Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.
A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.
A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.
A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.
The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.
The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.
Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.
Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.
A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.
A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
A specific mannose-binding member of the collectin family of lectins. It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY.
A 206-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.
Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.
Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).
A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.
A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.
A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.
GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.
Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.
A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.
Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.
A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.
Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
Polysaccharides found in bacteria and in capsules thereof.
Limbless REPTILES of the suborder Serpentes.
Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.
A species of gram-negative, anaerobic, rod-shaped bacteria originally classified within the BACTEROIDES genus. This bacterium has been isolated from the mouth, urine, feces, and infections of the mouth, soft tissue, respiratory tract, urogenital tract, and intestinal tract. It is pathogenic, but usually in association with other kinds of organisms.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.
A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.
Physiological processes and properties of the BLOOD.
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
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.
An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.
Polysaccharides consisting of mannose units.
Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
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.
A subclass of lectins that are specific for CARBOHYDRATES that contain MANNOSE.
The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.
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.
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues.
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.
Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.
Antibodies produced by a single clone of cells.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
A mitosporic Tremellales fungal genus whose species usually have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium.
Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Substances elaborated by bacteria that have antigenic activity.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
The body fluid that circulates in the vascular system (BLOOD VESSELS). Whole blood includes PLASMA and BLOOD CELLS.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
A species of the fungus CRYPTOCOCCUS. Its teleomorph is Filobasidiella neoformans.
A genus of gram-negative, anaerobic, rod-shaped bacteria. Its organisms are normal inhabitants of the oral, respiratory, intestinal, and urogenital cavities of humans, animals, and insects. Some species may be pathogenic.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
The rate dynamics in chemical or physical systems.
A hexose or fermentable monosaccharide and isomer of glucose from manna, the ash Fraxinus ornus and related plants. (From Grant & Hackh's Chemical Dictionary, 5th ed & Random House Unabridged Dictionary, 2d ed)
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
Physiologically inactive substances that can be converted to active enzymes.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Proteins prepared by recombinant DNA technology.
The single layer of pigment-containing epithelial cells in the RETINA, situated closely to the tips (outer segments) of the RETINAL PHOTORECEPTOR CELLS. These epithelial cells are macroglia that perform essential functions for the photoreceptor cells, such as in nutrient transport, phagocytosis of the shed photoreceptor membranes, and ensuring retinal attachment.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
A species of gram-negative, aerobic BACTERIA. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the NASOPHARYNX. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis (MENINGITIS, MENINGOCOCCAL). It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being A, B, C, Y, and W-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (REPERFUSION), including swelling; HEMORRHAGE; NECROSIS; and damage from FREE RADICALS. The most common instance is MYOCARDIAL REPERFUSION INJURY.
Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
A plasma protein that circulates in increased amounts during inflammation and after tissue damage.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Proteins found in any species of bacterium.
Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria.
Transport proteins that carry specific substances in the blood or across cell membranes.
An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992)
Established cell cultures that have the potential to propagate indefinitely.
Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.
Presence of warmth or heat or a temperature notably higher than an accustomed norm.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Infections with bacteria of the species STREPTOCOCCUS PNEUMONIAE.
Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
The sum of the weight of all the atoms in a molecule.
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.
The agent of South American trypanosomiasis or CHAGAS DISEASE. Its vertebrate hosts are man and various domestic and wild animals. Insects of several species are vectors.
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.
The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents.
Glycoproteins found on the membrane or surface of cells.
Proteins isolated from the outer membrane of Gram-negative bacteria.
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.
Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.
The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Elements of limited time intervals, contributing to particular results or situations.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

Role of antibody and complement in opsonization of group B streptococci. (1/449)

A requirement for the classic complement pathway in opsonization of group B streptococci was observed by using both a chemiluminescence and a radiolabeled bacterial uptake technique. The classic pathway increased levels of opsonization for types Ia and II stock and wild strains and for some type III wild strains. In contrast, other type III wild strains and the type III stock strain had accelerated kinetics of uptake in the presence of an intact classic pathway, but the level of opsonization was unchanged from that with antibody alone. We could not demonstrate a significant role for the alternative pathway in opsonizing stock or wild strains of group B streptococci. Futhermore, electrophoretic and complement consumption analysis by hemolytic titration failed to reveal alternative pathway activation by the majority of strains of this group. Therapy aimed at supplying opsonins for these organisms will require the presence of type-specific antibody.  (+info)

Alzheimer's beta-amyloid peptides can activate the early components of complement classical pathway in a C1q-independent manner. (2/449)

beta-Amyloid (beta-A) accumulates in the brain of patients with Alzheimer's disease (AD) and is presumably involved in the pathogenesis of this disease, on account of its neurotoxicity and complement-activating ability. Although assembly of beta-A in particular aggregates seems to be crucial, soluble non-fibrillar beta-A may also be involved. Non-fibrillar beta-A does not bind C1q, so we investigated alternative mechanisms of beta-A-dependent complement activation in vitro. On incubation with normal human plasma, non-fibrillar beta-A 1-42, and truncated peptide 1-28, induced dose-dependent activation of C1s and C4, sparing C3, as assessed by densitometric analysis of immunostained membrane after SDS-PAGE and Western blotting. The mechanism of C4 activation was not dependent on C1q, because non-fibrillar beta-A can still activate C1s and C4 in plasma genetically deficient in C1q (C1qd). In Factor XII-deficient plasma (F.XIId) the amount of cleaved C4 was about 5-10% less that in C1qd and in normal EDTA plasma; the reconstitution of F.XIId plasma with physiologic concentrations of F.XII resulted in an increased (8-15%) beta-A-dependent cleavage of C4. Thus our results indicate that the C1q-independent activation of C1 and C4 can be partially mediated by the activation products of contact system. Since the activation of contact system and of C4 leads to generation of several humoral inflammatory peptides, non-fibrillar beta-A might play a role in initiating the early inflammatory reactions leading to a multistep cascade contributing to neuronal and clinical dysfunction of AD brain.  (+info)

Cutting edge: C1q protects against the development of glomerulonephritis independently of C3 activation. (3/449)

C1q-deficient (C1qa-/-) mice develop antinuclear Abs and glomerulonephritis (GN) characterized by multiple apoptotic bodies. To explore the contribution of C3 activation to the induction of spontaneous GN, C1qa-/- mice were crossed with factor B- and C2-deficient (H2-Bf/C2-/-) mice. GN was present in 64% of the 45 C1qa/H2-Bf/C2-/- mice compared with 8% of the 65 H2-Bf/C2-/- mice and none of the 24 wild-type controls. IgG was detected in the glomeruli of diseased C1qa/H2-Bf/C2-/- kidneys. However, glomerular staining for C3 was absent. Increased numbers of glomerular apoptotic bodies were detected in undiseased C1qa/H2-Bf/C2-/- kidneys. These findings support the hypothesis that C1q may play a role in the clearance of apoptotic cells without the necessity for C3 activation and demonstrate that the activation of C3 is not essential for the development of GN in this spontaneous model of lupus-like disease.  (+info)

Consumption of C4b-binding protein (C4BP) during in vivo activation of the classical complement pathway. (4/449)

C4BP has a central role in regulating the classical complement (C') pathway, but it is still uncertain whether or not it is consumed during in vivo complement activation. Attempts to demonstrate changes in C4BP plasma levels in systemic lupus erythematosus and essential mixed cryoglobulinaemia have failed, probably due to up-regulation of this protein during the inflammatory reaction. We have studied one patient with severe post-transfusion complement-mediated anaphylaxis (CMA), and 67 patients with hereditary C1 inhibitor deficiency (hereditary angioedema (HAE)). The first of these two conditions is characterized by the absence of systemic inflammatory reaction and the second by acute and chronic activation of the C' classical pathway. C4BP, C4BP-C4b complex, and soluble terminal C' complex (sC5b-9) were measured in the patients' plasmas by ELISA techniques and C3a and C4a by radioimmunoassays. In CMA, 15 min after the transfusion, there was a massive C' activation, with increases in C4a, C3a, sC5b-9, C4BP-C4b complexes and decreases in C4, C3 and C4BP. All parameters reverted to preinfusion values within 24 h. Depletion of C4 was correlated with that of C4BP. In patients with HAE, the median value of C4BP (83% range 54-165) was significantly lower (P < 0.0001) than in normal controls (99% range 70-159), with no difference between patients in remission or during acute attacks. C4BP-C4b complexes could not be detected in HAE patients. The results of this study indicate that C4BP is consumed in vivo during acute, and possibly during chronic activation of the C' classical pathway, and that this protein, after interaction with C4b, not longer circulates in plasma.  (+info)

Alterations in C3 activation and binding caused by phosphorylation by a casein kinase released from activated human platelets. (5/449)

A casein kinase released from activated human platelets phosphorylates a number of plasma proteins extracellularly, and that activation of platelets in systemic lupus erythematosus patients parallels an increase in the phosphate content of plasma proteins, including C3. The present study was undertaken to characterize this platelet protein kinase and to further elucidate the effect(s) on C3 function of phosphorylation by platelet casein kinase. The phosphate content of human plasma C3 was increased from 0.15 to 0.60 mol phosphate/mol of C3 after platelet activation in whole blood or platelet-rich plasma. The platelet casein kinase was distinct from other casein kinases in terms of its dependence on cations, inhibition by specific protein kinase inhibitors, and immunological reactivity. C3 that had been phosphorylated with platelet casein kinase was tested for its susceptibility to cleavage by trypsin or the classical and alternative pathway convertases and its binding to EAC and IgG. Phosphorylation did not affect the cleavage of C3 into C3a and C3b, but the binding of fragments from phosphorylated C3 to EAC14oxy2 cells and to IgG in purified systems and in serum was increased by 1.6-4.5 times over that of unphosphorylated C3. A covariation was seen between the enhanced binding of C3 fragments to IgG after phosphorylation and an increased ratio of glycerol/glycine binding, from 2.0 for unphosphorylated C3 to 4.9 for phosphorylated C3. The present study suggests that an overall effect of phosphorylation of C3 by platelet casein kinase is to enhance the opsonization of immune complexes.  (+info)

Antibody-independent classical complement pathway activation and homologous C3 deposition in xeroderma pigmentosum cell lines. (6/449)

Of human malignantly transformed cell lines, xeroderma pigmentosum (XP) cell lines were found to be highly susceptible to homologous complement (C): cells were opsonized by C3 fragments on incubation with diluted normal human serum. C3 fragment deposition on XP cells was Ca2+-dependent and occurred on live cells but not UV-irradiated apoptotic cells. (Ca2+ is required for activation of the classical C pathway via C1q and the lactin pathway via mannose binding lectin (MBL), and the surface of apoptotic cells usually activates the alternative C pathway.) In this study we tested which of the pathways participates in XP cell C3 deposition. In seven cell lines that allowed C3 deposition (i), Clq was shown to be essential but MBL played no role in C activation, (ii) Cls but not MASP bound XP cells for activation, (iii) no antibodies recognizing XP cells were required for homologous C3 deposition, and (iv) the alternative pathway barely participated in C3 deposition. Furthermore, the levels of C-regulatory proteins for host cell protection against C, decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46), were found to be relatively low in almost all XP cell lines compared with normal cells. These results indicate that XP cells activate the classical C pathway in an antibody-independent manner through the expression of a molecule which directly attracts C1q in a C-activating form, and that relatively low levels of DAF and MCP on XP cells facilitate effective C3 deposition. The possible relationship between the pathogenesis of XP and our findings is discussed.  (+info)

Role of complement component C1q in the IgG-independent opsonophagocytosis of group B streptococcus. (7/449)

We investigated the role of complement component C1q in the IgG-independent opsonophagocytosis of type III group B Streptococcus (GBS) by peripheral blood leukocytes. We report that C1q binds to type III GBS both in normal human serum deficient in IgG specific for type III capsular polysaccharide and in a low-ionic strength buffer. The dissociation constant Kd ranged from 2.0 to 5.5 nM, and the number of binding sites Bmax ranged from 630 to 1360 molecules of C1q per bacterium (CFU). An acapsular mutant strain of GBS bound C1q even better than the wild type, indicating that the polysaccharide capsule is not the receptor for C1q. In serum, binding of C1q to GBS was associated with activation of the classical complement pathway. However, normal human serum retained significant opsonic activity after complete depletion of C1q, suggesting that the serum contains a molecule that is able to replace C1q in opsonization and/or complement activation. Mannan-binding lectin, known to share some functions with C1q, appeared not to be involved, since its depletion from serum had little effect on opsonic activity. Excess soluble C1q or its collagen-like fragment inhibited phagocytosis mediated by normal human serum, suggesting that C1q may compete with other opsonins for binding to receptor(s) on phagocytes. We conclude that, although C1q binds directly to GBS, C1q binding is neither necessary nor sufficient for IgG-independent opsonophagocytosis. The results raise the possibility that additional unknown serum factor(s) may contribute to opsonization of GBS directly or via a novel mechanism of complement activation.  (+info)

Antibodies against human heat-shock protein (hsp) 60 and mycobacterial hsp65 differ in their antigen specificity and complement-activating ability. (8/449)

Although complement activation appears to have an important role both in the early and late phases of atherosclerosis, the exact mechanism of the initiation of this activation is still unknown. Since injuries of the endothelial cells are known to result in increased stress-protein expression we tested the complement-activating ability of recombinant human 60 kDa heat-shock protein (hsp60). Human hsp60 was found to activate the complement system in normal human serum in a dose-dependent manner. Activation took place through the classical pathway. The lack of complement activation in agammaglobulinemic serum indicates that the classical pathway is triggered by anti-hsp60 antibodies. Hsp60 activated complement in the sera of 74 patients with coronary heart disease as well, and a strong positive correlation (r = 0.459, P < 0.0001) was found between the extent of complement activation and the level of anti-hsp60 IgG antibodies but there was no correlation to the level of anti-hsp65 IgG antibodies. Further distinction between anti-hsp60 and anti-hsp65 antibodies was obtained from competitive ELISA experiments: binding of anti-hsp60 antibodies to hsp60-coated plates was inhibited only by recombinant hsp60 and vice versa. Our present findings indicate that anti-hsp60 and anti-hsp65 antibodies are distinct, showing only partial cross-reactivity. Since complement activation plays an important role in the development of atherosclerosis and the levels of complement-activating anti-hsp60 antibodies are elevated in atherosclerosis-related diseases, our present findings may have important pathological implications.  (+info)

Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. Exp Neurol. 2017 Jun 07;: Authors: Wyatt SK, Witt T, Barbaro NM, Cohen-Gadol AA, Brewster AL Abstract Microglia-mediated neuroinflammation is widely associated with seizures and epilepsy. Although microglial cells are professional phagocytes, less is known about th...
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1C1q Classical complement pathway inhibition: A novel strategy for the inhibition of Alzheimers disease pathogenesis INTRODUCTION 1.1 Alzheimers disease From the development of the Smallpox
Misregulation of the innate immune response and other immune-related processes have been suggested to play a critical role in the pathogenesis of a number of different neurodegenerative diseases, including age related macular degeneration. In an animal model for photoreceptor degeneration, several genes of the innate and acquired immune system were found to be differentially regulated in the retina during the degenerative process. In addition to this differential regulation of individual genes, we found that in the rd1 retina a significantly higher number of genes involved in immune-related responses were expressed at any given time during the degenerative period. The peak of immune-related gene expression was at postnatal day 14, coinciding with the peak of photoreceptor apoptosis in the rd1 mouse. We directly tested the potential involvement of acquired and innate immune responses in initiation and progression of photoreceptor degeneration by analyzing double mutant animals. Retinal morphology ...
We reported inhibition of growth of primary rat mammary carcinomas after infusions of tumor-bearer plasma absorbed with Protein A-Sepharose or inactivated CNBr Sepharose. Absorbed plasmas were depleted of the third component of complement (C3) (other complement components defined similarly) and C5 but not C1, C4, or C2. These results suggested that activation of the alternative pathway of complement might be involved in the observed antitumor effects. To test this concept sera were treated with ethylenedinitrilotetraacetic acid or [ethylenebis(oxyethylenenitrilo)]tetraacetic acid before absorption with Protein A-Sepharose. Ethylenedinitrilotetraacetic acid, by chelating calcium and magnesium, prevents activation of both the alternative and classical complement pathways. [Ethylenebis(oxyethylenenitrilo)]tetraacetic acid, by chelating calcium but not magnesium, permits activation of the alternative pathway but inhibits activation of the classical complement pathway. Sera in the presence or absence ...
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Tissue destruction mediated by activation of classic complement pathway; C3a and C5a production with activated leukocytes producing cytokines (e.g., IL-1, TNF-alpha) which result in enhanced inflammatory cell response, fever, tissue damage, etc. ...
Host defense mechanisms can counteract the antiphagocytic bacterial capsule. Unlike classical complement pathway, the alternative complement pathway is not antibody-mediated and can easily overwhelm encapsulated bacteria. It is triggered by the cleavage of C3 into C3a and C3b and the attachment of C3b to MAMPs (Microbe Associated Molecular Patterns), such as the capsular polysaccharides. The C3b molecules osponsize the pathogen, facilitating its phagocytosis and intravascular clearance. Furthermore, the complement cascade leads to the formation of proteolytic C3and C5 convertases and the terminal membrane attack complex, which lyses the pathogen. However, a potentially fatal drawback from lysing the pathogen is the release of endotoxic lipopolysaccharides, which elicit an out-of-control immune response. [2 ...
The host genetic factors affecting susceptibility to disseminated candidiasis are incompletely defined. Peltz et al. (p. 4472-4479) used a next-generation computational genetic mapping program to identify genetic factors affecting inbred strain survival after disseminated candidiasis. Their analysis indicated that genetic variation within early classical complement pathway components (C1q, C1r, and C1s) affected survival. This result was verified by demonstrating that serum C1 binding to Candida albicans was strongly affected by C1rs alleles, as was survival in chromosome substitution strains. A combinatorial, conditional genetic model, involving an interaction between the C5 and C1r/s alleles, accurately predicted survival after disseminated candidiasis. Beyond its potential applicability to infectious diseases, this combinatorial genetic model could provide insight into the genetic architecture for susceptibility to autoimmune and neurodegenerative diseases. ...
About isatuximab. Isatuximab, an investigational anti-CD38 monoclonal antibody, targets a specific epitope on the CD38 receptor and is designed to trigger multiple, mechanisms of action that are believed to directly promote programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and cell surface receptors, making it a potential target for antibody-based therapeutics such as isatuximab.. Isatuximab is an investigational agent and its safety and efficacy have not been evaluated by the U.S. FDA, the European Medicines Agency, or any other regulatory authority.. About Sutimlimab. Sutimlimab is a C1s inhibitor that received breakthrough therapy designation and is currently being investigated for the treatment of CAD in Phase 3 clinical trials. A humanized, monoclonal antibody, sutimlimab is designed to target C1s, a serine protease within the C1-complex in the classical complement pathway of the immune system, which ...
|strong|Goat anti Human C4 antibody|/strong| recognises human C4, a secreted protein that plays a central role in activation of the classical pathway of the complement system.|br||br|C4 is split into …
The optimal reaction conditions for hemolytic assay of alternative complement pathway activity in mouse serum were investigated. A microtiter system was used, in which a number of 7.5×106 rabbit erythrocytes per test well appeared to be optimal. Rabbit erythrocytes were superior as target cells over erythtocytes from a number of ... read more other animal species. The optimal conditions were as follows: an incubation temperature of 39°C, an ionic strength of about 200 mM, and a magnesium concentration of 2.5 mM. Incubation during 60 min was not sufficient for an end-point titration. Addition of 1 mg of zymosan A per test well, however, enhanced and accelerated the hemolytic activity of mouse serum via the alternative pathway resulting in a maximum value after 45 min. This, most probably, proceeded by a mechanism involving the formation of a zymosan-C5-convertase and bystander lysis of the target cells. In contrast to the normal alternative pathway assay the zymosan-potentiated test did, most ...
Neuromyelitis optica (NMO) is an autoimmune CNS disorder mediated by pathogenic aquaporin-4 (AQP4) water channel autoantibodies (AQP4-IgG). Although AQP4-IgG-driven complement-dependent cytotoxicity (CDC) is critical for the formation of NMO lesions, the molecular mechanisms governing optimal classical pathway activation are unknown. We investigated the molecular determinants driving CDC in NMO using recombinant AQP4-specific autoantibodies (AQP4 rAbs) derived from affected patients. We identified a group of AQP4 rAbs targeting a distinct extracellular loop C epitope that demonstrated enhanced CDC on target cells. Targeted mutations of AQP4 rAb Fc domains that enhance or diminish C1q binding or antibody Fc-Fc interactions showed that optimal CDC was driven by the assembly of multimeric rAb platforms that increase multivalent C1q binding and facilitate C1q activation. A peptide that blocks antibody Fc-Fc interaction inhibited CDC induced by AQP4 rAbs and polyclonal NMO patient sera. ...
Neuromyelitis optica (NMO) is an autoimmune CNS disorder mediated by pathogenic aquaporin-4 (AQP4) water channel autoantibodies (AQP4-IgG). Although AQP4-IgG-driven complement-dependent cytotoxicity (CDC) is critical for the formation of NMO lesions, the molecular mechanisms governing optimal classical pathway activation are unknown. We investigated the molecular determinants driving CDC in NMO using recombinant AQP4-specific autoantibodies (AQP4 rAbs) derived from affected patients. We identified a group of AQP4 rAbs targeting a distinct extracellular loop C epitope that demonstrated enhanced CDC on target cells. Targeted mutations of AQP4 rAb Fc domains that enhance or diminish C1q binding or antibody Fc-Fc interactions showed that optimal CDC was driven by the assembly of multimeric rAb platforms that increase multivalent C1q binding and facilitate C1q activation. A peptide that blocks antibody Fc-Fc interaction inhibited CDC induced by AQP4 rAbs and polyclonal NMO patient sera. ...
The complement system is an enzyme cascade that is a collection of blood and cell surface proteins to help the abilities of antibodies to clear pathogens from an organism. The complement system that comprises 30 different proteins, including serum proteins, serosal proteins, and cell membrane receptors is an important part of the innate immune system. There are three different complement pathways, the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway.
Ischemia and reperfusion of organs is an unavoidable consequence of transplantation. Inflammatory events associated with reperfusion injury are in part attributed to excessive complement activation. Systemic administration of complement inhibitors reduces reperfusion injury but leaves patients vulnerable to infection. Here, we report a novel therapeutic strategy that decorates cells with an anti-complement peptide. An analog of the C3 convertase inhibitor Compstatin (C) was synthesized with a hexahistidine (His6) tag to create C-His6. To decorate cell membranes with C-His6, fusogenic lipid vesicles (FLVs) were used to incorporate lipids with nickel (Ni2+) tethers into cell membranes, and these could then couple with C-His6. Ni2+ tether levels to display C-His6 were modulated by changing FLV formulation, FLV incubation time and FLV levels. SKOV-3 cells decorated with C-His6 effectively reduced complement deposition in a classical complement activation assay. We conclude that our therapeutic ...
Acts as complement inhibitor by disrupting the formation of the classical C3 convertase. Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the classical and alternative complement pathways.
Anti-neutrophil cytoplasmic antibodies are linked to an increased prevalence of interstitial lung disease and pulmonary embolism in systemic sclerosis, according to data published in Arthritis Research & Therapy.. The clinical significance of ANCA in [systemic sclerosis (SSc)] patients who do not manifest [ANCA-associated vasculitis] is controversial. An association between ANCA in SSc and [interstitial lung disease] has been suggested, Mandana Nikpour, PhD, MBBS, FRACP, FRCPA, of the University of Melbourne, Australia, and colleagues wrote. However, this has not been consistently reported in all case series. It has also been suggested that ANCA in SSc patients may indicate an inflammatory component to the illness and that ANCA should be treated as a red flag, prompting a thorough investigation and follow-up. ...
TY - JOUR. T1 - Impaired Opsonization with C3b and Phagocytosis of Streptococcus pneumoniae in Sera from Subjects with Defects in the Classical Complement Pathway. AU - Yuste, Jose. AU - Sen, Ashwin. AU - Truedsson, Lennart. AU - Jonsson, Goran. AU - Tay, Liang-Seah. AU - Hyams, Catherine. AU - Baxendale, Helen. AU - Goldblatt, Fiona. AU - Botto, Marina. AU - Brown, Jeremy. PY - 2008. Y1 - 2008. M3 - Article. VL - 76. SP - 3761. EP - 3770. JO - Infection and Immunity. JF - Infection and Immunity. SN - 0019-9567. IS - 8. ER - ...
Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might give more insight into the disease. Markers from the classical complement pathway are elevated where ...
Abdullah, M.T., Nepliounev, I., Alfonina, G., Ram, S., Rice, P., Elkins, C. (2005). Killing of dsrA mutants of haemophilus ducreyi by normal human serum occurs via the classical complement pathway and is initiated by immunoglobulin m binding. Infection and Immunity. 73: 3431-3439 ...
The biosynthesis of steroid hormones is a difficult process in which Cholesterol is transformed into mineralocorticoids, glucocorticoids and sex hormones via a series of hydroxylation, oxidation and reduction steps. To better understand the molecular level of sexual organ maturation in humans, the classical pathway and the alternative pathway of this process are produced. The pathways produce the main steroid hormones in humans, namely Progestogen, Corticosteroids, Androgens and Estrogens. The classical pathway is meant to produce an important steroid called Androgen, which is a synthetic steroid hormone that regulates sexual development and the maintenance of the male sex organs via binding to androgen receptors. For more information and details about Androgens and the diseases linked with this molecular pathway, please visit Chapter 37 of the book of Blau (ISBN 978-3-642-40337-8) ...
From Lake Shore Drive to Lincoln Park, Vitners Sour Cream & Onion flavored chips are the classic complement to every get-together!
Two major NF-κB pathways activate different sets of target genes involved in immune and inflammatory responses based on the nuclear translocation of RelA:p50 and RelB:p52 dimers (12). The target genes of the IKKβ−regulated classic pathway include cytokines, adhesion molecules, inflammatory mediators, inhibitors of apoptosis, and antioxidant enzymes (31-33). However, the target genes of the IKKα-regulated alternative pathway and related biological functions have not been fully elucidated. Our finding that radiation induces nuclear import of RelB leading to activation of prosurvival gene sod2 suggests that this pathway may also regulate the cellular antioxidant system. We previously showed that TNF-α induces transcription of the sod2 gene through RelA:p50 dimer binding to an intronic NF-κB element of the gene (27). Recently, we also found that RelB is able to bind to the intronic NF-κB element, leading to the induction of MnSOD in response to radiation (25), which is prevented by vitamin ...
Combining with the C1q component of the classical complement cascade and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity.
Mannan is a prominent structural component displayed on the cell surface of C. albicans yeast cells (4), and antimannan IgG is present ubiquitously in the general human population (10, 14, 23). Previously, we showed that this naturally occurring antimannan IgG is required for activation of the classical complement pathway when C. albicans is incubated in NHS (40). We now present evidence that this naturally occurring antimannan IgG also regulates activation of the alternative pathway byC. albicans yeast cells. In NHS that is deficient in antimannan antibodies and lacks classical pathway activity as a result of EGTA chelation of serum Ca2+, addition of exogenous antimannan IgG accelerated C3 binding via the alternative pathway in a dose-dependent manner (Fig. 1 and 3). This accelerating effect of antimannan IgG was confirmed in a serum-free complement binding medium that consisted of only purified proteins of the alternative pathway (Fig. 2) as well as in immunofluorescence analysis (Fig. 5). A ...
Methods A cohort of 36 subjects with active SLE presenting with classical complement activation were enrolled and followed monthly for 1 year. At each study visit blood was collected, serum isolated and frozen until analysis. A total of 371 specimens were collected. Disease activity was scored on the day of each study visit according to the SELENA-SLEDAI method excluding anti-dsDNA or complement components (non-serological [ns] SELENA-SLEDAI). All specimens were tested using four different anti-dsDNA kits; QUANTA Lite, QUANTA Flash, a high Avidity anti-dsDNA ELISA, and the Crithidia luciliae indirect immunofluorescence assay (CLIFT) (Inova Diagnostics, San Diego, CA). Study visits presenting with inactive disease (ns-SELENA- SLEDAI score=0) were compared to those presenting with active disease (ns-SELENA- SLEDAI,0). The longitudinal data were analyzed using linear mixed effect modeling with the ns-SELENA-SLEDAI as dependent variable and the anti-dsDNA titers as fixed effect predictors. Marginal ...
Previous studies from this laboratory have demonstrated that Mycobacterium leprae, an obligate intracellular bacterial parasite, enters human mononuclear phagocytes via complement receptors on these host cells and bacterium-bound C3. The present study investigates the role of M. leprae surface molecules in C3 fixation and phagocytosis. By enzyme-linked immunosorbent assay, C3 binds selectively to phenolic glycolipid-1 (PGL-1), a major surface molecule of the leprosy bacillus. C3 fixation to PGL-1 is serum concentration dependent and is abolished in heat-inactivated serum or serum containing ethylenediaminetetraacetic acid. C3 fixation is also abolished in serum containing ethyleneglycol-bis (beta-aminoethyl ether)N,N,N-tetraacetic acid and MgCl2 indicating that isolated PGL-1 fixes C3 via the classical complement pathway. The capacity of PGL-1 to fix C3 is dependent upon its terminal trisaccharide since sequential removal of monosaccharide units of the trisaccharide results in a stepwise ...
Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed components of complement and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the ...
A growing body of evidence has recently accumulated about the pathogenic role of the complement system in AAV (1). In 2007, Xiao et al. (4) demonstrated how infusion of ANCA antibodies in wild-type mice could induce glomerular lesions typical of pauci-immune NCGN; interestingly, no lesion was observed when ANCA were injected in mice knocked out for C5 or complement factor B, whereas RPGN fully developed in C4-knockout mice; because C5 belongs to the terminal part of the complement cascade and complement factor B belongs to the cAP, while C4 is a key molecule of the classic pathway, these findings clearly showed that cAP plays a central role in experimental AAV (4). In keeping with this, Gou et al. showed that patients with active AAV have serologic signs of activation of the cAP (augmented serum levels of activated complement proteins, such as C3a, C5a, sC5b9, and Bb), which correlated with acute-phase reactants, number of crescents, and severity of kidney histology (9). The same group ...
The mechanism of protection of type-specific antipneumococcal antibody and complement in bacteremia was investigated with purified rabbit antibody and a guinea pig model of pneumococcal bacteremia. IgG and IgM were isolated from the sera of rabbits immunized with type 7 pneumococci (Pn), and their binding to Pn was quantitated. The number of antibody-binding sites on the pnuemococcal capsule was also determined. Pn were incubated with various amounts of the immunoglobulin preparations before intravenous injection into nonimmune guinea pigs. Whereas 120 molecules of IgM per Pn were sufficient to enhance bloodstream clearance of Pn, 1,400 molecules of IgG per bacterium were required to produce this effect. As the amount of either IgG or IgM added to the Pn was increased, the rate of bloodstream clearance accelerated. In striking contrast, greater than 1,000 molecules of IgM had no effect on the rate of clearance in C4-deficient guinea pigs, which cannot activate complement via the classic pathway. ...
