Complement pathway classical. Medical search

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)

Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ... The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune ... Activation of the complement pathway through the classical, lectin or alternative complement pathway is followed by a cascade ... The classical pathway is distinct from the other complement pathways in its unique activation triggers and cascade sequence. ...

https://en.wikipedia.org/wiki/Classical_complement_pathway

Classical complement pathway Lectin pathway Conrad DH, Carlo JR, Ruddy S (June 1978). "Interaction of beta1H globulin with cell ... The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the ... 2BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation ... The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, ...

https://en.wikipedia.org/wiki/Alternative_complement_pathway

... participates in all three of the complement pathways (classical, alternative, and lectin); the alternative pathway is " ... In the classical pathway, the complement component-hereafter abbreviated by the "C" preceding the protein number- termed C1s, a ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar A, ... Hakobyan S, Boyajyan A, Sim RB (February 2005). "Classical pathway complement activity in schizophrenia". Neuroscience Letters ...

https://en.wikipedia.org/wiki/Complement_component_4

"Expression of the complement classical pathway by human glioma in culture. A model for complement expression by nerve cells". ... "Synthesis of classical pathway complement components by chondrocytes". Immunology. 88 (4): 648-56. PMC 1456645. PMID 8881771. ... "Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r". The Biochemical Journal. 241 (3 ... Complement C1r subcomponent (EC 3.4.21.41, activated complement C1r, C overbar 1r esterase, C1r) is a protein involved in the ...

https://en.wikipedia.org/wiki/Complement_component_1r

... 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 ...

https://en.wikipedia.org/wiki/C1_complex

Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... Research from over the last decade has shown that complement proteins of the classical complement pathway have an important ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ...

https://en.wikipedia.org/wiki/Complement_system

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.[citation needed] Infection with Giardia ... "Involvement of lectin pathway activation in the complement killing of Giardia intestinalis". Biochemical and Biophysical ...

https://en.wikipedia.org/wiki/Giardiasis

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 ...

https://en.wikipedia.org/wiki/Xenotransplantation

The recruitment of the complement cascade via the classical pathway (antibody-antigen interaction). Membrane attack complex ( ...

https://en.wikipedia.org/wiki/Anti-NMDA_receptor_encephalitis

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 ( ...

https://en.wikipedia.org/wiki/Membranoproliferative_glomerulonephritis

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 ...

https://en.wikipedia.org/wiki/IgA_nephropathy

Activation of the C1 complex initiates the classical complement pathway of the complement system. The antibodies IgM and all ... The complement component 1q (or simply C1q) is a protein complex involved in the complement system, which is part of the innate ... C1q is a subunit of the C1 enzyme complex that activates the serum complement system. C1q comprises 6 A, 6 B and 6 C chains. ... "Entrez Gene: C1QA complement component 1, q subcomponent, A chain". Sellar GC, Blake DJ, Reid KB (March 1991). " ...

https://en.wikipedia.org/wiki/Complement_component_1q

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 ...

https://en.wikipedia.org/wiki/Isotype_(immunology)

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 ...

https://en.wikipedia.org/wiki/Cold_agglutinin_disease

Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are ... generated during activation through the classical pathway as well as the lectin pathway. C3a is an anaphylotoxin and the ... In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 ... Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement ...

https://en.wikipedia.org/wiki/Complement_component_3

The CH50 is testing the classical complement pathway in an individual thus requiring functioning C1-C9 factors. If an ... "Simplified assays of hemolytic activity of the classical and alternative complement pathways". Journal of Immunological Methods ... classical pathway deficiency (CH50 low, AH50 normal) or alternative pathway deficiency (AH50 low, CH50 normal). Michael T. ... For example, if and individual has normal C3/C4 values but a decreased CH50, that can indicate a terminal complement pathway ...

https://en.wikipedia.org/wiki/Total_complement_activity

Classical complement pathway Alternative complement pathway Mannan-binding lectin Wallis R, Mitchell DA, Schmid R, Schwaeble WJ ... In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The ... The lectin pathway or lectin complement pathway is a type of cascade reaction in the complement system, similar in structure to ... The MASPs are very similar to C1r and C1s molecules of the classical complement pathway, respectively. When the carbohydrate- ...

https://en.wikipedia.org/wiki/Lectin_pathway

In 2007, Stevens discovered that proteins of the classical complement pathway were required for synapse elimination. She has ... "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 ...

https://en.wikipedia.org/wiki/Beth_Stevens

The classical pathway of complement activation is initiated when the C1 complex, made up of C1r and C1s serine proteases, ... C1q mediates the classical pathway by activating the C1 complex, which cleaves C4 and C2 into smaller fragments (C4a, C4b, C2a ... The alternative pathway of complement activation is typically always active at low levels in blood plasma through a process ... 12th European Meeting on Complement in Human Disease12th European Meeting on CHD12th European Meeting on Complement in Human ...

https://en.wikipedia.org/wiki/C3a_(complement)

... fibromodulin activates the classical pathway of complement by directly binding C1q". The Journal of Biological Chemistry. 280 ( ...

https://en.wikipedia.org/wiki/Fibromodulin

"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 ...

https://en.wikipedia.org/wiki/Mark_Walport

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 ...

https://en.wikipedia.org/wiki/Borrelia_burgdorferi

Antibodies can also trigger the classical pathway - one of the three pathways of the complement cascade. Briefly, the C1 ... The formation of complement proteins (C3a, C3b, C5a, C5b, etc.) ultimately congregates into a membrane-attack complex to lyse ... In addition to the generation of complement proteins, C1 complex also induces the activation of B cells, monocytes, macrophages ... Warwick, Charles A.; Keyes, Alex L.; Woodruff, Trent M.; Usachev, Yuriy M. (2021-09-01). "The complement cascade in the ...

https://en.wikipedia.org/wiki/Passive_antibody_therapy

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 ... Complement C4-A is a kind of the Complement component 4 protein that in humans is encoded by the C4A gene. ... "Entrez Gene: C4A complement component 4A (Rodgers blood group)". Dawkins RL, Uko G, Christiansen FT, Kay PH (Sep 1983). "Low C4 ...

https://en.wikipedia.org/wiki/C4A

... 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 ...

https://en.wikipedia.org/wiki/PTX3

This gene encodes the basic form of complement factor 4, part of the classical activation pathway. The protein is expressed as ... Complement component 4 Complement component 4A HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency ... Complement component 4B (Chido blood group) is a kind of the Complement component 4 protein that in humans is encoded by the ... "Entrez Gene: Complement component 4B (Chido blood group)". Retrieved 2012-01-27. Zhou D, Rudnicki M, Chua GT, Lawrance SK, Zhou ...

https://en.wikipedia.org/wiki/Complement_component_4B

... 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 ...

