Complement Pathway, Alternative: 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 Pathway, Classical: 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.Complement Activation: 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.Complement C3: 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.Complement System Proteins: 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).Complement C4: 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.Complement Factor B: 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.Complement C1q: 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 Pathway, Mannose-Binding Lectin: 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.Complement C2: 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).Complement C3b: 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.Complement C1: 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.Complement C5: 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.Complement Inactivator Proteins: 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.Complement Factor D: 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.Complement C3-C5 Convertases: 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.Properdin: 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.Receptors, Complement: Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.Complement Factor H: 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).Complement Membrane Attack Complex: 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.Complement C4b: 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).Complement C6: 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.Complement C3b Inactivator Proteins: 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.Complement Activating Enzymes: 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.Complement Hemolytic Activity Assay: 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.Complement C9: 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.Complement Inactivating Agents: Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.Mannose-Binding Protein-Associated Serine Proteases: 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.Complement C3a: 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.Mannose-Binding Lectin: 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.Complement C3c: 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.Complement C1 Inactivator Proteins: Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.Complement C5a: 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.Complement C3d: 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).Hemolysis: The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.Blood Bactericidal Activity: 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.Opsonin Proteins: 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.Receptors, Complement 3b: 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.Complement Fixation Tests: 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.Complement C1s: 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).Complement Factor I: 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.Complement C4b-Binding Protein: 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).ZymosanComplement C5b: 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.Complement C4a: 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.Complement C3 Convertase, Alternative Pathway: 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.Antigens, CD55: 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.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Cobra Venoms: 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.Antigen-Antibody Complex: 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.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Collectins: 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.Complement C1r: 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.Complement C7: 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.Lectins: 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.Complement C8: 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.Anaphylatoxins: 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.Antigens, CD46: 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.Antigens, CD59: 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)Receptors, Complement 3d: 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.Immunoglobulin M: 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.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Guinea Pigs: 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.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Neutrophils: 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, Bacterial: Polysaccharides found in bacteria and in capsules thereof.Snakes: Limbless REPTILES of the suborder Serpentes.Cryoglobulins: Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.Prevotella melaninogenica: 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.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Macular Degeneration: 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.Streptococcus pneumoniae: 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.Blood Physiological Phenomena: Physiological processes and properties of the BLOOD.Immunoelectrophoresis: 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.Rabbits: 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.Edetic Acid: A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.Immunoglobulins: 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.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Macrophage-1 Antigen: 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.Mannans: Polysaccharides consisting of mannose units.Mice, Inbred C57BLSerum Amyloid P-Component: 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.Antibodies: 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).Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Mannose-Binding Lectins: A subclass of lectins that are specific for CARBOHYDRATES that contain MANNOSE.Serum: The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Glomerulonephritis, Membranoproliferative: 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.Sialic Acids: A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Glomerulonephritis: 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, Monoclonal: Antibodies produced by a single clone of cells.Sheep: 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.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Complement C1 Inhibitor Protein: 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.Immunity, Innate: 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.Cryptococcus: A mitosporic Tremellales fungal genus whose species usually have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium.Venoms: 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.Fluorescent Antibody Technique: 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.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Lipopolysaccharides: 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)Blood: The body fluid that circulates in the vascular system (BLOOD VESSELS). Whole blood includes PLASMA and BLOOD CELLS.Antibody Specificity: 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.Magnesium: 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.Enzyme-Linked Immunosorbent Assay: 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.Escherichia coli: 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.Immune Sera: 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.Cryptococcus neoformans: A species of the fungus CRYPTOCOCCUS. Its teleomorph is Filobasidiella neoformans.Bacteroides: 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.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.Kinetics: The rate dynamics in chemical or physical systems.Mannose: 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)Binding Sites, Antibody: 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.Receptor, Anaphylatoxin C5a: A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.Genetic Complementation Test: 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.Surface Plasmon Resonance: 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.Species Specificity: 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.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Disease Models, Animal: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Retinal Pigment Epithelium: 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.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Lupus Erythematosus, Systemic: 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.Neisseria meningitidis: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Macrophages: 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.)Reperfusion Injury: 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.Immunoglobulin Fab Fragments: 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.C-Reactive Protein: A plasma protein that circulates in increased amounts during inflammation and after tissue damage.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Bacterial Proteins: Proteins found in any species of bacterium.Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Mice, Inbred BALB CNeuraminidase: 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)Cell Line: Established cell cultures that have the potential to propagate indefinitely.Endotoxins: 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.Hot Temperature: Presence of warmth or heat or a temperature notably higher than an accustomed norm.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Pneumococcal Infections: Infections with bacteria of the species STREPTOCOCCUS PNEUMONIAE.Staphylococcus aureus: 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.PolysaccharidesMolecular Weight: The sum of the weight of all the atoms in a molecule.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Trypanosoma cruzi: 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.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Cell Wall: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Bacterial Outer Membrane Proteins: Proteins isolated from the outer membrane of Gram-negative bacteria.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Immunoglobulin A: 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.Neutralization Tests: 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).Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Blotting, Western: 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.Inflammation: 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.CHO Cells: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Graft Rejection: 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, Messenger: 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.Complement C5a, des-Arginine: 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).Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Models, Molecular: 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)

... Exp Neurol. 2017 Jun 07;: Authors: Wyatt SK, Witt T, Barbaro NM, Cohen-Gadol AA, Brewster AL Abstract Microglia-mediated neuroinflammation is widely associated with seizures and epilepsy. Although microglial cells are professional phagocytes, less is known about th...
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Centers RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.. ...
Misregulation of the innate immune response and other immune-related processes have been suggested to play a critical role in the pathogenesis of a number of different neurodegenerative diseases, including age related macular degeneration. In an animal model for photoreceptor degeneration, several genes of the innate and acquired immune system were found to be differentially regulated in the retina during the degenerative process. In addition to this differential regulation of individual genes, we found that in the rd1 retina a significantly higher number of genes involved in immune-related responses were expressed at any given time during the degenerative period. The peak of immune-related gene expression was at postnatal day 14, coinciding with the peak of photoreceptor apoptosis in the rd1 mouse. We directly tested the potential involvement of acquired and innate immune responses in initiation and progression of photoreceptor degeneration by analyzing double mutant animals. Retinal morphology ...
We reported inhibition of growth of primary rat mammary carcinomas after infusions of tumor-bearer plasma absorbed with Protein A-Sepharose or inactivated CNBr Sepharose. Absorbed plasmas were depleted of the third component of complement (C3) (other complement components defined similarly) and C5 but not C1, C4, or C2. These results suggested that activation of the alternative pathway of complement might be involved in the observed antitumor effects. To test this concept sera were treated with ethylenedinitrilotetraacetic acid or [ethylenebis(oxyethylenenitrilo)]tetraacetic acid before absorption with Protein A-Sepharose. Ethylenedinitrilotetraacetic acid, by chelating calcium and magnesium, prevents activation of both the alternative and classical complement pathways. [Ethylenebis(oxyethylenenitrilo)]tetraacetic acid, by chelating calcium but not magnesium, permits activation of the alternative pathway but inhibits activation of the classical complement pathway. Sera in the presence or absence ...
Thomson Reuters provides the knowledge, tools and expertise to support your drug discovery and development activities, optimize your IP portfolio, identify licensing and partnering opportunities, deliver successful regulatory submissions, keep you in touch with the rapidly-changing pharmaceutical and chemical markets, and make the best decisions for your business.
Host defense mechanisms can counteract the antiphagocytic bacterial capsule. Unlike classical complement pathway, the alternative complement pathway is not antibody-mediated and can easily overwhelm encapsulated bacteria. It is triggered by the cleavage of C3 into C3a and C3b and the attachment of C3b to MAMPs (Microbe Associated Molecular Patterns), such as the capsular polysaccharides. The C3b molecules osponsize the pathogen, facilitating its phagocytosis and intravascular clearance. Furthermore, the complement cascade leads to the formation of proteolytic C3and C5 convertases and the terminal membrane attack complex, which lyses the pathogen. However, a potentially fatal drawback from lysing the pathogen is the release of endotoxic lipopolysaccharides, which elicit an out-of-control immune response. [2 ...