Deficient or decreased levels of serum complement activity of the classical pathway are associated with a number of diseases. A normal CH50 assay indicates that C1 through C9 are present and functional in the serum being tested. Although CH50 can be used to assess the integrity of the classical pathway, it must not be used as a sensitive test for in vivo complement fixation. In vitro degradation can also cause low CH50 activity.. ...
POT-4 (Potentia Pharmaceuticals) a C3 complement inhibitor may be effective against both forms of macular degeneration. The announcement was made at the Asia
Nuclear factor kappa B (NF-κB) is a transcription factor that is associated with inflammation. Without stimulus, NF-κB is repressed by inhibitor of kappa B (IκB) proteins. Upon stimulation by TNF, IL-1, and/or pathogen-associated molecular patterns (e.g. LPS), adaptor proteins like MyD88 and TRAF will signal for the activation of inhibitor of kappa B kinase (IκBK), which goes on to phosphorylate either IκB (canonical pathway) or the p100 subunit of NF-κB (alternative pathway). The pathway of activation is dictated by the signal: TNF, IL-1 and TLR stimulation activate the classical pathway, while CD40L and BAFF activate the alternative pathway. In the classical pathway, phosphorylated IκB is ubiquitinated and then degraded, allowing for NF-κB to enter the nucleus and turn on transcription of genes for cytokines like TNFα and IL-1. The alternative pathway involves activation of the NF-κB-inducing kinase (NIK), which turns on IκB kinase-α (IKKα), leading to p100 phosphorylation.. Click ...
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However, both local and systemic antibodies attempt to block the rep-lication and spread of viruses, either circulating or being shed from a cell that has been infected and killed. IgG is the most prevalent anti-body of the immunoglobulin system and is a potent opsonizing agent. The complement system of serum proteins is activated by IgM and later by IgG. They opsonize target cells for the phagocytes, which are then bound by IgM or IgG, and this is the classical pathway. Cells synthesize interferon when infected by virus; it is secreted into extracellular fluid and binds to adjacent cells. Interferon-alpha is de-rived from lymphocytes and interferon-beta from fibroblasts and other cell types. The IFNs acton certain cell genes that either catalyse or retard factors responsible for protein synthesis, which in turn re-duces mRNA translation, while another factor results in the degrada-tion of host and viral mRNA. The total result is to establish a sort of cordon of uninfectable cells around the ...
Looking for Alternative complement pathway? Find out information about Alternative complement pathway. 1. Education courses taken by a student to gain entry to a higher course or towards a final qualification 2. Biochem a chain of reactions associated with a... Explanation of Alternative complement pathway
Lipooligosaccharide (LOS) heptose (Hep) glycan substitutions influence gonococcal serum resistance. Several gonococcal strains bind the classical complement pathway inhibitor, C4b-binding protein (C4BP), via their porin (Por) molecule to escape complement-dependent killing by normal human serum (NHS). We show that the proximal glucose (Glc) on HepI is required for C4BP binding to Por1B-bearing gonococcal strains MS11 and 1291 but not to FA19 (Por1A). The presence of only the proximal Glc on HepI (lgtE mutant) permitted maximal C4BP binding to MS11 but not to 1291. Replacing 1291 lgtE Por with MS11 Por increased C4BP binding to levels that paralleled MS11 lgtE, suggesting that replacement of the Por1B molecule dictated the effects of HepI glycans on C4BP binding. The remainder of the strain background did not affect C4BP binding; replacing the Por of strain F62 with MS11 Por (F62 PorMS11) and truncating HepI mirrored the findings in the MS11 background. C4BP binding correlated with resistance to killing
Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, Kenny J, Waters A, Jenkins D, Kaissi AA, Leal GF, Dallapiccola B, Carnevale F, Bitner-Glindzicz M, Lees M, Hennekam R, Stanier P, Burns AJ, Peeters H, Alkuraya FS, Beales PL. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat Genet. 2011 Mar;43(3):197-203.. ...
The complement system plays crucial roles in the immune system, but incorrect regulation causes inflammation and targeting of self-tissue, leading to diseases such as systemic lupus erythematosus, rheumatoid arthritis and age-related macular degeneration. In vivo , the initiating complexes of the classical complement and lectin pathways are controlled by SERPING1 [(C1 inhibitor) serpin peptidase inhibitor, clade G, member 1], which inactivates the components C1s and MASP-2 (mannan-binding lectin serine peptidase 2). GAGs (glycosaminoglycan) and DXS (dextran sulfate) are able to significantly accelerate SERPING1-mediated inactivation of C1s, the key effector enzyme of the classical C1 complex, although the mechanism is poorly understood. In the present study we have shown that C1s can bind to DXS and heparin and that these polyanions enhanced C1s proteolytic activity at low concentrations and inhibited it at higher concentrations. The recent determination of the crystal structure of SERPING1 has ...
Dr. Mohamed R. Daha, Department of Nephrology, University Hospital Leiden, Leiden University Medical Center, Building 1 C3-P, PO Box 9600, 2300 RC Leiden, South Holland, The Netherlands. Email: m.r.daha{at}lumc.nl ...
Principal Investigator:MATSUSHITA Misao, Project Period (FY):1996 - 1997, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Immunology
The C-reactive protein (CRP) is a cyclic pentameric pentraxin family acute phase protein compound of five identical noncovalently bound nonglycosylated subunits (each subunit 24 kDa; physiologic CRP molecule 117,5 kDa). CRP is produced by the liver and its plasma levels rise dramatically during inflammatory processes occuring in the body. CRP is an initiator of classical complement cascade, binds to several nuclear components (chromatin, histones, etc.) and is also believed to play an important role in innate immunity. Patients with elevated basal levels of CRP are at increased risk for hypertension and cardiovascular disease ...
Definition : Immunoassay reagents intended to perform qualitative and/or quantitative analyses on a body fluid sample (typically serum) to detect and/or measure levels of one or more of the proteins C5 to C9 found in the final complement pathway. Deficiency of complement components C5 to C9 are associated with several diseases, especially recurrent neisserial infections.. Entry Terms : C5-9 (Complement Component) Determination Reagents , Reagents, Immunoassay, Protein, Complement Component, C5-C9. UMDC code : 19804 ...
C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound to C4b and C2b (C4b2b3b complex) or when an additional C3b molecule binds to the C3bBb complex (C3bBb3b complex). C3bs ability to perform these important functions derives from its ability to covalently bind to the surface of invading pathogens within an organisms body. The cleavage of C3 leaves C3b with an exposed thioester bond, allowing C3b to effectively coat and tag foreign cells by covalently binding to hydroxyl (-OH) and amine (-NH2) groups on foreign cell surfaces. This cleavage can occur via three mechanisms (classical pathway, alternative pathway and lectin pathway) that ultimately lead to ...
With two holes open, the filtering effect of the downstream holes is clear at frequencies above about 1.5 kHz. Compare this spectrum with more regular impedance spectrum for D4 on the classical instrument with a D foot. The regular, harmonically spaced minima in the latter spectrum allow greater power in the higher harmonics, and thus a brighter tone for this note.. ...
TY - JOUR. T1 - Complement activation in acquired and hereditary amyloid neuropathy. AU - Hafer-Macko, Charlene E.. AU - Dyck, Peter J. AU - Koski, Carol Lee. PY - 2000. Y1 - 2000. N2 - The pathogenesis of the axonal degeneration in acquired or hereditary amyloidosis is unknown. In this immunohistochemistry study, we examined 20 sural nerve biopsies from individuals with amyloid neuropathy (14 acquired and 6 hereditary) for evidence of complement activation. Complement activation products were detected on and around amyloid deposits within peripheral nerves. We found no difference in the extent, location or pattern of complement activation products between the 2 forms of amyloidosis. The presence of early classical pathway activation markers in the absence of antibody in hereditary cases suggests an antibody-independent activation of the classical pathway through binding of C1q. The lack of Factor Bb-suggested alternative pathway activation was not significant in these cases. The detection of ...
MBL forms oligomers of subunits, which are trimers (6- to 18-heades correspond to a dimer and a hexamer, respectively). Multimers of MBL form a complex with MASP1 (Mannose-binding lectin-Associated Serine Protease), MASP2 and MASP3, that are protease zymogens. The MASPs are very similar to C1r and C1s molecules of the classical complement pathway, respectively, and are thought to have a common evolutionary ancestor. When the carbohydrate-recognising heads of MBL bind to specifically arranged mannose residues on the surface of a pathogen, MASP-1 and MASP-2 are activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. In addition, two smaller MBL-associated proteins (MAps) are found in complex with MBL. MBL-associated protein of 19 kDa (MAp19) and MBL-associated protein of 44 kDa (Map44). MASP-1, MASP-3 and MAp44 are alternative splice products of the MASP1 gene, while MASP-2 and MAp19 are alternative splice products of the MASP-2 gene. MAp44 has been suggested to act as a ...
Blocking the terminal complement pathway with the C5 inhibitor eculizumab has revolutionized the clinical management of several complement-mediated diseases and has boosted the clinical development of new inhibitors. Data on the C3 inhibitor Compstatin and the C5 inhibitors eculizumab and Coversin reported here demonstrate that C3/C5 convertases function differently from prevailing concepts. Stoichiometric C3 inhibition failed to inhibit C5 activation and lytic activity during strong classical pathway activation, demonstrating a C3 bypass activation of C5. We show that, instead of C3b, surface-deposited C4b alone can also recruit and prime C5 for consecutive proteolytic activation. Surface-bound C3b and C4b possess similar affinities for C5. By demonstrating that the fluid phase convertase C3bBb is sufficient to cleave C5 as long as C5 is bound on C3b/C4b-decorated surfaces, we show that surface fixation is necessary only for the C3b/C4b opsonins that prime C5 but not for the catalytic ...
Each pathway follows a sequence of reactions to generate a protease called a C3 convertase. The active protease is retained at the pathogen surface, and this ensures that the next complement zymogen in the pathway is also cleaved and activated at the pathogen surface. By contrast, the small peptide fragment is released from the site of the reaction and can act as a soluble mediator.. The early events of all three pathways of complement activation involve a series of cleavage reactions that culminate in the formation of an enzymatic activity called a C3 convertase, more The C3 convertases formed by these early events of complement activation are bound covalently to the pathogen surface. Here they cleave C3 to generate large amounts of C3bthe main effector molecule of the complement system, and C3a, a peptide mediator of inflammation.. The C3b molecules act as opsonins; they bind covalently to the pathogen and thereby target it for destruction by phagocytes equipped with receptors for C3b. These ...
Detailed description of complement system including classical pathway, alternate pathway and lectin pathway. Components of complement system includingC1, C2, C3, C4, C5, C6, C7, C8, C9, C1-INH, C3a-INA, Factors H and I, C3a-INA, C4-BP and Factor I, C3a-INA, Protein S (vitronectin).
The complement system is a key component of the innate immune system that is involved in eliminating unwanted self and nonself material via cellular and humoral mechanisms
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The activation of NF-κB is mainly by two signaling pathways - the canonical pathway (which is the classical pathway) and the non-canonical pathway (which is also called the alternative pathway). Lets discuss about each of the pathway in detail. But before going ahead, it is important to note the common regulatory step of both the cascades is the activation of IκBkinase (IKK) complex. In unstimulated cells, the inhibitor, NF-κB proteins are bound to IκB protein that maintains NF-κB in an inactive state. Hence, when IκB is activated i.e.; phosphorylated, it gets ubiquitinated and is degraded by proteasome. The IKK complex consists of kinase subunits that are catalytic (IKKα and/or IKKβ) and non-enzymatic protein that is regulatory in nature - known as NEMO which stands for NF-κB essential modulator, also known as IKKγ. ...
... is a protein complex involved in the complement system. It is the first component of the classical complement pathway and is ... Activation of the C1 complex initiates the classical complement pathway. This occurs when C1q binds to antigen-antibody ... The classical pathway C3-convertase (C4bC2b complex) is created, which promotes cleavage of C3. Janeway, CA Jr; Travers P; ... 2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease. New York: Garland ...
The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... Interruption of the complement cascade *The recipient's complement cascade can be inhibited through the use of cobra venom ... Expression of human complement regulators (CD55, CD46, and CD59) to inhibit the complement cascade.[27] ... complement pathway activation and delayed type hypersensitivity (DTH).. Acute vascular rejection[edit]. Also known as delayed ...
It is believed to be associated with the classical complement pathway. Also called recently as 'C3 nephropathy' The preferred ... Most cases are associated with the dysregulation of the alternative complement pathway. DDD is associated with deposition of ... Type III is very rare, it is characterized by a mixture of subepithelial and subendothelial immune and/or complement deposits. ... immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway ( ...
The classical pathway of complement is activated by antibodies specific against Giardia. Antibodies inhibit parasite ... The lectin pathway of complement is activated by mannose-binding lectin (MBL) which binds to N-acetylglucosamine. N- ... replication and also induce parasite death via the classical pathway of complement. Infection with Giardia typically results in ... "Involvement of lectin pathway activation in the complement killing of Giardia intestinalis". Biochemical and Biophysical ...
The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... complement pathway activation and delayed type hypersensitivity (DTH). Also known as delayed xenoactive rejection, this type of ... Interruption of the complement cascade The recipient's complement cascade can be inhibited through the use of cobra venom ... Nonetheless, it is known that XNAs and the complement system are not primarily involved. Fibrosis in the xenograft occurs as a ...
The recruitment of the complement cascade via the classical pathway (antibody-antigen interaction). Membrane attack complex ( ...
Early components of the classical complement pathway (C1q or C4) are usually not seen. Electron microscopy confirms electron- ... Some HLA alleles have been suspected along with complement phenotypes as being genetic factors. Non-aggressive Berger's disease ... complement levels, ANA, and LDH. Protein electrophoresis and immunoglobulin levels can show increased IgA in 50% of all ...
IgG3 is an efficient activator of pro-inflammatory responses by triggering the classical complement pathway. It has the ... Complement fixation by IgA is not a major effector mechanism at the mucosal surface but IgA receptor is expressed on ... and activation of complement cascade. As IgM antibodies are expressed early in a B cell response, they are rarely highly ... a unique profile of antigen binding and distinct capacity for complement activation. IgG1 antibodies are the most abundant IgG ...
Binding of antibodies to red blood cells activates the classical pathway of the complement system. If the complement response ... Jaffe, C J; Atkinson, J P; Frank, M M (1976-10-01). "The role of complement in the clearance of cold agglutinin-sensitized ... Detection of antibodies (cold or warm) and /or complement system on RBC from the patient is a direct Coombs antiglobulin test. ... In lieu of the membrane attack complex, complement proteins (particularly C3b and C4b) are deposited on red blood cells. This ...
This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as ... Complement component 4 Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency ... "Entrez Gene: C4A complement component 4A (Rodgers blood group)". Dawkins RL, Uko G, Christiansen FT, Kay PH (Sep 1983). "Low C4 ... Hessing M, van 't Veer C, Hackeng TM, Bouma BN, Iwanaga S (Oct 1990). "Importance of the alpha 3-fragment of complement C4 for ...
... the classical, lectin, and alternative pathways. Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... "Formation of classical C3 convertase during the alternative pathway of human complement activation". Biokhimiia (Moscow, Russia ... In the classical pathway, this is by sequential proteolytic activation of proteins within the C1 complex (C1q, C1r, C1s) in ...
... fibromodulin activates the classical pathway of complement by directly binding C1q". The Journal of Biological Chemistry. 280 ( ...
"The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in ... "A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo". Journal of ... He was awarded a PhD for research into complement receptors under the supervision of Peter Lachmann in 1986 at the University ... Walport, Mark Jeremy (1986). The biology of complement receptors (PhD thesis). University of Cambridge. OCLC 59761908. EThOS uk ...
In addition, Borrelia burgdorferi has a strategy to directly inhibit the classical pathway of complement system. A borrelial ... "Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex", PLoS Pathogens ... Zipfel P., Hallström T., Riesbeck K. (2013). "Human complement control and complement evasion by pathogenic microbes - Tipping ... binds the initiating protease complex C1 of the classical pathway. More specifically, BBK32 interacts with C1r subunit of C1. C ...