https://en.wikipedia.org/wiki/C3-convertase

C1s cleaves C4 and C2, which eventually leads to the production of the classical pathway C3-convertase. C1q - another part of ... Complement component 1s (EC 3.4.21.42, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... "Entrez Gene: C1S Complement component 1, s subcomponent". Luo C, Thielens NM, Gagnon J, Gal P, Sarvari M, Tseng Y, Tosi M, ... Complement+C1s at the US National Library of Medicine Medical Subject Headings (MeSH) Human C1S genome location and C1S gene ...

https://en.wikipedia.org/wiki/Complement_component_1s

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. ...

https://en.wikipedia.org/wiki/Apolipoprotein_E

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 ...

https://en.wikipedia.org/wiki/EGF-like_domain

Sykes, Egerton (2014), Who's Who in Non-Classical Mythology, Routledge, ISBN 978-1-136-41437-4 al-Tabari, Muhammad ibn Jarir ( ... Ṭayr and another Mujāwir al-Riḥ which was a pathway to Abu Kubais from where the Black Stone is reported to have originated. ... complemented by archaeological evidence. The civilizations of South Arabia are considered to have the most developed pantheon ... The Representation of Jesus in the Qur'an and the Classical Muslim Commentaries. Albany, New York: SUNY Press. ISBN 978-0-7914- ...

https://en.wikipedia.org/wiki/Religion_in_pre-Islamic_Arabia

Swami Satyananda was well versed in classical yoga tenets and encouraged adults to use the practices of Hatha Yoga. He ... Later, kirtan, mudras, fire ceremony (yajna), and satsang were introduced to complement a busy schedule. In 1972, as interest ... and the most straightforward pathway to progress in spiritual life. He learned temple masonry from a local mason and used those ... Attainment of higher states of concentration according to Rāja yoga (classical yoga of Patanjali) is rooted in development of ...

https://en.wikipedia.org/wiki/Baba_Hari_Dass

MASP2 and initiate the lectin pathway of complement activation which is somewhat similar to the classical complement pathway. ... dependent signaling pathway. MyD88 - dependent pathway is induced by various PAMPs stimulating the TLRs on macrophages and ... dependent pathway and triggers the signaling through NF-κB and the MAP kinase pathway and therefore the secretion of pro- ... The TRIF-dependent pathway is induced by macrophages and DCs after TLR3 and TLR4 stimulation. Molecules released following TLR ...

https://en.wikipedia.org/wiki/Pattern_recognition_receptor

Shamanna RA, Lu H, de Freitas JK, Tian J, Croteau DL, Bohr VA (2016). "WRN regulates pathway choice between classical and ... "Do mitochondrial DNA and metabolic rate complement each other in determination of the mammalian maximum longevity?". ... including core genes in several DNA repair pathways, at a higher level than did mice. In addition, several DNA repair pathways ... Pathway analyses identified a major association with DNA damage response genes, particularly those expressed during meiosis and ...

https://en.wikipedia.org/wiki/DNA_damage_theory_of_aging

In a classical turn-based system, only one character may act at a time; all other characters remain still, with a few ... In games where the player controls multiple characters, these magic-users usually complement the physical strength of other ... 364-367 Barton 2007a, p. 1 Barton 2008, p. 13 Justin Leeper (17 December 2004). "Pathway to Glory". GameSpy. Retrieved 19 May ...

https://en.wikipedia.org/wiki/Role-playing_video_game

The Way itself may be regarded as the highest level pathway of the street, and precautions have, by the erection of a dwarf ... It was the epitome of the High Victorian style, complemented by the surroundings new gardens. Its giant dome was 30 metres (100 ... The Tarpeian Way has an unusually dramatic, classical association through its name with the famous rock in Rome from which ... It exhibits Picturesque, naturalistic and Gardenesque design traits in its curvilinear pathway system with beds at junctions, ...

https://en.wikipedia.org/wiki/Royal_Botanic_Garden,_Sydney

John H. and his uncle, George S. Parks, opened the department store in 1884 to complement their lumber business. John H. Parks ... Built at the peak of Iron River's prosperity, the school was the most highly developed Neo-Classical structure in Iron County. ... "Iron County Heritage Trail Pathway Study: Iron County, Michigan" (PDF). Western U.P. Planning & Development Region. Retrieved ... The building is a three-story rectangular Neo-Classical structure built of red brick and sitting on a sandstone foundation. ...

https://en.wikipedia.org/wiki/Iron_County_MRA

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 ...

https://en.wikipedia.org/wiki/Diffuse_proliferative_nephritis

... and trigger the classical complement pathway. Complement activation leads to the recruitment of inflammatory cells (monocytes ... Antibody binding to cell surface receptors and altering its activity Activation of the complement pathway. Antibody-dependent ... Cell depletion or destruction without inflammation Inflammation mediated by complement or Fc receptor Cellular dysfunction by ...

https://en.wikipedia.org/wiki/Hypersensitivity

... complementing the existing subway-type MARTA train service for the area. North Beltline Trail (Under construction) Chastain ... Atlanta Classical Academy. Local private schools include the Atlanta International School, the Atlanta Speech School, Christ ... Park Trail Mountain To River Trail Paces Ferry Trail PATH400, which provides a 5.2 mile pathway throughout the heart of ...

https://en.wikipedia.org/wiki/Buckhead

Thus in his view Afrikaans is neither a creole nor a direct descendant of Dutch, but a fusion of two transmission pathways. ... Due to the early settlement of a Cape Malay community in Cape Town, who are now known as Coloureds, numerous Classical Malay ... nie or niet was needed to complement the -ne. With time the -ne disappeared in most Dutch dialects. The double negative ...

https://en.wikipedia.org/wiki/Afrikaans

In classical Hodgkin lymphoma, plasma miR-21, miR-494, and miR-1973 are promising disease response biomarkers. Circulating ... A new strategy for tumor treatment is to inhibit tumor cell proliferation by repairing the defective miRNA pathway in tumors. ... January 2020). "MirGeneDB 2.0: the metazoan microRNA complement". Nucleic Acids Research. 48 (D1): D132-D141. doi:10.1093/nar/ ... Winter J, Jung S, Keller S, Gregory RI, Diederichs S (March 2009). "Many roads to maturity: microRNA biogenesis pathways and ...

https://en.wikipedia.org/wiki/MicroRNA

The three different complement systems are classical, alternative and lectin. Classical: starts when antibody binds to bacteria ... Croize J, Arvieux J, Berche P, Colomb MG (December 1993). "Activation of the human complement alternative pathway by Listeria ... The complement system is a biochemical cascade of the immune system that helps, or "complements", the ability of antibodies to ... Both pathways converge in the recruitment and activation of the IKKε/TBK-1 complex, inducing dimerization of transcription ...

