Immunological Synapses: The interfaces between T-CELLS and ANTIGEN-PRESENTING CELLS. Supramolecular organization of proteins takes place at these synapses involving various types of immune cells. Immunological synapses can have several functions including LYMPHOCYTE ACTIVATION; enhancing, balancing, or terminating signaling; or directing cytokine secretion.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.Antigen-Presenting Cells: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Lymphocyte Function-Associated Antigen-1: An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (ANTIGENS, CD18) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.Microtubule-Organizing Center: An amorphous region of electron dense material in the cytoplasm from which the MICROTUBULES polymerization is nucleated. The pericentriolar region of the CENTROSOME which surrounds the CENTRIOLES is an example.Excitatory Postsynaptic Potentials: Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Membrane Microdomains: Detergent-insoluble CELL MEMBRANE components. They are enriched in SPHINGOLIPIDS and CHOLESTEROL and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins.Dendritic Spines: Spiny processes on DENDRITES, each of which receives excitatory input from one nerve ending (NERVE ENDINGS). They are commonly found on PURKINJE CELLS and PYRAMIDAL CELLS.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.Neuronal Plasticity: The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.Neuromuscular Junction: The synapse between a neuron and a muscle.Antigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Mice, Inbred C57BLMice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Antigens, CD28: Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.Nerve Tissue ProteinsLymphocyte Specific Protein Tyrosine Kinase p56(lck): This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.Receptors, AMPA: A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).Synaptic Membranes: Cell membranes associated with synapses. Both presynaptic and postsynaptic membranes are included along with their integral or tightly associated specializations for the release or reception of transmitters.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Electrical Synapses: Specialized junctions between NEURONS which connect the cytoplasm of one neuron to another allowing direct passage of an ion current.Models, Immunological: Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.Cell Adhesion Molecules, Neuronal: Surface ligands that mediate cell-to-cell adhesion and function in the assembly and interconnection of the vertebrate nervous system. These molecules promote cell adhesion via a homophilic mechanism. These are not to be confused with NEURAL CELL ADHESION MOLECULES, now known to be expressed in a variety of tissues and cell types in addition to nervous tissue.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.Agrin: A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development.Wiskott-Aldrich Syndrome Protein: WASP protein is mutated in WISKOTT-ALDRICH SYNDROME and is expressed primarily in hematopoietic cells. It is the founding member of the WASP protein family and interacts with CDC42 PROTEIN to help regulate ACTIN polymerization.Synaptophysin: A MARVEL domain-containing protein found in the presynaptic vesicles of NEURONS and NEUROENDOCRINE CELLS. It is commonly used as an immunocytochemical marker for neuroendocrine differentiation.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.Receptors, Glutamate: Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.Immunologic Capping: An energy dependent process following the crosslinking of B CELL ANTIGEN RECEPTORS by multivalent ligands (bivalent anti-antibodies, LECTINS or ANTIGENS), on the B-cell surface. The crosslinked ligand-antigen receptor complexes collect in patches which flow to and aggregate at one pole of the cell to form a large mass - the cap. The caps may then be endocytosed or shed into the environment.Proto-Oncogene Proteins c-vav: Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.Vesicular Glutamate Transport Protein 1: A vesicular glutamate transporter protein that is predominately expressed in TELENCEPHALON of the BRAIN.Antigen Presentation: The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Nonmuscle Myosin Type IIA: A nonmuscle isoform of myosin type II found predominantly in platelets, lymphocytes, neutrophils and brush border enterocytes.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Coculture Techniques: A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory.Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Guanylate Kinase: Catalyzes the ATP-dependent PHOSPHORYLATION of GMP to generate GDP and ADP.Synapsins: A family of synaptic vesicle-associated proteins involved in the short-term regulation of NEUROTRANSMITTER release. Synapsin I, the predominant member of this family, links SYNAPTIC VESICLES to ACTIN FILAMENTS in the presynaptic nerve terminal. These interactions are modulated by the reversible PHOSPHORYLATION of synapsin I through various signal transduction pathways. The protein is also a substrate for cAMP- and CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. It is believed that these functional properties are also shared by synapsin II.Animals, Newborn: Refers to animals in the period of time just after birth.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesAntigens, CD2: Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Motor Neurons: Neurons which activate MUSCLE CELLS.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Lymnaea: A genus of dextrally coiled freshwater snails that includes some species of importance as intermediate hosts of parasitic flukes.Purkinje Cells: The output neurons of the cerebellar cortex.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Receptors, Cholinergic: Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Post-Synaptic Density: Cytoskeleton specialization at the cytoplasmic side of postsynaptic membrane in SYNAPSES. It is involved in neuronal signaling and NEURONAL PLASTICITY and comprised of GLUTAMATE RECEPTORS; scaffolding molecules (e.g., PSD95, PSD93), and other proteins (e.g., CaCMKII).Interneurons: Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Cerebellum: The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Dendritic Cells: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Wiskott-Aldrich Syndrome: A rare, X-linked immunodeficiency syndrome characterized by ECZEMA; LYMPHOPENIA; and, recurrent pyogenic infection. It is seen exclusively in young boys. Typically, IMMUNOGLOBULIN M levels are low and IMMUNOGLOBULIN A and IMMUNOGLOBULIN E levels are elevated. Lymphoreticular malignancies are common.Models, Neurological: Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Neurogenesis: Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Aplysia: An opisthobranch mollusk of the order Anaspidea. It is used frequently in studies of nervous system development because of its large identifiable neurons. Aplysiatoxin and its derivatives are not biosynthesized by Aplysia, but acquired by ingestion of Lyngbya (seaweed) species.Intercellular Junctions: Direct contact of a cell with a neighboring cell. Most such junctions are too small to be resolved by light microscopy, but they can be visualized by conventional or freeze-fracture electron microscopy, both of which show that the interacting CELL MEMBRANE and often the underlying CYTOPLASM and the intervening EXTRACELLULAR SPACE are highly specialized in these regions. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p792)Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Receptor-Like Protein Tyrosine Phosphatases, Class 2: A subclass of receptor-like protein tryosine phosphatases that contain multiple extracellular immunoglobulin G-like domains and fibronectin type III-like domains. An additional memprin-A5-mu domain is found on some members of this subclass.Pyramidal Cells: Projection neurons in the CEREBRAL CORTEX and the HIPPOCAMPUS. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region.Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Synaptic Potentials: The voltages across pre- or post-SYNAPTIC MEMBRANES.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Intercellular Adhesion Molecule-1: A cell-surface ligand involved in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue.Luminescent Proteins: Proteins which are involved in the phenomenon of light emission in living systems. Included are the "enzymatic" and "non-enzymatic" types of system with or without the presence of oxygen or co-factors.Neural Cell Adhesion Molecules: Cell adhesion molecule involved in a diverse range of contact-mediated interactions among neurons, astrocytes, oligodendrocytes, and myotubes. It is widely but transiently expressed in many tissues early in embryogenesis. Four main isoforms exist, including CD56; (ANTIGENS, CD56); but there are many other variants resulting from alternative splicing and post-translational modifications. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, pp115-119)Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.T-Lymphocytes, Cytotoxic: Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.Vesicular Inhibitory Amino Acid Transport Proteins: A family of vesicular neurotransmitter transporter proteins that sequester the inhibitory neurotransmitters GLYCINE; GAMMA-AMINOBUTYRIC ACID; and possibly GAMMA-HYDROXYBUTYRATE into SECRETORY VESICLES.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Receptor-CD3 Complex, Antigen, T-Cell: Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.Pyridinium CompoundsLeeches: Annelids of the class Hirudinea. Some species, the bloodsuckers, may become temporarily parasitic upon animals, including man. Medicinal leeches (HIRUDO MEDICINALIS) have been used therapeutically for drawing blood since ancient times.Antigens, Differentiation, T-Lymphocyte: Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.Secretory Vesicles: Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface.Mice, Inbred BALB CMicroscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Long-Term Synaptic Depression: A persistent activity-dependent decrease in synaptic efficacy between NEURONS. It typically occurs following repeated low-frequency afferent stimulation, but it can be induced by other methods. Long-term depression appears to play a role in MEMORY.Organ Culture Techniques: A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Ganglia, Invertebrate: Clusters of neuronal cell bodies in invertebrates. Invertebrate ganglia may also contain neuronal processes and non-neuronal supporting cells. Many invertebrate ganglia are favorable subjects for research because they have small numbers of functional neuronal types which can be identified from one animal to another.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Nerve Fibers: Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM.Neural Pathways: Neural tracts connecting one part of the nervous system with another.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Mossy Fibers, Hippocampal: Axons of certain cells in the DENTATE GYRUS. They project to the polymorphic layer of the dentate gyrus and to the proximal dendrites of PYRAMIDAL CELLS of the HIPPOCAMPUS. These mossy fibers should not be confused with mossy fibers that are cerebellar afferents (see NERVE FIBERS).Cell Adhesion: Adherence of cells to surfaces or to other cells.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Antigens, CD43: A sialic acid-rich protein and an integral cell membrane mucin. It plays an important role in activation of T-LYMPHOCYTES.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Cell Degranulation: The process of losing secretory granules (SECRETORY VESICLES). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by EXOCYTOSIS.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.Cerebellar Cortex: The superficial GRAY MATTER of the CEREBELLUM. It consists of two main layers, the stratum moleculare and the stratum granulosum.Myelin and Lymphocyte-Associated Proteolipid Proteins: A family of MARVEL domain-containing proteolipid proteins involved in vesicular trafficking cycling between the GOLGI COMPLEX and the apical PLASMA MEMBRANE.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.cdc42 GTP-Binding Protein: A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.CTLA-4 Antigen: An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue.NFATC Transcription Factors: A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.Antigens, CD80: A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Immune System: The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.Antigens, CD58: Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.Nerve Net: A meshlike structure composed of interconnecting nerve cells that are separated at the synaptic junction or joined to one another by cytoplasmic processes. In invertebrates, for example, the nerve net allows nerve impulses to spread over a wide area of the net because synapses can pass information in any direction.
