Download or read book Molecular Interactions in Immunological Synapse Formation and T Cell Activation written by Shannon Kimberly Bromley and published by . This book was released on 2001 with total page 290 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Molecular Dynamics at the Immunological Synapse written by Pedro Roda-Navarro and published by Frontiers Media SA. This book was released on 2017-03-21 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt: The immunological synapse (IS) is a specialised cell-cell adhesion that mediates antigen acquisition and regulates the activation of lymphocytes. Initial studies of the IS showed a structure composed of stable supra-molecular activation clusters (SMAC) organised during the interaction of helper T lymphocytes with B lymphocytes, working as antigen presenting cells. A central SMAC of coalesced T cell receptors (TCRs) and a peripheral SMAC for cell-cell adhesion were observed. IS with similar structure was later described during antigen acquisition by B cells and during the interaction of NK cells with target and healthy cells. More recent research developed with microscopy systems that improve the spatial and temporal resolution has showed the complex molecular dynamics at the IS that governs lymphocyte activation. Currently, the IS is seen as a three-dimensional structure where signalling networks for lymphocyte activation and endosomal and cytoskeleton machinery are polarised. A view has emerged in which dynamic microclusters of signalling complexes are composed of molecular components attached to the plasma membrane and other components conveyed on sub-synaptic vesicles transported to the membrane by cytoskeletal fibers and motor proteins. Much information is nonetheless missing about how the dynamics of the endosomal compartment, the cytoskeleton, and signalling complexes are reciprocally regulated to achieve the function of lymphocytes. Experimental evidence also suggests that the environment surrounding lymphocytes exposed to different antigenic challenge regulates IS assembly and functional output, making an even more complex scenario still far from being completely understood. Also, although some signalling molecular components for lymphocyte activation have been identified and thoroughly studied, the function of other molecules has not been yet uncovered or deeply characterised. This research topic aims to provide the reader with the latest information about the molecular dynamics governing lymphocyte activation. These molecular dynamics dictate cell decisions. Thus, we expect that understanding them will provide new avenues for cell manipulation in therapies to treat different immune-related pathologies.
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 The Immune Synapse written by Cosima T. Baldari and published by Humana. This book was released on 2024-04-28 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new collection features the most up-to-date essential protocols that are currently being used to study the immune synapse. Beginning with methods for making biophysical measurements, the volume continues by covering the cell biology of synapses, methods for advanced substrate engineering, mechanobiology topics, new technologies to describe and manipulate synaptic components, as well as methods related to sites of action and immunotherapy. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and fully updated, The Immune Synapse: Methods and Protocols, Second Edition serves as an ideal practical guide for researchers working in this dynamic field. Chapters 5, 11,18, 27, 30, and 32 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
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 The Immune Synapse written by Cosima T. Baldari and published by Springer Nature. This book was released on 2023-04-27 with total page 518 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new collection features the most up-to-date essential protocols that are currently being used to study the immune synapse. Beginning with methods for making biophysical measurements, the volume continues by covering the cell biology of synapses, methods for advanced substrate engineering, mechanobiology topics, new technologies to describe and manipulate synaptic components, as well as methods related to sites of action and immunotherapy. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and fully updated, The Immune Synapse: Methods and Protocols, Second Edition serves as an ideal practical guide for researchers working in this dynamic field. Chapters 5, 11, 18, 27, 30, and 32 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Download or read book The Immune Synapse as a Novel Target for Therapy written by Luis Graca and published by Springer Science & Business Media. This book was released on 2007-12-18 with total page 201 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume gives an overview on the progress in immune synapse research, from basic science to clinical trials, and the major mechanisms involved. It discusses how interfering with T cell activation may lead to immune tolerance, immune modulation, and the recruitment of regulatory T cells; the role of monoclonal antibodies in tolerance induction; and mechanisms maintaining dominant tolerance.
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 Plasma Membrane Dynamics and Pattern Formation During T Cell Activation written by Adam D. Douglass and published by . This book was released on 2006 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: T cell activation entails a complex series of signal transduction events that begin with ligation of the T cell receptor by a cognate antigen, displayed on the surface of an antigen presenting cell. During T cell signaling proteins in the cell surface partition from one another into large, stereotyped molecular pattern that is known as the immunological synapse. This thesis attempts to understand the mechanisms by which this segregation occurs, and uses a number of fluorescence imaging techniques---in particular, single molecule microscopy---to this end. Contrary to reports that suggest a role for lipid raft domains in patterning the synapse, we find that protein-protein interactions, and not putative lipid raft associations, are a strong driving force in synapse formation. We also develop a method for reconstituting synapse formation in an immortalized T cell line that allows us to perform single molecule imaging on a fluid substrate of a defined composition. A common finding is that both passive mechanisms, involving diffusional trapping and exclusion, as well as active mechanisms, involving actin-driven transport, can act in concert to shape the immunological synapse.
