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Antibody: A type of glycoprotein molecule, also called immunoglobulin (ig), produced by B lymphocytes that binds antigens, often with a high degree of specificity and affinity. The basic structural unit of an antibody is composed of two identical heavy chains and two identical light chains. N-terminal variable regions of the heavy and light chains form the antigen-binding sites, whereas the C-terminal constant regions of the heavy chains functionally interacts with other molecules of the immune system. Every individual has millions of different antibodies, each with a unique antigen-binding site. Secreted antibodies perform various effector functions, including neutralizing antigens, activating complement, and promoting leukocyte-dependent destruction of microbes (1). Antibody repertoire: The collection of different antibody specificities expressed in an individual (1). Antibody secreting cell: A B lymphocyte that has undergone differentiation and produces the secretory form of immunoglobulin (Ig). Antibody secreting cells are produced in response to antigen and reside in the spleen and lymph nodes as well as in the bone marrow (1). In the brain, antibody-secreting (B lymphocytes) cells may be seen in the perivascular compartment during CSN inflammatory reactions (1). Antigen: A molecule that binds to an antibody or a T cell receptor (TCR). Antigens that bind to antibodies include all class of molecules. TCRs bind only peptide fragments of proteins complexed with MHC molecules; both the peptide ligand and the native protein from which it is derived ate called T cell antigens (1). Antigen-presenting cell (APC): A cell that displays peptide fragments of protein antigens, in association with MHC molecules, on its surface and activates antigen-specific T cells. In addition to displaying peptide-MHC complexes, APCs must also express costimulatory molecules to activate T lymphocytes optimally (1). Astrocytes: The most numerous of the neuroglial cells in the CNS derived from the neuroectoderm. Astrocytes function is fundamental for maintaining the homeostasis in the CNS. Astrocytes are part of the blood brain barrier, function as de-toxificating cells in the neuronal microenvironment and produce a variety of growth factors and mediators that contribute to the interaction betewwen neurons and their environment (neuronal-neuroglial interaction). Autoantibody: An antibody produced in an individual that is specific for a self antigen. Autoantibodies can cause damage to cells and tissues and are produced in excess in systemic autoimmune diseases, such as systemic lupus erythematous (1). Autoimmune disease: A disease caused by a break-down of self-tolerance such that the adaptive immune systems to self antigens and mediates cell and tissue damage. Autoimmune diseases can be organ specific (e.g. multiple sclerosis) or systemic (e.g. systemic lupus erythematous) (1). Autoimmune: The state of adaptive immune system responsiveness to self antigens that occurs when mechanisms of self-tolerance fail (1). B lymphocyte: The only cell type capable of producing antibody molecules and therefore the central cellular components of humoral immune responses. B lymphocytes or B cells, develop in the bone marrow and mature B cells are found mainly in lymphoid follicles in secondary lymphoid tissues, in bone marrow, and in low numbers in the circulation (1). In the brain, B lymphocytes may be seen in the perivascular space during inflammatory reactions and occasionally in normal CNS tissues (1). Blood
brain barrier (BBB):
The physiological barrier that separates blood from brain parenchyma.
It consists of endothelial cells with tight junctions that are surrounded
by a continuous basement membrane and astroglial end-feet. The blood
brain barrier is the central modulator of neuroimmune function
in the CNS (6). CD molecules: Cell surface molecules expressed on various cell types in the immune system that are designed by the "cluster of differentiation" or CD number (1). Cell mediated immunity (CMI): The form of adaptive immunity that is mediated by T lymphocytes and serves as the defense mechanism against microbes that survive within phagocytes or infect non-phagocytic cells. CMI responses include CD4 cell-mediated activation of macrophages that have phagocytosed microbes and CD8 CTL killing of infected cells (1). Cerebrospinal fluid (CSF): The serumlike fluid produced by the choroid plexus localized in the ventricles of the brain. The CSF circulates throughout the ventricles and subarachnoid space. The CSF may contain cells (e.g. lymphocytes, monocytes) and proteins that include cytokines or chemokines. Chemokines: A large family of structurally homologous, low molecular weight cytokines that stimulate leukocyte movement and regulate the migration of leukocytes from the blood to tissues (1). Chemokine receptors: Cell surface receptors for chemokines that transducer signals stimulating the migration of leukocytes. These receptors are members of the seven-transmembrane a-helical, G protein-linked family of receptors (1). Classical pathway of complement activation: The pathway of activation of the complement system that is initiated by binding of antigen-antibody complexes to the C1 molecule and induces a proteolytic cascade involving multiple other complement proteins. The classical pathway is an effector arm of the humoral immune system