Immunological synapse... the synapse formation leads to killing of the target cell via secretion of cytolytic enzymes. Immunological synapses were first ... An immunological synapse consists of molecules involved in T cell activation, which compose typical patterns-activation ... In CD4+ T cells, however, the whole process of the immunological synapse formation can take up to 6 hours. In CD8+ T cells, ... an immunological synapse (or immune synapse) is the interface between an antigen-presenting cell or target cell and a ...
As many of these cell types either do not express perforin or do not form immunological synapses, granzyme B is released ... The granules are released into an immune synapse formed with a target cell, where perforin mediates the delivery of the ... This inhibits proliferation and activation of T cells. TGF-β production is the most potent mechanism of immune avoidance used ... contains certain chemicals that allow it to cause proliferation in B cells to reduce the chance of cancer growth and formation ...
Audio help) More spoken articles Synapse Review for Kids Synapses Biologymad.com (2004) Synapse - Cell Centered Database Atlas ... electrical and immunological synapses also exist. Without a qualifier, however, "synapse" commonly means chemical synapse. ... Several types of activation are possible, as described in more detail below. In any case, this is the key step by which the ... The membrane added by the fusion process is later retrieved by endocytosis and recycled for the formation of fresh ...
... and somato-somatic synapses. The axon can synapse onto a dendrite, onto a cell body, or onto another axon or axon terminal, as ... It is widely accepted that the synapse plays a role in the formation of memory. As neurotransmitters activate receptors across ... In a chemical synapse, electrical activity in the presynaptic neuron is converted (via the activation of voltage-gated calcium ... Neuroscience portal Active zone Autapse Exocytosis Immunological synapse Neurotransmitter vesicle Postsynaptic density ...
... a direct TA1 receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization. "TAAR1". GenAtlas. ... stimulation at PFC potentiates PFC-NAc synapses but depresses hippocampal-NAc synapses. In light of the new functional evidence ... Kim Y, Teylan MA, Baron M, Sands A, Nairn AC, Greengard P (February 2009). "Methylphenidate-induced dendritic spine formation ... The literature indicates that there are many factors, such as regulation of the immunological system and protection against ...
... electrical and immunological synapses also exist. Without a qualifier, however, "synapse" commonly means chemical synapse. ... Chemical synapses pass information directionally from a presynaptic cell to a postsynaptic cell and are therefore asymmetric in ... Further information on formation of synapses: Synaptogenesis. Synapses are functional connections between neurons, or between ... Several types of activation are possible, as described in more detail below. In any case, this is the key step by which the ...
Synapses are essential to neuronal function: neurons are cells that are specialized to pass signals to individual target cells ... It is widely accepted that the synapse plays a role in the formation of memory. As neurotransmitters activate receptors across ... In a chemical synapse, electrical activity in the presynaptic neuron is converted (via the activation of voltage-gated calcium ... The vast majority of synapses in the mammalian nervous system are classical axo-dendritic synapses (axon synapsing upon a ...
T cell receptor antagonism interferes with MHC clustering and integrin patterning during immunological synapse formation | JCBCoordination of T cell activation and migration through formation of the immunological synapse. Ann. NY Acad. Sci. 987:51-59. ... Regulation of T cell migration through formation of immunological synapses: the stop signal hypothesis. Adv. Exp. Med. Biol. ... Hence, T cells were inhibited from activation, at least with respect to adherence and synapse formation, by prior exposure to a ... T cell receptor antagonism interferes with MHC clustering and integrin patterning during immunological synapse formation. Cenk ...
T Cell-Dendritic Cell Immunological Synapses Contain TCR-dependent CD28-CD80 Clusters That Recruit Protein Kinase Cθ | The...The dendritic cell cytoskeleton is critical for the formation of the immunological synapse. J. Immunol. 166: 1452-1456. ... The immunological synapse: a molecular machine controlling T cell activation. Science 285: 221-227. ... T Cell-Dendritic Cell Immunological Synapses Contain TCR-dependent CD28-CD80 Clusters That Recruit Protein Kinase Cθ. Su-Yi ... Stimulation of naive T-cell adhesion and immunological synapse formation by chemokine-dependent and -independent mechanisms. ...
Functional anatomy of T cell activation and synapse formation... transient contacts resulting from promigratory junctions called immunological kinapses or prolonged contacts from stable ... These cell contacts are characterized by two distinct dynamics in vivo: ... T cell activation and function require a structured engagement of antigen-presenting cells. ... Synapses are induced by T cell receptor (TCR) interactions with agonist pMHC under specific conditions and correlate with ...
Frontiers | Expanding the Therapeutic Window for CAR T Cell Therapy in Solid Tumors: The Knowns and Unknowns of CAR T Cell...... including immunological synapse formation, and the impact of target antigen density for induction of distinct T cell functions ... including immunological synapse formation, and the impact of target antigen density for induction of distinct T cell functions ... In this regard, it is critical to deeply understand the sensitivity of CAR T cells, especially against low-density targets and ... In this regard, it is critical to deeply understand the sensitivity of CAR T cells, especially against low-density targets and ...
Phosphoinositide binding by the SNX27 FERM domain regulates its localization at the immune synapse of activated T-cells |...P3 correlates with initial membrane recruitment of SNX27 during immunological synapse formation. Activation of type I PI3K is ... 2009). Dynamics of membrane trafficking downstream of B and T cell receptor engagement: impact on immune synapses. Traffic 10, ... although central immunological synapse localization was observed at later times. Immunological synapse formation contributes to ... In T-cells, SNX27 localizes to the immunological synapse in an activation-dependent manner, but the molecular mechanisms ...
Kinetic discrimination in T-cell activation | PNASCorrelation of a dynamic model for immunological synapse formation with effector functions: two pathways to synapse formation ... The molecular makeup and function of regulatory and effector synapses. Peter Reichardt, Bastian Dornbach, Matthias Gunzer ... The immunological synapse: required for T cell receptor signalling or directing T cell effector function? ... CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse ...