https://en.wikipedia.org/wiki/Innate_immune_system

... where the genes encode components of a metabolic pathway or network, developmental pathway, signalling pathway or transcription ... In classical genetics, if genes A and B are mutated, and each mutation by itself produces a unique phenotype but the two ... That is, each mutant alone upon infection cannot produce viable progeny, but upon mixed infection with two complementing ... This occurs when genes do not interact with each other, for example by acting through different metabolic pathways. Simply, ...

https://en.wikipedia.org/wiki/Epistasis

These models state that each IR monomer possesses 2 insulin binding sites; site 1, which binds to the 'classical' binding ... The activated IRS-1 initiates the signal transduction pathway and binds to phosphoinositide 3-kinase (PI3K), in turn causing ... where this is also true for each monomers mirrored complement (the opposite side of the ectodomain structure). Current ... Lopaczynski W (1999). "Differential regulation of signaling pathways for insulin and insulin-like growth factor I". Acta ...

https://en.wikipedia.org/wiki/Insulin_receptor

The classical method of detecting this is the Chromium-51 [51Cr] release assay; the Sulfur-35 [35S] release assay is a little ... As NK cells are not themselves specific to certain pathways of immune control, they are utilized a majority of the time in ADCC ... ADCC is independent of the immune complement system that also lyses targets but does not require any other cell. ADCC requires ... Afucosylated monoclonal antibodies Complement-dependent cytotoxicity Hashimoto, G.; Wright, P. F.; Karzon, D. T. (1983-11-01 ...

https://en.wikipedia.org/wiki/Antibody-dependent_cellular_cytotoxicity

Others argue that faith and science can be integrated and complement each other. In his 1874 book titled History of the ... Youssef Chouhoud (2016). "Modern Pathways to Doubt in Islam". Yaqeen Institute for Islamic Research. Retrieved October 26, 2016 ... and other modern and classical Islamic scholars have at times instead argued that the pair evolved naturally from a common ... Another scholar, Muneer Al-Ali, argues that faith and science can be integrated and complement each other in explaining the ...

https://en.wikipedia.org/wiki/Islamic_views_on_evolution

The RhoA pathway promotes assembly of the actin-myosin ring by two main effectors. First, RhoA stimulates nucleation of ... It thereby ensures that chromosome number and complement are maintained from one generation to the next and that, except in ... New Latin from Classical Latin and Ancient Greek, reflecting "cell" and kinesis ("motion, movement"). It was coined by Charles ... cells is ensured through the tight temporal coordination of the above individual events by molecular signaling pathways. Animal ...

https://en.wikipedia.org/wiki/Cytokinesis

Synaptic plasticity is caused by changes in use of the synaptic pathway, namely, the frequency of synaptic potentials and the ... demonstrated that eyeblink conditioning (EBC), a form of classical conditioning for studying neural structures and mechanisms ... Intrinsic plasticity contributes to encoding memory and complements other forms of activity-dependent plasticity including ... Drugs of abuse typically affect the mesolimbic system, or more specifically, the reward pathway of the nervous system. Amongst ...

https://en.wikipedia.org/wiki/Nonsynaptic_plasticity

Adiponectin (adipocyte complement-related protein of 30 kDa) is a cytokine produced by adipose tissue and its deficiency is ... Unlike classical cadherins, which are necessary for cell-cell adhesion, dynamic regulation of morphogenetic processes in ... survival pathway regulator), resulting in reduced levels of caspase activation and increased survival after exposure to ... activate small GTPases and the beta-catenin/Wnt pathway, and play important roles in dynamic cytoskeleton reorganization, the ...

https://en.wikipedia.org/wiki/T-cadherin

Loeb Classical Library 49, 50, 182, 196, 211, 223, 241, 267. Vol. 1. Translated by Jones, Horace Leonard; Sterrett, John Robert ... These maps of finds remain valid today, but they have been complemented with additional finds that cover a wider area, ... although its evolutionary pathways remains uncertain.[citation needed] According to one scenario, proto-Thracian populations ... Crossland, R.A. (1982). "Linguistic problems of the Balkan area in the late prehistoric and early Classical period". In ...

https://en.wikipedia.org/wiki/Dacian_language

Also the ruler of Pathways and Choices. - South or descending Node. Also the ruler of Karma and the Past. In astrology, " ... the classical source of copper. "To optimise the chances of finding even remote relationships between date of birth and ... but the opposition can work well if the two parts of the aspect are made to complement each other in a synthesis. - Trine 120°( ... being the brightest planets were given rulership of the brightest months of the year and Saturn the coldest furthest classical ...

https://en.wikipedia.org/wiki/Western_astrology

IgG activates all the classical pathway of the complement system, a cascade of immune protein production that results in ... However, both human and mouse antibodies have different abilities to fix complement and to bind to Fc receptors.[citation ... According to Finkelman, there are two pathways of systemic anaphylaxis: antigens can cause systemic anaphylaxis in mice through ... In the alternative pathway antigens form complexes with IgG, which then cross-link macrophage receptor FcγRIII and stimulates ...

https://en.wikipedia.org/wiki/Immunoglobulin_G

Green CR, Cowan P, Elk R, O'Neil KM, Rasmussen AL (June 2015). "National Institutes of Health Pathways to Prevention Workshop: ... In long-term psychoses, CBT is used to complement medication and is adapted to meet individual needs. Interventions ... that influenced Hans Eysenck and Arnold Lazarus to develop new behavioral therapy techniques based on classical conditioning. ... however a National Institutes of Health Pathways to Prevention Workshop stated that in respect of improving treatment options ...

https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy

Alternatives Pathways to Civilization. Moscow: Logos, 2000 . Sociobiology of Ritual and Group Identity: A Homology of Animal ... One of his particular contributions in this field is connected with the classical anthropological issue of determinants of ... while a subjectivist history of consciousness is a necessary complement to the "post-Axial" condition. Korotayev succeeds in ...

https://en.wikipedia.org/wiki/Andrey_Korotayev

Some examples include: Classical mechanics The laws of classical mechanics can be said to emerge as a limiting case from the ... Architects may not design all the pathways of a complex of buildings. Instead they might let usage patterns emerge and then ... a symbol of the unity underlying complements like open/shut, peace/war) to illustrate how the two perspectives (strong vs. weak ... In classical dynamics, a snapshot of the instantaneous momenta of a large number of particles at equilibrium is sufficient to ...

https://en.wikipedia.org/wiki/Emergence

A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions ... ACTIVATION OF THE CLASSICAL COMPLEMENT PATHWAY. A complement cascade similar to that of the alternative pathway can be ... The functions of the classical complement pathway are similar to those described for the alternative pathway, i.e. opsonization ... where this pathway is also compared to the alternative pathway. In the classical pathway the initiating step is the specific ...