The host genetic factors affecting susceptibility to disseminated candidiasis are incompletely defined. Peltz et al. (p. 4472-4479) used a next-generation computational genetic mapping program to identify genetic factors affecting inbred strain survival after disseminated candidiasis. Their analysis indicated that genetic variation within early classical complement pathway components (C1q, C1r, and C1s) affected survival. This result was verified by demonstrating that serum C1 binding to Candida albicans was strongly affected by C1rs alleles, as was survival in chromosome substitution strains. A combinatorial, conditional genetic model, involving an interaction between the C5 and C1r/s alleles, accurately predicted survival after disseminated candidiasis. Beyond its potential applicability to infectious diseases, this combinatorial genetic model could provide insight into the genetic architecture for susceptibility to autoimmune and neurodegenerative diseases. ...
|strong|Goat anti Human C4 antibody|/strong| recognises human C4, a secreted protein that plays a central role in activation of the classical pathway of the complement system.|br||br|C4 is split into …
The optimal reaction conditions for hemolytic assay of alternative complement pathway activity in mouse serum were investigated. A microtiter system was used, in which a number of 7.5×106 rabbit erythrocytes per test well appeared to be optimal. Rabbit erythrocytes were superior as target cells over erythtocytes from a number of ... read more other animal species. The optimal conditions were as follows: an incubation temperature of 39°C, an ionic strength of about 200 mM, and a magnesium concentration of 2.5 mM. Incubation during 60 min was not sufficient for an end-point titration. Addition of 1 mg of zymosan A per test well, however, enhanced and accelerated the hemolytic activity of mouse serum via the alternative pathway resulting in a maximum value after 45 min. This, most probably, proceeded by a mechanism involving the formation of a zymosan-C5-convertase and bystander lysis of the target cells. In contrast to the normal alternative pathway assay the zymosan-potentiated test did, most ...
Neuromyelitis optica (NMO) is an autoimmune CNS disorder mediated by pathogenic aquaporin-4 (AQP4) water channel autoantibodies (AQP4-IgG). Although AQP4-IgG-driven complement-dependent cytotoxicity (CDC) is critical for the formation of NMO lesions, the molecular mechanisms governing optimal classical pathway activation are unknown. We investigated the molecular determinants driving CDC in NMO using recombinant AQP4-specific autoantibodies (AQP4 rAbs) derived from affected patients. We identified a group of AQP4 rAbs targeting a distinct extracellular loop C epitope that demonstrated enhanced CDC on target cells. Targeted mutations of AQP4 rAb Fc domains that enhance or diminish C1q binding or antibody Fc-Fc interactions showed that optimal CDC was driven by the assembly of multimeric rAb platforms that increase multivalent C1q binding and facilitate C1q activation. A peptide that blocks antibody Fc-Fc interaction inhibited CDC induced by AQP4 rAbs and polyclonal NMO patient sera. ...
Neuromyelitis optica (NMO) is an autoimmune CNS disorder mediated by pathogenic aquaporin-4 (AQP4) water channel autoantibodies (AQP4-IgG). Although AQP4-IgG-driven complement-dependent cytotoxicity (CDC) is critical for the formation of NMO lesions, the molecular mechanisms governing optimal classical pathway activation are unknown. We investigated the molecular determinants driving CDC in NMO using recombinant AQP4-specific autoantibodies (AQP4 rAbs) derived from affected patients. We identified a group of AQP4 rAbs targeting a distinct extracellular loop C epitope that demonstrated enhanced CDC on target cells. Targeted mutations of AQP4 rAb Fc domains that enhance or diminish C1q binding or antibody Fc-Fc interactions showed that optimal CDC was driven by the assembly of multimeric rAb platforms that increase multivalent C1q binding and facilitate C1q activation. A peptide that blocks antibody Fc-Fc interaction inhibited CDC induced by AQP4 rAbs and polyclonal NMO patient sera. ...
The complement system is an enzyme cascade that is a collection of blood and cell surface proteins to help the abilities of antibodies to clear pathogens from an organism. The complement system that comprises 30 different proteins, including serum proteins, serosal proteins, and cell membrane receptors is an important part of the innate immune system. There are three different complement pathways, the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway.
Ischemia and reperfusion of organs is an unavoidable consequence of transplantation. Inflammatory events associated with reperfusion injury are in part attributed to excessive complement activation. Systemic administration of complement inhibitors reduces reperfusion injury but leaves patients vulnerable to infection. Here, we report a novel therapeutic strategy that decorates cells with an anti-complement peptide. An analog of the C3 convertase inhibitor Compstatin (C) was synthesized with a hexahistidine (His6) tag to create C-His6. To decorate cell membranes with C-His6, fusogenic lipid vesicles (FLVs) were used to incorporate lipids with nickel (Ni2+) tethers into cell membranes, and these could then couple with C-His6. Ni2+ tether levels to display C-His6 were modulated by changing FLV formulation, FLV incubation time and FLV levels. SKOV-3 cells decorated with C-His6 effectively reduced complement deposition in a classical complement activation assay. We conclude that our therapeutic ...
Acts as complement inhibitor by disrupting the formation of the classical C3 convertase. Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the classical and alternative complement pathways.
Anti-neutrophil cytoplasmic antibodies are linked to an increased prevalence of interstitial lung disease and pulmonary embolism in systemic sclerosis, according to data published in Arthritis Research & Therapy.. "The clinical significance of ANCA in [systemic sclerosis (SSc)] patients who do not manifest [ANCA-associated vasculitis] is controversial. An association between ANCA in SSc and [interstitial lung disease] has been suggested," Mandana Nikpour, PhD, MBBS, FRACP, FRCPA, of the University of Melbourne, Australia, and colleagues wrote. "However, this has not been consistently reported in all case series. It has also been suggested that ANCA in SSc patients may indicate an inflammatory component to the illness and that ANCA should be treated as a red flag, prompting a thorough investigation and follow-up." ...
Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might give more insight into the disease. Markers from the classical complement pathway are elevated where ...
Abdullah, M.T., Nepliounev, I., Alfonina, G., Ram, S., Rice, P., Elkins, C. (2005). Killing of dsrA mutants of haemophilus ducreyi by normal human serum occurs via the classical complement pathway and is initiated by immunoglobulin m binding. Infection and Immunity. 73: 3431-3439 ...
The biosynthesis of steroid hormones is a difficult process in which Cholesterol is transformed into mineralocorticoids, glucocorticoids and sex hormones via a series of hydroxylation, oxidation and reduction steps. To better understand the molecular level of sexual organ maturation in humans, the classical pathway and the alternative pathway of this process are produced. The pathways produce the main steroid hormones in humans, namely Progestogen, Corticosteroids, Androgens and Estrogens. The classical pathway is meant to produce an important steroid called Androgen, which is a synthetic steroid hormone that regulates sexual development and the maintenance of the male sex organs via binding to androgen receptors. For more information and details about Androgens and the diseases linked with this molecular pathway, please visit Chapter 37 of the book of Blau (ISBN 978-3-642-40337-8) ...
Combining with the C1q component of the classical complement cascade and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity.
Mannan is a prominent structural component displayed on the cell surface of C. albicans yeast cells (4), and antimannan IgG is present ubiquitously in the general human population (10, 14, 23). Previously, we showed that this naturally occurring antimannan IgG is required for activation of the classical complement pathway when C. albicans is incubated in NHS (40). We now present evidence that this naturally occurring antimannan IgG also regulates activation of the alternative pathway byC. albicans yeast cells. In NHS that is deficient in antimannan antibodies and lacks classical pathway activity as a result of EGTA chelation of serum Ca2+, addition of exogenous antimannan IgG accelerated C3 binding via the alternative pathway in a dose-dependent manner (Fig. 1 and 3). This accelerating effect of antimannan IgG was confirmed in a serum-free complement binding medium that consisted of only purified proteins of the alternative pathway (Fig. 2) as well as in immunofluorescence analysis (Fig. 5). A ...