Spinophilin participates in information transfer at immunological synapses | Journal of Cell Biology | Rockefeller University...Immune synapse formation requires ZAP-70 recruitment by ezrin and CD43 removal by moesin. J. Cell Biol. ... a. ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC ... The "immunological synapse" (IS) refers to the contact site between APCs and T cells where T cell receptors (TCRs) engage their ... Immune synapse formation requires ZAP-70 recruitment by ezrin and CD43 removal by moesin. J. Cell Biol. ...
Structure, Expression, and Function of ICAM-5The developmental appearance of ICAM-5 parallels the time of dendritic elongation and branching, and synapse formation in the ... As a novel cell adhesion molecule, ICAM-5 shares many structural similarities with the other members of IgSF, especially the ... to the telencephalic neurons of the central nervous system whereas all the other ICAM members are expressed mostly by cells in ... Cell adhesion is of utmost importance in normal development and cellular functions. ICAM-5 (intercellular adhesion molecule-5, ...
Protocols and Video Articles Authored by Michael Dustin (Translated to Dutch)Imaging van HIV-1 Envelope-geïnduceerde Virologische Synapse en signalering op synthetische lipidendubbellagen ... Coordination of T Cell Activation and Migration Through Formation of the Immunological Synapse Annals of the New York Academy ... T-cell Activation Through Immunological Synapses and Kinapses Immunological Reviews. Feb, 2008 , Pubmed ID: 18275476 T-cell ... The immunological synapse is a specialized cell-cell junction between T cell and antigen-presenting cell surfaces. It is ...
B cells or mutating the putative PDZ-binding motif in the BCR tail impaired formation of the immunological synapse, initiation ... SAP97 accumulated and bound to IgG BCRs in the immunological synapses that formed in response to B cell engagement with antigen ... There were two activation energies for the intercalation of glycine into kaolinite, one being 21kJ/mol within the temperature ... After their first encounter with a foreign antigen, naïve B cells that have immunoglobulin M (IgM) B cell receptors (BCRs) ...
... triggers the formation of stable cell-cell interactions with immature DCs that are reminiscent of the immunological synapse. ... Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation. Amanda Carroll-Portillo, ... Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation ... T cell activation and proliferation assay. MC/9 cells and BMDCs were generated as described in Animals and cells. For T cell ...
Skirball Institute - Michael Dustin's LabDustin, M.L. (2003). Coordination of T cell activation and migration through formation of the immunological synapse. Ann N Y ... T cell-dendritic cell immunological synapses contain TCR-dependent CD28-CD80 clusters that recruit protein kinase Ctheta. J ... interaction lowers the threshold of B cell activation by facilitating B cell adhesion and synapse formation. Immunity 20, 589- ... of a dynamic model for immunological synapse formation with effector functions: two pathways to synapse formation. Trends ...
Keystone Symposia | Scientific Conferences on Biomedical and Life Science TopicsShort Talk: The Regulation of Protein Spatial Sorting and its Effect on T Cell Signaling in the Immunological Synapse. ... Immunological Synapse Formation in Normal and Pathological Immune Responses. Ronald N. Germain, NIAID, National Institutes of ... The Role of the Localization of Vav1 during T Cell Activation Aaron J. Marshall, University of Manitoba, Canada The ... Short Talk: Membrane Nanotubes Support Sub-Micron Scale Immune Synapses and Aid Cytolysis of Distant Target Cells ...
The Immunological Synapse: A Molecular Machine Controlling T Cell Activation | Science2G). Low and high densities of agonist MHC-peptide triggered formation of well-organized immunological synapses whereas, as ... Model for immunological synapse formation. Side view of T cell forming an immunological synapse with an APC. Stage 1: Junction ... 2, H and I). Thus, full T cell activation correlated with formation of an immunological synapse with a threshold density of ≥60 ... the formation of an immunological synapse provides the machinery to integrate cell surface events into the T cell activation ...
Viruses | Free Full-Text | Dendritic Cells and HIV-1 Trans-Infection... to lymphoid tissues and signaling immune specific activation of T cells through the formation of the immunological synapse. ... Dendritic cells can also transfer intact, infectious HIV-1 to CD4 T cells through an analogous structure, the infectious ... synapse. This replication independent mode of HIV-1 transmission, known as trans-infection, greatly increases T cell infection ... Dendritic cells initiate and sustain immune responses by migrating to sites of pathogenic insult, transporting antigens ...
The HIV-1 gp120/V3 modifies the response of uninfected CD4 T cells to antigen presentation: mapping of the specific...Canonical pathways involved in energy and cell cycle regulation, and in the co-activation of T cells were also enriched. Taken ... that the presence of specific gp120/V3 peptides during antigen presentation can modify the activation of normal T-cells leading ... Our results revealed that the most highly modulated transcripts could almost entirely be categorized as related to the cell ... We then evaluated the changes in the T-cell transcriptional profile using oligonucleotide microarrays and performed Ingenuity ...
JCI Insight -
ICAM1+ neutrophils promote chronic inflammation via ASPRV1 in B cell-dependent autoimmune encephalomyelitisICAM1 facilitates cell-cell interactions such as the formation of immunological synapses (29). Our results suggest that ... B-cell activation influences T-cell polarization and outcome of anti-CD20 B-cell depletion in central nervous system ... to form several different types of immunological synapses (29, 30). The most traditional synapse is characterized by a ring of ... T cells immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response ...
Mark M. DavisWe have helped define the molecular structure and kinetics of synapse formation. Much of the rearrangement is cytoskeletal and ... and on how ligand binding triggers T cell activation. Video microscopy and other advanced imaging techniques, such as super- ... a dramatic rearrangement of surface molecules and cytoarchitecture takes place to form what is called an immunological synapse ... We also showed that synapses may last for many hours but require continuous TCR engagement. ...
Imaging Immune Cell Infiltration and Function in Brain Injury(1)... including the formation and signaling of the immunological synapses between T cells and antigen presenting cells, the ... Imaging Immune Cell Infiltration and Function in Brain Injury. Immune cell infiltration, glial activation, and neuronal damage ... Significance: The research may lead to development of new anti-inflammatory treatment strategies to accelerate synapse ... These include innate immune cells called "microglia" that reside in the brain, These cells activate glial cells, which support ...
... including HLA-B27-associated dendritic cell disturbances, HLA-B27 misfolding properties and T helper 17 cells. In addition, ... There are several arguments favouring a role for haematopoietic cells in the pathophysiology of spondyloarthritis, ... recent studies have pointed toward a pivotal role for stromal cells. A major challenge, however, remains to determine how ... Recently, a hypothesis that implies aberrant formation of immunological synapses was proposed. Additional cell transfer ...
Research | Mark M. Davis Lab | Stanford Medicine... peptide-MHC on the surface of another cell but that activation-in terms of full calcium elevation and stable synapse formation ... a dramatic rearrangement of surface molecules and cytoarchitecture takes place to form what is called an immunological synapse ... We also showed that synapses may last for many hours but require continuous TCR engagement. ... but which concatenate upon T cell activation. These islands may be a general organizing principal for cell surface proteins, ...
WASp and WAVE Proteins: From Structure, Through Function, to Clinical Aspects | Open Access Journals... both in cell mediated cytotoxicity and in the activation of the humoral immune response. In order to perf.. ... T cells play a pivotal role in adoptive immunity, ... the formation of an immunological synapse (IS) with an antigen- ... Dustin ML (2008) T-cell activation through immunological synapses and kinapses. Immunol Rev 221: 77-89. ... When naïve T cells engage APCs, dynamic cytoskeletal rearrangements support the formation of the immunological synapse (IS), ...