https://www.pharmacy180.com/article/activation-of-the-classical-complement-pathway-498/

involved_in complement activation, classical pathway IBA Inferred from Biological aspect of Ancestor. more info ... Physicochemical and functional characterization of the C1r subunit of the first complement component. Ziccardi RJ, et al. J ... involved_in B cell receptor signaling pathway IBA Inferred from Biological aspect of Ancestor. more info ... involved_in B cell receptor signaling pathway IC Inferred by Curator. more info ...

https://www.ncbi.nlm.nih.gov/gene/28834

Killing of Parasites by the Alternative Pathway and Requirement of IgG for Classical Pathway Activation1 Ferrucio Santoro; ... were able to initiate complement activation also through the classical pathway (CP). However, the CP does not appear to play a ... Killing of Parasites by the Alternative Pathway and Requirement of IgG for Classical Pathway Activation1. J Immunol 1 October ... The following data indicate that this action is dependent on the activation of the alternative complement pathway (AP): a) the ...

https://journals.aai.org/jimmunol/article/123/4/1551/12461/Activation-of-Complement-by-Schistosoma-Mansoni

Complement (801). * Classical Pathway (396). * Regulatory (175). * MAC (126). * Alternative Pathway (117). ...

https://www.abcam.com/products?selected.researchAreas=Immunology--Innate+Immunity--Complement

Here, we show that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice, a lupus-prone murine ... 3d) and the classical complement pathway (KEGG term the complement and coagulation cascades, Fig. 2c). In the above category ... These indicated that the classical complement-dependent pathway may not be essential for C1q label-based synaptic removal in ... and the classical complement pathway (C1qa, which encodes C1QA; C6, which encodes C6; C1s, which encodes C1S; and Cfp, which ...

https://www.nature.com/articles/s41392-021-00867-y?error=cookies_not_supported&code=f3315543-a0fe-402e-8108-67dbd0f21d4e

C1s cleaves C4, which is the first step in activating the classical complement pathway. It is indicated treatment of hemolysis ... Adcetris (brentuximab vedotin) - Indication for previously untreated high-risk classical Hodgkin lymphoma (cHL) in combination ... triggering signaling pathways that control cell differentiation, proliferation, migration, and survival. It is indicated to ... that selectively targets and inhibits complement protein component 1, s subcomponent (C1s), a serine protease. ...

https://www.medscape.com/viewarticle/988610

The Classical pathway of complement activation. C1 is the first protein activated in the classical pathway, the C1 protein ... The complement protein cascade is the same for the classical pathway, alternative pathway, and lectin pathway beginning with ... Complement component C3, in the classical pathway, is split by ________.. C2aC4b Which of the following occurs first, setting ... All of the following are true of the classical pathway of complement activation C5b joins C6, C7, C8, and C9 to form the ...

https://www.studystack.com/flashcard-485339

Name: complement component 2 (within H-2S). Synonyms: classical-complement pathway C3/C5 convertase ...

https://www.mmrrc.org/catalog/sds.php?mmrrc_id=38808

The data also showed a sustained improvement in fatigue scores, and a durable decline in classical component pathway activity. ... "Thus, an alternative treatment that is non-cytotoxic, rapid, and durable in controlling classical complement-mediated hemolysis ... which activates the classical component pathway, leading to hemolysis. The ongoing CARDINAL study is a prospective, single-arm ... 1-year interim results of the ongoing CARDINAL study demonstrate continued inhibition of the classical component pathway at C1s ...

https://www.ajmc.com/view/interim-results-from-cardinal-trial-show-sutimlimab-effective-in-cad

We demonstrated that Hsp60 complexed with specific antibodies induces a strong classical pathway (CP) activation. Here, we show ... No complement activation was found in the case of human Hsp90. Our data further support the hypothesis that chaperones may ... Complement-like molecules and primitive immune cells appeared together early in evolution. A joint action of these arms of ... GA induced the degradation of AR through the proteasomal pathway. AR in cells treated with proteasomal inhibitor lactacystin, ...

https://bioone.org/journals/cell-stress-and-chaperones/volume-7/issue-1

KSHV Kaposin to classical/Lectin pathway of complement cascade, C4b breakdown. N01528 KSHV Kaposin to alternative pathway of ... Kaposis sarcoma-associated herpes virus complement control protein: KCP--complement inhibition and more. ... KSHV vBCL2 to crosstalk between extrinsic and intrinsic apoptotic pathways. N00165 KSHV vIAP to crosstalk between extrinsic and ... KSHV non-structural membrane proteins involved in the activation of intracellular signaling pathways and the pathogenesis of ...

https://www.genome.jp/dbget-bin/www_bget?pathway+hsa05167

... and immunochemical assays that measure total complement components of the classical and alternative activation pathways (CH50, ... Assessment of complement components and function. *Functional ...

https://www.cdc.gov/genomics/events/conference/pi/pimeeting3.htm

Classical and Lectin Complement Pathway Activity in Polyneuropathy Associated with IgM Monoclonal Gammopathy ... Anti-MAG Autoantibodies ELISA Citations: Stork AC et al.; Classical and lectin complement pathway activity in polyneuropathy ...

https://www.buhlmannlabs.ch/tag/anti-mag-antibodies-de/page/4/

Surface mediated immune complement activation can be detected by a variety of antibody utilizing methods such as ELISA, ... Experiments in EGTA-serum showed that anticoagulants interfered directly with both the classical and alternative pathways. ... fondaparinux and sodium citrate affected the binding of anti-complement factor 3c (anti-C3c) on a model complement activator ... Surface mediated immune complement activation can be detected by a variety of antibody utilizing methods such as ELISA, ...

https://pubmed.ncbi.nlm.nih.gov/18006286/

Enjaymo, targeting C1s in the classical complement pathway. Enjaymo is a humanized monoclonal antibody that is designed to ... selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. By blocking ... Enjaymo does not inhibit the lectin and alternative pathways.. Enjaymo Phase 3 pivotal CARDINAL study results supporting ... we have a treatment that targets complement-mediated hemolysis, which is the underlying cause of the red blood cell destruction ...

https://www.sanofi.com/en/media-room/press-releases/2022/2022-02-04-22-00-00-2379517

Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model.. PLoS One. 2021 ... Alantolactone reduced neuron injury via activating PI3K/Akt signaling pathway after subarachnoid hemorrhage in rats.. PLoS One ... ischemic injury after stroke and promotes angiogenesis via activation of EPO mediated Src and VEGF signaling pathways.. PLoS ... ameliorates short-term memory impairment by suppressing cerebral ischemia-induced inflammation via MAPK pathway.. PLoS One. ...

https://amedeo.com/medicine/cvd/j1020.htm

Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma. ... RPE cells constitutively express many complement pathway components that can be upregulated by both macrophages and microglia ... There are three main pathways that are involved in complement activation; all lead to C3 activation and the subsequent ... The Preiss-Handler and the salvage pathways are the other sources of NAD+ [37,38,39]. The Preiss-Handler pathway comprises ...