Methods A cohort of 36 subjects with active SLE presenting with classical complement activation were enrolled and followed monthly for 1 year. At each study visit blood was collected, serum isolated and frozen until analysis. A total of 371 specimens were collected. Disease activity was scored on the day of each study visit according to the SELENA-SLEDAI method excluding anti-dsDNA or complement components (non-serological [ns] SELENA-SLEDAI). All specimens were tested using four different anti-dsDNA kits; QUANTA Lite, QUANTA Flash, a high Avidity anti-dsDNA ELISA, and the Crithidia luciliae indirect immunofluorescence assay (CLIFT) (Inova Diagnostics, San Diego, CA). Study visits presenting with inactive disease (ns-SELENA- SLEDAI score=0) were compared to those presenting with active disease (ns-SELENA- SLEDAI,0). The longitudinal data were analyzed using linear mixed effect modeling with the ns-SELENA-SLEDAI as dependent variable and the anti-dsDNA titers as fixed effect predictors. Marginal ...
Previous studies from this laboratory have demonstrated that Mycobacterium leprae, an obligate intracellular bacterial parasite, enters human mononuclear phagocytes via complement receptors on these host cells and bacterium-bound C3. The present study investigates the role of M. leprae surface molecules in C3 fixation and phagocytosis. By enzyme-linked immunosorbent assay, C3 binds selectively to phenolic glycolipid-1 (PGL-1), a major surface molecule of the leprosy bacillus. C3 fixation to PGL-1 is serum concentration dependent and is abolished in heat-inactivated serum or serum containing ethylenediaminetetraacetic acid. C3 fixation is also abolished in serum containing ethyleneglycol-bis (beta-aminoethyl ether)N,N,N-tetraacetic acid and MgCl2 indicating that isolated PGL-1 fixes C3 via the classical complement pathway. The capacity of PGL-1 to fix C3 is dependent upon its terminal trisaccharide since sequential removal of monosaccharide units of the trisaccharide results in a stepwise ...
Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed components of complement and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the ...
A growing body of evidence has recently accumulated about the pathogenic role of the complement system in AAV (1). In 2007, Xiao et al. (4) demonstrated how infusion of ANCA antibodies in wild-type mice could induce glomerular lesions typical of pauci-immune NCGN; interestingly, no lesion was observed when ANCA were injected in mice knocked out for C5 or complement factor B, whereas RPGN fully developed in C4-knockout mice; because C5 belongs to the terminal part of the complement cascade and complement factor B belongs to the cAP, while C4 is a key molecule of the classic pathway, these findings clearly showed that cAP plays a central role in experimental AAV (4). In keeping with this, Gou et al. showed that patients with active AAV have serologic signs of activation of the cAP (augmented serum levels of activated complement proteins, such as C3a, C5a, sC5b9, and Bb), which correlated with acute-phase reactants, number of crescents, and severity of kidney histology (9). The same group ...
Wiley Online Library is migrating to a new platform powered by Atypon, the leading provider of scholarly publishing platforms. The new Wiley Online Library will be migrated over the weekend of February 24 and 25 and will be live on February 26, 2018. For more information, please visit our migration page:http://www.wileyactual.com/WOLMigration ...
However, both local and systemic antibodies attempt to block the rep-lication and spread of viruses, either circulating or being shed from a cell that has been infected and killed. IgG is the most prevalent anti-body of the immunoglobulin system and is a potent opsonizing agent. The complement system of serum proteins is activated by IgM and later by IgG. They opsonize target cells for the phagocytes, which are then bound by IgM or IgG, and this is the classical pathway. Cells synthesize interferon when infected by virus; it is secreted into extracellular fluid and binds to adjacent cells. Interferon-alpha is de-rived from lymphocytes and interferon-beta from fibroblasts and other cell types. The IFNs acton certain cell genes that either catalyse or retard factors responsible for protein synthesis, which in turn re-duces mRNA translation, while another factor results in the degrada-tion of host and viral mRNA. The total result is to establish a sort of cordon of uninfectable cells around the ...
Lipooligosaccharide (LOS) heptose (Hep) glycan substitutions influence gonococcal serum resistance. Several gonococcal strains bind the classical complement pathway inhibitor, C4b-binding protein (C4BP), via their porin (Por) molecule to escape complement-dependent killing by normal human serum (NHS). We show that the proximal glucose (Glc) on HepI is required for C4BP binding to Por1B-bearing gonococcal strains MS11 and 1291 but not to FA19 (Por1A). The presence of only the proximal Glc on HepI (lgtE mutant) permitted maximal C4BP binding to MS11 but not to 1291. Replacing 1291 lgtE Por with MS11 Por increased C4BP binding to levels that paralleled MS11 lgtE, suggesting that replacement of the Por1B molecule dictated the effects of HepI glycans on C4BP binding. The remainder of the strain background did not affect C4BP binding; replacing the Por of strain F62 with MS11 Por (F62 PorMS11) and truncating HepI mirrored the findings in the MS11 background. C4BP binding correlated with resistance to killing
Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, Kenny J, Waters A, Jenkins D, Kaissi AA, Leal GF, Dallapiccola B, Carnevale F, Bitner-Glindzicz M, Lees M, Hennekam R, Stanier P, Burns AJ, Peeters H, Alkuraya FS, Beales PL. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat Genet. 2011 Mar;43(3):197-203.. ...
Principal Investigator:MATSUSHITA Misao, Project Period (FY):1996 - 1997, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Immunology
The C-reactive protein (CRP) is a cyclic pentameric pentraxin family acute phase protein compound of five identical noncovalently bound nonglycosylated subunits (each subunit 24 kDa; physiologic CRP molecule 117,5 kDa). CRP is produced by the liver and its plasma levels rise dramatically during inflammatory processes occuring in the body. CRP is an initiator of classical complement cascade, binds to several nuclear components (chromatin, histones, etc.) and is also believed to play an important role in innate immunity. Patients with elevated basal levels of CRP are at increased risk for hypertension and cardiovascular disease ...
Definition : Immunoassay reagents intended to perform qualitative and/or quantitative analyses on a body fluid sample (typically serum) to detect and/or measure levels of one or more of the proteins C5 to C9 found in the final complement pathway. Deficiency of complement components C5 to C9 are associated with several diseases, especially recurrent neisserial infections.. Entry Terms : "C5-9 (Complement Component) Determination Reagents" , "Reagents, Immunoassay, Protein, Complement Component, C5-C9". UMDC code : 19804 ...
C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound to C4b and C2b (C4b2b3b complex) or when an additional C3b molecule binds to the C3bBb complex (C3bBb3b complex). C3bs ability to perform these important functions derives from its ability to covalently bind to the surface of invading pathogens within an organisms body. The cleavage of C3 leaves C3b with an exposed thioester bond, allowing C3b to effectively coat and tag foreign cells by covalently binding to hydroxyl (-OH) and amine (-NH2) groups on foreign cell surfaces. This cleavage can occur via three mechanisms (classical pathway, alternative pathway and lectin pathway) that ultimately lead to ...
With two holes open, the filtering effect of the downstream holes is clear at frequencies above about 1.5 kHz. Compare this spectrum with more regular impedance spectrum for D4 on the classical instrument with a D foot. The regular, harmonically spaced minima in the latter spectrum allow greater power in the higher harmonics, and thus a brighter tone for this note.. ...
TY - JOUR. T1 - Complement activation in acquired and hereditary amyloid neuropathy. AU - Hafer-Macko, Charlene E.. AU - Dyck, Peter J. AU - Koski, Carol Lee. PY - 2000. Y1 - 2000. N2 - The pathogenesis of the axonal degeneration in acquired or hereditary amyloidosis is unknown. In this immunohistochemistry study, we examined 20 sural nerve biopsies from individuals with amyloid neuropathy (14 acquired and 6 hereditary) for evidence of complement activation. Complement activation products were detected on and around amyloid deposits within peripheral nerves. We found no difference in the extent, location or pattern of complement activation products between the 2 forms of amyloidosis. The presence of early classical pathway activation markers in the absence of antibody in hereditary cases suggests an antibody-independent activation of the classical pathway through binding of C1q. The lack of Factor Bb-suggested alternative pathway activation was not significant in these cases. The detection of ...
MBL forms oligomers of subunits, which are trimers (6- to 18-heades correspond to a dimer and a hexamer, respectively). Multimers of MBL form a complex with MASP1 (Mannose-binding lectin-Associated Serine Protease), MASP2 and MASP3, that are protease zymogens. The MASPs are very similar to C1r and C1s molecules of the classical complement pathway, respectively, and are thought to have a common evolutionary ancestor. When the carbohydrate-recognising heads of MBL bind to specifically arranged mannose residues on the surface of a pathogen, MASP-1 and MASP-2 are activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. In addition, two smaller MBL-associated proteins (MAps) are found in complex with MBL. MBL-associated protein of 19 kDa (MAp19) and MBL-associated protein of 44 kDa (Map44). MASP-1, MASP-3 and MAp44 are alternative splice products of the MASP1 gene, while MASP-2 and MAp19 are alternative splice products of the MASP-2 gene. MAp44 has been suggested to act as a ...