... activates the classical pathway of complement activation and facilitates pathogen recognition by macrophages and DCs. ... suggesting a role for PTX3 in the complement-mediated clearance of apoptotic cells. Moreover, in the presence of dying cells, ... PTX3 binds with high affinity to the complement component C1q, the extracellular matrix component TNFα induced protein 6 ( ... protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response ...
APOE qualifies as a checkpoint inhibitor of the classical complement pathway by complex formation with activated C1q. ... Statin Pathway edit]] The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430". GRCh38: Ensembl ... APOE is produced by macrophages and APOE secretion has been shown to be restricted to classical monocytes in PBMC, and the ... Ye J (August 2007). "Reliance of host cholesterol metabolic pathways for the life cycle of hepatitis C virus". PLOS Pathogens. ...
C1r is a highly specific serine protease initiating the classical pathway of complement activation during immune response. Both ... The two main proposed types of EGF-like domains are the human EGF-like (hEGF) domain and the complement C1r-like (cEGF) domain ... Circolo A, Garnier G, Volanakis JE (2003). "A novel murine complement-related gene encoding a C1r-like serum protein". ... like Module of Human Complement Protease C1r, an Atypical Member of the EGF Family". Biochemistry. 37 (5): 1204-14. doi:10.1021 ...
In the classical pathway, the microbial pathogen is coated in antibodies (IgG and IgM) released by B cells. The C1 complement ... This cleavage can occur via three mechanisms (classical pathway, alternative pathway and lectin pathway) that ultimately lead ... inactivate the complement component. Given the C3 is constantly being turned over in the alternative pathway and its ability to ... In the alternative pathway, C3, present in the blood stream, spontaneously cleaves at low rates into C3b and C3a. If a microbe ...
... classical or lectin pathway) or C3 (alternative pathway). Interaction of DAF with cell-associated C4b of the classical and ... Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene. DAF ... CCP2 and CCP3 alone are involved in its inhibition of the classical pathway. Because DAF is a GPI-anchored protein, its ... DAF contains four complement control protein (CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2 ...
The complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin ... Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system. Another important ... The subsequent complement cascade catalyzed by C3-convertase results in creating a membrane attack complex, which causes lysis ... In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), ...
In 2007, Stevens discovered that proteins of the classical complement pathway were required for synaptic pruning by microglia. ... "The classical complement cascade mediates CNS synapse elimination". Cell. 131 (6): 1164-78. doi:10.1016/j.cell.2007.10.036. ... She has helped to identify the role of microglia and complement proteins in the "pruning" or removal of synaptic cells during ... Stephan, AH; Barres, BA; Stevens, B (2012). "The complement system: an unexpected role in synaptic pruning during development ...
... classical complement pathway). In brief, the crucial role of C1q in the pathway is its importance as the first protein to start ... The complement pathway is composed of several subset pathways: the lectin/mannose pathway, alternative pathway and the ... in the complement pathway) named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement ... which instigates activation of the entire complement pathway. Consequently, levels of all complement proteins become low. ...
Matsushita M, Fujita T (December 1992). "Activation of the classical complement pathway by mannose-binding protein in ... This enzyme catalyses the following chemical reaction Selective cleavage after Arg223 in complement component C2 (-Ser-Leu-Gly- ... Arg-Lys-Ile-Gln-Ile) and after Arg76 in complement component C4 (-Gly-Leu-Gln-Arg-Ala-Leu-Glu-Ile) This mannan-binding lectin ( ... "A second serine protease associated with mannan-binding lectin that activates complement". Nature. 386 (6624): 506-10. doi: ...
1994). "Expression of the components and regulatory proteins of the classical pathway of complement in normal and diseased ... 1992). "Human immunodeficiency virus type 1 activates the classical pathway of complement by direct C1 binding through specific ... Complement C1q subcomponent subunit A is a protein that in humans is encoded by the C1QA gene. This gene encodes a major ... "Entrez Gene: C1QA complement component 1, q subcomponent, A chain". Human C1QA genome location and C1QA gene details page in ...
In all three pathways of complement activation, there is a target for the protease to manipulate. In the classical pathway, ... The aureolysin derived C3a and C3b are further degraded by host complement inhibitor factor H and I. In the lectin pathway, ... One major way aureolysin contributes to infection, is by inactivating certain targets within the complement system. Of all the ... Further immune evasion outside of the complement system occurs in various ways. Aureolysin cleaves and inactivates protease ...
... irreversibly binds to and inactivates C1r and C1s proteases in the C1 complex of classical pathway of complement. ... The activation of the complement cascade can cause damage to cells, therefore the inhibition of the complement cascade can work ... which triggers the complement cascade. Activation of the complement cascade attracts phagocytes that leak peroxide and other ... Inhibition of the complement cascade can decrease this damage. C1-inhibitor is contained in the human blood; it can, therefore ...
The classical pathway, lectin pathway, and alternative pathway of complement are all involved in glomerulonephritis, depending ... There are no current clinical trials for DPGN happening.[citation needed] Activating complement pathways plays a large role in ... There are currently drugs available that will target the complement pathway. It has been proposed that if fluorescently tagged ... then identification of specific pathways involved and the accumulated complement proteins in the glomeruli should be achievable ...
IgG activates all the classical pathway of the complement system, a cascade of immune protein production that results in ... The relative ability of different IgG subclasses to fix complement may explain why some anti-donor antibody responses do harm a ... Nevertheless, it remains true that both human and mouse antibodies have different abilities to fix complement and to bind to Fc ... Given the opposing properties of the IgG subclasses (fixing and failing to fix complement; binding and failing to bind FcR), ...
Each of the three pathways ensures that complement will still be functional if one pathway ceases to work or a foreign invader ... consists of three pathways that are activated in distinct ways. The classical pathway is triggered when IgG or IgM is bound to ... Though the pathways are activated differently, the overall role of the complement system is to opsonize pathogens and induce a ... The alternative pathway is activated by foreign surfaces such as viruses, fungi, bacteria, parasites, etc., and is capable of ...
These antibodies can activate the classical complement pathway leading to lysis of enveloped virus particles long before the ... these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement ... Complement activation (fixation), in which antibodies that are latched onto a foreign cell encourage complement to attack it ... "classical" complement system.[30] This results in the killing of bacteria in two ways.[5] First, the binding of the antibody ...
There are three different complement systems: Classical, alternative, Lectin *Classical: starts when antibody bind to bacteria ... Both pathways converge in the recruitment and activation of the IKKε/TBK-1 complex, inducing dimerization of transcription ... Complement system[edit]. Main article: Complement system. The complement system is a biochemical cascade of the immune system ... Elements of the complement cascade can be found in many non-mammalian species including plants, birds, fish, and some species ...
Most of these pathways are derived from products found in glycolysis and other pathways. For example, one pathway goes through ... Treatment can be orally or by intramuscular or intravenous injection.[2] Scurvy was known to Hippocrates in the classical era. ... "Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence". Molecular ... Plants use multiple pathways to synthesize vitamin C. The major pathway starts with glucose, fructose or mannose (all simple ...
Complement 3 deficiency. *Terminal complement pathway deficiency. *Paroxysmal nocturnal hemoglobinuria. *Complement receptor ... The classical method of detecting this is the Chromium-51 [51Cr] release assay; the Sulfur-35 [35S] release assay is a little ... ADCC is independent of the immune complement system that also lyses targets but does not require any other cell. ADCC requires ... 1987). "Functional role of the alpha-chain of complement receptor type 3 in human eosinophil-dependent antibody-mediated ...
IgE, the IgE synthesis pathway, and the IgE-mediated allergic/inflammatory pathway are all important targets in intervening ... which are the isotypes responsible for most of the classical adaptive immune response-it is capable of triggering the most ... Drugs targeting the IgE pathway[edit]. Currently, allergic diseases and asthma are usually treated with one or more of the ... The B lymphocyte differentiation and maturation pathway that eventually generate IgE-secreting plasma cells go through the ...
... an EGF-like domain and a complement-binding protein-like domains (same as complement regulatory proteins: CRP) having short ... "Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway". Mol. Biol. Cell ... which can stimulate endothelial-cell release of P-selectin and recent studies suggest an additional Ca2+-independent pathway ...
The total complement of proteins present at a time in a cell or cell type is known as its proteome, and the study of such large ... This technique also uses an antibody to the protein of interest, along with classical electron microscopy techniques. The ... can conserve energy by taking up the amino acids from their surroundings and downregulating their biosynthetic pathways. ... The total complement of biologically possible such interactions is known as the interactome.[56] A systematic attempt to ...
Design of the classical garden[edit]. A Chinese garden was not meant to be seen all at once; the plan of a classical Chinese ... It also is the complement to the mountain, the other central element of the garden, and represents dreams and the infinity of ... Bridges are often built from rough timber or stone-slab raised pathways. Some gardens have brightly painted or lacquered ... These Chinese classical gardens, or scholar's gardens (wenren yuan), were inspired by, and in turn inspired, classical Chinese ...
These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 ... with classical autoimmune diseases at one extreme and diseases driven by the innate immune system at the other extreme. Within ... Autoreactive B cells in spontaneous autoimmunity are seen as surviving because of subversion both of the T cell help pathway ... It remains entirely possible that the disease is due to e.g. an unusual interaction between immune complexes, complement ...
... classical pathway. • immune system process. • innate immune response. • complement activation, lectin pathway. • complement ... Complement component 1s (EC 3.4.21.42, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... C1s cleaves C4 and C2, which eventually leads to the production of the classical pathway C3-convertase. ... Sim RB (1981). "The human complement system serine proteases C1r and C1s and their proenzymes". Methods in Enzymology. 80 Pt C ...
The aggregate effect of these bias signals is to guide the flow of neural activity along pathways that establish the proper ... Cognitive control and stimulus control, which is associated with operant and classical conditioning, represent opposite ... and teacher-report behavior checklist measures of EF have been developed for both screening purposes and to complement the ...
The Art of the Actor: The Essential History of Acting, From Classical Times to the Present Day. London: Methuen. ISBN 0-413- ... "Stanislavsky's System: Pathways for the Actor". In Hodge (2000, 11-36).. *Clark, Katerina et al., ed. 2007. Soviet Culture and ... Their abilities complemented one another: Stanislavski brought his directorial talent for creating vivid stage images and ... In contrast, Stanislavski recommended to Stella Adler an indirect pathway to emotional expression via physical action. ...
Defects in the NER pathway have been linked to progeroid syndromes. There are 28 genes in this pathway. Individuals with ... CSA is caused by mutations in the cross-complementing gene 8 (ERCC8), which encodes for the CSA protein. These mutations are ... Individuals with the type I (or classical) form of the disorder usually first show symptoms between one and three years and ... These genes are all involved in the NER repair pathway that repairs damaged DNA. The variant form, XP-V, is caused by mutations ...
Clustered Band 3 proteins with attached antibodies activate complement, and complement C3 fragments are opsonins recognized by ... It has several different pathways that all end with the virus being unable to replicate. One of the pathways is siRNA in which ... two classical reasons may explain how the fetus is tolerated. The first is that the fetus occupies a portion of the body ... MiRNA pathway in cytoplasm binds to Ago1-RISC complex and functions as a template for viral RNA degradation. Last one is piRNA ...
Classical complement pathway. • positive regulation of apoptotic process. • phosphatidylinositol 3-kinase signaling. • innate ... regulation of complement activation. • negative regulation of RIG-I signaling pathway. • positive regulation of cell adhesion. ... The human complement subcomponent C1q associates with C1r and C1s in order to yield the first component of the serum complement ... C1QBP, GHABP1, SF2p32, gC1Q-R, gC1qR, p32, complement component 1, q subcomponent binding protein, complement C1q binding ...
It can complement other measures of brain physiology such as EEG and NIRS. Newer methods which improve both spatial and time ... For example, the hippocampus has been shown to be activated during classical conditioning,[79] however lesion studies have ... with calcium ions often being the messengers for cellular signalling pathways in active neurons. Neuronal magnetic field ... The fMRI technique can complement or supplement other techniques because of its unique strengths and gaps. It can noninvasively ...
Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... Lectin pathwayEdit. Main article: Lectin pathway. The lectin pathway is homologous to the classical pathway, but with the ... Alternative pathwayEdit. Main article: Alternative complement pathway. The alternative pathway is continuously activated at a ... Reaction Cascade of the Complement System: Classical, Alternative and Lectin Pathway, Amplification Loop, Terminal Pathway, and ...
Classical period. The classical period began when the disease was first recognized in the Middle Ages. The term lupus is ... "Complement C3 (Blood)-Health Encyclopedia-University of Rochester Medical Center". www.urmc.rochester.edu. Archived from the ... Impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease. This includes ... In the complement system low C3 levels are associated with systemic lupus erythematosus[62] ...
For much of its history, the technology underlying shotgun sequencing was the classical chain-termination method or 'Sanger ... researchers which were once limited to the study of a single gene product can now simultaneously compare the total complement ... gene pathways, or comparatively. ... these approaches co-exist and complement each other in the same ...
IFNAR activates the JAK-STAT signalling pathway, along with MAPK, PI3K, and Akt signaling pathways.[2] IFNAR agonism results in ... While type I IFNs are one of the classical cytokines required for an effect antiviral response, higher type I IFN levels are ... "Mutant U5A cells are complemented by an interferon-αβ receptor subunit generated by alternative processing of a new member of ... Activation of various innate immune signaling pathways (TLR3, TLR4, TLR7, TLR8, TLR9, cGAS, RIG-I, MDA-5) leads to the rapid ...
Multiple immunofluorescence stains are performed to evaluate for antibody, protein and complement deposition. Finally, ultra- ... It is only in mammals that the kidney takes on its classical "kidney" shape, although there are some exceptions, such as the ... "Mechanism of the Antidiuretic Effect Associated with Interruption of Parasympathetic Pathways". Journal of Clinical ...
Ly49s are receptor for classical (polymorphic) MHC I molecules.. Function[edit]. Cytolytic granule mediated cell apoptosis[edit ... The MHC-dependent receptors (described above) use an alternate pathway to induce apoptosis in infected cells. Natural killer ... Though indirect, this is a way to survey the levels of classical (polymorphic) HLA molecules. ... and are the main receptors for both classical MHC I (HLA-A, HLA-B, HLA-C) and nonclassical Mamu-G (HLA-G) in primates. Some ...
Rieger R. Michaelis A., Green M. M. (1976). Glossary of genetics and cytogenetics: Classical and molecular. Heidelberg - New ... These results suggest that X-rays induce DNA damages that are repaired by a crossover pathway leading to chiasma formation. ... An individual gamete inherits a complete haploid complement of alleles on chromosomes that are independently selected from each ... Multiple MMR pathways have been implicated in the maintenance of complex organism genome stability, and any of many possible ...
Three biochemical pathways activate the complement system: the classical complement pathway, the alternate complement pathway, ... and the mannose-binding lectin pathway. The classical complement pathway typically requires antibodies for activation and is a ... Complement systemEdit. Main article: Complement system. The complement system is a biochemical cascade of the innate immune ... 12 of which are directly involved in the complement pathways.[1] The complement system is involved in the activities of both ...
The classical PKA holoenzyme structure consists of two regulatory subunits and two catalytic subunits. The catalytic subunit ... Manning, G.; Whyte, D. B.; Martinez, R.; Hunter, T.; Sudarsanam, S. (2002-12-06). "The protein kinase complement of the human ... Protein Kinase A signal transduction pathway helps in modulation of ethanol consumption and its sedative effects. A mouse study ... PKA regulation and cAMP regulation are involved in many different pathways. ...
