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.
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.
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.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
A 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.
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.
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.
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).
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.
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.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
A 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.
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.
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).
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).
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.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).
A 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.
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.
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
A 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.
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
A 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 activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
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.
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.
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.
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).
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
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.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
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.
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
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.
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.
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
A 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.
A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.
A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).
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.
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.
Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.
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)
Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).
Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
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.
A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).
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.
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.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
A serine protease that cleaves multiple COMPLEMENT C5 into COMPLEMENT C5A (anaphylatoxin) and COMPLEMENT C5B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. It is the complex of ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) with an additional COMPLEMENT C3B, or C3bBb3b.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
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.
Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A 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.
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).
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.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
A 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.
A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts.
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.
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.
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.
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.
Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.
Antibodies produced by a single clone of cells.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
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.
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.
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.)
Established cell cultures that have the potential to propagate indefinitely.
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
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.
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.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
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).
Proteins prepared by recombinant DNA technology.
An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
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.
Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
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.
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).
Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
Plasmids containing at least one cos (cohesive-end site) of PHAGE LAMBDA. They are used as cloning vehicles.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Proteins found in any species of bacterium.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
A group of inherited disorders of the ADRENAL GLANDS, caused by enzyme defects in the synthesis of cortisol (HYDROCORTISONE) and/or ALDOSTERONE leading to accumulation of precursors for ANDROGENS. Depending on the hormone imbalance, congenital adrenal hyperplasia can be classified as salt-wasting, hypertensive, virilizing, or feminizing. Defects in STEROID 21-HYDROXYLASE; STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; 3-beta-hydroxysteroid dehydrogenase (3-HYDROXYSTEROID DEHYDROGENASES); TESTOSTERONE 5-ALPHA-REDUCTASE; or steroidogenic acute regulatory protein; among others, underlie these disorders.
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.
An individual in which both alleles at a given locus are identical.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Biologically active substances whose activities affect or play a role in the functioning of the immune system.
Elements of limited time intervals, contributing to particular results or situations.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
Glycoproteins found on the membrane or surface of cells.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
The sum of the weight of all the atoms in a molecule.
The rate dynamics in chemical or physical systems.
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
The presence of proteins in the urine, an indicator of KIDNEY DISEASES.
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.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
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.
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.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A plasma protein that circulates in increased amounts during inflammation and after tissue damage.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
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)
Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.
A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A mass spectrometric technique that is used for the analysis of large biomolecules. Analyte molecules are embedded in an excess matrix of small organic molecules that show a high resonant absorption at the laser wavelength used. The matrix absorbs the laser energy, thus inducing a soft disintegration of the sample-matrix mixture into free (gas phase) matrix and analyte molecules and molecular ions. In general, only molecular ions of the analyte molecules are produced, and almost no fragmentation occurs. This makes the method well suited for molecular weight determinations and mixture analysis.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.
The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
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.
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.
Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
The systematic study of the complete complement of proteins (PROTEOME) of organisms.
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.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.

A Schistosoma protein, Sh-TOR, is a novel inhibitor of complement which binds human C2. (1/10)

Human complement regulatory (also called inhibitory) proteins control misdirected attack of complement against autologous cells. Trypanosome and schistosome parasites which survive in the host vascular system also possess regulators of human complement. We have shown Sh-TOR, a protein with three predicted transmembrane domains, located on the Schistosoma parasite surface, to be a novel complement regulatory receptor. The N-terminal extracellular domain, Sh-TOR-ed1, binds the complement protein C2 from human serum and specifically interacts with the C2a fragment. As a result Sh-TOR-ed1 pre-incubated with C2 inhibits classical pathway (CP)-mediated haemolysis of sheep erythrocytes in a dose-dependent manner. In CP-mediated complement activation, C2 normally binds to C4b to form the CP C3 convertase and Sh-TOR-ed1 has short regions of sequence identity with a segment of human C4b. We propose the more appropriate name for TOR of CRIT (complement C2 receptor inhibitory trispanning).  (+info)

Complement C2 receptor inhibitor trispanning and the beta-chain of C4 share a binding site for complement C2. (2/10)