Cytotoxic T lymphocytes form an antigen-independent ring junctionImmunological synapses are organized cell-cell junctions between T lymphocytes and APCs composed of an adhesion ring, the ... the central supramolecular activation cluster (cSMAC). In CD8+ cytotoxic T lymphocytes, the immunological synapse is thought to ... MICA, a ligand for NKG2D, facilitated the ring junction formation at lower surface densities of ICAM-1. ICAM-1 and MICA are ... Activated CD8+ T cells formed fivefold more ring junctions than did activated CD4+ T cells. The ring junction contained ...
Scientists create new way to study T cell signaling | EurekAlert! Science NewsBy going inside a living cell and physically moving its T cell signaling molecules, they showed that the ... enabled them to directly control signaling activity in living T cells from the immune system. ... antigen-presenting cell surfaces that enabled the formation of functional immunological synapses with living T cells," said ... "immunological synapse" because it resembles the synapse between two communicating nerve cells. At the immunological synapse, a ...
DiVA - Search resultCTLs kill target cells via fusion of lytic granules (LGs) at the immunological synapse (IS). Soluble N-ethylmaleimide-sensitive ... T cells and determined their co-localization with LGs and CD3 after IS formation with target cells. We found that several key ... CaV1.2 channels in DCT-/- myocytes fail to respond to activation of adenylyl cyclase by forskolin, and the localized expression ... Knockdown of VAMP8 blocked both recycling endosome and cytotoxic granule fusion at immune synapses, without affecting ...
Signal TransductionReceptorsAntigensLigandsJunctionsPlasma membraneDendritic cellsLymphocytesFunctionalMoleculesKineticsStableAdhesionNeuronal synapsesCentral supramolecular activationImmunityReceptor-ligandMolecularMembrane domainsAntigen recognitionSupramolecular activationPeptidesImmune cellsMature synapseCytoskeletalLymphocyteProteinMaturationAccumulationCellularKinaseIntegrinsIntegrin engagementClusterInteractionCTLsInteractionsEngagementDifferentiationCytokinesSubsequentDustinEffector functionsComplexesJunctionProliferationMast cellsMembranesMechanismSIGNALINGAPCsDependentInflammatoryMicroscopyImmunologyMiceCSMACNascentSensitivityMyosinPhysiological
- We have sought signal transduction components of the neuronal synapse that were also expressed by DCs. (rupress.org)
- This interest includes the structural and biochemical underpinnings of T cell receptor binding and signal transduction and the dynamics of molecular movement at the T cell/antigen-presenting cell interface. (stanford.edu)
- Thus, it is crucial for T cell mediated immune responses, providing a dynamic and flexible platform for signal transduction, cellular and subcellular remodeling, and for driving effector functions. (omicsonline.org)
- We propose that Dlgh1 coordinates TCR/CD28-induced actin-driven T cell synapse assembly, signal transduction, and effector function. (rupress.org)
- The synapse enhances TCR engagement and signal transduction through the recruitment, concentration, and juxtaposition of receptors and transducers ( 1 , 2 ). (rupress.org)
- Paradoxically, the immune synapse also attenuates TCR signal transduction by directing TCR endocytosis, transducer ubiquitination, and proteolysis and by functioning as a target for the delivery of down-regulatory CTLA-4 ( 1 , 2 , 7 ). (rupress.org)
- Integrins are important components not only for the structure and architecture of tissues but also for signal transduction leading to regulation of many biological functions in cells. (scielo.br)
- Focal adhesion kinase (FAK) becomes tyrosine-phosphorylated during integrin-mediated cell adhesion and is believed to play important roles in integrin signal transduction (7,8). (scielo.br)
- The specialized junction between a T lymphocyte and an antigen-presenting cell, the immunological synapse, consists of a central cluster of T cell receptors surrounded by a ring of adhesion molecules. (sciencemag.org)
- This is mediated by the interaction of T cell antigen receptors (TCRs) with their ligands, major histocompatibility molecule-peptide complexes (MHC-peptide) ( 1 ). (sciencemag.org)
- SNX27 is a member of the sorting nexin family that plays an important role in the recycling of receptors from endosomes to the cell surface. (pubmedcentralcanada.ca)
- Specifically, we will determine the role of chemokine receptors CCR2 and CXCR6 in regulating the infiltration of immune cells into the injured brain and investigate the role of endogenous versus recruited immune cells in structural changes of synapses. (dana.org)
- At the immunological synapse, a central cluster of T cell receptors surrounded by a ring of adhesion molecules form what co-author Dustin has described as a sort of "bull's-eye. (eurekalert.org)
- The duration of the activation signal is related to the spatial organization of the T cell receptors rather than cluster size. (eurekalert.org)
- Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. (scielo.br)
- Recently, two types of signaling by integrins have been extensively discussed: transmission of signals into the cell following binding of ligands or counter-receptors to the integrins (outside-in signaling), and regulation of the avidity and conformation of integrins by signals generated by other receptors within the cell (inside-out signaling) (5). (scielo.br)
- Differing recognition patterns of innate versus adaptive cells is accomplished via the use of distinct receptors. (biomedcentral.com)
- NK and iNKT cell receptors provide broad recognition for the innate response via a limited repertoire of activating and inhibitory NK cell receptors (for NK cells) [ 1 ] or a semi-invariant NK T-cell receptor (TCR) (for iNKT cells) [ 2 ], while CTLs provide the highly specific recognition of the adaptive response by use of many different TCRs. (biomedcentral.com)
- Although NK cells, CTLs and iNKT cells all use different receptors to recognise their targets, they deliver a virtually identical lethal hit that destroys the target cell recognised [ 3 ]. (biomedcentral.com)
- At the heart of the adaptive immune response lies the ability of T cells to recognize processed foreign antigens. (rupress.org)
- A major obstacle for chimeric antigen receptor (CAR) T cell therapy in solid tumors is the lack of truly tumor-specific target antigens, which translates to the targeting of tumor-associated antigens (TAAs) overexpressed on tumors but shared with normal organs, raising safety concerns. (frontiersin.org)
- Among the many challenges of CAR T cell therapy in solid tumors, a major obstacle is the lack of truly tumor-specific target antigens, which forces cellular immunologists to target tumor-associated antigens (TAAs) overexpressed on tumors but also expressed on normal tissues and organs, raising safety concerns. (frontiersin.org)
- The most potent of APCs are dendritic cells (DCs), which are present in tissues throughout the body, where they sample antigens and process them into short peptides bound to major histocompatibility complex (MHC) class I or II molecules ( Mellman, 2007 ). (rupress.org)
- Lymphocytes mediate the adaptive immune responses to antigens derived from infectious agents, transformed cells, transplanted organs and, in the setting of autoimmunity, ones own cells. (keystonesymposia.org)
- Dendritic cells initiate and sustain immune responses by migrating to sites of pathogenic insult, transporting antigens to lymphoid tissues and signaling immune specific activation of T cells through the formation of the immunological synapse. (mdpi.com)
- This shows that T cells can be as sensitive to foreign antigens as any sensory cells in the nervous system. (hhmi.org)
- At the inflamed tissue, the phagocytosis of antigens by antigen-presenting cells (APCs) requires protrusion and retraction of the cell membrane, processes which are regulated by the actin cytoskeleton [ 1 ]. (omicsonline.org)
- The process starts when "antigens," special markers on the surface of a cell, identify another cell as "non-self," and signal the cellular warriors of the immune system to kill the invader. (eurekalert.org)
- It has also been established that the control center for T cell signaling is at the junction or point of contact between T cells and antigens, dubbed the "immunological synapse" because it resembles the synapse between two communicating nerve cells. (eurekalert.org)
- Animals can be rendered tolerant toward antigens presented by naive B cells. (bloodjournal.org)
- We find that synapses formed on membranes presenting antagonist-agonist complexes display reduced MHC density, which leads to reduced T cell proliferation that is not overcome by the costimulatory ligands CD48 and B7-1. (rupress.org)
- Integrins link cytoskeletal rearrangement and cell adhesion to engagement of extracellular matrix or cell surface ligands. (rupress.org)