All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. ... Media related to Complement membrane attack complex at Wikimedia Commons. *Complement+Membrane+Attack+Complex at the US ... The membrane attack complex (MAC) or terminal complement complex (TCC) is a structure typically formed on the surface of ... Reid K. B. M., The complement system, in: B. D. Hames and D. M. Glover (eds.), Molecular Immunology, Oxford: IRL Press, 1988, ...
The Romantik epoch of German philosophy and literature, was described as a movement against classical and realistic theories of ... Traditionally, Heidelberg's philosophers and university professors would walk and talk along the pathway. Farther up the ... Carsharing increasingly provides a complement to public transport. More than 50 car-sharing stations are available to users in ... and classical concerts performed by the Heidelberg Philharmonics. ...
multivesicular body sorting pathway. • chromosome segregation. • regulation of vesicle-mediated transport. • receptor catabolic ... This gene complements the ultraviolet sensitivity of xeroderma pigmentosum group C cells and encodes a protein with a C2 domain ... double-strand break repair via classical nonhomologous end joining. • regulation of cytokinesis. • regulation of protein serine ... 1990). "Isolation by polymerase chain reaction of a cDNA whose product partially complements the ultraviolet sensitivity of ...
Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion, Bio-energetics ... High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimers ... Video articles in JoVE about classical complement pathway include Time-lapse 3D Imaging of Phagocytosis by Mouse Macrophages ... Complement Pathway, Classical: Complement activation initiated by the binding of Complement c1 to Antigen-antibody complexes at ...
Mohamed R. Daha on The classical pathway of complement, part of a collection of online lectures. ... The evolution of complement and the alternative pathway The evolution of complement and the alternative pathway ... The classical pathway of complement. *Prof. Mohamed R. Daha - Leiden University Medical Center, The Netherlands ... Daha, M.R. (2017, December 31). The classical pathway of complement [Video file]. In The Biomedical & Life Sciences Collection ...
Complement Activation, Classical Pathway Data-Source=GenMAPP 2.0 Version=20041203 Author=Nathan Salomonis Email= ... Return to Complement Activation, Classical Pathway (Mus musculus).. Retrieved from "https://www.wikipathways.org/index.php/ ... You do not have permission to edit pages in the Pathway namespace. ... complement component 2 (within H-2S) GraphId=e55, ,Graphics Color=Transparent CenterX=6350.0 CenterY=4200.0 Width= ...
... Exp Neurol. ... Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy.. *. ... Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. Exp Neurol. ... Recent evidence supports that phagocytosis-associated molecules from the classical complement (C1q-C3) play novel roles in ...
We demonstrate that IgG-laden exosomes in plasma activate the classical complement pathway and that the quantity of these ... Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway. ... Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway ... Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway ...
Inhibition of Classical Complement Pathway and Differences in the Level of Expression in Amoebic Liver Abscess ... Entamoeba histolytica and E. dispar Calreticulin: Inhibition of Classical Complement Pathway and Differences in the Level of ...
These findings are relevant for the design of interventions aimed at inhibition of complement-mediated damage in RA. ... Our findings indicate that anti-CCP antibodies activate the complement system in vitro via the classical and alternative ... Results: Anti-CCP antibodies activated complement in a dose-dependent manner via the classical pathway of complement, and, ... arthritogenic antibodies activate the alternative pathway of complement rather than the expected classical pathway. This study ...
Several studies in rodents suggest that the alternative pathway of the complement system plays a pivotal role in renal ische … ... Therapeutic targeting of classical and lectin pathways of complement protects from ischemia-reperfusion-induced renal damage Am ... In conclusion, we demonstrated the activation and a pathogenic role of classical and lectin pathways of complement in a swine ... Several studies in rodents suggest that the alternative pathway of the complement system plays a pivotal role in renal ischemia ...
Need Classical Complement Pathway, Pig, Assay for research? Find and compare commercial and governmental sources for ... Classical Complement Pathway, Pig, Assay. Description. The HIT430 measures the classical pathway activity mediated via IgM. ... Complement deficiencies or other defects in the complement system can easily be screened by running an assay for each pathway ... Complement deficiencies or other defects in the complement system can easily be screened by running an assay for each pathway ...
Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement.. M K ... Taken together, these data demonstrate that BC isoforms preferentially protect against the classical pathway of complement. ... Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement. ... Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement. ...
... Nilsson, U R Uppsala University ... Simplified hemolytic assays for the classical (CP) and alternative (AP) pathways of complement (C) were developed. The CP ... Each pathway was tested independently of the other. Serum C levels, measured as described, correlated strongly with those ...
Complement: Classical and Lectin pathways Nicole Thielens 1 Christine Gaboriaud 1 Steffen Thiel 2 Details. ... Complement: Classical and Lectin pathways. Encyclopedia of Life Sciences, 2015, ⟨10.1002/9780470015902.a0000510.pub4⟩. ⟨inserm- ...
... factor C4 are resistant to antibody and complement mediated experimental autoimmune myasthenia gravis (EAMG). Anti-C1q antibody ... Mice deficient for classical complement pathway (CCP) factor C4 are resistant to antibody and complement mediated experimental ... Tüzün E., Li J., Saini S., Yang H., Christadoss P. (2008) Targeting Classical Complement Pathway to Treat Complement Mediated ... Membrane Attack Complex Hereditary Angioedema Classical Complement Pathway Cobra Venom Factor Major Pathogenic Factor ...
Classical Pathway of Complement Activation: Longitudinal Associations of C1q and C1-INH With Cardiovascular Outcomes. The CODAM ... Objective-The classical complement pathway has been assigned both protective and pathological effects in cardiovascular disease ... Classical Pathway of Complement Activation: Longitudinal Associations of C1q and C1-INH With Cardiovascular Outcomes ... Classical Pathway of Complement Activation: Longitudinal Associations of C1q and C1-INH With Cardiovascular Outcomes ...
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Centers RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.. ...
Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... Complement System Made Easy- Immunology- Classical Alternate & Lectin pathway Video Sep 07, 2018 ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ... C5 convertase is also formed by the Classical Pathway when C3b binds C4b and C2a. C5a is an important chemotactic protein, ...
The complement cascade. Both the classical and alternative pathways of complement activation are represented, although details ... Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. ... BrkA Protein of Bordetella pertussisInhibits the Classical Pathway of Complement after C1 Deposition. Michael G. Barnes, Alison ... Antigen-antibody complexes on the surface of a microorganism can activate the classical pathway of complement, a part of the ...
Rohrer, B; Demos, C; Frigg, R; Grimm, C (2007). Classical complement activation and acquired immune response pathways are not ... Classical complement activation and acquired immune response pathways are not essential for retinal degeneration in the rd1 ... Download PDF Classical complement activation and acquired immune response pathways are not essential for retinal degeneration ... no functional classical complement activation pathway) knockout was followed during the degenerative process using light ...
The mechanism for the Ab-mediated change in C3 localization to the capsule edge involved both classical C pathway activation ... The mechanism for the Ab-mediated change in C3 localization to the capsule edge involved both classical C pathway activation ... The mechanism for the Ab-mediated change in C3 localization to the capsule edge involved both classical C pathway activation ... The mechanism for the Ab-mediated change in C3 localization to the capsule edge involved both classical C pathway activation ...
2009) C1q, the recognition subcomponent of the classical pathway of complement, drives microglial activation. Journal of ... C1q, the recognition subcomponent of the classical pathway of complement, drives microglial activation ... We have shown previously that microglial biosynthesis of the complement subcomponent C1q may serve as a reliable marker of ...
Pathway maps. Immune response_Classical complement pathway. Object List (links open in MetaCore):. Antigen, C5b, C3dg, IgG1, ... Classical complement pathway. Complement system is a major effector of the humoral branch of the immune system, acting to ... Complement fragments interact with each another to form functional complexes.. Complement activation by the classical pathway ... complement component C3a + complement component C3b, H(,2)O + Complement component iC3b = Complement component C3c + complement ...
The molecular switches controlling the interaction between complement proteases of the classical and lectin pathways and their ... The molecular switches controlling the interaction between complement proteases of the classical and lectin pathways and their ... The molecular switches controlling the interaction between complement proteases of the classical and lectin pathways and their ... T1 - The molecular switches controlling the interaction between complement proteases of the classical and lectin pathways and ...
The classical pathway of complement activation usually begins with the formation of soluble antigen-antibody complexes (immune ... Home » Immunology » Classical Pathway of Complement Activation. Classical Pathway of Complement Activation. August 10, 2021. ... Steps of activation of classical pathway. The classical pathway of complement activation usually begins with the formation of ... Tags Classical Pathway, Complement, Complement Activation Post navigation Mutation- Causes, Mechanisms, Agents and Significance ...
1C1q Classical complement pathway inhibition: A novel strategy for the inhibition of Alzheimers disease pathogenesis ... the C1q pathway (classical pathway), an amplification loop (alternative complement pathway) and the lectin pathway (Fig 1.5). ... ukdiss.com/examples/classical-complement-pathway-alzheimer.php?vref=1 ,title=C1q Classical Complement Pathway Inhibition of ... C1q Classical Complement Pathway Inhibition of Alzheimers Disease Pathogenesis. Info: 9880 words (40 pages) Dissertation. ...
In addition, recent evidence has shown the role of the complement cascade in synaptic pruning in glaucoma and other diseases. ... We next determine the role of complement component 1 (C1) in early synaptic loss and dendritic atrophy during glaucoma. Using a ... This study further supports assessing the potential for complement-modulating therapeutics for the prevention of retinal ... Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma. ...
P5 Is Required for Resistance of Nontypeable Haemophilus influenzae to Both the Classical and Alternative Complement Pathways. ...
... he classical complement pathway plays a central role in immunity. Malfunction or disruption of this pathway is at the core of ... the initiating molecule of the classical complement cascade. They block activation of the entire classical pathway, including ... The complement pathway contains three arms - classical, alternative and lectin - all of which converge on C3, potentially ... has raised over $75M investment to build classical complement pathway treatments. Annexon Biosciences Inc. (San Francisco, ...
Complement C1q is the activator from the classical pathway. T cells15.. Complement C1q is the activator from the classical ... endothelial cells and trophoblasts39 49 Although C1q deposition is usually regarded as an indication of classical pathway. ... pathway. T cells15. The supplement (C) program a well-known arm of innate immunity16 17 is among the immune players within the ...
... terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to ... terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to ... and a CD59-like protein or molecules which indirectly counteract complement activation by binding various complement regulators ... and a CD59-like protein or molecules which indirectly counteract complement activation by binding various complement regulators ...
The Classical Pathway * The Alternate (Properdin) Pathway * The Lectin Pathway * Biological Activity of Complement and Its ...
  • These findings are relevant for the design of interventions aimed at inhibition of complement-mediated damage in RA. (nih.gov)
  • Therefore, inhibition of these two pathways might represent a novel therapeutic approach in the prevention of delayed graft function in kidney transplant recipients. (nih.gov)
  • Furthermore, CCP inhibition preserves alternative complement pathway activation, which is required for host defense against microorganisms. (springer.com)
  • Therefore, CCP inhibition might constitute a specific treatment approach for not only myasthenia gravis but also other complement mediated autoimmune diseases. (springer.com)
  • Biesecker, G. and Gomez, C.M. (1989) Inhibition of acute passive transfer experimental autoimmune myasthenia gravis with Fab antibody to complement C6. (springer.com)
  • The discovery of a novel mechanism of complement inhibition by a medically-relevant human pathogen expands our knowledge of host pathogens interactions and contributes to previously unknown pathophysiological immune evasion by B. burgdorferi. (ecu.edu)
  • 4 This concept has been supported by studies including those using C3 knockout (KO) mice or C3 inhibitors in mice, in which complement-mediated hemolysis (both extravascular and intravascular) was shown to be significantly reduced in various models in the absence or inhibition of mouse C3. (ashpublications.org)
  • Functional analysis identified that Ts -CRT was able to bind to human C1q, resulting in the inhibition of C1q-initiated complement classical activation pathway reflected by reduced C4/C3 generation and C1q-dependent lysis of antibody-sensitized sheep erythrocytes. (frontiersin.org)
  • Inhibition of complement activation was also demonstrated for HAstV serotypes 2 to 4, suggesting that this phenomenon is a general feature of these human pathogens. (realtalifesciences.com)
  • Since complement is a major contributor to the initiation and amplification of inflammation, the observed CP-mediated inhibition of complement activity may contribute to the lack of inflammation associated with astrovirus-induced gastroenteritis. (realtalifesciences.com)
  • Although diverse mechanisms of inhibition of complement activation have been described for many enveloped animal viruses, this is the first report of a nonenveloped icosahedral virus CP inhibiting classical pathway activation at C1. (realtalifesciences.com)
  • Inhibition of Immune Complex Complement Activation And Neutrophil Extracellular. (realtalifesciences.com)
  • Inhibition of Complement Activation, Myeloperoxidase, NET Formation And Oxidant. (realtalifesciences.com)
  • Fingerprint Dive into the research topics of 'Inhibition of the Classical Complement Pathway by Synthetic Peptides from the Second Constant Domain of the Heavy Chain of Human Immunoglobulin G'. Together they form a unique fingerprint. (elsevier.com)
  • Prystowsky, MB , Kehoe, JM & Erickson, BW 1981, ' Inhibition of the Classical Complement Pathway by Synthetic Peptides from the Second Constant Domain of the Heavy Chain of Human Immunoglobulin G ', Biochemistry , vol. 20, no. 22, pp. 6349-6356. (elsevier.com)
  • C1-inhibitor ( C1-inh , C1 esterase inhibitor ) is a serine protease inhibitor (serpin) protein, the main function of which is the inhibition of the complement system to prevent spontaneous activation. (bionity.com)
  • The activation of the complement cascade can cause damage to cells, therefore the inhibition of the complement cascade can work as a medicine in certain conditions [1] . (bionity.com)
  • Therefore, to identify a potential role for complement and microglia in the synaptodendritic pathology of epilepsy, we determined the protein levels of classical complement proteins (C1q-C3) along with other phagocytosis signaling molecules in human epilepsy. (medworm.com)
  • Western blotting was used to determine the levels of phagocytosis signaling proteins such as the complements C1q and C3, MerTK, Trem2, and Pros1 along with cleaved-caspase 3. (medworm.com)
  • Exosomes, small vesicles that are secreted into the extracellular environment, have a cargo of complement proteins in plasma, suggesting that they can participate in causing the vascular damage associated with DR. We demonstrate that IgG-laden exosomes in plasma activate the classical complement pathway and that the quantity of these exosomes is increased in diabetes. (diabetesjournals.org)
  • The complement system consist of a complex family of proteins and receptors which are found in the circulation, in tissues and other body-fluids. (linscottsdirectory.com)
  • Complement activation proceeds in a sequential fashion through the proteolytic cleavage of a series of proteins leading to the generation of activated products that mediate various biological activities through their interaction with specific cellular receptors and other serum proteins The three pathways, designated classical, lectin and alternative pathway, converge at a central component into a final common pathway. (linscottsdirectory.com)
  • The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver, and normally circulating as inactive precursors (pro-proteins). (technologynetworks.com)
  • Over 30 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. (technologynetworks.com)
  • Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes. (technologynetworks.com)
  • Deposition of complement proteins on the bacteria was monitored by Western blotting. (asm.org)
  • The complement system is a series of proteins that act in a defined sequence (Fig. 1 ) to promote immune clearance by opsonizing or killing microorganisms and augmenting the inflammatory response. (asm.org)