Each pathway follows a sequence of reactions to generate a protease called a C3 convertase. The active protease is retained at the pathogen surface, and this ensures that the next complement zymogen in the pathway is also cleaved and activated at the pathogen surface. By contrast, the small peptide fragment is released from the site of the reaction and can act as a soluble mediator.. The early events of all three pathways of complement activation involve a series of cleavage reactions that culminate in the formation of an enzymatic activity called a C3 convertase, more The C3 convertases formed by these early events of complement activation are bound covalently to the pathogen surface. Here they cleave C3 to generate large amounts of C3bthe main effector molecule of the complement system, and C3a, a peptide mediator of inflammation.. The C3b molecules act as opsonins; they bind covalently to the pathogen and thereby target it for destruction by phagocytes equipped with receptors for C3b. These ...
Detailed description of complement system including classical pathway, alternate pathway and lectin pathway. Components of complement system includingC1, C2, C3, C4, C5, C6, C7, C8, C9, C1-INH, C3a-INA, Factors H and I, C3a-INA, C4-BP and Factor I, C3a-INA, Protein S (vitronectin).
The complement system is a key component of the innate immune system that is involved in eliminating unwanted self and nonself material via cellular and humoral mechanisms
The Complement System is one of the subject in which we provide homework and assignment help. Our feature includes 24x7 live online statistics tutors available to help you. You can get speedy and cost Immunology help at assignmenthelp.net
The activation of NF-κB is mainly by two signaling pathways - the canonical pathway (which is the classical pathway) and the non-canonical pathway (which is also called the alternative pathway). Lets discuss about each of the pathway in detail. But before going ahead, it is important to note the common regulatory step of both the cascades is the activation of IκBkinase (IKK) complex. In unstimulated cells, the inhibitor, NF-κB proteins are bound to IκB protein that maintains NF-κB in an inactive state. Hence, when IκB is activated i.e.; phosphorylated, it gets ubiquitinated and is degraded by proteasome. The IKK complex consists of kinase subunits that are catalytic (IKKα and/or IKKβ) and non-enzymatic protein that is regulatory in nature - known as NEMO which stands for NF-κB essential modulator, also known as IKKγ. ...
C1-INH is a heavily glycosylated, single chain, plasma glycoprotein with an apparent molecular weight of 105 kd on sodium dodecyl sulfate-PAGE. It consists of 478 amino acids comprising a backbone molecular weight of 52,880 (1). The protein acts as a serine protease inhibitor (serpin) binding to and forming covalent bonds with a variety of plasma proteases and thus inhibiting their activity (2, 3). The protein is known to inhibit C1s and C1r, two subcomponents of the complement protein C1. It is for these properties that it received its name. However, it is a known inhibitor of factor FXIIa and FXIIf, kallikrein, FXIa, plasmin, MASP1, and MASP2. Thus it inhibits proteins of the intrinsic coagulation, kinin generating, and fibrinolytic pathways, as well as the mannan binding lectin pathway of complement activation (5-9). As such, it is a potent down regulator of inflammation. C1-INH has been administered to animals in a variety of animal models of disease and shown to have profound inhibitory ...
The complement system provides a fundamental component of the body's immune response to invading microorganisms. This chapter highlights the various roles of the complement system in the orchestration of the immune response towards microbial infections, gives examples of microbial strategies to evade complement-mediated clearance, and discusses how acquired and inherited complement deficiencies may predispose an organism to infectious disease. Complement is activated by three pathways: the classical pathway, the alternative pathway, and the lectin pathway. The lectin pathway is activated by carbohydrate recognition molecules that bind to polysaccharide on the surface of a pathogen. Factor B, factor D, and properdin (factor P) are specific components of the alternative pathway of complement activation. The complement activation is tightly regulated by membrane-bound and fluid-phase regulatory components to avoid runaway activation of the enzymatic cascade that could lead to excess host tissue damage
The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individuals lifetime. However, it can be recruited and brought into action by the adaptive immune system. The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. [source: Wikipedia] The Classical Pathway begins with circulating C1Q binding to an antigen on the surface of a pathogen, which goes on to active and recruit 2 copies of each C1R and C1S, forming a C1 complex. The activated C1 complex cleaves C2 and C4. Activated cleavage products C2A and C4B combine to form C3 convertase, which cleaves C3. The cleavage product C3B joins the complex to form C5 convertase, which cleaves C5. The cleavage product C5B joins C6, C7, C8 and multiple copies of C9 to form ...
CH50 and CH100 measures the integrity of the classical and terminal complement pathways. Indicated in the investigation of suspected immune deficiency associated with recurrent pyogenic infections, recurrent/atypical meningococcal infections and atypical immune complex disorders.AP100 measures the integrity of the alternative and terminal complement pathways. Rare deficiencies of AP components predispose to neisserial infections.AP100 measures the integrity of the alternative and terminal complement pathways. Rare deficiencies of AP components predispose to neisserial infections ...
We are interested in interactions between the two fundamental cell types of the nervous system, neurons and glia. My laboratory seeks to understand how neuron-glia communication facilitates the formation, elimination and plasticity of synapses-the points of communication between neurons-during both healthy development and disease.. We focus on the role of neuron-glia and neural-immune interactions in the patterning of neural circuits. We and our collaborators have identified an unexpected role for glia and components of the innate immune system in synaptic pruning. We find that astrocytes induce neuronal expression of complement C1q, the initiating protein of the classical complement cascade (which tags unwanted cells and debris for elimination in the immune system). C1q and downstream complement proteins target synapses and are required for synapse elimination in the developing visual system. Importantly, we find that C1q becomes aberrantly upregulated and is relocalized to synapses in the ...
... The activated complement system recognizes and eliminates invading microorganisms and thus is beneficial for the host.
Background C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind...
FUNCTION: This gene encodes a member of the kallikrein subfamily of serine proteases that have diverse physiological functions such as regulation of blood pressure and desquamation. The encoded protein is a precursor that undergoes proteolytic cleavage of the activation peptide to generate the functional enzyme. The encoded enzyme was found to activate the complement pathway by cleavage of C3 to release C3a anaphylotoxin. This gene is one of the several glandular kallikrein genes located in a cluster on chromosome 7. [provided by RefSeq, Aug 2015 ...
Prior absorption of normal human serum (NHS) or C2-deficient human serum (C2D) with zymosan at 0 degrees C results in diminished consumption of C3 and factor B during subsequent incubation of the sera in Mg-EGTA buffer with zymosan at 37 degrees C for 30 min. An acid eluate from the zymosan restores the defect of absorbed NHS and C2D, and also enhances C3 and factor B utilization in hypogammaglobulinemic serum (H gamma S) in a dose-dependent fashion. The activity is specific in that the eluate from zymosan fails to enhance C3 and B depletion in H gamma S or absorbed NHS by lipopolysaccharide or Sepharose. The active component of th zymosan eluate emerges from both Sepharose 4B and Sephacryl S-200 in the region of molecules with m.w. of 150,000. Absorption with protein A-Sepharose removes the activity, demonstrating that it is IgG. Digestion of the IgG with pepsin fails to diminish activity, indicating that the Fc region is not required for activity; reduction to monovalent Fab fragments, ...
We previously described a simplified quantitative hemolytic assay for classical pathway (CP) hemolytic function in serum that has been shown to correlate with the 50% hemolytic complement (CH50) assay. In the present study, we used this assay to compare CP functions; plasma levels of C3, C4, and C3dg; and ratios of C3dg to C3 in healthy individuals and patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) with different degrees of complement activation. A significant depression in CP function and levels of C4 and C3 and increased C3dg levels and C3dg/C3 ratios were observed in the SLE patients. In patients with RA, CP function was normal, whereas C3, C4, and C3dg levels and the C3dg/C3 ratio were elevated. The SLE results are compatible with systemic complement consumption, whereas the RA data suggest an acute-phase reaction with a normal C3 catabolic rate. To facilitate the handling of patient samples, we also developed a method to restore the hemolytic function of ...