Download or read book Driving Forces in the Immunological Synapse written by Andrew Lambert DeMond and published by . This book was released on 2007 with total page 134 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Immunological Synapse written by Sung-Joo Eugene Lee and published by . This book was released on 2003 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Molecular Biology of The Cell written by Bruce Alberts 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 Cell Polarity 1 written by Klaus Ebnet and published by Springer. This book was released on 2015-03-04 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work provides a state-of-the art overview on the most relevant aspects of cell polarity. Volume 1 addresses cell polarity and cell migration (front-rear polarity), cell polarity and barrier formation (apico-basal polarity) and neuronal polarity. It particularly focuses on cell polarity at the molecular level and the underlying molecular mechanisms. It also elaborates the common principles and mechanisms that regulate cellular polarization in different cell types and contexts. Both volumes are intended for professors, group leaders and researchers in cell biology as well as medical professionals in the fields of anatomy, cell biology, physiology, pathology and tumor biology.
Download or read book Co signal Molecules in T Cell Activation written by Miyuki Azuma and published by Springer Nature. This book was released on 2019-11-22 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book equips young immunologists and health professionals with a clear understanding of the fundamental concepts and roles of co-signal molecules and in addition presents the latest information on co-stimulation. The first part of the book is devoted to co-signal molecules and the regulation of T cells. Following an initial overview, subsequent chapters examine each co-signal molecule in turn and discuss the mechanisms by which co-signal molecules regulate the different types of T cell. The second part covers various clinical applications, including in autoimmune disease, neurological disorders, transplantation, graft-versus-host disease, and cancer immunotherapy. To date, co-stimulation blockade and co-inhibition blockade have shown beneficial effects and many additional clinical trials targeting co-signal molecules are ongoing. The mechanisms underlying these successful treatments are explained and the future therapeutic potential in the aforementioned diseases is evaluated. Co-signal Molecules in T Cell Activation will be a valuable reference guide to co-stimulation for basic and clinical researchers in the fields of both immunology and pharmaceutical science.
Download or read book Monitoring Cellular Interactions During T Cell Activation at the Single Molecule Level Using Semiconductor Quantum Dots written by and published by . This book was released on 2005 with total page 8 pages. Available in PDF, EPUB and Kindle. Book excerpt: Enhanced peptide-coated quantum dots (with high brightness and high saturation intensity) were developed. Two high-affinity targeting "velcro-pairs" based on avidin-biotin and fluorescine-antibody interactions were demonstrated and used to specifically target single proteins in membranes of live cells. Single molecule spectroscopy and imaging of individual quantum dot-labeled lipid rafts receptors were performed. Software tools were developed to analyze individual diffusion and trafficking trajectories. These studies provide strong support for the lipid raft hypothesis. Cloning and fusion of avidin to four immune synapse components were achieved. These mutants are being characterized by flow cytometry and fluorescence microscopy. This report provides information on the following new findings: (1) hybrid approach to the synthesis of highly luminescent infrared CdTe/ZnS and CdHgTe/ZnS quantum dots; (2) bioactivation and cell targeting of semiconductor CdSe/ZnS quantum dots with phytochelatin-related peptides; (3) development of bright Cd+ rich peptide-coated quantum dots; (4) comparison of the photophysical and colloidal properties of biocompatible quantum dots using fluorescence correlation spectroscopy (FCS); (5) testing the lipid raft hypothesis by single molecule imaging of targeted peptide-coated quantum dots; and (6) molecular cloning and fusion of avidin to immunological synapse (IS) components.
Download or read book Immunological Synapse Arrays written by Junsang Doh and published by . This book was released on 2006 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: (Cont.) Using a photolithographic strategy we developed employing this novel PNMP photoresist polymer, we created multicomponent protein surfaces presenting micron-scale arrays of tethered T cell receptor (TCR) ligands (anti-CD3 'activation sites') surrounded by a field of tethered intercellular adhesion molecule-I (ICAM-1), as a model substrate on which T cells could be seeded to mimic T cell-APC interactions. CD4+ T cells seeded on these surfaces polarized and migrated; on contact with activation sites, T cells assembled an IS with a structure modulated by the physical pattern of ligand encountered. On surfaces patterned with focal spots of TCR ligand, T cells stably interacted with activation sites, proliferated, and secreted cytokines. In contrast, T cells interacting with activation sites patterned to preclude centralized clustering of TCR ligand failed to form stable contacts with activation sites, exhibited aberrant PKC-[Theta] clustering in a fraction of cells, and had significantly reduced production of interferon-[gamma]. These results suggest that focal clustering of TCR ligand characteristic of the 'mature' IS may be required under some conditions for full T cell activation.
Download or read book Protein Kinase mediated Decisions Between Life and Death written by Ayse Basak Engin and published by Springer Nature. This book was released on 2021-02-04 with total page 415 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein phosphorylation via protein kinases is an inevitable process that alters physiological and pathological functions of the cells. Thus, protein kinases play key roles in the regulation of cell life or death decisions. Protein kinases are frequently a driving factor in a variety of human diseases including aging and cellular senescence, immune system and endothelial dysfunctions, cancers, insulin resistance, cholestasis and neurodegenerative diseases, as well as bacterial resistance in persistent infections. Recent developments in quantitative proteomics provide important opinions on kinase inhibitor selectivity and their modes of action in the biological context. Protein Kinase-mediated Decisions Between Life and Death aims to have the reader catch insights about up-to-date opinions on “Protein Kinases” related pathways that threaten human health and life. As “Protein Kinases” are related to many health problems, clinicians, basic science researchers and students need this information. Chapter “Signal Transduction in Immune Cells and Protein Kinases” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