  • The nonactivated complement proteins are indicated above and to the right of the wide arrows, and the arrows pointing from them show the product that is released during activation. (asm.org)
  • To elucidate the molecular basis for complement resistance by BrkA, in this study we have attempted to determine which step in the complement cascade is affected by BrkA by monitoring the deposition of complement proteins on the surface of strains either expressing or not expressing BrkA. (asm.org)
  • C5 convertase (C2aC4bC3b) involved in classical pathway is assembled of two proteins, C4b and C2a , and additional C3b molecules. (pathwaymaps.com)
  • The complement cascade is an innate part of the immune defence system, consisting of over 30 serum proteins. (euretina.org)
  • However, certain complement proteins may also help trigger inflammation. (euretina.org)
  • The latter group of genetically and structurally unrelated proteins has been collectively referred to as "complement regulator-acquiring surface proteins" and consists of CspA, CspZ, ErpA, ErpC, ErpP, and the as yet unidentified protein p43. (frontiersin.org)
  • This convertase, the alternative pathway C3-convertase, although only produced in small amounts, can cleave multiple C3 proteins into C3a and C3b. (wikipedia.org)
  • The complement system is an organized proteolytic cascade of dozens of proteins that functions in the recognition, opsonization, and lysis of pathogenic and altered-host cells. (ecu.edu)
  • Many studies have demonstrated that some pathogens produce proteins such as human astrovirus coat protein ( 7 ), scabies mite inactive serine proteases ( 8 ), and Streptococcus pneumoniae endopeptidase O (PepO) ( 9 ), which can bind human C1q and inhibit the classical pathway of complement activation as a strategy to evade complement attack in the host. (frontiersin.org)
  • Complement is the term used to describe a group of serum proteins that are critically important in our defense against infection. (primaryimmune.org)
  • The complement system consists of more than 30 proteins, present in blood and tissues, as well as other proteins anchored on the surfaces of cells. (primaryimmune.org)
  • Complement proteins in the circulation are not activated until triggered by an encounter with a bacterial cell, a virus, an immune complex, damaged tissue or other substance not usually present in the body. (primaryimmune.org)
  • The circulating proteins have been grouped into three activation pathways, based on the types of substances and proteins that initiate the activation. (primaryimmune.org)
  • The complement system is made up of a large number of distinct plasma proteins that react with one another to opsonize pathogens and induce a series of inflammatory responses that help to fight infection. (nih.gov)
  • A number of complement proteins are proteases that are themselves activated by proteolytic cleavage. (nih.gov)
  • In this way, the activation of a small number of complement proteins at the start of the pathway is hugely amplified by each successive enzymatic reaction, resulting in the rapid generation of a disproportionately large complement response. (nih.gov)
  • First, it generates large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement. (nih.gov)
  • Second, the small fragments of some complement proteins act as chemoattractants to recruit more phagocytes to the site of complement activation, and also to activate these phagocytes. (nih.gov)
  • The 14-3-3s are a family of regulatory proteins that is present in all eukaryotes and involved in protein interactions mediating signal transduction pathways. (qiagen.com)
  • Several studies indicate that complement proteins exert functions that are either more complex than previously thought, or go well beyond the innate immune character of the system. (springer.com)
  • This unit describes several assay methods that can be used to determine the functional status of the classical pathway of complement and to quantitate its component proteins. (currentprotocols.com)
  • These can be used to measure the concentrations of most circulating complement proteins and to evaluate the functional status of C1‐esterase inhibitor. (currentprotocols.com)
  • The complement system is one of the major contributors to innate immunity and contains a series of soluble and cell surface proteins, including plasma components, specific receptors and diverse regulators. (nature.com)
  • Furthermore, it is a crucial factor in connecting the recognition pathways of the overall system instigated by antibody-antigen (Ab-Ag) complexes to the other effector proteins of the innate immune response. (wikipedia.org)
  • More specifically, the two proteins, Ch and Rg, function together as a medium for interaction between the Ab-Ag complex and other complement components. (wikipedia.org)
  • Hereditary deficiency in one of the complement proteins will usually lead to a high frequency of recurrent microbial infections. (labcorp.com)
  • Complement protein levels are usually increased, along with other unrelated proteins called acute phase reactants, during acute or chronic inflammation. (labcorp.com)
  • Inefficient coagulation inhibitory pathways involving endothelial proteins such as thrombomodulin and tissue factor pathway inhibitor (TFPI) result in increase of thrombosis, although porcine endothelium exposed to human blood have somewhat similar mechanism compared to that of human endothelium exposed to human blood (Pierson et al. (thefreelibrary.com)
  • 1989) Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. (cosmobio.co.jp)
  • The complement system is a collection of blood and cell surface proteins that is a major primary defense and a clearance component of innate and adaptive immune responses. (virology.ws)
  • At least 30 different complement proteins act sequentially to produce a wide ranges of activities, from cell lysis to augmentation of the adaptive response. (virology.ws)
  • Activation of inflammation - Several peptides produced by proteolytic cleavage of complement proteins bind to vascular endothelial cells and lymphocytes. (virology.ws)
  • Opsonization - Certain complement proteins can bind to virions. (virology.ws)
  • Phagocytic cells with receptors for these complement proteins can then engulf the virus particles and destroy them. (virology.ws)
  • Some complement proteins can disrupt these complexes and facilitate their clearance from the circulatory system. (virology.ws)
  • Unfortunately the nomenclature of the complement proteins is confusing, because they were named as they were discovered, not according to their function (see illustration below of the classical pathway). (virology.ws)
  • So, in order to understand what the position of complement is in our innate immune system and acquired defense, I would like to give you a view what innate and acquired immunity is. (hstalks.com)
  • And many investigators have shown that deficiencies of complements are very important for the mounting of an efficient immune response and especially the production of antibodies. (hstalks.com)
  • To exert their pathologic effects, ACPAs must recruit immune effector mechanisms such as activation of the complement system. (nih.gov)
  • The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's plasma membrane. (technologynetworks.com)
  • The classical complement pathway typically requires antigen-antibody complexes (immune complexes) for activation (specific immune response), whereas the alternative pathway can be activated by C3 hydrolysis, foreign material, pathogens, or damaged cells. (technologynetworks.com)
  • The mannose-binding lectin pathway can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). (technologynetworks.com)
  • Antigen-antibody complexes on the surface of a microorganism can activate the classical pathway of complement, a part of the acquired immune system (Fig. 1 ), by providing a binding site for C1. (asm.org)
  • Complement is also part of the innate immune defenses and provides a defense against pathogens that have not previously infected the host by recognizing repeating structures such as lipopolysaccharide (LPS) found on the surface of bacteria. (asm.org)
  • However, an acquired immune response can lead to killing of the bacteria by activating the antibody-dependent classical pathway. (asm.org)
  • Our results suggest that both, the classical complement system of innate immunity and a functional acquired immune response are not essential for the degenerative process in the rd1 mouse retina. (uzh.ch)
  • Complement system is a major effector of the humoral branch of the immune system, acting to protect the host from microorganisms such as bacteria. (pathwaymaps.com)
  • Complement activation by the classical pathway commonly begins with the formation of soluble antigen-antibody complexes (immune complexes) or with the binding of antibody (Immunoglobulins such as IgG1 and IgM ) to antigen on a suitable target, such as a bacterial cell. (pathwaymaps.com)
  • Complement represents a major bridge between the innate and adaptive immune systems of the body. (monash.edu)
  • Soluble antibody-antigen complexes are often referred to as immune complexes , and only complexes formed by IgM or certain subclasses of IgG antibodies are capable of activating the classical complement pathway. (microbenotes.com)
  • In regard to complement resistance, Borrelia utilize a plethora of immune evasion strategies involves capturing of host-derived complement regulators, terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to expeditiously inhibit human complement. (frontiersin.org)
  • This review focuses on the current knowledge of immune evasion mechanisms exhibited by Lyme disease spirochetes and highlights the role of complement-interfering, infection-associated molecules playing an important part in these processes. (frontiersin.org)
  • The alternative pathway of the complement system is an innate component of the immune system 's natural defense against infections. (wikipedia.org)
  • Complement, a key part of the innate immune system, is composed of multiple components and needs to be activated to function. (ashpublications.org)
  • Complement activation is a critical means of host defense against infection and the clearance of immune complexes. (ashpublications.org)
  • Here, we identified that T. spiralis calreticulin ( Ts -CRT), a Ca 2+ -binding protein, facilitated T. spiralis immune evasion by interacting with the first component of human classical complement pathway, C1q. (frontiersin.org)
  • All of these results suggest that T. spiralis -expressed Ts -CRT plays crucial roles in T. spiralis immune evasion and survival in host mostly by directly binding to host complement C1q, which not only reduces C1q-mediated activation of classical complement pathway but also inhibits the C1q-induced non-complement activation of macrophages. (frontiersin.org)
  • As a major innate immune component, the complement system is an early barrier for intruding pathogens and is activated directly by pathogens or indirectly by pathogen-bound antibodies. (frontiersin.org)
  • In fact, the pathogen's immune evasion often targets the host complement system ( 6 ). (frontiersin.org)
  • In particular, she investigates the molecular functioning of the complement system, a large protein network in plasma that plays an essential role in the immune response against all invading bacteria. (umcutrecht.nl)
  • Complement is essential in immune eradication of Gram-positive bacteria. (umcutrecht.nl)
  • Here we demonstrate that HAstV type 1 (HAstV-1) virions, specifically the viral coat protein (CP), suppress the complement system, a fundamental component of the innate immune response in vertebrates. (realtalifesciences.com)
  • The primary functions of the complement system are to protect from infection, to remove particulate substances, (like damaged or dying cells, microbes or immune complexes) and to help modulate adaptive immune responses. (primaryimmune.org)
  • As part of the innate immune system, complement acts immediately to start the process of removal and resolution of the problem. (primaryimmune.org)
  • Complement works with the inflammatory cells of the innate immune system and those of adaptive or acquired immunity. (primaryimmune.org)
  • The Classical Pathway (CP) is activated primarily by immunoglobulins (antibodies, including autoantibodies) that are bound to antigens - either in the fluid phase as soluble immune complexes, or on cell membrane surfaces or other tissues. (primaryimmune.org)
  • C2 and C4 also participate in the LP. The LP is thought to be the most evolutionarily primitive of the complement pathways and the first to react before the adaptive immune response occurs. (primaryimmune.org)
  • Complement C3b may be an opsonin for antigen-antibody complexes which helps prevent damage from the formation of large, insoluble immune aggregates. (sigmaaldrich.com)
  • Complement inhibitors are being studied as potential therapeutics for immune diseases and Alzheimer's. (sigmaaldrich.com)
  • Indeed, it now seems clear that complement first evolved as part of the innate immune system , where it still plays an important role. (nih.gov)
  • Complement has long been regarded as a pivotal effector arm of the innate immune response, eliciting important immunoregulatory functions in the context of inflammation and also serving as a vital link between the innate and adaptive immune response. (springer.com)
  • Complement system - This article is about an aspect of the immune system. (academic.ru)
  • It may also be ordered when a health practitioner suspects that someone may have an immune complex-related condition and wants to check the status of the person's complement system. (labcorp.com)
  • Complement system is an important component of innate immunity and involved in the modulation of several immune and inflammatory responses. (hindawi.com)
  • We propose that this localized deposition of complement fragments aids in the fusion process between the spermatozoa and egg, in a role akin to that of complement in immune adherence. (jci.org)
  • The complement system is an integral part of the immate immune system. (ncl.ac.uk)
  • Type III is very rare, it is characterized by a mixture of subepithelial and subendothelial immune and/or complement deposits. (rug.nl)
  • Complement C1r subcomponent (EC 3.4.21.41, activated complement C1r, C overbar 1r esterase, C1r) is a protein involved in the complement system of the innate immune system. (wikipedia.org)
  • Pathway analyses revealed over-representation of deregulated genes in the networks of proliferation, cell cycle, extracellular matrix biology, and inflammatory immune response. (springer.com)
  • why human immune system has three complement pathways when all of them ultimately converge in cell lysis? (virology.ws)
  • Bordetella pertussis produces a 73-kDa protein, BrkA (Bordetella resistance to killing), which inhibits the bactericidal activity of complement. (asm.org)
  • For example, the mannose binding protein is a pattern recognition molecule with structural similarity to C1 that bridges the classical and alternative pathways ( 18 ). (asm.org)
  • Mannose binding protein activates the classical pathway by binding to mannose residues on microbial surfaces and activating C4 in a manner similar to that for C1. (asm.org)
  • The Bordetella resistance to killing (BrkA) protein has been shown to inhibit killing by this pathway ( 7 ). (asm.org)
  • Although complement factor C1qalpha was highly up-regulated in the rd1 retina concomitantly with the degenerative process, lack of this protein did not protect the rd1 retina. (uzh.ch)
  • CD46 molecule, complement regulatory protein ( MCP ) is a cofactor for the Factor I -mediated degradation of C3b and C4b deposited on host cells [13] . (pathwaymaps.com)
  • The pathway is triggered when the C3b protein directly binds a microbe . (wikipedia.org)
  • CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating activity and is able to bind preferentially to C3b at host surfaces. (wikipedia.org)
  • Complement component 1s ( EC 3.4.21.42 , C1 esterase , activated complement C1s , complement C overbar 1r , C1s ) is a protein involved in the complement system . (wikipedia.org)
  • Patients with complement deficiencies encounter clinical problems that depend on the role of the specific complement protein in normal function. (primaryimmune.org)
  • Properdin makes it possible for the amplification loop of the alternative pathway to set up a very efficient mechanism for putting lots of C3b onto the surface of the activating cells, protein complexes or particles in the immediate vicinity of the activation site. (primaryimmune.org)
  • I wrote about The Classical Pathway of Complement Activation, but I need more specific information about C1q protein with its structure and put figure about it. (peakessaywriters.com)
  • I wrote about Lectin Pathway of Complement Activation, but I need more specific information about MASP-2 Protein with its structure and put figure about it. (peakessaywriters.com)
  • The classical pathway can be initiated by the binding of C1q, the first protein in the complement cascade, directly to the pathogen surface. (nih.gov)
  • The mannan-binding lectin pathway ( MB-lectin pathway ) is initiated by binding of the mannan-binding lectin, a serum protein, to mannose-containing carbohydrates on bacteria or viruses. (nih.gov)
  • Explore and order pathway-specific siRNAs, real-time PCR assays, or optimized protein expression vectors. (qiagen.com)
  • Complement research is now faced with the challenge of trying to integrate isolated biochemical pathways into complex gene and protein regulatory circuits. (springer.com)
  • This volume represents a collection of topics on the "novel" functions of complement, patho-physiology, protein structures, design of complement inhibitors, and complement assays discussed during the conference. (springer.com)
  • Complement component 4 (C4), in humans, is a protein involved in the intricate complement system, originating from the human leukocyte antigen (HLA) system. (wikipedia.org)
  • So far, the exact pathogenesis of DR is still unclear and is known to be involved in several physiopathologic pathways, such as angiogenesis factors, oxidative stress, apoptosis, and protein kinase C (PKC) [ 8 - 10 ]. (hindawi.com)
  • Using FACS to simultaneously evaluate viability, acrosomal status, and complement deposition, we found that complement activation was initiated by C-reactive protein (CRP) and was C1q, C2, and factor B dependent. (jci.org)
  • Stimulation of the complement regulatory protein CD46 on T cells triggers the conversion of inflammatory effector cells into interleukin-10 (IL-10)-secreting type 1 regulatory T (Tr1) cells, a process that is defective in MS patients. (sciencemag.org)
  • A lack of regulatory T cell function is a critical factor in the pathogenesis of autoimmune diseases, such as multiple sclerosis (MS). Ligation of the complement regulatory protein CD46 facilitates the differentiation of T helper 1 (T H 1) effector cells into interleukin-10 (IL-10)-secreting type 1 regulatory T cells (Tr1 cells), and this pathway is defective in MS patients. (sciencemag.org)
