by signals generated upon engagement of TCR by agonist peptide:MHC. At the site of T cell interaction with an antigen presenting cell, TCR, accessory proteins such as CD28 and LFA-1, and the Src family kinases (SFK) Lck and Fyn, accumulate and form the immunological synapse. Lck is the key signaling molecule, initiating TCR signals by phosphorylating the ITAM in the CD3/ subunits resulting in the recruitment and activation of Zap-70 and further propagation of the signaling cascade. Fyn is a positive mediator of T cell signaling, sharing specific substrates in common with Lck, and also acts as a negative regulator by phosphorylating the adaptor protein, PAG. Phosphorylated PAG binds Csk and its recently identified binding partner, the protein phosphatase PEP, recruiting them to the plasma membrane where they can inhibit the SFK. The differential localisation of the kinases, with Fyn compartmentalised to lipid rafts in mature T cells and the majority of Lck being non-lipid raft associated could explain the unique functions attributed to each kinase. In order to examine the interactions between SFK and their negative regulators in T cell activation, CD8+ T cells from mice expressing the class I MHC-restricted TCR, F5, were investigated. In naïve T cells Lck, Fyn, Csk and PEP were shown to co-localise to the site of activation-induced tyrosine phosphorylation following early TCR crosslinking. In contrast, in memory T cells Csk, PEP and Fyn not only co-localised with the site of TCR activation but also distributed at the distal end of the cell, suggesting differential redistribution of key negative regulators away from the site of TCR engagement in these cells. In the absence of Fyn there was no change in Csk localisation despite the loss of PAG phosphorylation, suggesting another adaptor protein can recruit Csk to the plasma membrane. Caveolin-1, a cholesterol-rich membrane protein was investigated as a possible candidate for recruiting Csk and was shown to be present in CD8+ T cells. Moreover, caveolin-1 was shown to be phosphorylated by Lck, Fyn and Abl kinases upon TCR engagement and to redistribute and polarise to the cSMAC, co-localising with Csk. In summary we have shown that there are alterations in the distribution of the negative regulators Csk, PEP and Fyn, once T cells have encountered antigen, and that this could be associated to the more efficient responses of memory cells upon re-exposure to antigen. Furthermore, its appears there is redundancy of both signaling molecules and adaptor proteins, which may contribute to the fine tuning of the TCR signaling pathway, such that signals derived from the TCR can still modulate an appropriate immune response even in the absence of key regulators.
Download or read book Janeway s Immunobiology written by Kenneth Murphy and published by Garland Science. This book was released on 2010-06-22 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Download or read book T Cell Activation I written by Gary A. Koretzky and published by . This book was released on 2003 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Cytokines of the Immune System written by Zlatko Dembic and published by Academic Press. This book was released on 2015-05-23 with total page 323 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Cytokines of the Immune System catalogs cytokines and links them to physiology and pathology, providing a welcome and hugely timely tool for scientists in all related fields. In cataloguing cytokines, it lists their potential for therapeutic use, links them to disease treatments needing further research and development, and shows their utility for learning about the immune system. This book offers a new approach in the study of cytokines by combining detailed guidebook-style cytokine description, disease linking, and presentation of immunologic roles. - Supplies new ideas for basic and clinical research - Provides cytokine descriptions in a guidebook-style, cataloging the origins, structures, functions, receptors, disease-linkage, and therapeutic potentials - Offers a textbook-style view on the immune system with the immunologic role of each cytokine
Download or read book Regulatory Mechanisms of Early Intracellular Signaling in T Lymphocytes written by Enrique Aguado and published by Frontiers Media SA. This book was released on 2021-05-21 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Immunology for Pharmacy E Book written by Dennis Flaherty and published by Elsevier Health Sciences. This book was released on 2014-06-25 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: With a new pharmacy-specific approach to immunology, Immunology for Pharmacy prepares pharmacists for practice by providing a complete understanding of the basis of immunology and the consequences of either suppressing or enhancing immune function. It covers key subjects such as prophylaxis and vaccination, antibodies as therapeutic and diagnostic agents, biological modifiers, and the rationale for use and mechanisms of therapeutic agents. Written by experienced author and educator Dennis Flaherty, this book presents topics with a logical, step-by-step approach, explaining concepts and their practical application. A companion Evolve website reinforces your understanding with flashcards and animations. Pharmacy-specific coverage narrows the broad field of immunology to those areas most pertinent and clinically relevant to pharmacy students. 165 full-color illustrations help to illuminate difficult concepts. Factors That Influence the Immune Response chapter covers biological agents including bacteria, viruses, and fungi, and their related toxins and how they relate to the immune system. Three chapters on vaccinations prepare you for this important part of the pharmacist's role by discussing cancer treatment with whole tumor vaccines, cell vaccines, and viral vector vaccines, describing other vaccines such as recombinant vaccines and plant vaccines, and examining how diseases such as diphtheria, whooping cough, and tetanus respond to vaccinations. A summary of drugs used in treating each condition helps you understand typical treatments and their immunological mechanisms, so you can choose proper treatments. Integrated information makes it easier to understand how various parts of the immune system work together, leading to a better understanding of immunology as a whole. A unique focus on practical application and critical thinking shows the interrelationship of concepts and makes it easier to apply theory to practice. Information on AIDS covers the identification and treatment of both strains of HIV as well as AIDS, preparing you for diseases you will see in practice. Unique student-friendly features simplify your study with learning objectives and key terms at the beginning of each chapter, bulleted summaries and self-assessment questions at the end of each chapter, and a glossary at the back of the book. Over 60 tables summarize and provide quick reference to important material. A companion Evolve website includes animations and pharmacy terminology flashcards.