https://www.mdpi.com/2072-6643/12/9/2871

It has been shown that M. bovis BCG may activate the three pathways of complement: the classical pathway by binding to the C1q ... Mtb can activate the classical and alternate pathways by binding C3. This enables complement to perform its major functions- ... Carroll MV, Lack N, SimE et al, Multiple routes of complement activation by Mycobacterium bovis BCG. Mol Immunol 2009; 46:3367. ... The complement is the humoral arm of the innate immune system. ... or L-ficolin and the alternate pathway through the deposition ...

https://www.intechopen.com/chapters/43706

They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE. ... The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. ... Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections. ... MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are ...

https://connects.catalyst.harvard.edu/Profiles/display/Concept/Mannose-Binding%20Protein-Associated%20Serine%20Proteases

Serum lectin with known structure activates complement through the classical pathway. J. Biol. Chem ... 7C), and enter terminal differentiation pathways to form the dorsal ganglion, pharynx, digestive tract and other organs and ... D) Respective progenitor cells enter the terminal differentiation pathways to become nerves, gastric epithelium, pharyngeal ... D) Respective progenitor cells enter the terminal differentiation pathways to become nerves, gastric epithelium, pharyngeal ...

https://journals.biologists.com/dev/article/128/17/3339/41347/A-novel-C-type-lectin-regulating-cell-growth-cell?searchresult=1

IgG or IgM can bind to C1q, but IgA cannot, therefore IgA does not activate the classical complement pathway.[18] ... 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 ...

https://en.m.wikipedia.org/wiki/Antibody

The chelation tests indicated that complement activation occurred via the alternative pathway, rather than via the classical ... The authors suggest that activation of the alternative complement pathway by grain dusts may be a factor in the respiratory ... complement pathway. Dust activity in NHS correlated with that in C4D serum. No relationship was found between endotoxin ... The dusts also were tested with guinea pig serum that was deficient in the fourth component of complement (C4D). The dust and ...

http://www2a.cdc.gov/nioshtic-2/BuildQyr.asp?s1=agricultur%2A+or+farm%2A&f1=%2A&Adv=0&terms=1&PageNo=643&RecNo=6429&View=f&

The C2 gene provides instructions for making the complement component 2 protein. Learn about this gene and related health ... Complement component C2, inhibiting a latent serine protease in the classical pathway of complement activation. Biochemistry. ... When a foreign invader is detected, the complement pathway is turned on (activated) and the complement component 2 protein ... Complement component 2 deficiency. At least five mutations in the C2 gene have been found to cause complement component 2 ...

https://medlineplus.gov/genetics/gene/c2/

Mannose-Binding Lectin Complement Pathway 16% * Classical Complement Pathway 14% * Islet Amyloid Polypeptide 14% ... The hijackers guide to escaping complement: Lessons learned from pathogens. Ermert, D., Ram, S. & Laabei, M., 2019 Oct, In: ...

https://portal.research.lu.se/en/persons/david-ermert/publications/?type=%2Fdk%2Fatira%2Fpure%2Fresearchoutput%2Fresearchoutputtypes%2Fcontributiontojournal%2Fsystematicreview&ordering=type&descending=false

Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in ... Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in ... Complement C1, the first component of the complement system and activator of the classical pathway, is a complex of three ... C1q activates the classical pathway by binding to IgG-antigen complexes. However, pertinent data have recognized that C1q ...

https://www.frontiersin.org/articles/10.3389/fimmu.2020.01292/full

National Jewish Health Complement Laboratory performs a variety of complement activation tests for preclinical and clinical ... Complement Diagnostic Tests. * CH50 (classical pathway) and AH50 (alternative pathway) screening for total complement function ... Complement Preclinical & Clinical Testing Services. * Clinical, in-vitro, and in-vivo complement studies, including access to a ... The complement system is the innate immune systems first line of defense against infection. When the complement system becomes ...

https://www.nationaljewish.org/for-professionals/diagnostic-testing/adx/our-laboratories/complement-laboratory

10 Hypoxemia and acidosis facilitate the NO3−-NO2−-NO pathway, thereby complementing the classical pathway, during exercise.10 ... The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7(2):156-167. ... However, NO can additionally be synthesized from an O2-and NOS-independent pathway.10 ...

https://www.dovepress.com/dietary-beetroot-juice-effects-on-physical-performance-in-copd-patient-peer-reviewed-fulltext-article-COPD

C resulting in agglutination and classical complement pathway activation.9 The thermal amplitude describes the temperature ... Promising studies have examined proximal complement inhibition to inhibit extravascular hemolysis. Complement inhibition ... 24 Use of the C5 inhibitor eculizumab rapidly abrogates the terminal complement pathway with a short time to response. However ... In a phase III study of anti-C1s, sutimlimab, versus best supportive care, it was seen that the complement inhibitor rapidly ...

https://haematologica.org/article/view/haematol.2022.280953

Next Generation Complement Therapeutics; with a focus on current market landscape and future growth opportunities ... Target Pathway (Alternate, Classical, Lectin and Terminal Pathway), Type of Therapy (Monotherapy and Combination Therapy), ... Next Generation Complement Therapeutics Market: Distribution by Target Disease Indication (Atypical Hemolytic Uremic Syndrome, ...

https://www.rootsanalysis.com/reports/next-generation-complement-therapeutics-market/free-insights.html

The host proteins that serve key regulatory functions within the alternative pathway (DAF, CR1 factor I, CD59) also serve similar functions within the classical pathway. (pharmacy180.com)
The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. (medlineplus.gov)
Together, these proteins form a complex called C3 convertase, which triggers further activation of the pathway, allowing the proteins of the complement system to participate in an immune response. (medlineplus.gov)
Complement C1, the first component of the complement system and activator of the classical pathway, is a complex of three proteins: C1q, C1r, and C1s ( 7 , 8 ). (frontiersin.org)
Here, the complement proteins interact with other endogenous molecules to keep microbes from entering the parenteral tissues. (helsinki.fi)
One of the mucosal proteins known to interact with the early complement components of both the classical and the lectin pathway is the salivary scavenger and agglutinin (SALSA). (helsinki.fi)
The complement system consists of a number of small proteins found in the blood, made by the liver. (searchandrestore.com)
Complement is a system of plasma proteins that can be activated directly by pathogens or indirectly by pathogen-bound antibody, leading to a cascade of reactions that occurs on the surface of pathogens and generates active components with various effector functions. (searchandrestore.com)
The complement system can be activated when antibodies, which are proteins produced by cells in the immune system, bind to potentially harmful substances, or antigens. (searchandrestore.com)
Complement, in immunology, a complex system of more than 30 proteins that act in concert to help eliminate infectious microorganisms. (searchandrestore.com)
The complement system consists of a number of small proteins that are synthesized by the liver, and circulate in the blood as inactive precursors. (searchandrestore.com)
Up-regulation of genes encoding acute phase proteins, complement, and lectins indicated mild inflammation but without characteristic features of viral or bacterial infections. (nofima.no)
In IgA nephropathy, complement proteins in the circulation have also been studied and found to have predictive relevance. (alliedacademies.org)
Vav proteins have guanine exchange activity in converting GDP to GTP on proteins such as Rac1, Cdc42 and RhoA to stimulate intracellular signaling pathways. (bvsalud.org)
Taken together, the results suggest that PspA-Pd fusion proteins comprise a promising vaccine strategy, able to increase the immune response mediated by cross-reactive antibodies and complement deposition to heterologous strains, and to confer protection against fatal challenge. (cdc.gov)
This review summarizes some immunological factors involved in the development and control of this oral disease, such as: the participation of inflammatory cells in local inflammation, the synthesis of chemotaxis proteins with activation of the complement system and a range of antimicrobial peptides, such as defensins, cathelicidin and saposins. (bvsalud.org)