Complement C2 receptor inhibitor trispanning (CRIT) of the Schistosoma parasite binds human C2 via the C2a segment. The receptor in vivo functions as C2 decoy receptor by directly competing with C4b for binding to C2. As a result, CRIT is able to limit the extent of classical pathway (CP) C3 convertase formation. We report that the CRIT-extracellular domain 1 (ed1) peptide inhibits CP-mediated complement activation with an ICH(50) of approximately 0.1 microM, the C-terminal 11 aa of CRIT-ed1, named H17, even more effectively. The beta-chain region F222-Y232 of C4 shares 55% identity and 73% similarity with H17. Peptides based on this region also inhibit CP in a dose-dependent manner. As further evidence of C2 binding we showed CRIT-ed1 peptides and homologous C4 beta-chain peptides to inhibit complement in C2 hemolytic assays. We have predicted C4 beta-c F222-Y232 as a C2 binding site which we have termed the CRIT-ed1 domain, and the sequence [F/H]EVKX(4/5)P as a consensus C2-binding sequence. Anti-CRIT-ed1 cross-reacts with the C4 beta-chain and F222EVKITPGKPY232 appears to be the key epitope recognized by this Ab. Furthermore, anti-CRIT-ed1 was found to inhibit CP activation in a total hemolytic assay. We believe that Schistosoma CRIT-ed1, as well as C4 beta-chain peptides based on the CRIT-ed1 domain, function as interface peptides. These peptides, based on C2-binding sequences in CRIT, or C4, competitively inhibit the binding of C2 to C4b and thus limit the activation of C. The C4 peptides, unlike CRIT-ed1, did not inhibit the cleavage of C2 by C1s.  (+info)

Activation of postsynaptic Ca(2+) stores modulates glutamate receptor cycling in hippocampal neurons. (3/10)

We show that activation of postsynaptic inositol 1,4,5-tris-phosphate receptors (IP(3)Rs) with the IP(3)R agonist adenophostin A (AdA) produces large increases in AMPA receptor (AMPAR) excitatory postsynaptic current (EPSC) amplitudes at hippocampal CA1 synapses. Co-perfusion of the Ca(2+) chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid strongly inhibited AdA-enhanced increases in EPSC amplitudes. We examined the role of AMPAR insertion/anchoring in basal synaptic transmission. Perfusion of an inhibitor of synaptotagmin-soluble n-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor SNARE-mediated exocytosis depressed basal EPSC amplitudes, whereas a peptide that inhibits GluR2/3 interactions with postsynaptic density-95 (PDZ) domain proteins glutamate receptor interacting protein (GRIP)/protein interacting with C-kinase-1 (PICK1) enhanced basal synaptic transmission. These results suggest that constitutive trafficking and anchoring of AMPARs help maintain basal synaptic transmission. The regulation of postsynaptic AMPAR trafficking involves synaptotagmin-SNARE-mediated vesicle exocytosis and interactions between AMPARs and the PDZ domains in GRIP/PICK1. We show that inhibitors of synaptotagmin-SNARE-mediated exocytosis, or interactions between AMPARs and GRIP/PICK1, attenuated AdA-enhanced increases in EPSC amplitudes. These results suggest that IP(3)R-mediated Ca(2+) release can enhance AMPAR EPSC amplitudes through mechanisms that involve AMPAR-PDZ interactions and/or synaptotagmin-SNARE-mediated receptor trafficking.  (+info)

Structure of complement component C2A: implications for convertase formation and substrate binding. (4/10)

C2a provides the catalytic center to the convertase complexes of the classical and lectin-binding pathways of complement activation. We determined two crystal structures of full-length C2a, with and without a pseudo ligand bound. Both structures reveal a near-active conformation of the catalytic center of the serine protease domains, while the von Willebrand factor A-type domains display an intermediate activation state of helix alpha7 with an open, activated metal-ion-dependent adhesion site. The open adhesion site likely serves to enhance the affinity for the ligand C4b, similar to "inside-out" signaling in integrins. Surprisingly, the N-terminal residues of C2a are buried in a crevice near helix alpha7, indicative of a structural switch between C2 and C2a. Extended loops on the protease domain possibly envelop the protruding anaphylatoxin domain of the substrate C3. Together with a putative substrate-induced completion of the oxyanion hole, this may contribute to the high substrate specificity of the convertases.  (+info)

The crystal structure of C2a, the catalytic fragment of classical pathway C3 and C5 convertase of human complement. (5/10)

The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. Formation of these convertases requires the Mg(2+)-dependent binding of C2 to C4b, and the subsequent cleavage of C2 by C1s or MASP2, respectively. The C-terminal fragment C2a consisting of a serine protease (SP) and a von Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3 convertase, C4b2a. Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the alternative pathway C3 convertase, C3bBb. Although the overall domain arrangement of C2a is similar to Bb, there are certain structural differences. Unexpectedly, the conformation of the metal ion-dependent adhesion site and the position of the alpha7 helix of the vWFA domain indicate a co-factor-bound or open conformation. The active site of the SP domain is in a zymogen-like inactive conformation. On the basis of these structural features, we suggest a model for the initial steps of C3 convertase assembly.  (+info)

