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Role Of Clustering In Determining Spatial Organization At The Immunological Synapse


Role Of Clustering In Determining Spatial Organization At The Immunological Synapse
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Role Of Clustering In Determining Spatial Organization At The Immunological Synapse


Role Of Clustering In Determining Spatial Organization At The Immunological Synapse
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Author : Nina Caculitan Hartman
language : en
Publisher:
Release Date : 2010

Role Of Clustering In Determining Spatial Organization At The Immunological Synapse written by Nina Caculitan Hartman and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.


Micron-scale assemblies of molecules are thematic in biology, although their mechanism of formation and exact functional role are oftentimes unknown. The immunological synapse (IS)--the gateway event to the body's initiation of an immune response against infection--is a hallmark example. T cell detection of pathogenic invasion on an antigen-presenting cell leads to the arrangement of receptor-ligand pairs into well-defined concentric zones referred to as supramolecular activation clusters (SMACs). The main signaling molecule, the T cell receptor (TCR), binds its specific foreign peptide-presenting ligand, major histocompatibility complex (pMHC). These complexes form a central cluster in the central SMAC (cSMAC) at the center of the intermembrane junction. Immediately surrounding the cSMAC is the peripheral SMAC (pSMAC), populated by a ring of leukocyte function associated antigen-1 (LFA-1) bound to intercellular adhesion molecule-1 (ICAM-1). In this dissertation, we determine how the final IS pattern emerges from a uniform distribution of receptor-ligand pairs. It is known that the actin cytoskeleton drives the centripetal transport of these proteins, but it is unclear how actin sorts them into their final destinations. We postulate that the large-scale sorting of proteins into the different SMACs is a natural consequence of smaller scale protein sorting into microclusters, which may contain hundreds of molecules. To test this, we increase the LFA-1 cluster size two additional degrees beyond its native state with antibody crosslinkers. We either crosslink LFA-1 directly or indirectly with antibodies against its ICAM-1 ligand, which is presented on a supported membrane with the activating pMHC. Progressively more central localization of LFA-1 proportional to the degree of crosslinking results until LFA-1 occupies the cSMAC with TCR. Based on these results, we propose a sorting mechanism based on frictional protein coupling to actin. In the frictional force coupling model, the extent of radial protein transport by actin is determined by the specific coupling chemistry and the protein cluster size. This model predicts cluster size-based protein sorting across the IS. Using fluorescence fluctuation measurements and a small illumination area, we detect a gradient of LFA-1:ICAM-1 cluster sizes across the pSMAC in the native IS, as predicted by our model. Thus, we demonstrate that the well-regulated event of protein clustering is a critical parameter in regulating spatial patterning in the IS.



Molecular Dynamics At The Immunological Synapse


Molecular Dynamics At The Immunological Synapse
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Author : Pedro Roda-Navarro
language : en
Publisher: Frontiers Media SA
Release Date : 2017-03-21

Molecular Dynamics At The Immunological Synapse written by Pedro Roda-Navarro and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-03-21 with categories.


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.



The Role Of Tissue Resident Nk Cells During Homeostasis Primary And Secondary Infection


The Role Of Tissue Resident Nk Cells During Homeostasis Primary And Secondary Infection
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Author : Silke Paust
language : en
Publisher: Frontiers Media SA
Release Date : 2022-02-11

The Role Of Tissue Resident Nk Cells During Homeostasis Primary And Secondary Infection written by Silke Paust and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-02-11 with Medical categories.




Encyclopedia Of Immunobiology


Encyclopedia Of Immunobiology
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Author :
language : en
Publisher: Academic Press
Release Date : 2016-04-27

Encyclopedia Of Immunobiology written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-04-27 with Medical categories.