(lek tin) The lectin pathway for complement activation is triggered by the binding of a serum lectin (mannan binding lectin; MBL) to mannose containing proteins or to carbohydrates on viruses or bacteria
Complement pathways function to identify and remove pathogens and infected cells. There are three complement pathways: the classical, lectin and alternative pathway (AP). While all pathways are activated following pathogen stimuli, the AP is constitutively active and tightly controlled by activators (e.g., Factor B, Factor D) and negative regulators (e.g., Factor H). Complement activity can be measured by well-established methods that are often used in a diagnostic setting to determine the CH50 (50% complement hemolytic activity) or AP50, specifically to measure AP activity. The protocol here has adapted the traditional AP50 method designed to measure AP activity in human sera, to measure the positive or negative AP regulatory activity within a given test sample. The assay relies on the ability of AP components in human serum to lyse rabbit erythrocytes under in vitro conditions specific for the AP with subsequent release of hemoglobin that is quantitated by measurement of optical density. Our method
Looking for Complement system? Find out information about Complement system. The sequential activation of complement proteins resulting in lysis of a target cell Explanation of Complement system
Adsorption, Blood Proteins/*chemistry/immunology/*metabolism, Coated Materials; Biocompatible/*chemistry/*metabolism, Complement Activation/*physiology, Complement C3/immunology/*metabolism, Complement Pathway; Alternative/physiology, Humans, Materials Testing, Polystyrenes/*chemistry, Protein Binding, Surface Properties ...
The classical pathway begins with the formation of antigen-antibody complex (immune complex). When an antigen enters the body, the antibody (IgM/IgG) binds to it. This induces conformational changes in the Fc portion of the antibody which exposes a binding site for C1 protein. Hence, the antibody activates the complement system only when bound to an antigen.. C1 is a large, multimeric, protein complex composed of one molecule of C1q and two molecules each of C1r and C1s subunits. C1q binds to the antigen bound antibody (Fc portion). C1r and C1s are proteases which help to cleave C4 and C2.. The immune complex bound to C1 calls another protein C4 which is cleaved into C4a and C4b. C4a goes away whereas activated C4b attaches to the target surface near C1q. Now, C4b attracts C2 which is also cleaved into C2a and C2b. C2a binds C4b forming the C4b2a complex whereas C2b goes away. The active C4bC2a activates C3. The C4b2a complex is also known as C3 convertase as this converts C3 into an active form ...
Avhandlingar om COMPLEMENT ACTIVATION. Sök bland 90495 avhandlingar från svenska högskolor och universitet på Avhandlingar.se.
There is an urgent need to develop effective therapies for COVID-19. Here, we urge immunologists and clinicians to consider the potential of targeting the complement system in these patients. This Comment article from Lambris and colleagues considers the therapeutic potential of targeting the complement system in patients with COVID-19.
1, adequate supply of high protein and protein in children with enough heat, per kilogram of body weight 2.5 ~ 4 grams. Heat 100 to 120 thousand cards (per kg body weight per day), to complement consumption. 2, fat intake should not be too
This gene encodes a serine protease that functions as a component of the lectin pathway of complement activation. The complement pathway plays an essential role in the innate and adaptive immune response. The encoded protein is synthesized as a zymogen and is activated when it complexes with the pathogen recognition molecules of lectin pathway, the mannose-binding lectin and the ficolins. This protein is not directly involved in complement activation but may play a role as an amplifier of complement activation by cleaving complement C2 or by activating another complement serine protease, MASP-2. The encoded protein is also able to cleave fibrinogen and factor XIII and may may be involved in coagulation. A splice variant of this gene which lacks the serine protease domain functions as an inhibitor of the complement pathway. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010 ...
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. . ...
When antigens enter into the body, normally this antigen will be recognized by the antibody that has been generated before during first exposure. The antibody binds to the soluble antigen forming the antibody-antigen complexes in the circulation in order to clear up all of the pathogens. According to Levinson (n.d), the reticuloendothelial system or macrophages system and other phagocytes have the ability to remove the immune antibody-antigen complexes very effectively in a normal condition. However, in type III hypersensitivity, these systems are not capable to remove these complexes. As a result, this antigen-antibody complexes tends to deposit on the wall of the blood vessels. Some of the immune complex deposition on the blood vessel will activate the complement protein such as C1, C4, C3 and C5-9 resulting membrane attack complex, leukocytes chemotaxis, leukocytes polymorphism and phagocytosis as well as inflammation. So that, in classical pathway C1 binds to the antigen-antibody complex and ...
Successful with- drawal of oral long-acting nitrates to facilitate phos- phodiesterase type 5 inhibitor use in stable coronary disease patients buy viagra at store 918540 erectile dysfunction. Hyperconsumption indicates activation of the alternative complement pathway. Malbran E, Dodds R, Hulsbus R Traumatic retinal detachment. Cell 1980; 19821.
Jun 10, 2002 (CIDRAP News) The smallpox virus has a protein that inhibits the human complement system far more effectively than does its counterpart protein in the closely related vaccinia virus, used in smallpox vaccine, according to researchers who compared the two proteins. This difference may be an important reason for the virulence of smallpox and may offer an avenue for research on treatments, they suggest. ...
Title: CH50: A Revisited Hemolytic Complement Consumption Assay for Evaluation of Nanoparticles and Blood Plasma Protein Interaction. VOLUME: 8 ISSUE: 3. Author(s):Ameena Meerasa, Jasper G. Huang and Frank X. Gu. Affiliation:Department of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1.. Keywords:CH50 assay, complement activation, hemolytic assay, nanoparticles, opsonization, protein interaction, stealth, toxicity, Plasma Protein, vasculature. Abstract: The use of nanoparticles as platforms or vehicles for applications in nanomedicine, such as drug delivery and medical imaging, has been widely reported in the literature. A key area of potential improvement in the development and implementation of nanoparticles is the design of surface treatments to maximize residence time in the bloodstream. Major obstacles to the prolonged circulation of nanoparticles include complement activation and opsonization, both of which contribute to the removal of foreign ...
Eighty-nine sera from nineteen patients with systemic lupus erythematosus (SLE) have been studied to determine the relationship between levels of DNA-binding activity, complement consumption and evidence of circulating immune complexes. There was a good correlation between the height of DNA binding, …
Microglia, central nervous system (CNS) resident phagocytic cells, persistently police the integrity of CNS tissue and respond to any kind of damage or pathophysiological changes. These cells sense and rapidly respond to danger and inflammatory signals by changing their cell morphology; by release of cytokines, chemokines, or nitric oxide; and by changing their MHC expression profile. We have shown previously that microglial biosynthesis of the complement subcomponent C1q may serve as a reliable marker of microglial activation ranging from undetectable levels of C1q biosynthesis in resting microglia to abundant C1q expression in activated, nonramified microglia. In this study, we demonstrate that cultured microglial cells respond to extrinsic C1q with a marked intracellular Ca2+ increase. A shift toward proinflammatory microglial activation is indicated by the release of interleukin-6, tumor necrosis factor-alpha, and nitric oxide and the oxidative burst in rat primary microglial cells, an ...
C3 glomerulonephritis is a recently described entity which is due to dysregulation in the alternative complement pathway. Patients typically present with hematuria and/or proteinuria in the face of persistently low serum levels of C3. The annual incidence of biopsy-proven disease is 1 to 2 per million with both sexes affected equally. The median age of diagnosis is 21 years of age, but there is a second spike after the age of 50 due to paraprotein-associated disease. The most common glomerular disease pattern is a membranoproliferative pattern. The hallmark of the disease is dominant C3 staining on immunofluorescence which is defined ...
Results of studies published since 2002 reveal that T cells and antigen-presenting cells (APCs) produce complement proteins. The immune cell-derived, alternative pathway complement components activate
Decay-accelerating factor (CD55), a regulator of the alternative and classical pathways of complement activation, is expressed on all serum-exposed cells. It is used by pathogens, including many enteroviruses and uropathogenic Escherichia coli, as a receptor prior to infection. We describe the x-ray structure of a pathogen-binding fragment of human CD55 at 1.7 A resolution containing two of the three domains required for regulation of human complement. We have used mutagenesis to map biological functions onto the molecule; decay-accelerating activity maps to a single face of the molecule, whereas bacterial and viral pathogens recognize a variety of different sites on CD55.