- LFA-1 (αLβ2) is arguably the most important integrin for leukocyte function, regulating T cell activation and contact formation via interactions with its cell surface ligands ICAM-1, -2, or -3. (rupress.org)
- Primary helper T cell activation requires the presentation of MHC class II-antigenic peptide complexes (MHCp) 4 and costimulatory ligands by dendritic cells (DC). (jimmunol.org)
- High-resolution imaging has revealed that the synapse is highly coordinated, integrating cell adhesion, TCR recognition of pMHC complexes, and an array of activating and inhibitory ligands to promote or prevent T cell signaling. (nih.gov)
- Costimulation and Endogenous MHC Ligands Contribute to T Cell Recognition Nature Immunology. (jove.com)
- Thus, low-affinity ligands can contribute to synapse formation and T cell signaling. (jove.com)
- Immunological synapse formation is now shown to be an active and dynamic mechanism that allows T cells to distinguish potential antigenic ligands. (sciencemag.org)
- Initially, T cell receptor ligands were engaged in an outermost ring of the nascent synapse. (sciencemag.org)
- We also developed single peptide-MHC labeling methods that allow us to determine exactly how many ligands are present in an initial T cell synapse and what the subsequent response is. (hhmi.org)
- We used this method to show that all T cells surveyed thus far can detect a single molecule of peptide-MHC on the surface of another cell but that activation-in terms of full calcium elevation and stable synapse formation only occur with 8 to 10 ligands. (stanford.edu)
- Killing by cytotoxic T cells requires three or more ligands, showing that sensitivity is distinct from the threshold necessary for a cell to embark on an irreversible action. (stanford.edu)
- This artificial substrate provides identical ligands to CD4+ and CD8+ T cells, allowing a quantitative comparison. (washington.edu)
- T cell activation is initiated when the TCR encounters specific antigen-MHC complexes and costimulatory ligands on the surface of an APC. (rupress.org)
- These cell contacts are characterized by two distinct dynamics in vivo: transient contacts resulting from promigratory junctions called immunological kinapses or prolonged contacts from stable junctions called immunological synapses. (nih.gov)
- Initial views of antigen-specific T cell junctions have revealed the formation of a specialized contact, termed the immunological synapse ( 10 , 11 ). (sciencemag.org)
- We first examined the kinetics and pattern of MHC-peptide accumulation in T cell junctions to determine whether specific stages in the formation of immunological synapse could be discerned. (sciencemag.org)
- Immunological synapses are organized cell-cell junctions between T lymphocytes and APCs composed of an adhesion ring, the peripheral supramolecular activation cluster (pSMAC), and a central T cell receptor cluster, the central supramolecular activation cluster (cSMAC). (washington.edu)
- Activated CD8+ T cells formed fivefold more ring junctions than did activated CD4+ T cells. (washington.edu)
- Lipid raft membrane compartmentalization and membrane-associated guanylate kinase (MAGUK) family molecular scaffolds function in establishing cell polarity and organizing signal transducers within epithelial cell junctions and neuronal synapses. (rupress.org)
- At the immunological synapse of activated T-cells, cell signaling regulates phosphoinositide dynamics, and we find that perturbing phosphoinositide binding by the SNX27 FERM domain alters the SNX27 distribution in both endosomal recycling compartments and PtdIns(3,4,5) P 3 -enriched domains of the plasma membrane during synapse formation. (biologists.org)
- Christie DA, Kirchhof MG, Vardhana S, Dustin ML, Madrenas J. Mitochondrial and plasma membrane pools of stomatin-like protein 2 coalesce at the immunological synapse during T cell activation . (nyu.edu)
- In order to fuse lytic granules (LGs) with the plasma membrane at the immunological synapse, cytotoxic T lymphocytes (CTLs) have to render these LGs fusion-competent through the priming process. (diva-portal.org)
- In cytotoxic T lymphocytes (CTLs), this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. (biomedcentral.com)
- High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked') with the plasma membrane within the immunological synapse. (biomedcentral.com)
- The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse. (biomedcentral.com)
- Morphologically, the overall structure of the immunological synapses formed by NK and iNKT cells are very similar to those formed by CTLs, with both exocytic and endocytic organelles polarised towards the centrosome at the plasma membrane, which forms a focal point for exocytosis and endocytosis within the immunological synapse. (biomedcentral.com)
- The adaptive immune response is initiated by the presentation of peptides bound to major histocompatibility complex molecules on dendritic cells (DCs) to antigen-specific T lymphocytes at a junction termed the immunological synapse. (rupress.org)
- Dendritic cells can also transfer intact, infectious HIV-1 to CD4 T cells through an analogous structure, the infectious synapse. (mdpi.com)
- 9 However, the biophysics of the underlying T-B contact was very different from bona fide T-cell activation by dendritic cells (DCs). (bloodjournal.org)
- The adaptive immune response depends on the ability of antigen-presenting cells (APCs) to communicate with effector cells such as T lymphocytes about the molecular nature of invading pathogens. (rupress.org)
- A critical event in the initiation of the adaptive immune response is the activation of T lymphocytes. (sciencemag.org)
- First, we try to understand in molecular detail how T lymphocytes, one of the key cell types in the immune system, distinguish foreign entities from self and mount a response. (hhmi.org)
- In CD8+ cytotoxic T lymphocytes, the immunological synapse is thought to facilitate specific killing by confining cytotoxic agents to the synaptic cleft. (washington.edu)
- Leading this attack will be the T cells, lymphocytes from the thymus. (eurekalert.org)
- CD43 interacts with moesin and ezrin and regulates its redistribution to the uropods of T lymphocytes at the cell-cell contacts. (medecinesciences.org)
- Cytotoxic T lymphocytes (CTLs), natural killer (NK) cells and invariant NKT (iNKT) cells are cytolytic cells of the immune system that are able to destroy cells infected with subsets of intracellular pathogens. (biomedcentral.com)
- There are several DC subsets (myeloid DCs, Langerhans cells, plasmacytoid DCs, dermal DCs, etc.) with phenotypic differences, increasing the functional complexity of these cells ( Shortman and Liu, 2002 ). (rupress.org)
- We now report real-time imaging and quantitative analysis of the formation of a functional immunological synapse. (sciencemag.org)
- The fluidity of our membranes created artificial antigen-presenting cell surfaces that enabled the formation of functional immunological synapses with living T cells," said Groves. (eurekalert.org)
- Our finding might help to explain old observations on tolerance induction by B cells, identify the mature immunologic synapse as a central functional module of this process, and suggest the use of naive B-cell-primed regulatory T cells, "bTregs," as a useful approach for therapeutic intervention in adverse adaptive immune responses. (bloodjournal.org)
- The relationship between TCR and costimulatory molecules in the physiological IS of T cell-dendritic cell (DC) is obscure. (jimmunol.org)
- metabolic checkpoints, such as hypoxia and immunological barriers, such as immunosuppressive cytokines/molecules and immunosuppressive immune cells. (frontiersin.org)
- This suggests that costimulation-driven active transport of T cell surface molecules helps to drive immunological synapse formation. (jove.com)
- The mature immunological synapse is defined by a specific pattern of receptor segregation with a central cluster of TCRs surrounded by a ring of integrin family adhesion molecules ( 11 ). (sciencemag.org)
- The immune system is a complex constellation of cells and molecules that is principally responsible for preventing us from certain death from a myriad of pathogenic microorganisms. (hhmi.org)
- To pursue our first goal, we have focused on developing advanced imaging techniques to understand the molecular interactions that underlie the process by which a particular T cell recognizes fragments of an antigen (peptide) that are bound to molecules of the major histocompatibility complex (MHC) and displayed on the surfaces of cells. (hhmi.org)
- Our previous work and that of others characterized the biochemistry and genetics of TCRs, but in recent years we have focused on how these molecules operate in the larger context of T cell recognition, a context that includes other molecules on the T cell surface that work with the TCR, and on how ligand binding triggers T cell activation. (hhmi.org)
- In the first few minutes after a T cell recognizes another cell, a dramatic rearrangement of surface molecules and cytoarchitecture takes place to form what is called an immunological synapse. (hhmi.org)