Download or read book Innate Immunity in Health and Disease written by Shailendra K. Saxena and published by BoD – Books on Demand. This book was released on 2021-08-25 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book focuses on various aspects and properties of innate immunity, whose deep understanding is integral for safeguarding the human race from further loss of resources and economies due to innate immune response-mediated diseases. Throughout this book, we examine the individual mechanisms by which the innate immune response acts to protect the host from pathogenic infectious agents and other non-communicable diseases. Written by experts in the field, the volume discusses the significance of macrophages in infectious disease, tumor metabolism, and muscular disorders. Chapters cover such topics as the fate of differentiated macrophages and the molecular pathways that are important for the pathologic role of macrophages.
Download or read book T Cell Development written by Rémy Bosselut and published by Humana. This book was released on 2015-08-22 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides simple and accessible experiment protocols to explore thymus biology. T-Cell Development: Methods and Protocols is divided into three parts presenting short reviews on T cell development, analysis strategies, protocols for cell preparation, flow cytometry analyses, and multiple aspects of thymocyte biology. As a volume in the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, T-Cell Development: Methods and Protocols aims to ensure successful results in the further study of this vital field.
Download or read book Persistent Viral Infections written by R. Ahmed and published by Wiley-Blackwell. This book was released on 1999 with total page 754 pages. Available in PDF, EPUB and Kindle. Book excerpt: Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.
Download or read book The Immune Response written by Tak W. Mak and published by Academic Press. This book was released on 2005-11-11 with total page 1217 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Immune Response is a unique reference work covering the basic and clinical principles of immunology in a modern and comprehensive fashion. Written in an engaging conversational style, the book conveys the broad scope and fascinating appeal of immunology. The book is beautifully illustrated with superb figures as well as many full color plates. This extraordinary work will be an invaluable resource for lecturers and graduate students in immunology, as well as a vital reference for research scientists and clinicians studying related areas in the life and medical sciences. - Current and thorough 30 chapter reference reviewed by luminaries in the field - Unique 'single voice' ensures consistency of definitions and concepts - Comprehensive and elegant illustrations bring key concepts to life - Provides historical context to allow fuller understanding of key issues - Introductory chapters 1-4 serve as an 'Immunology Primer' before topics are discussed in more detail
Download or read book Imaging Initial Events in T cell Activation written by Lawrence Otto Klein and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis is organized in four chapters. Chapter I is intended to give a general introduction to [alpha][beta] T cells, their role in the immune system, their T cell receptor (TCR), and the specific TCR transgenic system used in this work. In chapter II the TCR signaling pathway is introduced, and a photoactivation method we developed for interrogating proximal events in this pathway is described. We describe experiments using this method that defined delay times between TCR-pMHC binding and initiation of various TCR proximal signaling events. We found delays much shorter than previous measurements suggested, and propose that they may represent a feature of the pathway predicted by the kinetic-proofreading model of TCR signaling. In this chapter we also describe experiments that took advantage of the ability to precisely define a sub-cellular region of TCR stimulation to interrogate the spatial dynamics of TCR signaling. We found that the T cell membrane was compartmentalized such that even rapidly diffusible second-messengers were confined to the local region of stimulation. By stimulating distinct regions of T cells sequentially, we showed that desensitization occurred rapidly in some branches of the TCR signaling pathway but not at all in others. In chapter III we introduce previous research that sought to define properties of the TCR-pMHC interaction that determine stimulatory potency, and explain how these studies have led to interest in measuring kinetic parameters of the TCR-pMHC interaction in a native two-dimensional environment. We describe development of a new method to measure two-dimensional kinetics using a combination of our photoactivation system and direct detection of receptor-ligand binding via FRET. Using this method we showed that the rate of pMHC binding in a T cell contact interface was not influenced by a variety of cellular factors, but was defined by the kinetics of TCR-pMHC binding measured in vitro. We developed a quantitative method for analyzing our data and found that it fit very well to a simple bimolecular binding model, yielding kinetic parameters in clear agreement with 3D in vitro measurements. Our technique allowed direct, bulk measurement of 2D receptor-ligand binding and has the potential to measure kinetics too fast to measure by previous methods. Finally, in chapter IV we discuss earlier work describing molecular movements that occur during formation of the T cell-APC contact, called the immunological synapse. We describe the results of a series of experiments using our combined FRET and photoactivation assay that revealed the dynamics of TCR-pMHC interactions during immunological synapse formation. Our experiments showed that ligand binding was initiated in small clusters that were stable for tens of seconds while being actively transported toward the center of the cell. We describe the interesting observations that TCR-pMHC binding occurred in a distribution more heterogeneous than either the receptor or ligand distribution, and was regulated by cytoskeletal activity. We showed that in naïve cells this distribution was markedly different than in antigen-experienced cells, indicating that these two cell types may search for antigen in different ways. The results in this chapter indicate that molecular interactions in the synapse are actively regulated by cellular processes and are much more complex than would be expected from measurements of molecular distributions.
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.