In the late 19th century, blood serum was found to contain a "factor" or "principle" which was capable of killing bacteria. In 1896, Jules Bordet, a young Belgian scientist in Paris at the Pasteur Institute, demonstrated that this principle could be analyzed into two components: a heat-stable and a heat-labile component. (Heat-labile meaning that it lost its effectiveness if the serum was heated.) The heat-stable component was found to confer immunity against specific microorganisms, while the heat-labile component was found to be responsible for the non-specific antimicrobial activity conferred by all normal serum. This heat-labile component is what we now call "complement". The term "complement" was introduced by Paul Ehrlich in the late 1890s, as part of his larger theory of the immune system. According to this theory, the immune system consists of cells which have specific receptors on their surface to recognize antigens. Upon immunization with an antigen, more of these receptors are formed, ...
Introduction to the Complement System The innate and adaptive immune systems are no longer considered as distinct separate entities but are now recognized
Hereditary Factors:, Life-History Effects:, Serology: Antigen, Genes: Hc - Hemolytic complement, MuBl,, Strains: A/HE, AKR, BALB/C, BSVS, CBA, CE, C57BL, C57BL/6, C57BR/CD, C57L, C58, DBA/1 (12), DBA/2 (212), MA (MARSH), MO, P, SIMPSON, PL (PLA, PLB), RF (W), SJL, SL, SM, SWR, T6T6, WHT (WH/HT), 129, BUB. ...
Human SUSD3 full-length ORF ( NP_659443.1, 1 a.a. - 255 a.a.) recombinant protein with GST-tag at N-terminal. (H00203328-P01) - Products - Abnova
8. This allows further bacterial multi- plication topama subsequent production of an increased amount of inflammatory mediators via the complement system and other pathways.
The neuronal microtubule-associated protein tau becomes hyperphosphorylated and forms aggregates in tauopathies but the processes leading to this pathological hallmark are not understood. Because tauopathies are accompanied by neuroinflammation and the complement cascade forms a key innate immune pathway, we asked whether the complement system has a role in the development of tau pathology. We tested this hypothesis in two mouse models, which expressed either a central inhibitor of complement or lacked an inhibitor of the terminal complement pathway. Complement receptor-related gene/protein y is the natural inhibitor of the central complement component C3 in rodents. Expressing a soluble variant (sCrry) reduced the number of phospho-tau (AT8 epitope) positive neurons in the brain stem, cerebellum, cortex, and hippocampus of aged P301L mutant tau/sCrry double-transgenic mice compared with tau single-transgenic littermates (JNPL3 line). CD59a is the major inhibitor of formation of the membrane attack
The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation pathways of complement in fighting streptococcal infection, little is known about the role of the lectin pathway, mainly due to the lack of appropriate experimental models of lectin pathway deficiency. We have recently established a mouse strain deficient of the lectin pathway effector enzyme mannan-binding lectin associated serine protease-2 (MASP-2) and shown that this mouse strain is unable to form the lectin pathway specific C3 and C5 convertases. Here we report that MASP-2 deficient mice (which can still activate complement via the classical pathway and the alternative pathway) are highly susceptible to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. ...
We have examined the relative roles of the macrophage (M phi) plasma membrane receptor for the cleaved third complement component (iC3b, CR3) and of the mannosyl/fucosyl receptor (MFR) in binding and ingestion of Leishmania donovani. In the absence of exogenous complement, the binding and ingestion of promastigotes, which are good activators of the alternative complement pathway, were inhibited by the anti-CR3 monoclonal antibody M1/70, by the Fab portion of an anti-C3 antibody, or by the nucleophile, sodium salicyl hydroxamate, an inhibitor of C3 fixation. This provides strong evidence that M phi-derived, cleaved C3 (iC3b) present on the promastigote surface mediates binding to CR3. Equivalent inhibition of promastigote binding and ingestion was also observed using the soluble inhibitors of MFR activity, mannan or ribonuclease B. No additive effect for blocking the two M phi receptors simultaneously was observed. For amastigotes, which are poor activators of the alternative pathway, a lesser ...
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 ...
Jun 10, 2002 (CIDRAP News) The smallpox virus has a protein that inhibits the human complement system far more effectively than does its counterpart protein in the closely related vaccinia virus, used in smallpox vaccine, according to researchers who compared the two proteins. This difference may be an important reason for the virulence of smallpox and may offer an avenue for research on treatments, they suggest.
This gene encodes a plasma glycoprotein that positively regulates the alternative complement pathway of the innate immune system. This protein binds to many microbial surfaces and apoptotic cells and stabilizes the C3- and C5-convertase enzyme complexes in a feedback loop that ultimately leads to formation of the membrane attack complex and lysis of the target cell. Mutations in this gene result in two forms of properdin deficiency, which results in high susceptibility to meningococcal infections. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Feb 2009 ...
Takematsu et al reported that disruption of the epidermal wall of Henderson-Paterson bodies induces acute inflammatory changes by activation of the alternative complement pathway on exposure to the ti... more
We have reported recently that C1qa−/− mice develop autoimmunity characterized by the production of ANA and immune complex-mediated GN associated with the presence of increased numbers of apoptotic bodies (4). IgG and C3 were present in the glomeruli of the diseased kidneys, which suggested that complement was being activated, most likely by the alternative pathway. This possibility led to the question of whether the development of glomerular injury in this model was dependent upon the activation of C3 in glomeruli by the alternative pathway. To test this hypothesis, we crossed mice deficient in C1q with mice deficient in factor B and C2.. Mice deficient in complement activation by disruption of the C2 and factor B genes did not develop spontaneous autoimmunity. When deficiency of C1q was added, renal damage and autoantibody production developed, suggesting a discrete role for the first component of the classical pathway, and possibly C4, in protection from autoimmunity. A striking feature ...
1G40: Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans.
Learn how uncontrolled or excessive complement activation may play a role in several autoimmune and inflammatory diseases, and why APL-2 (pegcetacoplan) targeting of complement proteins at the level of C3 is being investigated as a treatment.
Human VTN (Vitronectin) is a 478 amino acid protein (1-19 = signal domain) that belongs to a member of the pexin family. Vitronectin is an abundant glycoprotein found in serum and the extracellular matrix. It promotes cell adhesion and spreading, inhibits the membrane-damaging effect of the terminal cytolytic complement pathway, and binds to several serpin serine protease inhibitors. It is a secreted protein and exists in either a single chain form or a clipped, two chain form held together by a disulfide bond. Vitronectin has been speculated to be involved in hemostasis and tumor malignancy. Recent publication from James Thomsons group indicated that coated recombinant human vitronectin protein alone benefits iPS cell generation when combined with E8 culture medium. ...
Antibody testing standards are well underway. But validation relies on numerous orthogonal methods, and for best results, a combination of antibody-dependent and antibody-independent testing methods is suggested.
ex invites Dr Simon Fillatreau (Deutsches Rheuma Forschungszentrum, Berlin, Allemagne) in the frame of Mercredis de Bichat Beaujon seminars.. The seminar will be entitled:. "Antibody-independent functions of B cells and plasma cells". Seminar will take place in the "salle des thèses S179" of the Faculté de médecine Bichat, from 12.30 on Wenesday, December the 2nd 2015.. ...
may be part of the humoral arm of innate immunity and behave as functional ancestor of antibodies by mediating agglutination, complement activation and opsonization (Martinez de la Torre 2010 ...
The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... Interruption of the complement cascade *The recipient's complement cascade can be inhibited through the use of cobra venom ... Expression of human complement regulators (CD55, CD46, and CD59) to inhibit the complement cascade.[27] ... complement pathway activation and delayed type hypersensitivity (DTH).. Acute vascular rejection[edit]. Also known as delayed ...
... 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 ...
It is believed to be associated with the classical complement pathway. The preferred name is "dense deposit disease". Most ... Most cases are associated with the dysregulation of the alternative complement pathway. Spontaneous remissions of MPGN II are ... A candidate gene has been identified on chromosome 1. Complement component 3 is seen under immunofluorescence. Colville D, ... activating complement and damaging the glomeruli. MPGN accounts for approximately 4% of primary renal causes of nephrotic ...