The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. (harvard.edu)
It inhibits the lectin pathway of complement activation, an early and potent driver of SARS COV-2-triggered inflammation, which, in severe disease, culminates in hypocomplementemia with increased secondary infection risk and in a devastating cytokine storm. (morningstar.com)

The C1s subunit then enzymically cleaves the bound C2a to generate on the membrane a new complex termed C4b2b, which is the C3 convertase of the classical pathway. (pharmacy180.com)
This C3 convertase molecule is distinct from that within the alternative pathway, but it is from this point onwards that parallels can be drawn between the two cascades. (pharmacy180.com)
Without this protein to form C3 convertase, activation of the complement system is stalled. (medlineplus.gov)
The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation. (medlineplus.gov)
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 . (bvsalud.org)
These structural changes allow Factors B (FB) and D (FD) to bind to the bioactive form of C3, C3(H2 O), resulting in the formation of fluid phase C3 convertase and therefore enhancing complement activation. (alliedacademies.org)
It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a). (nih.gov)

A further complement protein, C2, binds to this membrane complex to give C4b2. (pharmacy180.com)

The antibodies that activate the classical complement pathway are IgM and IgG. (pharmacy180.com)
The complement system helps or "complements" the ability of antibodies and phagocytic cells to clear pathogens from an organism. (searchandrestore.com)
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, promote inflammation, and attack the pathogen's cell membrane. (searchandrestore.com)
When antibodies attach to antigens, this can activate the complement system's classical pathway. (searchandrestore.com)
In cold agglutinin disease, certain abnormal bone marrow cells produce antibodies called cold agglutinins, which activate a part of the immune system known as the complement pathway. (understandingcad.com)
Synergistic complement lysis by monoclonal antibodies to the human leukocyte common antigen requires both the classical and alternative pathways. (ox.ac.uk)
Importance of antigen specificity for complement-mediated lysis by monoclonal antibodies. (ox.ac.uk)

In the present work we investigated how the common anticoagulants heparin, dalteparin, fondaparinux and sodium citrate affected the binding of anti-complement factor 3c (anti-C3c) on a model complement activator surface, immobilised IgG, after incubation in human blood serum. (nih.gov)
MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked. (harvard.edu)
The rate of conversion of the third component of complement (C3PA) to its activator form (C3A) was measured, along with total hemolytic activity of complement. (cdc.gov)

Experiments in EGTA-serum showed that anticoagulants interfered directly with both the classical and alternative pathways. (nih.gov)
Control C3a-des arg ELISA measurements show that the lowered antibody surface binding was not a result of complement depletion in serum. (nih.gov)
Serum serine proteases which participate in COMPLEMENT ACTIVATION. (harvard.edu)
The dusts also were tested with guinea pig serum that was deficient in the fourth component of complement (C4D). (cdc.gov)
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX . (bvsalud.org)
fungal wall- Zymosan, Viral NA's and foreign DNA Receptors for AB's and serum glycoproteins Complement also present. (kupdf.net)

18 Genetic or pharmacologic blockade of the complement pathway can prevent synaptic stripping and alleviate multiple age- and inflammation-related disorders. (nature.com)
have done is to show that pharmacological blockade of the complement system is therapeutic in mouse models of Alzheimer's. (alzforum.org)

Once this occurs, a complement protein termed C1 (which comprises a single C1q subunit, two C1r subunits and two C1s subunits) binds to adjacent Fc domains in the antibody-antigen complex. (pharmacy180.com)
When a foreign invader is detected, the complement pathway is turned on (activated) and the complement component 2 protein attaches (binds) to a similar protein called complement component 4. (medlineplus.gov)
C1q has two classical cell surface receptors (C1qRs): cC1qR binds to the collagen "stalks" tail, whereas gC1qR binds to the globular "heads" ( 11 ). (frontiersin.org)
The classical pathway is activated when C1q binds to antibody attached to antigen, activating C1r and C1s, which cleave C4 and C2. (searchandrestore.com)

CAD is a type of autoimmune hemolytic anemia in which patients experience chronic hemolysis brought about by the activation of the classical component pathway, said corresponding author Alexander Röth, PhD, of the University of Duisburg-Essen, in Germany, and colleagues. (ajmc.com)
1. Berentsen S. Complement activation and inhibition in autoimmune hemolytic anemia: focus on cold agglutinin disease. (understandingcad.com)

A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions. (pharmacy180.com)
By blocking C1s, Enjaymo inhibits the activation of the complement cascade in the immune system and inhibits C1-activated hemolysis in CAD to prevent the abnormal destruction of healthy red blood cells. (sanofi.com)
It had already been long known that classical complement cascade is profoundly overactivated in Alzheimer's disease brains. (alzforum.org)
Not only did we show that the classical cascade mediated synapse pruning, we showed that the classical complement pathway became reactivated again as the earliest sign of pathology in the neurodegenerative disease glaucoma. (alzforum.org)
So Beth and I proposed that C1q and the classical complement cascade would be a universal driver of synapse loss in many neurodegenerative diseases, including Alzheimer's. (alzforum.org)
I became so enthusiastic about this that four years ago I co-founded a company, Annexon Biosciences, that has made the first therapeutic that targets C1q and blocks the classical complement cascade. (alzforum.org)
have now provided further direct evidence for a role of the complement cascade component C3 in driving synapse loss in mouse models of Alzheimer's. (alzforum.org)
Because there are not yet any good drugs to block the classical complement cascade, they could only test an already-established C3aR blocking drug. (alzforum.org)
The problem with this approach is that it is very indirect, because C3aR is not required for the classical complement cascade to mediate synapse loss. (alzforum.org)
I think the critical question now is whether direct pharmacological blockers of C1q and the classical complement cascade will be neuroprotective. (alzforum.org)
These findings point to the complement cascade as a viable therapy target for chronic renal disease. (alliedacademies.org)