that generates inflammatory mediators, opsonins for phagocytosis of antigens, and lytic complexes that destroy cells (1). CNS: Central nervous system. Choroid plexus: A site of production of cerebrospinal fluid in the adult brain. It is formed by the invagination of ependymal cells into the ventricles, which become richly vascularized (3). Complement: A system of serum and cell surface proteins that interact with one another and with other molecules of the immune system to generate important effectors of innate and adaptive immune responses. The classical and alternative pathways of the complement system are activated by antigen-antibody complexes or microbial surfaces, respectively, and consist of a cascade of proteolytic enzymes that generate inflammatory mediators and opsonins. Both pathways lead to the formation of a common cell lytic complex that is inserted in cell membranes (1). Cytokines: Proteins produced by many different cell types that mediate inflammatory and immune reactions. Cytokines are principal mediators of communication between cells of the immune system (1). Cytolytic (or cytotoxic) T lymphocyte (CTL): A type of T lymphocyte whose mayor effector function is to recognize and kill host cells infected with viruses or other intracellular microbes. CTLs usually express CD8 and recognize microbial peptides displayed by class I MHC molecules. CTL killing of infected cells involves the release of cytoplasmatic granules whose contents include membrane pore forming proteins and enzymes. CTLs are important mediators of neurological disorders such as Rasmussen's syndrome and multiple sclerosis (1). Granular cells (neurons): Small and densely packed neurons in the innermost region of the cerebellum. Growth and differentiation factor: Proteins produced by cells to maintain a normal growth or functional activity. The differentiation factors contribute to the determination of specific cellular types or cellular specialization. Endothelia: Cells that are major constituent of blood vessel structures. Endothelia interact with perivascular macrophages, smooth muscle cells, and end feet of astrocytes to form blood vessels. Enzyme - Linked immunosorbent assay (ELISA): A method of quantifying an antigen immobilized on a solid surface by use of a specific antibody with covalently coupled enzyme. The amount of antibody that binds the antigen is proportional to the amount of antigen present and is determined by spectrophotometrically measuring the conversion of a clear substrate to a color product by the coupled enzyme (1). Human
leukocyte antigens (HLA):
MHC molecules expressed on the surface of human cells human MHC were first
identified as alloantigens on the surface of white blood cells leukocytes)
that bind serum antibodies from individuals previously exposed to other
individuals' cells. (e.g., mothers or transfusion recipients) (1). Humoral immunity: The type of adaptive immunity response mediated by antibodies produced by B lymphocytes. Humoral immunity is the principal defense mechanism against extracellular microbes and their toxins (1). Immune inflammation: Inflammation that is a result of an adaptive immune response to antigen. The cellular infiltrate at the inflammatory site may include cells of the innate immune system such as neutrophils and macrophages, which are recruited as a result of the actions of T cell cytokines (1). Immune response: A collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system (1). Immune surveillance: The concept that a physiologic function of the immune system is to recognize and destroy clones of transformed cells before they grow into tumors and to kill tumors after they are formed. The term immune surveillance is sometime use in a general sense to describe function of T lymphocytes to destroy and detect any cell, not necessarily a tumor cell, that is expressing foreign (e.g., microbial) antigens (1). Immune system: The molecules, cells, tissue and organs that collectively function to provide immunity, or protection, against foreign organisms (1). Immunity: Protection against disease, usually infectious disease, mediated by a collection of molecules, cells and tissues collectively called the immune system. In a broader sense, immunity refers to the ability to respond to foreign substances, including microbes or molecules (1). Immunoblot: An analytical technique in which antibodies are used to detect the presence of an antigen bound to a (i.e., blotted on) solid matrix such as filter paper (also known as western blot) (1). Immunohistochemistry: A technique to detect the presence of an antigen in histologic tissue sections by use of an enzyme-coupled antibody that is specific for the antigen. The enzyme converts a colorless substrate to a colored insoluble substance that precipitates at the site where the antibody and thus the antigen are localized. The position of the colored precipitate, and there for the antigen, in the tissue section is observed by conventional microscopy Immunohistochemestry is a routine technique in diagnostic pathology and various fields of research (1). Immunosuppression: Inhibition of one or more components of the adaptive or innate immune system as a result of an underlying disease or intentionally induce by drugs for the purpose of preventing or treating graft rejection or autoimmune disease. Steroids such as methylprednisolone or prednisone have immunosuppressant effects. Commonly