The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... complement pathway activation and delayed type hypersensitivity (DTH). Also known as delayed xenoactive rejection, this type of ... Interruption of the complement cascade The recipient's complement cascade can be inhibited through the use of cobra venom ... Nonetheless, it is known that XNAs and the complement system are not primarily involved. Fibrosis in the xenograft occurs as a ...
The recruitment of the complement cascade via the classical pathway (antibody-antigen interaction). Membrane attack complex ( ...
The antigen-antibody complex can also activate complement through the classical complement pathway. Phagocytic cells do not ... Antibodies can also activate complement via the classical pathway, resulting in deposition of C3b and C4b onto the antigen ... C3b, C4b, and C1q are important complement molecules that serve as opsonins. As a part of the alternative complement pathway, ... The C1 complement complex can also interact with the Fc region of IgG and IgM immune complexes activating the classical ...
These antibodies can activate the classical complement pathway leading to lysis of enveloped virus particles long before the ... these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement ... Complement activation (fixation), in which antibodies that are latched onto a foreign cell encourage complement to attack it ... "classical" complement system.[30] This results in the killing of bacteria in two ways.[5] First, the binding of the antibody ...
IgG3 is an efficient activator of pro-inflammatory responses by triggering the classical complement pathway. It has the ... Complement fixation by IgA is not a major effector mechanism at the mucosal surface but IgA receptor is expressed on ... and activation of complement cascade. As IgM antibodies are expressed early in a B cell response, they are rarely highly ... a unique profile of antigen binding and distinct capacity for complement activation. IgG1 antibodies are the most abundant IgG ...
Binding of antibodies to red blood cells activates the classical pathway of the complement system. If the complement response ... 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 ... In the formation of the membrane attack complex, several complement proteins are inserted into the red blood cell membrane, ...
... fibromodulin activates the classical pathway of complement by directly binding C1q". The Journal of Biological Chemistry. 280 ( ...
"The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in ... "A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo". Journal of ... He was awarded a PhD for research into complement receptors under the supervision of Peter Lachmann in 1986 at the University ... Walport, Mark Jeremy (1986). The biology of complement receptors (PhD thesis). University of Cambridge. "Mark Walport, PhD, MB ...
This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as ... Hessing M, van 't Veer C, Hackeng TM, Bouma BN, Iwanaga S (Oct 1990). "Importance of the alpha 3-fragment of complement C4 for ... Complement C4-A is a protein that in humans is encoded by the C4A gene. ... Hortin G, Sims H, Strauss AW (Feb 1986). "Identification of the site of sulfation of the fourth component of human complement ...
... 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 ...
"Formation of classical C3 convertase during the alternative pathway of human complement activation". PubMed Article. Retrieved ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... C3 convertase formation can occur in three different pathways: the classical, lectin, and alternative pathways. Cleavage of ... In the classical pathway, this is by sequential proteolytic activation of proteins within the C1 complex (C1q, C1r, C1s) in ...
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 ...
... classical or lectin pathway) or C3 (alternative pathway). Interaction of DAF with cell-associated C4b of the classical and ... Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene. DAF ... CCP2 and CCP3 alone are involved in its inhibition of the classical pathway. Because DAF is a GPI-anchored protein, its ... DAF contains four complement control protein (CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2 ...
In the classical pathway, the microbial pathogen is coated in antibodies (IgG and IgM) released by B cells. The C1 complement ... This cleavage can occur via three mechanisms (classical pathway, alternative pathway and lectin pathway) that ultimately lead ... inactivate the complement component. Given the C3 is constantly being turned over in the alternative pathway and its ability to ... In the alternative pathway, C3, present in the blood stream, spontaneously cleaves at low rates into C3b and C3a. If a microbe ...
The complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin ... Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system. Another important ... The subsequent complement cascade catalyzed by C3-convertase results in creating a membrane attack complex, which causes lysis ... In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), ...
Matsushita, M.; Fujita, T. (1992). "Activation of the classical complement pathway by mannose-binding protein in association ... This enzyme catalyses the following chemical reaction Selective cleavage after Arg223 in complement component C2 (-Ser-Leu-Gly- ... Arg-Lys-Ile-Gln-Ile) and after Arg76 in complement component C4 (-Gly-Leu-Gln-Arg-Ala-Leu-Glu-Ile) This mannan-binding lectin ( ... "A second serine protease associated with mannan-binding lectin that activates complement". Nature. 386 (6624): 506-510. doi: ...
1994). "Expression of the components and regulatory proteins of the classical pathway of complement in normal and diseased ... 1992). "Human immunodeficiency virus type 1 activates the classical pathway of complement by direct C1 binding through specific ... Complement C1q subcomponent subunit A is a protein that in humans is encoded by the C1QA gene. This gene encodes a major ... "Entrez Gene: C1QA complement component 1, q subcomponent, A chain". Human C1QA genome location and C1QA gene details page in ...
IgG activates the classical pathway of the complement system, a cascade of immune protein production that results in pathogen ... The relative ability of different IgG subclasses to fix complement may explain why some anti-donor antibody responses do harm a ... Nevertheless, it remains true that both human and mouse antibodies have different abilities to fix complement and to bind to Fc ... Given the opposing properties of the IgG subclasses (fixing and failing to fix complement; binding and failing to bind FcR), ...
... irreversibly binds to and inactivates C1r and C1s proteases in the C1 complex of classical pathway of complement. ... The activation of the complement cascade can cause damage to cells, therefore the inhibition of the complement cascade can work ... which triggers the complement cascade. Activation of the complement cascade attracts phagocytes that leak peroxide and other ... Inhibition of the complement cascade can decrease this damage. C1-inhibitor is contained in the human blood; it can, therefore ...
... activating the classical pathway of the complement system. The complement cascade system instead binds C1Q complex attached to ... Complement Component receptors CR2, CR3 and CR4 have been found to mediate this Complement -Mediated enhancement of infection. ... ADE in HIV can be complement mediated or Fc receptor mediated. Complements in presence of HIV-1 positive sera have been found ... The infection of HIV-1 leads to activation of complements fragments of these complements can assist viruses with infection by ...
IgG deposition and activation of the classical complement pathway involvement in the activation of human granulocytes by ...
"Killing of dsrA Mutants of Haemophilus ducreyi by Normal Human Serum Occurs via the Classical Complement Pathway and Is ...
Bowden, Hugh (2005). Classical Athens and the Delphic Oracle: Divination and Democracy. Cambridge University Press. ISBN 0-521- ... Pythia used oleander as a complement during the oracular procedure, chewing its leaves and inhaling their smoke. The toxic ... suggesting a specific pathway by which intoxicating gases could have risen into the oracle's sanctum... What delighted de Boer ... Parke, Herbert William, Sibyls and Sibylline Prophecy in Classical Antiquity, Routledge, London, ISBN 978-0-415-07638-8 ( ...
... Exp Neurol. ... Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy.. *. ... Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. Exp Neurol. ... Recent evidence supports that phagocytosis-associated molecules from the classical complement (C1q-C3) play novel roles in ...
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. ...
Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion, Bio-energetics ... High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimers ... Video articles in JoVE about classical complement pathway include Time-lapse 3D Imaging of Phagocytosis by Mouse Macrophages ... Complement Pathway, Classical: Complement activation initiated by the binding of Complement c1 to Antigen-antibody complexes at ...
We demonstrate that IgG-laden exosomes in plasma activate the classical complement pathway and that the quantity of these ... Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway. ... Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway ... Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway ...
Need Classical Complement Pathway, Pig, Assay for research? Find and compare commercial and governmental sources for ... Classical Complement Pathway, Pig, Assay. Description. The HIT430 measures the classical pathway activity mediated via IgM. ... Complement deficiencies or other defects in the complement system can easily be screened by running an assay for each pathway ... Complement deficiencies or other defects in the complement system can easily be screened by running an assay for each pathway ...
Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement.. M K ... Taken together, these data demonstrate that BC isoforms preferentially protect against the classical pathway of complement. ... Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement. ... Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement. ...
Human serum amyloid P component oligomers bind and activate the classical complement pathway via residues 14-26 and 76-92 of ... Human serum amyloid P component oligomers bind and activate the classical complement pathway via residues 14-26 and 76-92 of ... Human serum amyloid P component oligomers bind and activate the classical complement pathway via residues 14-26 and 76-92 of ... Human serum amyloid P component oligomers bind and activate the classical complement pathway via residues 14-26 and 76-92 of ...