  • Complement component 4 is a protein involved in the complement system . (thefullwiki.org)
  • ab222866 Human Complement C4-Binding Protein ELISA Kit is designed for the quantitative measurement of Complement C4-Binding Protein in plasma, serum, urine, milk, saliva, cerebrospinal fluid (CSF), and cell culture samples. (abcam.com)
  • The kit employs a quantitative sandwich enzyme immunoassay technique that measures human Complement C4-Binding Protein (C4BP) in less than 4 hours. (abcam.com)
  • Complement component C4-binding protein (C4BP) regulates the complement system by accelerating the decay of the complement component C3 convertase and by acting as a cofactor to the serine protease factor I in the degradation of C4b. (abcam.com)
  • The major form of C4BP is composed of seven identical 70-kDa alpha chains, each containing a binding site for the complement protein C4b, and a unique 45 kDa beta chain which contains a binding site for the vitamin K-dependent protein S. C4BP was overexpressed in the synovial membranes of patients with rheumatoid arthritis. (abcam.com)
  • Activated C1s cleaves Complement c4 and Complement c2 forming the membrane-bound classical C3 convertase ( C4b2a ) and the subsequent C5 convertase ( C4b2a3b ) leading to cleavage of Complement c5 and the assembly of Complement membrane attack complex . (jove.com)
  • The three pathways of activation all generate homologous variants of the protease C3-convertase. (technologynetworks.com)
  • In all three pathways, C3-convertase cleaves and activates component C3, creating C3a and C3b, and causes a cascade of further cleavage and activation events. (technologynetworks.com)
  • C5 convertase is also formed by the Classical Pathway when C3b binds C4b and C2a. (technologynetworks.com)
  • C1r cleaves and activates C1s , which translates the activation of the Complement component C1 complex into complement activation via cleavage of C4 and C2 to form a C3 convertase (C2aC4b) . (pathwaymaps.com)
  • The addition of properdin forms the complex C3bBbP, a stable compound which can bind an additional C3b to form alternative pathway C5-convertase. (wikipedia.org)
  • The C5-convertase of the alternative pathway consists of (C3b) 2 BbP (sometimes referred to as C3b 2 Bb). (wikipedia.org)
  • After the creation of C5 convertase (either as (C3b) 2 BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). (wikipedia.org)
  • The formation of a C3 convertase can also be prevented when a plasma protease called complement factor I cleaves C3b into its inactive form, iC3b. (wikipedia.org)
  • C1s cleaves C4 and C2 , which eventually leads to the production of the classical pathway C3-convertase . (wikipedia.org)
  • The two activated C1s subunits are then able to catalyze the assembly of the C3 convertase (complement C4b2a) from complements C2 and C4. (sigmaaldrich.com)
  • Diffusion of the Ba subunit results in an active alternate pathway C3 convertase (C3bBb). (sigmaaldrich.com)
  • Three pathways of complement activation: the classic pathway, lectin pathway, and alternative pathway, which of them converge at the level of complement component 3 (C3) convertase, from which functional products are generated in a sequential manner 5 . (nature.com)
  • It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. (abcam.com)
  • Mouse models of RA have shown that, surprisingly, arthritogenic antibodies activate the alternative pathway of complement rather than the expected classical pathway. (nih.gov)
  • This study was undertaken to investigate whether human anti-cyclic citrullinated peptide (anti-CCP) antibodies activate the complement system in vitro and, if so, which pathways of complement activation are used. (nih.gov)
  • We set up novel assays to analyze complement activation by anti-CCP antibodies, using cyclic citrullinated peptide-coated plates, specific buffers, and normal and complement-deficient sera as a source of complement. (nih.gov)
  • Anti-CCP antibodies activated complement in a dose-dependent manner via the classical pathway of complement, and, surprisingly, via the alternative pathway of complement. (nih.gov)
  • The lectin pathway was not activated by anti-CCP antibodies. (nih.gov)
  • Our findings indicate that anti-CCP antibodies activate the complement system in vitro via the classical and alternative pathways but not via the lectin pathway. (nih.gov)
  • Zaragoza, O & Casadevall, A 2006, ' Monoclonal antibodies can affect complement deposition on the capsule of the pathogenic fungus Cryptococcus neoformans by both classical pathway activation and steric hindrance ', Cellular microbiology , vol. 8, no. 12, pp. 1862-1876. (elsevier.com)
  • Lead drug candidates, ANX005 and ANX007, are potent inhibitory antibodies against C1q, the initiating molecule of the classical complement cascade. (euretina.org)
  • The present invention refers to recombinant antibodies of human origin specific for the C5 component of the activated complement and characterised by the ability to inhibit the conversion of the C5 alpha chain to C5a and C5b. (google.com)
  • Moreover the present invention refers to the nucleotide sequences coding for such antibodies and to the therapeutic use of both polypeptide and nucleotide sequences, in particular for the therapy of diseases involving tissue damage deriving from uncontrolled activation of the complement system. (google.com)
  • The classical pathway is initiated by the binding of antibodies to cell surface antigens. (sigmaaldrich.com)
  • The alternate pathway does not require the action of antibodies to inititate the cascade, but is initiated by foreign cell surface components. (sigmaaldrich.com)
  • Synergistic complement lysis by monoclonal antibodies to the human leukocyte common antigen requires both the classical and alternative pathways. (ox.ac.uk)
  • In a previous study we isolated a series of rat monoclonal antibodies to the human leukocyte common (LC) antigen and demonstrated that synergistic complement lysis was possible between IgG2b antibodies which recognised different epitopes. (ox.ac.uk)
  • This is the first demonstration of the need for the alternative pathway in complement lysis by monoclonal antibodies. (ox.ac.uk)
  • Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria by antibodies and allows antibodies to kill some bacteria. (nih.gov)
  • Although first discovered as an effector arm of the antibody response, complement can also be activated early in infection in the absence of antibodies. (nih.gov)
  • Immobilization of the amebae by cytochalasin B (10 µg/ml) increased the susceptibility to cytolytic effects of specific antibodies or complement, or both. (ajtmh.org)
  • Monoclonal antibodies (mAb) that block programmed death (PD)-1 signaling pathway hold great potential as a novel cancer immunotherapy. (biomedcentral.com)
  • The complement system helps or "complements" the ability of antibodies and phagocytic cells to clear pathogens from an organism. (academic.ru)
  • C4d is the degradation product of the activated complement factor C4, a component of the classical complement cascade which is typically initiated by binding of antibodies to specific target molecules. (thefullwiki.org)
  • AVR is generally known to be initiated by xeno-reactive antibodies, including non-Gal antibodies and subsequent activation of the graft endothelium, the complement and the coagulation systems. (thefreelibrary.com)
  • Antibodies targeting the CD 154/CD40 pathway were used to improve the rejection of T cell and B cell response to xenoantigen (Kawai et al. (thefreelibrary.com)
  • The classical pathway is initiated by binding of C1q to antibody complexes, whereas the alternative and lectin pathway are activated in an antibody-independent fashion through the interaction of complement components with respectively specific carbohydrate groups and lipopolysaccharides (LPS) on the surface of foreign pathogens. (linscottsdirectory.com)
  • Kupffer cells and other macrophage cell types help clear complement-coated pathogens. (technologynetworks.com)
  • Complement resistance is common among respiratory pathogens. (asm.org)
  • To survive and establish a persistent infection in the human host, pathogens must evade the first line of host defense by counteracting complement as an essential part of innate immunity. (frontiersin.org)
  • The alternative pathway is one of three complement pathways that opsonize and kill pathogens. (wikipedia.org)
  • Bloodborne pathogens like the etiologic agent of Lyme disease, Borrelia burgdorferi, encounter complement during their bloodmeal and in their dissemination through the body. (ecu.edu)
  • Therefore, to avoid complement mediated destruction, these pathogens have developed mechanisms that aid in complement evasion and defense. (ecu.edu)
  • The activation of complement system leads to a cascade of reactions occurring on the surface of pathogens and generates membrane-attack complex (MAC) to attack the invaded pathogens ( 5 ). (frontiersin.org)
  • The complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. (genome.jp)
  • The main consequences of complement activation are the opsonization of pathogens, the recruitment of inflammatory and immunocompetent cells, and the direct killing of pathogens. (genome.jp)
  • We advise to include in your study your own reference sample for 100% complement activity and negative control (eg non-preserved activated serum) to determine the level of activation of your samples. (linscottsdirectory.com)
  • Although often overlooked as a defense of the respiratory tract, complement levels in this location are normally 10 to 20% of that found in serum and increase during inflammation ( 21 ). (asm.org)
  • HAstV-1 CP bound the A chain of C1q and inhibited serum complement activation, resulting in decreased C4b, iC3b, and terminal C5b-9 formation. (realtalifesciences.com)
  • The relative importance of the classical and alternative complement pathways in serum bactericidal activity against Escherichia coli strains of the common urinary O-serogroups has been assessed with strains that differ widely in their sensitivity to normal human serum. (microbiologyresearch.org)
  • With most promptly serum-sensitive strains, rapid killing occurred, mediated by the classical pathway and, when this pathway was eliminated, delayed killing by alternative-pathway activity occurred. (microbiologyresearch.org)
  • Strains with delayed sensitivity to normal human serum were largely, and in some cases exclusively, affected by the classical pathway. (microbiologyresearch.org)
  • The complement system is a complex cascade involving proteolytic cleavage of serum glycoproteins often activated by cell receptors. (sigmaaldrich.com)
  • Despite the large number of C1q molecules bound with the optimal synergistic pair and the increased rate of C1 activation, lysis was inefficient in serum depleted of Factor D, suggesting a requirement for the alternative pathway. (ox.ac.uk)
  • complement - Ehrlich term for the thermolabile substance, normally present in serum, that is destructive to certain bacteria and other cells sensitized by a specific c. fixing antibody. (academic.ru)
  • Upon exposure of human spermatozoa to autologous serum or follicular fluid, we unexpectedly observed that acrosome-reacted spermatozoa activated the complement cascade efficiently through C3 but not beyond. (jci.org)
  • C1r along with C1q and C1s form the C1 complex, which is the first component of the serum complement system. (wikipedia.org)
  • Zhao Y, Yu L, Xu S, Qiu F, Fan Y, Fu G. (2011) "Down-regulation of connexin43 gap junction by serum deprivation in human endothelial cells was improved by (-)-Epigallocatechin gallate via ERK MAP kinase pathway. (cosmobio.co.jp)
  • Furthermore some assays have been described to measure the activity of the MBL pathway. (linscottsdirectory.com)
  • Additionally, cytoprotection assays of individual clones of transfected isoforms bearing equivalent copy numbers demonstrated that the BC isoforms also provided enhanced protection in a classical pathway-mediated system and cleaved cell-bound C4b more efficiently than the C isoforms. (jimmunol.org)
  • Simplified assays of hemolytic activity of the classical and alternative complement pathways. (diva-portal.org)
  • Simplified hemolytic assays for the classical (CP) and alternative (AP) pathways of complement (C) were developed. (diva-portal.org)
  • Hemolytic assays utilizing sera depleted of individual complement factors as well as adding back purified factors demonstrated that HAstV CP suppresses classical pathway activation at the first component, C1. (realtalifesciences.com)
  • The ELISA contains a positive control which can be used as process control to ensure that the classical complement cascade has run completely. (linscottsdirectory.com)
  • The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, proxy inflammation to attract additional phagocytes, and activation of the cell-killing membrane attack complex. (technologynetworks.com)
  • In this study we characterized the step in the complement cascade where BrkA acts, using three strains: a wild-type strain, a strain containing an insertional disruption of brkA , and a strain containing two copies of the brkA locus. (asm.org)
  • The complement cascade. (asm.org)
  • The classical pathway is a chain of events in which complement components react in specific sequences as a cascade resulting in cell lysis. (microbenotes.com)
  • In addition, recent evidence has shown the role of the complement cascade in synaptic pruning in glaucoma and other diseases. (biomedcentral.com)
  • In general, substances on the surface of microbes or other infectious agents can trigger the complement cascade, which then activates a series of biochemical steps leading to the lysis (or bursting) of invading cells. (euretina.org)
  • Several components of the complement cascade have been found in drusen deposits which led to the hypothesis that AMD may result from dysfunctional inflammation which incorporates inappropriate complement activation. (euretina.org)
  • If you visualize a trident, the three tines represent the different initiation routes, while the handle represents the lytic mechanism by which this cascade ultimately destroys the threat, no matter which activation pathway started the response. (primaryimmune.org)
  • Ischaemic infarction may also cause initiation of the complement cascade. (sigmaaldrich.com)
  • The complement system activates through a triggered-enzyme cascade. (nih.gov)
  • In such a cascade, an active complement enzyme generated by cleavage of its zymogen precursor then cleaves its substrate, another complement zymogen, to its active enzymatic form. (nih.gov)
  • Schematic overview of the complement cascade. (nih.gov)
  • In the early phases of an infection, the complement cascade can be activated on the surface of a pathogen through any one, or more, of the three pathways shown in Fig. 2.8 . (nih.gov)
  • The Classical Complement Cascade Mediates CNS Synapse Elimination. (freepatentsonline.com)
  • Complement activation initiated by the binding of Complement c1 to Antigen-antibody complexes at the Complement c1q subunit. (jove.com)
  • Mice deficient for classical complement pathway (CCP) factor C4 are resistant to antibody and complement mediated experimental autoimmune myasthenia gravis (EAMG). (springer.com)
  • Formation of an antigen-antibody complex induces conformational changes in the Fc part of the IgM molecule that expose a binding site for the Complement component C1 . (pathwaymaps.com)
  • For example, eculizumab, a monoclonal antibody specific for complement component 5 (C5) has been approved for clinical use and was shown to effectively reduce complement-mediated hemolysis in patients with PNH, atypical hemolytic uremic syndrome, or CAD. (ashpublications.org)
  • The work will pave the way for several therapeutic applications, including targeted complement-dependent cytotoxicity (CDC) and antibody therapy of clinically important Gram-positive bacteria. (umcutrecht.nl)
  • Complement may contribute to donor-specific antibody (DSA)-triggered transplant injury. (atcmeetingabstracts.com)
  • Associations of these genotypes with blood complement profiles and morphologic/molecular rejection features were evaluated in a cohort of 83 DSA-positive patients [antibody-mediated rejection (ABMR): n=47] identified upon cross-sectional screening of 741 kidney allograft recipients ≥180 days post-transplantation. (atcmeetingabstracts.com)
  • 9. A chimeric antibody characterized in that it comprises at least one of the sequences corresponding to SEQ ID NO: 2, 4, 6, 8, or 12, wherein the antibody recognizes a region corresponding to sequence 727-744 (SEQ ID NO:15) of the C5 component of human complement or a region having at least 80% homology thereto. (google.com)
  • The classical pathway mediates specific antibody responses. (sigmaaldrich.com)
  • Subsequent binding of the antibody to complement C1q subunits of C1 result in catalytically active C1s subunits. (sigmaaldrich.com)
  • This activity was said to ' complement ' the antibacterial activity of antibody , hence the name. (nih.gov)
  • lectin pathway - a pathway of complement activation initiated in the absence of antibody by the binding of mannose binding lectin (MBL) to carbohydrates on the surface of microorganisms. (academic.ru)
  • However, it should be kept in mind that apart from the classical antibody-mediated route of complement activation, C4 can also be activated via an alternative, antibody-independent mechanism, the 'mannan-binding lectin' pathway. (thefullwiki.org)
  • A polyclonal antibody specific for human complement C4BP has been pre-coated onto a 96-well microplate with removable strips. (abcam.com)
  • Complement C4BP in standards and samples is sandwiched by the immobilized antibody and biotinylated polyclonal antibody specific for complement C4BP, which is recognized by a streptavidin-peroxidase conjugate. (abcam.com)
  • The smaller flowchart in the box indicates the membrane-bound products and complexes formed by the classical pathway on the bacterial surface. (asm.org)
  • Complement fragments interact with each another to form functional complexes. (pathwaymaps.com)
  • MASP-1 and MASP-2 proteinases in MBL complexes of the lectin pathway are also inactivated. (bionity.com)
  • Complement deficiencies or other defects in the complement system can easily be screened by running an assay for each pathway in parallel or separately. (linscottsdirectory.com)
  • There are deficiencies of each of the individual components of complement. (primaryimmune.org)
  • I wrote about Deficiencies of the classical pathway, but I need more specific information about C1q Deficiency in mice. (peakessaywriters.com)