immunosuppressive drugs include cyclosporine, which blocks T cell cytokines production, methotrexate, cyclophosphamide and tacrolymus (1). Immunotherapy: The treatment of a disease with therapeutic agents that promote or inhibit immune response. Cancer immunotherapy, for example, involves promoting active immune responses to tumor antigens or administering anti-tumor antibodies or T cells to establish passive immunity (1). Inflammation: A complex reaction of the innate immune system in vascularized tissues that involves the accumulation and activations of leukocytes and plasma proteins at the site of infection, toxin exposure or cell injury. Inflammation is initiated by changes in blood vessels that promote leukocyte recruitment. Local adaptive immune responses can promote inflammation. Although inflammation serves a protective function in controlling infections and promoting tissue repair, it can also cause tissue damage and disease (1). Innate immunity: Protection against infection that relies on mechanisms that exist before infection, are capable of a rapid response to microbes, and react in essentially the same way to repeated infections. The innate immune system includes epithelial barriers, phagocytic cells (neutrophils, macrophages), NK cells, the complement system, and cytokines, largely made by mononuclear phagocytes that regulate and coordinate many of the activities of the cells of innate immunity(1). Lymphocyte homing: The directed migration of subsets of circulating lymphocytes into particular tissue sites. Lymphocyte homing is regulated by the selective expression of adhesion molecules, called homing receptors, on the lymphocytes and tissue-specific expression of endothelial ligands for these homing receptors, called addressins, in different vascular beds. For example, some T lymphocytes preferentially home to intestinal lymphoid tissue (i.e., Peyer's patches) and this directed migration is regulated by binding of the VLA-4 integrin on the T cells to the Mad CAM addressin on Peyer's patch endothelium (1). Lymphocyte
infiltration:
Process of migration of lymphocytes to areas of tissue injury or damage.
Migration mechanisms are modulated by blood vessels and chemical mediators
that facilitate the selection and homing of specific groups of leukocytes. Macrophage: A tissue-based phagocytic cell derived from blood monocytes that plays important roles in innate and adaptive immune responses. Macrophages are activated by microbial products such as endotoxin and by T cell cytokines such as IFN- ?. Activated macrophages phagocyte and kill microorganisms, secrete proinflammatory cytokines, and present antigens to helper T cells . Macrophages may assume different morphologic forms, in different tissue including the microglia of the central nervous system, Kuppffer cells in the liver, alveolar macrophages in the lung, and osteoclasts in bone (1). Major histocompatibiliy complex (MHC): There are two classes of MHC molecules. MHC class I molecules are found on the surface of most cells and present proteins that are generated in the cytosol to T lymphocytes. MHC class II molecules are expressed only at the surface of activated antigen-presenting cells, and they present peptides that have been degradated in cellular vesicles to T cells (3). Major histocompatibility complex (MHC) molecule: A heterodimeric membrane protein encoded in the MHC locus that serve as a peptide display molecule for recognition by T lymphocytes. Two structurally distinct types of MHC molecules exist. Class I MHC molecules are present on most nucleated cells, bind peptides derived from cytosolic proteins and are recognized by CD8+ T cells. Class II MHC molecules are restricted largely to professional APCs , bind peptides from endocytosed proteins , and are recognized by CD 4+ T cells (1).
Molecular mimicry: A postulated mechanism of autoimmunity triggered by infection with a microbe containing antigens that cross-react with self antigens. Immune responses to the microbe result in reaction against self tissues. Monocyte: A type of bone marrow -derived circulating blood cell that is the precursor of tissue macrophages. Monocytes are actively recruited into inflammatory sites, where they differentiate into macrophages or in the case of CNS, in perivascular macrophages. Natural Killer (NK) cells: A subset of bone marrow-derived lymphocytes, distinct from B or T cells, that function in innate immune responses to kill microbe infected cells by direct lytic mechanisms and by secreting INF-?. NK cells do not express clonally distributed antigen receptors like Ig receptors or TCRs, and their activation is coordinated by a combination of cell surface stimulatory and inhibitory receptors, the later recognizing self MHC molecules. Neonatal immunity: Passive humoral immunity to infections in mammals in the first months of live, before full development of the immune system. Neonatal immunity is mediated by maternally produced antibodies transport across the placenta into the fetal circulation before birth or derived from ingested milk and transport across the gut epithelium. Neurons: Cells that act as the main signaling units of the nervous system. Neuronal-neuroglial interaction: Mechanisms of communication between astrocytes, microglia and neurons that facilitate function and metabolism in CNS microenvironments. Neuroglia: General term to describe a group of cells in the CNS that include neuroectoderm derivated cells such as astrocytes, oligodendrocytes, ependyma and mesoderm-derived microglia. Oligodendrocyte: Neuroglia cell specialized in the production of myelin and processes of myelination of nerve fibers. Perivascular