Encyclopedia of Immunobiology, Five Volume Set provides the largest integrated source of immunological knowledge currently available. It consists of broad ranging, validated summaries on all of the major topics in the field as written by a team of leading experts. The large number of topics covered is relevant to a wide range of scientists working on experimental and clinical immunology, microbiology, biochemistry, genetics, veterinary science, physiology, and hematology. The book is built in thematic sections that allow readers to rapidly navigate around related content. Specific sections focus on basic, applied, and clinical immunology. The structure of each section helps readers from a range of backgrounds gain important understanding of the subject. Contains tables, pictures, and multimedia features that enhance the learning process In-depth coverage allows readers from a range of backgrounds to benefit from the material Provides handy cross-referencing between articles to improve readability, including easy access from portable devices



Handbook Of Cell Signaling Three Volume Set


Handbook Of Cell Signaling Three Volume Set
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Author : Ralph A. Bradshaw
language : en
Publisher: Academic Press
Release Date : 2003-12-02

Handbook Of Cell Signaling Three Volume Set written by Ralph A. Bradshaw and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003-12-02 with Science categories.


The Handbook of Cell Signaling is a comprehensive work covering all aspects of intracellular signal processing, including extra/intracellular membrane receptors, signal transduction, gene expression/translation, and cellular/organotypic signal responses. The subject matter has been divided into five main parts (each of which is headed by a recognized expert in the field):* Initiation: Extracellular and Membrane Events* Transmission: Effectors and Cytosolic Events * Nuclear Responses: Gene Expression and Translation* Events in Intracellular Compartments* Cell-Cell and Cell-Matrix Interactions Covered in extensive detail, these areas will appeal to a broad, cross-disciplinary audience interested in the structure, biochemistry, molecular biology and pathology of cellular effectors. Tabular and well-illustrated, the Handbook will serve as an in-depth reference for this complex and evolving field.Tabular and well illustrated, the Handbook will serve as an in-depth reference for this complex and evolving field!* Contains approximately 470 articles* Provides well-organized sections on each essential area in signaling* Includes discussion on everything from ligand/receptor interactions to organ/organism responses* Extremely user-friendly



The Journal Of Immunology


The Journal Of Immunology
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Author :
language : en
Publisher:
Release Date : 2007

The Journal Of Immunology written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with Immunology categories.




The Role Of Biomembranes And Biophysics In Immune Cell Signaling


The Role Of Biomembranes And Biophysics In Immune Cell Signaling
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Author : Yan Shi
language : en
Publisher: Frontiers Media SA
Release Date : 2021-11-15

The Role Of Biomembranes And Biophysics In Immune Cell Signaling written by Yan Shi and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-11-15 with Medical categories.




Super Resolution Imaging In Biomedicine


Super Resolution Imaging In Biomedicine
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Author : Alberto Diaspro
language : en
Publisher: CRC Press
Release Date : 2016-11-03

Super Resolution Imaging In Biomedicine written by Alberto Diaspro and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-11-03 with Science categories.


This book encompasses the full breadth of the super-resolution imaging field, representing modern techniques that exceed the traditional diffraction limit, thereby opening up new applications in biomedicine. It shows readers how to use the new tools to increase resolution in sub-nanometer-scale images of living cells and tissue, which leads to new information about molecules, pathways and dynamics. The book highlights the advantages and disadvantages of the techniques, and gives state-of-the-art examples of applications using microscopes currently available on the market. It covers key techniques such as stimulated emission depletion (STED), structured illumination microscopy (SSIM), photoactivated localization microscopy (PALM), and stochastic optical reconstruction microscopy (STORM). It will be a useful reference for biomedical researchers who want to work with super-resolution imaging, learn the proper technique for their application, and simultaneously obtain a solid footing in other techniques.



Regulatory Mechanisms Of Early Intracellular Signaling In T Lymphocytes


Regulatory Mechanisms Of Early Intracellular Signaling In T Lymphocytes
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Author : Enrique Aguado
language : en
Publisher: Frontiers Media SA
Release Date : 2021-05-21

Regulatory Mechanisms Of Early Intracellular Signaling In T Lymphocytes written by Enrique Aguado and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-05-21 with Science categories.




Roles Of Fc Receptors In Disease And Therapy


Roles Of Fc Receptors In Disease And Therapy
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Author : Latha P. Ganesan
language : en
Publisher: Frontiers Media SA
Release Date : 2020-07-22

Roles Of Fc Receptors In Disease And Therapy written by Latha P. Ganesan and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-07-22 with categories.