Thus, an alternative treatment that is non-cytotoxic, rapid, and durable in controlling classical complement-mediated hemolysis and its clinical manifestations in CAD patients is needed," the authors said. (ajmc.com)
Sutimlimab is a humanized monoclonal antibody targeting the complement-specific serine protease C1s, which activates the classical component pathway, leading to hemolysis. (ajmc.com)
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, potentially life-threatening disease characterized by complement-mediated hemolysis with or without hemoglobinuria, an increased susceptibility to thrombotic episodes and/or some degree of bone marrow dysfunction. (globenewswire.com)
Complement activity can activate C5, leading to intravascular hemolysis and chronic inflammation. (understandingcad.com)
The complement inhibitor, sutimlimab, was approved by the FDA in February 2022 to decrease RBC transfusion causes by hemolysis in patients with cold agglutinin disease. (medscape.com)
Inhibition of the classical complement pathway may decrease hemolysis in patients with cold agglutinin disease. (medscape.com)

The classical pathway can additionally lead to complement protein deposition on insoluble antibody- antigen immune complexes circulating within blood, and in doing so promote the clearance of such potentially harmful complexes by Kupffer cells of the liver. (pharmacy180.com)
Enjaymo is a humanized monoclonal antibody that is designed to selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. (sanofi.com)
Surface mediated immune complement activation can be detected by a variety of antibody utilizing methods such as ELISA, fluorescence- or radiolabelling techniques, QCM, and ellipsometry. (nih.gov)
This protein helps regulate a part of the body's immune response known as the complement system. (medlineplus.gov)
The complement system, a component of the innate immune system, has traditionally been considered to be an ancient defense mechanism that resists a broad range of invasive pathogens. (frontiersin.org)
The complement system is the innate immune system's first line of defense against infection. (nationaljewish.org)
Some strains express a polysaccharide capsule, a principal virulence factor that protects bacteria from immune defenses, e.g., complement-dependent bacteriolysis. (cdc.gov)
Ehrlich, therefore, named this heat-labile component "complement", because it is something in the blood that "complements" the cells of the immune system. (searchandrestore.com)
Genes encoding products involved in complement control and interaction with immune complexes are found within these regions. (alliedacademies.org)

As a result, the complement system's ability to fight infections is diminished. (medlineplus.gov)

However, in contrast to the alternative pathway the activation step in the classical pathway requires specific antibody-antigen interactions. (pharmacy180.com)
Specifically, it is a fully human IgG4 monoclonal antibody against MASP-2, the effector enzyme of the lectin pathway of complement. (morningstar.com)
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. (bvsalud.org)
Recent case reports demonstrating the efficacy of the humanised anti-C5 monoclonal antibody eculizumab support this notion, but more research into the involvement of complement in IgA nephropathy is needed to guide future treatment strategies. (alliedacademies.org)
Sutimlimab is an immunoglobulin G (IgG), subclass 4 (IgG4) monoclonal antibody (mAb) that selectively targets and inhibits complement protein component 1, s subcomponent (C1s), a serine protease. (medscape.com)

Usually, C1q activates the classical pathway by binding to IgG-antigen complexes. (frontiersin.org)

Complement component C2, inhibiting a latent serine protease in the classical pathway of complement activation. (medlineplus.gov)

and WALTHAM, Mass., Dec. 02, 2018 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals Inc. (Nasdaq:APLS), a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds to treat disease through the inhibition of the complement system, today announced interim data from its Phase 1b study of APL-2 in treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH). (globenewswire.com)

Key steps in the activation of the classical pathway are shown in Figure 9.7, where this pathway is also compared to the alternative pathway. (pharmacy180.com)
The functions of the classical complement pathway are similar to those described for the alternative pathway, i.e. opsonization, leucocyte activation and membrane lysis of target cells. (pharmacy180.com)
The presence of two complement pathways provides for rapid (alternative) and specific (classical) activation of a key defence mechanism, and offers greater protection against the development of microbial resistance mechanisms. (pharmacy180.com)
Enjaymo does not inhibit the lectin and alternative pathways. (sanofi.com)
The chelation tests indicated that complement activation occurred via the alternative pathway, rather than via the classical complement pathway. (cdc.gov)
The authors suggest that activation of the alternative complement pathway by grain dusts may be a factor in the respiratory response of exposed workers. (cdc.gov)
Complement can be activated through three pathways: classical, lectin, and alternative. (searchandrestore.com)
In renal biopsy specimens, markers indicating the activation of the alternative and mannan-binding lectin (MBL) pathways are linked to disease activity and portend a worse renal outcome. (alliedacademies.org)
Complement is found in the bloodstream in a physiologically inactive state and can be triggered by three mechanisms: the classical (CP), lectin (LP), and alternative (AP) pathways (AP). (alliedacademies.org)

Candidate genes within 250,000 base pairs of significant SNPs were identified to determine biological pathways associated with AMIR and CMIR. (biomedcentral.com)
Candidate genes included those within the bovine Major Histocompatability Complex such as BoLA-DQ, BoLA-DR and the non-classical BoLA-NC1 for AMIR and BoLA-DQ for CMIR, the complement system including C2 and C4 for AMIR and C1q for CMIR, and cytokines including IL-17A, IL17F for AMIR and IL-17RA for CMIR and tumor necrosis factor for both AMIR and CMIR. (biomedcentral.com)

Physicochemical and functional characterization of the C1r subunit of the first complement component. (nih.gov)
The data also showed a sustained improvement in fatigue scores, and a durable decline in classical component pathway activity. (ajmc.com)
The C2 gene provides instructions for making the complement component 2 protein. (medlineplus.gov)
At least five mutations in the C2 gene have been found to cause complement component 2 deficiency. (medlineplus.gov)
More than 90 percent of people with complement component 2 deficiency have a mutation that deletes 28 DNA building blocks (nucleotides) from the C2 gene. (medlineplus.gov)
This mutation prevents the production of any complement component 2 protein. (medlineplus.gov)
It is unclear how complement component 2 deficiency leads to increased susceptibility to autoimmune disorders. (medlineplus.gov)
It is likely that other factors, both genetic and environmental, play a role in the variability of the signs and symptoms of complement component 2 deficiency. (medlineplus.gov)

Biopharmaceuticals or medical devices can cause off-target complement activation that leads to destructive inflammation. (nationaljewish.org)
Narsoplimab was selected for inclusion in the I-SPY COVID Trial because of its demonstrated ability to inhibit complement activation, inflammation, and coagulation, the three components that characterize COVID-19. (morningstar.com)
Specifically, the complement system causes the lysis (bursting) of foreign and infected cells, the phagocytosis (ingestion) of foreign particles and cell debris, and the inflammation of surrounding tissue. (searchandrestore.com)

Additionally, Vav/Rac/RhoA signaling pathways may present tractable targets for therapeutic intervention or molecular rationale for disease severity in CZS. (bvsalud.org)
The AKT and MAPK pathways may be potential molecular targets for the treatment of endometriosis. (webpediatrica.com)