macrophage:
Perivascular macrophages are part
of the blood vessel structure in the CNS. Various names have been used
to describe these cells, including perivascular cells, perivascular macrophages,
perivascular microglia, and fluorescent granular perithelial cells (Mato
cells). Perivascular macrophages are a minor population in the CNS situated
adjacent to endothelial cells immediately beyond the basement membrane
of medium to small vessels. Perivascular macrophages along with astrocytes,
foot processes of parenchymal microglia and endothelia comprise the blood-brain
barrier (BBB). Perivascular macrophages are bone marrow derived and continuously
replaced by monocytes. Experimental studies have demonstrated the perivascular
macrophages are minimally required antigen presenting cells. (5) Perivascular space or Virchow-Robin space: The compartment that surrounds blood vessels in the CNS.The Virchow-Robin space is an important structure for neuroimmune function cells such as perivascular macrophages, end-feet of astrocytic processes and other immune cells interact. Phagocytosis: The process by which certain cells of the innate immune system, including macrophages and neutrophils, engulf large particles ( >0.5 µm in diameter) such as intact microbes. The cell surrounds the particle with extensions of its plasma membrane by an energy and cytoskeleton- dependent process; this process results in the formation of an intracellular vesicle called phagosome, which contains the ingested particles. In the CNS, the "phagocytic" microglia play a major role in phagocytosis.
Purkinje neuron: Large and specialized neurons in the cerebellum that project to the white matter and provide the output of the cerebellar cortex. The main role of the Purkinje neuron is inhibitory and mediated by the neurotransmitter ?- aminoburytic acid (GABA). Reactive oxygen intermediates (ROIs): Highly reactive metabolites of oxygen, including superoxide anion, hydroxyl radical , and hydrogen peroxide, that are produced by activated phagocytes. ROIs are used by the phagocytes to form oxyhalides that damage ingested bacteria. ROIs may also be released by cells and promote inflammatory responses or cause tissue damage. Secondary immune response: An adaptive immune response that occurs on second exposure to an antigen. A secondary response is characterized by more rapid kinetics and greater magnitude relatively to the primary immune response , which occurs on first exposure. Subarachnoid space: A space between the arachnoid and pial membranes that surround the brain and spinal cord that is filled with cerebrospinal fluid. It contains fibrous trabeculae, blood vessels and antigen presenting cells (6). T cell receptor (TCR): The clonally distributed antigen receptor on CD4 and CD8 T lymphocytes that recognizes complexes of foreign peptides bound to self MHC molecules on the surface of APCs. The most common form of TCR is composed of a heterodimer of disulfide-linked transmembrane polypeptide chains, designated a and ß, each containing one terminal Ig -like variable (v) domain, one Ig-like constant (c) domain , a hydrophobic transmembrane region, and a short cytoplasmatic region. (Another less common type of TCR , composed of ? and d chains, is found on a small subset of T cells and recognizes different forms of antigens ) T cell receptor complex: A multi protein plasma membrane complex on T lymphocytes that is composed of the highly variable , antigen -biding TCR heterodimer and the invariant proteins CD3 d, e, and the ? and the ? chain. T lymphocyte: The cell type that mediates cell mediated immune responses in the adaptive immune system. T lymphocytes mature in the thymus, circulate in the blood, populate secondary lymphoid tissues, and are recruited to peripheral sites of antigen exposure. They express antigen receptors (TCRs) that recognize peptide fragments of foreign proteins bind to self MHC molecules. Functional subsets of T Lymphocytes include CD4+ helper T cells and CD8 +CTLs (1). In the CNS, T lymphocytes play major roles in neuroinflammatory reactions during infection (e.g. encephalitis and meningitis), autoimmune disease (e.g. multiple sclerosis) and injury. TH1 cells: A functional subset of helper T cells that secrete a particular set of cytokines, including INF-?, and whose principal function is to stimulate phagocyte-mediated defense against infections, especially with intracellular microbes. TH2 cells: A functional subset of helper T cells that secrete a particular set of cytokines, including IL-4 and IL-5, and whose principal functions are to stimulate Ig E and eosinophil /mast cell mediated immune reactions and to down-regulate TH1 responses. Virchow-Robin space: see perivascular space. Western Blot: An immunologic technique to determine the presence of a protein in a biologic sample. The method involves separation of proteins in the sample by electrophoresis, transfer of the protein array from the electrophoresis gel to a support membrane by capillary action (blotting), and finally detection of the protein by binding of an enzymatically or radioactively labeled antibody specific for that protein.
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