- We also found that TCRs and other molecules on the T cell surface are clustered in what we term 'protein islands' and that these structures segregate specific molecules in the TCR signaling cascade. (stanford.edu)
- This marriage of inorganic nanotechnology with organic molecules and cells enables us to go inside a living cell and physically move around its signaling molecules with molecular precision," said Jay Groves, a chemist who holds a joint appointment with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Chemistry Department. (eurekalert.org)
- 3 Indeed, evidence suggests that B cells can take part in antigen presentation via major histocompatibility complex (MHC) II molecules 4 ⇓ ⇓ - 7 and might even be required to reach full T-cell effector potential. (bloodjournal.org)
- Information transfer between T cell and APC during cell-cell interaction is characterized by the formation of a supramolecular assembly of signaling and adhesion molecules termed immunologic synapse (IS). (bloodjournal.org)
- 13 , 14 , 14 A mature IS presents with a distinguished central part of the supramolecular activation cluster (c-SMAC) enriched in signaling molecules like T-cell receptor (TCR) and MHC, and a peripheral part (p-SMAC) enriched in adhesion molecules. (bloodjournal.org)
- Transport of these complexes into the central cluster was dependent on T cell receptor-ligand interaction kinetics. (sciencemag.org)
- This quantitative analysis has revealed that immunological synapse formation is a multistage process and provides new insights into how MHC-peptide number and TCR-ligand interaction kinetics are translated into T cell activation decisions. (sciencemag.org)
- Using fluorescently tagged lipid-binding probes, we studied the kinetics of distinct PIs in living T cells during IS formation. (pubmedcentralcanada.ca)
- We have helped define the molecular structure and kinetics of synapse formation. (hhmi.org)
- Modeling receptor-ligand binding kinetics in immunological synapse formation. (leibniz-hki.de)
- Figge MT, Meyer-Hermann M (2009) Modeling receptor-ligand binding kinetics in immunological synapse formation. (leibniz-hki.de)
- These interactions induce T cell deceleration and formation of stable T cell-DC synapses ( 1 , 2 , 3 , 4 , 5 ). (jimmunol.org)
- Most of what we know about the molecular details of the stable immunological synapse (IS) comes from the study of simplified model systems that replace the DC with a transformed non-DC cell type or supported planar bilayer ( 6 , 7 , 8 , 9 , 10 , 11 , 12 ). (jimmunol.org)
- Activation of MCs through FcεRI cross-linking triggers the formation of stable cell-cell interactions with immature DCs that are reminiscent of the immunological synapse. (rupress.org)
- Finally, formation of a stable central cluster at the heart of the synapse was a determinative event for T cell proliferation. (sciencemag.org)
- However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. (bloodjournal.org)
- 10 While T-cell contacts to DCs were dynamic and sequential, contacts to B cells were mostly very stable in vitro and in vivo. (bloodjournal.org)
- MCs and γδ T cells appeared to form stable contacts that were visualized after isolation. (jci.org)
- F ) No stable contacts between MCs and γδ T cells were observed in cytospins from similarly prepared uninfected peritoneal cells. (jci.org)
- As adhesion precedes mature synapse formation, integrins serve an indispensable function in the formation of the immunological synapse ( Dustin and Chan, 2000 ). (rupress.org)
- Cell adhesion is of utmost importance in normal development and cellular functions. (hindawi.com)
- We show that T cell activation is reconstituted by MHC-peptide and an adhesion ligand, ICAM-1, in a glass-supported planar bilayer. (sciencemag.org)
- Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. (scielo.br)
- The developmental defect observed in FAK-deficient mice may be associated with impairment of cell migration and enhancement of cell adhesion, as suggested by studies with FAK-/- fibroblasts (10). (scielo.br)
- Negative regulation of T-cell adhesion and activation by CD43. (medecinesciences.org)
- Proteins with a PDZ domain are often found in the postsynaptic density of neuronal synapses, where SNX27 participates specifically in glutamate and β-adrenoreceptor trafficking. (pubmedcentralcanada.ca)
- Short-lived TCR microclusters and a longer-lived protein kinase Cθ-focusing central supramolecular activation cluster (cSMAC) have been defined in model immunological synapses (IS). (jimmunol.org)
- The center of this bull's eye has been dubbed the "central supramolecular activation cluster," or c-SMAC, because it was believed to be the source of T cell activation. (eurekalert.org)
- T cells play a pivotal role in adoptive immunity, both in cell mediated cytotoxicity and in the activation of the humoral immune response. (omicsonline.org)
- Proper T cell activation is central to the generation of protective adaptive immunity and in the maintenance of self-tolerance. (rupress.org)
- Long-term immunity to many viral and bacterial pathogens requires CD8 + memory T cell development, and the induction of long-lasting CD8 + memory T cells from a na?ve, undifferentiated state is a major goal of vaccine design. (molcells.org)
- We believe immune synapse formation between MCs and γδ T cells is a novel mechanism to induce specific and protective immunity at sites of viral infection. (jci.org)
- Pubmed ID: 11731799 To initiate an immune response, key receptor-ligand pairs must cluster in "immune synapses" at the T cell-antigen-presenting cell (APC) interface. (jove.com)
- In this review, we examine the molecular components, geometry, and timing underlying kinapses and synapses. (nih.gov)
- In T-cells, SNX27 localizes to the immunological synapse in an activation-dependent manner, but the molecular mechanisms underlying SNX27 translocation remain to be clarified. (biologists.org)
- It is well established that the key to T cell activation is the molecular signal coming off antigen-presenting cell surfaces. (eurekalert.org)
- These findings highlight common molecular strategies used to regulate cell polarity, synapse assembly, and transducer organization in diverse cellular systems. (rupress.org)
- Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp) motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. (scielo.br)
- Based on these arguments, we reasoned that the molecular organization of the IS between T cells and naive B cells might be different from the one found in T-DC pairs. (bloodjournal.org)
- Our results suggest that SNX27 undergoes dynamic partitioning between different membrane domains during immunological synapse assembly, and underscore the contribution of unique lipid interactions for SNX27 orchestration of cargo trafficking. (biologists.org)
- Membrane Domains and the Immunological Synapse: Keeping T Cells Resting and Ready The Journal of Clinical Investigation. (jove.com)
- In this review, we discuss the recent findings of mechanisms of antigen recognition through CAR, including immunological synapse formation, and the impact of target antigen density for induction of distinct T cell functions. (frontiersin.org)
- We visualized the accumulation of a major histocompatibility complex (MHC) class II molecule, I-E(k), at a T cell-B cell interface and found it was dependent on both antigen recognition and costimulation. (jove.com)
- Model ISs are characterized by formation of radially symmetric multimicrometer scale supramolecular activation clusters (SMACs). (jimmunol.org)
- Here, we study the effect of antagonist peptides on immunological synapse formation by T cells. (rupress.org)
- Antagonist peptides clearly have physiological relevance, as some pathogens may use antagonist peptide mutants of dominant MHC epitopes to hinder the T cell response during the course of infection. (rupress.org)
- We have previously demonstrated that the presence of specific gp120/V3 peptides during antigen presentation can modify the activation of normal T-cells leading to altered immune function. (biomedcentral.com)
- The investigators will remove a part of the skull in laboratory animals, replace it with a glass plate, and image the response of immune cells. (dana.org)
- These include innate immune cells called "microglia" that reside in the brain, These cells activate glial cells, which support the synaptic connections between the brain's neurons. (dana.org)
- The researchers hypothesize that this damage occurs not by the microglial cells, but by the circulating immune cells that they recruit into the brain to serve as reinforcements. (dana.org)
- Using cellular imaging through the glass plate, investigators will determine how activation of microglia, and their subsequent recruitment of circulating immune cells, occurs and subsequently regulates changes in synapses. (dana.org)
- They also will determine whether the resultant loss and gain ("remodeling") of synapses requires primarily the resident microglial cells or also the recruited immune cells. (dana.org)