The three main consequences of complement activation are opsonization of pathogens, the recruitment of inflammatory cells, and direct killing of pathogens. (searchandrestore.com)

If not controlled, this process can rapidly amplify, leading to the activation of the terminal pathway, which is marked by the release of C5a and the creation of the membrane attack complex (MAC - C5b9). (alliedacademies.org)

Several inherited deficiencies in the complement system occur in humans. (studystack.com)
Researchers speculate that the dysfunctional complement system is unable to distinguish what it should attack, and it sometimes attacks normal tissues, leading to autoimmunity. (medlineplus.gov)
Alternatively, the dysfunctional complement system may perform partial attacks on invading molecules, which leaves behind foreign fragments that are difficult to distinguish from the body's tissues, so the complement system sometimes attacks the body's own cells. (medlineplus.gov)
Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in MM patients. (frontiersin.org)
However, few studies actually focus on the immunomodulatory effects of the complement system on MM. (frontiersin.org)
However, pertinent data have recognized that C1q possesses various independent functions associated with cancer progression that are not directly related to the complement system ( 10 ). (frontiersin.org)
When the complement system becomes inappropriately activated - or when it does not activate as it should - serious health problems can result. (nationaljewish.org)
Through these interactions SALSA regulates activation of the complement system. (helsinki.fi)
What is the main function of the complement system? (searchandrestore.com)
What is the complement system in biology? (searchandrestore.com)
Why is the complement system important? (searchandrestore.com)
What triggers complement system? (searchandrestore.com)
Why is it called complement system? (searchandrestore.com)
Scheme of the complement system. (searchandrestore.com)
How can the complement system be activated? (searchandrestore.com)
What is the definition of complement system? (searchandrestore.com)
What does the complement system contain? (searchandrestore.com)
The complement system is a key player in innate immunity as well as a powerful link between innate and adaptive immunity. (alliedacademies.org)
In physiological situations, the AP is always active at low levels and is responsible for complement system functioning. (alliedacademies.org)
Phototoxic reaction is a known feature of EPP at least in part triggered by the oxidative status, complement system activation, and mast cell response. (elsevier.com)
Peritoneal stomata constitute the principal pathways for the drainage of intraperitoneal contents from the PERITONEAL CAVITY to the LYMPHATIC SYSTEM. (bvsalud.org)

Synergy and interference in complement-mediated lysis. (ox.ac.uk)

The researchers provide further evidence for the role of C3 and complement in neuronal function and dysfunction in Alzheimer's disease as well as the complement pathway as a potential therapeutic target in AD and other neurodegenerative diseases. (alzforum.org)
This paper argues that some of the strong beliefs held by humans have deep biological roots in our evolutionary past, and the neuronal pathways and structures that support them can be found in other species. (bvsalud.org)

Advanced Diagnostic Laboratories has a comprehensive menu of diagnostic tests that help clinicians determine whether complement defects or deficiencies are factors in patients with recurrent severe infections or symptoms of autoimmune disease. (nationaljewish.org)
Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases. (cdc.gov)
Autoimmune-associated HLA-B8-DR3 haplotypes in Asian Indians are unique in C4 complement gene copy numbers and HSP-2 1267A/G. (cdc.gov)

Therefore, when C3 is cleaved upon complement activation, the C3a fragment does not bind to the synapse, rather it is a chemotactic factor that helps recruit microglia to eat the synapse. (alzforum.org)
It is primarily regulated by complement Factor H (CFH), which, in cooperation with Factor I, degrades C3 to an inactive version known as iC3b (FI). (alliedacademies.org)

Activation of the intrinsic pathway, alternatively, will probably describe both their capability to cause cell death also to restore awareness to Path, since it was evidenced these substances could induce the downregulation of survivin and XIAP. (researchreportone.com)

Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections. (harvard.edu)

What is the biological consequences of complement activation? (searchandrestore.com)

Various pathways were identified, including the antigen processing and presentation pathway, important in host defense. (biomedcentral.com)

Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjögren's Syndrome. (cdc.gov)

Endogenous and natural complement inhibitor attenuates myocardial injury and arterial thrombogenesis. (harvard.edu)

Each pathway converges on C3 cleavage to produce the anaphylatoxin C3a and active fragment C3b once activated [ 1 ][ 2 ]. (alliedacademies.org)

Phagocytic, they have special enzymatic pathways for enhanced bacteriocidal action. (kupdf.net)

The pathway starts with a protein called C1 binding to the red blood cell. (understandingcad.com)

However, the CP does not appear to play a role in the schistosomulicidal activity of complement. (aai.org)

Anatomy13

Organisms17

Diseases9

Chemicals and Drugs92

Analytical, Diagnostic and Therapeutic Techniques and Equipment14

Phenomena and Processes23

Information Science2

Health Care1

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

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

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

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

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

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

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

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

Complement Pathway, Alternative

Complement Pathway, Classical

Complement Activation

Complement C3

Complement System Proteins

Complement C4

Complement Factor B

Complement C1q

Complement Pathway, Mannose-Binding Lectin

Complement C2

Complement C3b

Complement C1

Complement C5

Complement Inactivator Proteins

Complement Factor D

Complement C3-C5 Convertases

Properdin

Receptors, Complement

Complement Factor H

Complement Membrane Attack Complex

Complement C4b

Complement C6

Complement C3b Inactivator Proteins

Complement Activating Enzymes

Complement Hemolytic Activity Assay

Complement C9

Complement Inactivating Agents

Mannose-Binding Protein-Associated Serine Proteases

Complement C3a

Mannose-Binding Lectin

Complement C3c

Complement C1 Inactivator Proteins

Complement C5a

Complement C3d

Hemolysis

Blood Bactericidal Activity

Opsonin Proteins

Receptors, Complement 3b

Complement Fixation Tests

Complement C1s

Complement Factor I

Complement C4b-Binding Protein

Zymosan

Complement C5b

Complement C4a

Complement C3 Convertase, Alternative Pathway

Antigens, CD55

Phagocytosis

Cobra Venoms

Antigen-Antibody Complex

Immunoglobulin G

Collectins

Complement C1r

Complement C7

Lectins

Complement C8

Anaphylatoxins

Antigens, CD46

Antigens, CD59

Receptors, Complement 3d

Immunoglobulin M

Erythrocytes

Guinea Pigs

Egtazic Acid

Neutrophils

Polysaccharides, Bacterial

Snakes

Cryoglobulins

Prevotella melaninogenica

Antibodies, Bacterial

Macular Degeneration

Streptococcus pneumoniae

Blood Physiological Phenomena

Immunoelectrophoresis

Rabbits

Edetic Acid

Immunoglobulins

Protein Binding

Macrophage-1 Antigen

Mannans