... factor C4 are resistant to antibody and complement mediated experimental autoimmune myasthenia gravis (EAMG). Anti-C1q antibody ... Mice deficient for classical complement pathway (CCP) factor C4 are resistant to antibody and complement mediated experimental ... Tüzün E., Li J., Saini S., Yang H., Christadoss P. (2008) Targeting Classical Complement Pathway to Treat Complement Mediated ... Membrane Attack Complex Hereditary Angioedema Classical Complement Pathway Cobra Venom Factor Major Pathogenic Factor ...
Classical Pathway of Complement Activation: Longitudinal Associations of C1q and C1-INH With Cardiovascular Outcomes. The CODAM ... Objective-The classical complement pathway has been assigned both protective and pathological effects in cardiovascular disease ... Classical Pathway of Complement Activation: Longitudinal Associations of C1q and C1-INH With Cardiovascular Outcomes ... Classical Pathway of Complement Activation: Longitudinal Associations of C1q and C1-INH With Cardiovascular Outcomes ...
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Centers RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.. ...
... Nilsson, U R Uppsala University ... Simplified hemolytic assays for the classical (CP) and alternative (AP) pathways of complement (C) were developed. The CP ... Each pathway was tested independently of the other. Serum C levels, measured as described, correlated strongly with those ...
Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... Complement System Made Easy- Immunology- Classical Alternate & Lectin pathway Video Sep 07, 2018 ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ... C5 convertase is also formed by the Classical Pathway when C3b binds C4b and C2a. C5a is an important chemotactic protein, ...
Rohrer, B; Demos, C; Frigg, R; Grimm, C (2007). Classical complement activation and acquired immune response pathways are not ... Classical complement activation and acquired immune response pathways are not essential for retinal degeneration in the rd1 ... Download PDF Classical complement activation and acquired immune response pathways are not essential for retinal degeneration ... no functional classical complement activation pathway) knockout was followed during the degenerative process using light ...
2009) C1q, the recognition subcomponent of the classical pathway of complement, drives microglial activation. Journal of ... C1q, the recognition subcomponent of the classical pathway of complement, drives microglial activation ... We have shown previously that microglial biosynthesis of the complement subcomponent C1q may serve as a reliable marker of ...
Pathway maps. Immune response_Classical complement pathway. Object List (links open in MetaCore):. Antigen, C5b, C3dg, IgG1, ... Classical complement pathway. Complement system is a major effector of the humoral branch of the immune system, acting to ... Complement fragments interact with each another to form functional complexes.. Complement activation by the classical pathway ... complement component C3a + complement component C3b, H(,2)O + Complement component iC3b = Complement component C3c + complement ...
The molecular switches controlling the interaction between complement proteases of the classical and lectin pathways and their ... The molecular switches controlling the interaction between complement proteases of the classical and lectin pathways and their ... The molecular switches controlling the interaction between complement proteases of the classical and lectin pathways and their ... T1 - The molecular switches controlling the interaction between complement proteases of the classical and lectin pathways and ...
In addition, recent evidence has shown the role of the complement cascade in synaptic pruning in glaucoma and other diseases. ... We next determine the role of complement component 1 (C1) in early synaptic loss and dendritic atrophy during glaucoma. Using a ... This study further supports assessing the potential for complement-modulating therapeutics for the prevention of retinal ... Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma. ...
... he classical complement pathway plays a central role in immunity. Malfunction or disruption of this pathway is at the core of ... the initiating molecule of the classical complement cascade. They block activation of the entire classical pathway, including ... The complement pathway contains three arms - classical, alternative and lectin - all of which converge on C3, potentially ... has raised over $75M investment to build classical complement pathway treatments. Annexon Biosciences Inc. (San Francisco, ...
Novel Evasion Mechanisms of the Classical Complement Pathway. Brandon L. Garcia, Seline A. Zwarthoff, Suzan H. M. Rooijakkers, ... The Central Role of the Alternative Complement Pathway in Human Disease. Joshua M. Thurman and V. Michael Holers. J Immunol ... The Complement System and Antibody-Mediated Transplant Rejection. Erik Stites, Moglie Le Quintrec, and Joshua M. Thurman. J ... Is the Complement Activation Product C3a a Proinflammatory Molecule? Re-evaluating the Evidence and the Myth. Liam G. Coulthard ...
... terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to ... terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to ... and a CD59-like protein or molecules which indirectly counteract complement activation by binding various complement regulators ... and a CD59-like protein or molecules which indirectly counteract complement activation by binding various complement regulators ...
The Classical Pathway * The Alternate (Properdin) Pathway * The Lectin Pathway * Biological Activity of Complement and Its ...
... classical pathway. • immune system process. • innate immune response. • complement activation, lectin pathway. • complement ... Complement component 1s (EC 3.4.21.42, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... C1s cleaves C4 and C2, which eventually leads to the production of the classical pathway C3-convertase. ... Sim RB (1981). "The human complement system serine proteases C1r and C1s and their proenzymes". Methods in Enzymology. 80 Pt C ...
... which specifically recognize and inactivate components of the classical or alternative pathways of complement activation (5, 6 ... The second cascade is the classical MAPK pathway induced by Grb-2/mSOS recruiting, which activates p21ras. The third one (the ... Inhibition by mAb of Crry regulatory activity on the classical pathway. The effect of mAb on Crry-mediated protection of C3 ... On the other hand, the main functions of membrane proteins showing complement regulatory activity are decreasing complement ...
Title: Classical Pathway of Complement Activation: Longitudinal Associations of C1q and C1-INH With Cardiovascular Outcomes: ... It plays a pivotal role in regulating the activation of the classical complement pathway and of the contact system, via ... It plays a pivotal role in regulating the activation of the classical complement pathway and of the contact system, via ... negative regulation of complement activation, lectin pathway IDA Inferred from Direct Assay. more info ...
complement activation TAS Traceable Author Statement. more info. complement activation, classical pathway TAS Traceable Author ... Physicochemical and functional characterization of the C1r subunit of the first complement component. Ziccardi RJ, et al. J ... Fc-gamma receptor signaling pathway involved in phagocytosis TAS Traceable Author Statement. more info ...
  • 5. An immunotherapeutic preparation for activation of the alternate pathway of complement (APC) in a human or animal body, which comprises as the active component thereof particles of inulin in the gamma polymorphic form, wherein said particles are virtually insoluble in aqueous media at 37 C. (google.es)
  • She also postulated that the activation of complement by an alternate pathway is more important than activation by the classical pathway in the pathogenesis of rheumatoid arthritis and these findings have assisted in a wider understanding of autoimmune rheumatic diseases such as Juvenile idiopathic arthritis and their pathogenesis. (wikipedia.org)
  • Such findings indicate a physiologic role for isoform variation and have therapeutic implications for use of MCP isoforms as complement inhibitors in such areas as xenotransplantation. (jimmunol.org)
  • Annexon Biosciences Inc. (San Francisco, California, USA) has raised $75 million investment to fund development of its lead complement inhibitors through several clinical stages, according to the company. (euretina.org)
  • Understanding the foundation from the connection between C1s and its own physiological substrates will probably result in insights you can use to design effective inhibitors from the enzyme for make use of in treating illnesses caused by swelling as consequence of over-activity from the traditional go with pathway. (bassresearch.com)
  • 2 Consequently, efforts are underway to develop inhibitors that target different complement components as novel therapeutic agents. (ashpublications.org)
  • Complement inhibitors are being studied as potential therapeutics for immune diseases and Alzheimer's. (sigmaaldrich.com)
  • The contribution of individual activation pathways to different biological processes can be assessed by using pathway-selective inhibitors. (jimmunol.org)
  • Because the lectin pathway has been implicated in several life-threatening pathological states, these inhibitors should be considered as lead compounds toward developing lectin pathway blocking therapeutics. (jimmunol.org)
  • We next determine the role of complement component 1 (C1) in early synaptic loss and dendritic atrophy during glaucoma. (biomedcentral.com)
  • This review focuses on the current knowledge of immune evasion mechanisms exhibited by Lyme disease spirochetes and highlights the role of complement-interfering, infection-associated molecules playing an important part in these processes. (frontiersin.org)