- How immune cells such as microglia and T cells populate the brain after injury and whether they contribute to the remodeling of neuronal connections are not known. (dana.org)
- Recently, we have used intravital two-photon laser scanning imaging to directly observe dynamic changes of neuronal connections and immune cells in the adult mouse cerebral cortex through either a thinned-skull window or an open-skull window. (dana.org)
- These findings provide an outstanding experimental system for assessing the infiltration and function of immune cells in the adult brain at sites of tissue inflammation and damage. (dana.org)
- Recruitment of immune cells to inflammatory sites is dependent on dynamic cell shape changes to allow cell mobility from the blood stream, through the vascular endothelium into the underlying tissue. (omicsonline.org)
- The rolling and tethering of immune cells in the blood vessels, and extravasation through the endothelium, require the actin cytoskeleton rearrangement. (omicsonline.org)
- 9 It is unclear whether a mature synapse can form under these circumstances. (bloodjournal.org)
- When naïve T cells engage APCs, dynamic cytoskeletal rearrangements support the formation of the immunological synapse (IS), during T cell priming. (omicsonline.org)
- Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin. (medecinesciences.org)
- The study of lymphocyte activation and gene expression is central to understanding the complex biology of these cells and offers hope for regulating these cells in different clinical settings. (keystonesymposia.org)
- In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. (scielo.br)
- Sorting nexin 27 (SNX27) controls the endosomal-to-cell-surface recycling of diverse transmembrane protein cargos. (biologists.org)
- Using the T cell immune synapse (IS) as a model for polarized protein recycling, we recently identified an additional mechanism that enhances SNX27 localization to the endosomal recycling compartment (ERC). (pubmedcentralcanada.ca)
- 7-10 Although in peptide array experiments, SNX27 bound a large variety of transmembrane proteins harboring FxNPxY sequences, 9 in cells, no specific cargos have yet been reported to interact with this protein via its FxNPxY-binding site. (pubmedcentralcanada.ca)
- The actin-regulatory proteins, Wiskott-Aldrich syndrome protein (WASp) and WASp family Verprolin-homologous protein (WAVE) play key roles in T cell biology. (omicsonline.org)
- Here, we elucidate a role for the MAGUK protein, Dlgh1, in polarized T cell synapse assembly and T cell function. (rupress.org)
- TCR/CD28 engagement induces the formation of endogenous Lck-Dlgh1-Zap70-Wiskott-Aldrich syndrome protein (WASp) complexes in which Dlgh1 acts to facilitate interactions of Lck with Zap70 and WASp. (rupress.org)
- ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. (medecinesciences.org)
- Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. (biomedcentral.com)
- MC-dependent γδ T cell activation and proliferation during DENV infection required T cell receptor (TCR) signaling and the nonconventional antigen presentation molecule endothelial cell protein C receptor (EPCR) on MCs. (jci.org)
- Mast cells (MCs) produce soluble mediators such as histamine and prostaglandins that are known to influence dendritic cell (DC) function by stimulating maturation and antigen processing. (rupress.org)
- Importantly, we observed massive activation and accumulation of microglia underneath the open-skull window but not thinned-skull window within the first 2 weeks of surgery. (dana.org)
- It can be located in both sacral and iliac bones and consists of an accumulation of mononuclear cells. (biomedcentral.com)
- This cellular communication process features early integrin engagement and T cell motility arrest, referred to as the "stop signal. (rupress.org)
- The most statistically significant enriched categories and networks identified by IPA were associated with cell cycle, gene expression, immune response, infection mechanisms, cellular growth, proliferation and antigen presentation. (biomedcentral.com)
- Groves is the principal co-author, along with Michael Dustin, a cellular immunologist at New York University (NYU), of a paper published in the November 18, 2005 issue of the journal Science, entitled: "Altered TCR Signaling from Geometrically Repatterned Immunological Synapses. (eurekalert.org)
- During the early stages of development, cell division is characterized by the asymmetric segregation of cell fate determinants into daughter cells to promote cellular heterogeneity and differentiation through an evolutionarily conserved mechanism known as asymmetric cell division (ACD). (molcells.org)
- 1-3 In other polarized models such as activated T cells, the PDZ domain mediates SNX27 interaction with diacylglycerol kinase zeta (DGKζ), a negative regulator of T cell activation that attenuates diacylglycerol (DAG)-mediated signals by catalyzing DAG conversion into phosphatidic acid (PA). (pubmedcentralcanada.ca)
- In the absence of myosin IIA or its ATPase activity, T cell signaling was interrupted 'downstream' of the kinase Lck and the synapse was destabilized. (nih.gov)
- Synapse formation requires integrin engagement and facilitates the transfer of internalized MC-specific antigen from MCs to DCs. (rupress.org)
- The original idea behind the c-SMAC was that the larger the T cell receptor cluster, the stronger the T cell activation signal," said Groves. (eurekalert.org)
- This simple vision of strength in numbers had begun to show cracks, and now we have demonstrated that just the opposite is true, the coalescence of the c-SMAC cluster extinguishes the T cell activation signal. (eurekalert.org)
- Although multiple specializations contributing to antigen uptake and processing have been described ( Mellman, 2007 ), mechanisms controlling the final interaction of DCs with their target cells have been incompletely studied. (rupress.org)
- We have investigated the interaction of human CTLs and helper T cells with supported planar bilayers containing ICAM-1. (washington.edu)
- These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system) direct secretory lysosomes to the immunological synapse. (biomedcentral.com)
- We conclude that centrosomal polarisation provides a rapid, responsive and precise mechanism for secretory lysosome delivery to the immunological synapse in CTLs, NK cells and iNKT cells. (biomedcentral.com)
- To study the dynamic relationship of CD28-CD80 and TCR interactions in the T cell-DC IS during Ag-specific T cell activation, we generated CD80-eCFP mice using bacterial artificial chromosome transgenic technology. (jimmunol.org)
- Synapses are induced by T cell receptor (TCR) interactions with agonist pMHC under specific conditions and correlate with robust immune responses that generate effector and memory T cells. (nih.gov)
- Whether direct cell-cell interactions are important in modulating MC/DC function is unclear. (rupress.org)
- Dynamic interactions were further probed by fluorescence photobleaching recovery to assess the stability of complexes formed within the synapse. (sciencemag.org)
- We find that Dlgh1 translocates to the immune synapse and lipid rafts in response to T cell receptor (TCR)/CD28 engagement and that LckSH3-mediated interactions with Dlgh1 control its membrane targeting. (rupress.org)
- Development within and egress from these sites is dependent on several factors, including cell-cell interactions, cytokine and chemokine signals, and receptor expression level. (molcells.org)
- T cell activation and function require a structured engagement of antigen-presenting cells. (nih.gov)
- In contrast, more complex functions, such as T cell proliferation, require TCR engagement and signaling for many minutes or hours. (sciencemag.org)
- Sustained TCR engagement, although essential for T cell activation, faces many barriers. (sciencemag.org)
- We hypothesize that the formation of the immunological synapse provides a mechanism for sustained TCR engagement and signaling. (sciencemag.org)
- We also showed that synapses may last for many hours but require continuous TCR engagement. (hhmi.org)
- Integrin clusters in macromolecular complexes, ligand occupancy, and tyrosine phosphorylation are the key events that result in diverse processes such as cell migration and differentiation, tissue remodelling, cell proliferation, angiogenesis, and tumor cell invasion and metastasis (3,6). (scielo.br)
- Immunological synapses are initiated by signaling in discrete T cell antigen receptor microclusters and are important for the differentiation and effector functions of T cells. (nih.gov)
- This review aims to highlight the cellularity of various niches within the lymph node and emphasize recent evidence suggesting that distinct types of T cell activation and differentiation occur within different immune contexts in lymphoid organs. (molcells.org)