  • Complement tests, most commonly C3 and C4, are used to determine whether deficiencies or abnormalities in the complement system are causing, or contributing to, a person's disease or condition. (labcorp.com)
  • Other complement components are ordered as needed to look for deficiencies. (labcorp.com)
  • Also found with Sjögren syndrome , rheumatoid arthritis , inherited complement deficiencies (esp C2 deficiency), scleroderma , Celiac disease . (rug.nl)
  • Hence, for cells with large capsule, C3 cannot interact with the complement receptor (CR) and is not opsonic. (elsevier.com)
  • [15] it is associated with complement receptor 6 deficiency. (rug.nl)
  • Such findings indicate a physiologic role for isoform variation and have therapeutic implications for use of MCP isoforms as complement inhibitors in such areas as xenotransplantation. (jimmunol.org)
  • Annexon Biosciences Inc. (San Francisco, California, USA) has raised $75 million investment to fund development of its lead complement inhibitors through several clinical stages, according to the company. (euretina.org)
  • Understanding the foundation from the connection between C1s and its own physiological substrates will probably result in insights you can use to design effective inhibitors from the enzyme for make use of in treating illnesses caused by swelling as consequence of over-activity from the traditional go with pathway. (bassresearch.com)
  • 2 Consequently, efforts are underway to develop inhibitors that target different complement components as novel therapeutic agents. (ashpublications.org)
  • CD46) is a widely distributed C3b/C4b-binding glycoprotein that inhibits complement activation on host cells. (jimmunol.org)
  • These studies show that BrkA inhibits the classical pathway of complement activation and prevents accumulation of deposited C4. (asm.org)
  • Serpin peptidase inhibitor clade G member 1 ( C1 inhibitor ) inhibits activated C1r and C1s and thus regulates complement activation [9] . (pathwaymaps.com)
  • CD55 molecule decay accelerating factor for complement ( DAF ) inhibits the assembly of the complement system C3/C5 convertases by complex formation with C4b and C3b [10] , [11] . (pathwaymaps.com)
  • Although named after its complement inhibitory activity, C1-inh also inhibits proteinases of the fibrinolytic, clotting, and kinin pathways. (bionity.com)
  • Aisha AF, Ismail Z, Abu-Salah KM, Siddiqui JM, Ghafar G, Abdul Majid AM. (2013) "Syzygium campanulatum korth methanolic extract inhibits angiogenesis and tumor growth in nude mice" BMC Complement Altern Med. (cosmobio.co.jp)
  • This cleavage activates the terminal complement pathway leading to eventually the formation of the terminal C5b-9 complement complex (TCC). (linscottsdirectory.com)
  • This in turn cleaves and activates the next zymogen in the complement pathway. (nih.gov)
  • They block activation of the entire classical pathway, including downstream C3 and C5, while leaving the protective functions of other complement pathways (lectin and alternative pathways) intact. (euretina.org)
  • Complement testing may be ordered when a person has unexplained inflammation or edema or symptoms of an autoimmune disorder such as SLE. (labcorp.com)
  • This includes the role of chronic inflammation, including the complement system, the cell signalling pathways that initiate a fibrotic response and testing novel therapeutic interventions in pre-clinical model systems of fibrosis. (ncl.ac.uk)
  • Complement and Inflammation. (wikipedia.org)
  • In most cases, the smaller fragment resulting from cleavage of a Complement component is designated 'a' and the larger fragment designated 'b' (e.g. (pathwaymaps.com)
  • As a protease it has very restricted specificity, cleaving only C3b or C4b in the presence of a cofactor such as Complement factor H ( Factor H ). Cleavage of C3b by Factor I yields iC3b , a major opsonin [12] . (pathwaymaps.com)
  • Smaller fragments resulting from complement cleavage, C3a and C5a , called anaphylatoxins, bind to their cognate receptors ( CR3aR and CR5aR ) on the surface of mast cells and blood basophils and induce degranulation, upon release of histamine and other biologically active mediators [3] . (pathwaymaps.com)
  • In the alternate pathway complement C3 undergoes spontaneous cleavage resulting in complement B binding to C3b. (sigmaaldrich.com)
  • This way, C1-inh prevents the proteolytic cleavage of later complement components C4 and C2 by C1 and MBL. (bionity.com)
  • Also, C4 and C2 cleavage goes unchecked, resulting in auto-activation of the complement system. (bionity.com)
  • The C1s protease from the classical complement pathway propagates the original activation of the pathway of the machine by cleaving and thereby activating the C4 and C2 complement components. (bassresearch.com)
  • Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. (uniprot.org)
  • The alternative pathway also acts as an amplification loop of the other pathways. (linscottsdirectory.com)
  • Alterations in the alternative pathway, like properdin or ficolin deficiency, increase the susceptibility to infection. (linscottsdirectory.com)
  • A common way to measure the activity of the classical or alternative pathway is the haemolysis of erythrocytes. (linscottsdirectory.com)
  • Several studies in rodents suggest that the alternative pathway of the complement system plays a pivotal role in renal ischemia-reperfusion injury. (nih.gov)
  • Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway, and the lectin pathway. (technologynetworks.com)
  • In the alternative pathway, C3b binds to Factor B. Factor D releases Factor Ba from Factor B bound to C3b. (technologynetworks.com)
  • Both the classical and alternative pathways of complement activation are represented, although details are given only for the classical pathway. (asm.org)
  • Interestingly, B. pertussis does not activate the alternative pathway of complement ( 7 ). (asm.org)
  • Capsule-mediated activation of the alternative complement (C) pathway results in component 3 (particularly, C3) binding to the capsule near the cell wall surface. (elsevier.com)
  • The complement pathway contains three arms - classical, alternative and lectin - all of which converge on C3, potentially making the molecule a key therapeutic target. (euretina.org)
  • The classical and alternative complement pathways. (wikipedia.org)
  • [5] Alternative pathway activation might also play a significant role in kidney pathology associated with lupus . (wikipedia.org)
  • Mechanistic studies on ErpB and ErpQ also support further understanding of molecular interactions between complement proteases and their substrates, which provides alternative means for the development of specific complement therapeutics toward complement-mediated diseases. (ecu.edu)
  • Absence of C3 abolishes alternative pathway-mediated hemolysis. (ashpublications.org)
  • In all of the in vitro and in vivo experiments, we found that the loss of C3 did not prevent classical pathway-mediated hemolysis, but it did almost abolish alternative pathway-mediated hemolysis. (ashpublications.org)
  • Our results suggest that targeting C3 should effectively inhibit hemolysis and tissue damage mediated by the alternative pathway of complement activation, but this approach might have limited efficacy in treating classical pathway-mediated pathological conditions. (ashpublications.org)
  • Complement can be activated through 3 major activation pathways: classical, alternative, and lectin. (ashpublications.org)
  • Here, we investigated whether the intrinsic strength of classical (CP) and alternative complement pathways (AP) relates to the pathogenicity of DSA. (atcmeetingabstracts.com)
  • However, one strain of serogroup O1 was affected by the classical pathway only and a strain of serogroup O9 was killed rapidly by the alternative pathway. (microbiologyresearch.org)
  • The Alternative Pathway (AP) is initiated by fragments of the complement component C3. (primaryimmune.org)
  • Finally, the alternative pathway can be initiated when a spontaneously activated complement component binds to the surface of a pathogen. (nih.gov)
  • A composition comprising particles of inulin or an inulin derivative in the gamma polymorphic form is characterized in that the particles have a low rate of solution in aqueous media above 30 C., particularly above 37 C. The composition is effective as the active component of an immunotherapeutic preparation for activation of the alternative pathway of complement, or for antitumor treatment. (google.es)
  • 14. A method for the activation of the alternative pathway of complement (APC) in a human or animal body, which comprises administering to the human or animal body an effective amount for said activation of an immunotherapeutic preparation according to claim 5. (google.es)
  • There are three pathways of complement activation: the classical pathway, the lectin pathway, and the alternative pathway. (genome.jp)
  • In our previous studies, genetic variants in the CFH and CFB genes, both involved in complement alternative pathway, have been evaluated and identified as susceptibility genes for DR [ 18 ]. (hindawi.com)
  • This pattern is consistent with engagement of the classical pathway followed by amplification through the alternative pathway. (jci.org)
  • Most cases are associated with the dysregulation of the alternative complement pathway . (rug.nl)
  • The presence of C3 without significant immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway (AP). (rug.nl)
  • classical , alternative , and mannan-binding . (virology.ws)
  • Do you know of any good primary literature sources documenting that most viruses do not fix complement by the alternative route. (virology.ws)
  • Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. (medworm.com)
  • Recent evidence supports that phagocytosis-associated molecules from the classical complement (C1q-C3) play novel roles in microglia-mediated synaptic pruning. (medworm.com)
  • Other projects in the lab involve unravelling processes underlying complement-mediated phagocytosis. (umcutrecht.nl)
  • Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine. (genecards.org)
  • Lysis - Polymerization of specific activated complement components on a foreign cell or enveloped virus leads to the formation of pores. (virology.ws)
  • Recent studies have implicated the complement system as a player in the development of vascular damage and progression of DR. However, the role and activation of the complement system in DR are not well understood. (diabetesjournals.org)
  • [3] Complement factor H preferentially binds to vertebrate cells (because of affinity for sialic acid residues), allowing preferential protection of host (as opposed to bacterial) cells from complement-mediated damage. (wikipedia.org)
  • C1-inh irreversibly binds to and inactivates C1r and C1s proteinases in the C1 complex of classical pathway of complement. (bionity.com)
  • It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. (abcam.com)
  • Pike, RN & Wijeyewickrema, LC 2013, ' The molecular switches controlling the interaction between complement proteases of the classical and lectin pathways and their substrates ', Current Opinion in Structural Biology , vol. 23, no. 6, pp. 820 - 827. (monash.edu)
  • Complement C5a, like C3a is an anaphylatoxin, and is a chemotactic attractant for induction of neutrophilic release of antimicrobial proteases and oxygen radicals. (sigmaaldrich.com)
  • Complement component 3 (C3) is the central component of all 3 major complement activation pathways required for both complement-mediated opsonization and membrane attack complex (MAC) formation. (ashpublications.org)
  • DDD is associated with deposition of complement C3 within the glomeruli with little or no staining for immunoglobulin. (rug.nl)
  • See also intrinsic pathway of coagulation and extrinsic pathway of coagulation . (thefreedictionary.com)
  • extrinsic pathway of coagulation the mechanism that produces fibrin following tissue injury, beginning with formation of an activated complex between tissue factor and factor vii and leading to activation of factor x , which induces the reactions of the common pathway of coagulation . (thefreedictionary.com)
  • Activated factor X (factor Xa) initiates the common pathway of coagulation . (thefreedictionary.com)
  • complement component 1 q subcomponent. (wikipathways.org)
  • We have shown previously that microglial biosynthesis of the complement subcomponent C1q may serve as a reliable marker of microglial activation ranging from undetectable levels of C1q biosynthesis in resting microglia to abundant C1q expression in activated, nonramified microglia. (warwick.ac.uk)
  • 5. An immunotherapeutic preparation for activation of the alternate pathway of complement (APC) in a human or animal body, which comprises as the active component thereof particles of inulin in the gamma polymorphic form, wherein said particles are virtually insoluble in aqueous media at 37 C. (google.es)
  • Complement components are designated by numerals ( C1 - C9 ), by letter symbols (e.g. (pathwaymaps.com)
  • The terminal sequence of complement activation involves Complement components C5b , C6 , C7 , C8 , and C9 , which interact sequentially to form a macromolecular structure called Membrane attack complex . (pathwaymaps.com)
  • The initial stage of activation involves the complement components C1, C2, C3, and C4, which are present in plasma as zymogens. (microbenotes.com)
  • Third, the terminal complement components damage certain bacteria by creating pores in the bacterial membrane. (nih.gov)
  • Despite uncontrolled auto-activation, it is important to note that levels of key complement components are low during an acute attack, because they are being consumed - indeed, low levels of C4 are a key diagnostic test for hereditary angioedema. (bionity.com)
  • Individual complement components may be ordered when the total complement activity (CH50, sometimes called CH100) is abnormal to help determine which of the components are deficient or abnormal. (labcorp.com)
  • C3bBb is stabilized by binding to properdin prior to merging into the common pathway and conversion of C3. (sigmaaldrich.com)
  • Fibrosis is the common pathway that leads to organ failure in many diverse diseases affecting different organs. (ncl.ac.uk)
  • Despite the effectiveness and abundance of complement, LD spirochetes are able to overcome its destructive defense mechanisms ( 11 - 13 ). (frontiersin.org)
  • Complements C3a and C4b are opsonins that bridge phagocytes to microorganisms. (sigmaaldrich.com)
  • disruption of complement regulation can lead to several distinct downstream inflammatory actions en route to the pathogenesis of DR [ 14 , 15 ]. (hindawi.com)
  • These pathways depend on different molecules for their initiation, but they converge to generate the same set of effector molecules ( Fig. 2.7 ). (nih.gov)
  • All of these pathways generate a crucial enzymatic activity that, in turn, generates the effector molecules of complement. (genome.jp)
  • Complement activation proceeded in vitro up to the formation of the membrane attack complex, indicating that all activation steps, including the release of C5a, took place. (nih.gov)
  • Experiments using preassembled classical pathway C3 convertases confirmed that C4b2a directly activated complement component 5 (C5), leading to membrane attack complex formation and hemolysis. (ashpublications.org)
  • The Terminal Pathway (TP) is the final set of steps in the complement activation process that forms a membrane lesion or hole (membrane attack complex or MAC) that kills susceptible bacteria or other cells that activate complement on their surfaces. (primaryimmune.org)
  • A complex of complements C5b,C6, C7, and C8 mediates the polymerization of up to eighteen C9 molecules into a tube-like membrane attack complex that is inserted into the plasma membrane of an unwanted organism such as of gram-negative bacteria and viral infected cells. (sigmaaldrich.com)
  • Membranoproliferative glomerulonephritis ( MPGN ) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane ( GBM ) thickening, [2] activating complement and damaging the glomeruli. (rug.nl)
  • Under certain conditions, the complement system can be unfavorable to the host leading to e.g. autoimmune diseases and infections. (linscottsdirectory.com)
  • Malfunction or disruption of this pathway is at the core of many diseases and represents an attractive target for therapeutic intervention. (euretina.org)
  • Dysregulation of the complement system has been implicated in several diseases and pathologies. (wikipedia.org)
  • These activation pathways play different roles in the pathogenesis of different diseases. (ashpublications.org)
  • 1 However, excessive complement activation causes tissue damage such as hemolysis, which is seen in diseases such as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, and cold agglutinin disease (CAD). (ashpublications.org)
  • C3 has generated considerable interest as another promising target for the treatment of diseases in which complement is an integral pathogenic mechanism, including diseases associated with complement-mediated hemolysis. (ashpublications.org)
  • In this respect, scientists from around the world convened at the Fourth Aegean Conferences Workshop on Complement Associated Diseases, Animal Models, and Therapeutics (June 10-15, 2007), to discuss recent advances in this fast evolving field. (springer.com)
  • In addition to the episodes of facial swelling and/or abdominal pain, it also predisposes to autoimmune diseases , most markedly lupus erythematosus , due to its consumptive effect on complement factors 3 and 4. (bionity.com)
  • For example, the severity of a dysfunctional complement system can lead to fatal diseases and infections. (wikipedia.org)
  • The goal of these experiments was to characterize the complement inhibitory profile of the four commonly expressed isoforms. (jimmunol.org)
  • Complement levels may be decreased due to increased consumption or, more rarely, a hereditary deficiency. (labcorp.com)
  • If the deficiency is due to an underlying acute or chronic condition, complement levels will usually return to normal if the underlying condition can be resolved. (labcorp.com)
  • Familial deficiency of two subunits of the first component of complement. (wikipedia.org)
  • A fluid phase form of the MAC, called the Terminal Complement Complex (TCC) can be found in the circulation after complement activation occurs and makes a useful laboratory marker for complement activation. (primaryimmune.org)
  • Mannose binding lectin (MBL), a major component of the lectin pathway, is associated with bacterial, fungal and viral infection. (linscottsdirectory.com)
  • Although the MAC is an evolutionary conserved mechanism to kill bacterial cells, we currently do not understand how complement activation results in bacterial killing. (umcutrecht.nl)
  • Furthermore, her studies will create new avenues for blocking the undesired complement activation during systemic bacterial infections and sepsis. (umcutrecht.nl)