- We found that administration of baicalin significantly downregulated the number of Th17 cells and the levels of Th17-related cytokines (IL-17 and IL-6) and retinoic acid receptor-related orphan receptor ?t. (jove.com)
- These changes enable their binding to and extravasation through the vascular endothelium into the neighboring tissue, the formation of an immunological synapse (IS) with an antigen-presenting cell (APC), and subsequently, the polarized secretion of cytokines and/or cytolytic granules, leading to the execution of effector functions. (omicsonline.org)
- Armed T cells subsequently home to the inflamed tissue, where again the actin cytoskeleton supports the polarized secretion of cytokines and/or lytic granules and the execution of effector functions [ 2 ]. (omicsonline.org)
- The asymptomatic phase of HIV-1 infection is characterized by the progressive depletion of uninfected peripheral effector/memory (CD45RO+) CD4+ T cells [ 1 ] that leads to subsequent immunodeficiency and AIDS symptoms. (biomedcentral.com)
- Thus, T cell antigen receptor signaling and the subsequent formation of immunological synapses are active processes dependent on myosin IIA. (nih.gov)
- Ondersteunde Planar dubbellagen voor de vorming van studie van immunologische synapsen en Kinapse Santosha Vardhana 1 , Michael Dustin 1 1 Helen and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular, New York University - NYU Ondersteund vlakke bilagen zijn krachtige instrumenten die kunnen worden gebruikt om de moleculaire interacties in een immunologische synaps model. (jove.com)
- These early signals may be sufficient to trigger some effector functions, such as killer T cell execution of target cells. (sciencemag.org)
- T cell activation by nonself peptide-major histocompatibility complex (MHC) antigenic complexes can be blocked by particular sequence variants in a process termed T cell receptor antagonism. (rupress.org)
- Although only agonist peptide-MHC class II (agonist pMHC class II) complexes can initiate T cell activation, endogenous pMHC class II complexes also appeared to accumulate. (jove.com)
- Third, the number of antigenic complexes on the antigen-presenting cell (APC) can be very low ( 6 ). (sciencemag.org)
- These peptide-MHC complexes are then recognized by the T cell antigen receptor (TCR), an antibody-like molecule present on most T cells. (hhmi.org)
- MICA, a ligand for NKG2D, facilitated the ring junction formation at lower surface densities of ICAM-1. (washington.edu)
- This recognition induces dramatic T cell polarization and the formation of a specialized "immunological synapse" at the T cell-APC junction ( 1 ). (rupress.org)
- These data could be invaluable to determine the underlying mechanism by which HIV-1 epitopes interfere with uninfected CD4+ T-cell function causing hyper proliferation and AICD. (biomedcentral.com)
- B cells induce substantial proliferation but, contrary to DCs, no loss of L-selectin in T cells. (bloodjournal.org)
- We have previously shown that naive B cells, despite low efficiency on a per cell basis, when loaded with specific peptide antigen can induce antigen-specific proliferation in naive T cells. (bloodjournal.org)
- Stem cells interact with the niche through integrin-dependent contacts, receiving homeostatic, survival, and proliferation signals. (molcells.org)
- These studies define 2 independent binding sites for PtdIns-derived lipids in SNX27, that contribute to the dynamic recruitment of SNX27 to distinct membranes during T cell activation. (pubmedcentralcanada.ca)
- Researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley, combining nanotechnology with biochemistry, have created unique synthetic membranes that, for the first time ever, enable them to directly control signaling activity in living T cells from the immune system. (eurekalert.org)
- This enabled the researchers to preserve the membranes in their naturally fluid state, allowing lipids and T cell receptor proteins to diffuse and interact freely over macroscopic distances. (eurekalert.org)
- We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK) and invariant NKT (iNKT) cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. (biomedcentral.com)
- After SMACs are established, the ongoing formation of TCR microclusters is required for sustained signaling when T cells are activated by planar bilayers ( 13 , 18 , 19 ), but this remains to be clearly demonstrated with cells presenting MHCp. (jimmunol.org)
- MHC-peptide strength plays an important role in sustained signaling and T cell commitment. (sciencemag.org)
- In view of the potential involvement of V3 in the abnormal AICD process of uninfected CD4+ T cells, we addressed in this study the effects of V3 on the intracellular signaling of CD4+ T cells. (biomedcentral.com)
- Three years ago, we had this fantasy pipe dream about an experiment to measure how alterations in the geometric shapes of the synapses - what we call spatial mutations - would affect T cell signaling. (eurekalert.org)
- In vitro studies have suggested that FAK-generated signaling is involved in cell survival (9) and seems to be essential for development. (scielo.br)
- Gautreau A, Louvard D, Arpin M. ERM proteins and NF2 tumor suppressor: the Yin and Yang of cortical actin organization and cell growth signaling. (medecinesciences.org)
- In DCs interacting with T cells, spinophilin is polarized dynamically to contact sites in an antigen-dependent manner. (rupress.org)
- To test this directly, we labeled a "null" pMHC class II complex and found that, although it lacked major TCR contact residues, it could be driven into the synapse in a TCR-dependent manner. (jove.com)
- Surprisingly, while DC-triggered T cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. (bloodjournal.org)
- Formation of the memory CD8 + T cell compartment is highly dependent on the early activation cues received by na?ve CD8 + T cells during primary infection. (molcells.org)
- Using mouse models of MC deficiency, we report on MC-dependent recruitment and activation of multiple T cell subsets to the skin and draining lymph nodes (DLNs) during dengue virus (DENV) infection. (jci.org)
- Newly recruited and locally proliferating γδ T cells were the first T cell subset to respond to MC-driven inflammation, and their production of IFN-γ was MC dependent. (jci.org)
- Inflammatory and immunological responses were evaluated by pathology, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blot analysis, and flow cytometry. (jove.com)
- Our results suggest that the anti-inflammatory effect of baicalin may be linked to modulation of the balance between Th17 and Treg cells in TNBS-induced ulcerative colitis. (jove.com)
- Investigators will use two-photon microscopy in laboratory animals undergoing surgical removal of a part of the skull, to determine how the surgery activates an immune inflammatory response that may result in damage to synaptic connections between brain cells. (dana.org)
- The research may lead to development of new anti-inflammatory treatment strategies to accelerate synapse stabilization following stroke, brain injury, or brain surgery. (dana.org)
- The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. (scielo.br)
- NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. (biomedcentral.com)
- Second, we are investigating ways to understand the human immune system, both for what it can tell us about immunology in general and because inbred mice have not, in most cases, been a reliable guide for developing treatments for immunological diseases. (stanford.edu)
- It is also required for optimal T cell activation because DCs derived from mice lacking spinophilin exhibit defects in antigen presentation both in vitro and in vivo. (rupress.org)
- Additional representative images of MC-γδ T cell conjugates in cytospins from DENV-infected mice and of control cytospins are provided in Supplemental Figure 14 . (jci.org)
- In the T cell-DC synapse CD80 clusters were colocalized with CD28 and PKCθ, a characteristic of the cSMAC. (jimmunol.org)
- Although this organization was observed with mature DC in one study, others have found that T cell-DC interfaces have multiple large TCR clusters rather than a single cSMAC ( 16 , 17 ). (jimmunol.org)
- Before SMAC formation, TCR are engaged in the periphery of the nascent IS ( 7 ) in microclusters ( 10 ). (jimmunol.org)
- In this regard, it is critical to deeply understand the sensitivity of CAR T cells, especially against low-density targets and the possible therapeutic window of antigen density targeted by CAR T cells. (frontiersin.org)
- Recent studies indicate that the organized immune synapse is a multitasking platform performing several functions essential to the determination of TCR sensitivity and responsiveness. (rupress.org)
- Here we show that myosin IIA was necessary for complete assembly and movement of T cell antigen receptor microclusters. (nih.gov)
- The physiological outcomes of the MC-DC synapse suggest a new role for intercellular crosstalk in defining the immune response. (rupress.org)