The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation. (6/10)

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Postsynaptic regulation of synaptic plasticity by synaptotagmin 4 requires both C2 domains. (7/10)

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The mechanism of action of decay-accelerating factor (DAF). DAF inhibits the assembly of C3 convertases by dissociating C2a and Bb. (8/10)

DAF is a 70,000-Mr membrane protein that inhibits the amplification of the complement cascade on the cell surface, and protects cells from damage by complement. The precise mechanism of action of DAF is not entirely clear. Purified DAF was incorporated into the membrane of EAC4b cells. EAC4b2 and EDAF AC4b2 cells were prepared with radiolabeled C2. The same amount of labeled C2 bound to both cells, showing that DAF does not prevent the binding of C2 zymogen to C4b. After adding Cl, the radioactivity of bound C2 dissociated more rapidly from EDAF AC4b cells than from EAC4b cells. In EAC4b cells, bound C2 was converted to C2a, which gradually dissociated into the supernatants. In the DAF-treated cells, on the other hand, a large amount of C2a rapidly appeared in the supernatants and only a small amount of C2a remained on the cells. In a similar experiment using EhuAC4b, DAF on human erythrocyte membrane also dissociated the C2a from the cells. These results were confirmed by hemolytic assay and the accelerated decay of C2a caused the rapid depletion of C2 from the fluid phase. In addition, we found that DAF functions on the alternative pathway C3 convertase, C3bBb in the same manner. Thus, DAF, which associates with C4b and C3b in the membrane, acts on C2a and Bb, but not on intact C2 and B, and dissociates them rapidly from the binding sites, thereby preventing the assembly of the classical and alternative pathways C3 convertases.  (+info)

Upon entrance into the insect from ingesting an infected humans blood, the so called stumpy form of T. brucei enters and must adjust itself to survive within the environment of the fly. This initial transformation is composed of a variety of chemical transformations that are not yet fully understood. It is assumed that proteases that exist within the insects midgut ignite a response to the new environment. [9] Beyond this idea, some believe that the microbe posses a cold-shock response that appears as the microbe travels from the warm-blooded human to the exothermic fly. Despite the controversy of this transformation, the stumpy form of the trypanosome remodels into the first form, the procyclic form. [9] This form only lasts a very short period of time before it transforms again. The microbe attaches itself onto the cells within the gut of the fly, a space referred to as the ecto peritrophic space. The connection to the cells within this space allows the form to change into one more ...
Cancer cells possess a broad spectrum of migration and invasion mechanisms. These include both individual and collective cell-migration strategies. Cancer therapeutics that are designed to target adhesion receptors or proteases have not proven to be effective in slowing tumour progression in clinica …
1) SARAH KATHERINE GRATE vs. PATRICK J. COLLINS, Administrator ad Litem for the ESTATE OF JAMES RUSSELL HADLEY, and STATE FARM MUTUAL AUTOMOBILE INSURANCE COMPANY (Circuit Court of Baldwin County, Alabama). County/Docket #/Judge: Baldwin / CV-2015-900510 / Jody W. Bishop. Plaintiff(s) Attorney(s): Lucy E. Tufts of Cunningham Bounds, LLC, Mobile, AL. Defendant(s) Attorney(s): Judson W. Wells, Sr., and Jonathan R. Maples of Carr Allison, Daphne, AL for Estate of James Russell Hadley/Patrick Collins; Steven P. Savarese, Jr., of Holtsford, Gilliland, et al., P.C., Daphne, AL for State Farm. Age/Sex/Occupation Of Plaintiff: n/a / F / n/a. Cause Of Injury: Negligence/Motor Vehicle Collision/Disputed Liability and Causation of Damages. On June 5, 2013, plaintiff Sarah Katherine Grate was involved in a motor vehicle collision with James Russell Hadley. Plaintiff filed a negligence action against Hadley and State Farm Mutual Automobile Insurance Company, her uninsured underinsured motorist carrier, on ...
Malaria and toxoplasmosis are infectious diseases caused by the apicomplexan parasites Plasmodium and Toxoplasma gondii, respectively. These parasites have developed an invasion mechanism involving the formation of a moving junction (MJ) that anchors the parasite to the host cell and forms a ring through which the parasite penetrates. The composition and the assembly of the MJ, and in particular the presence of protein AMA1 and its interaction with protein RON2 at the MJ, have been the subject of intense controversy. Here, using reverse genetics, we show that AMA1, a vaccine candidate, interacts with RON2 to maintain the MJ structural integrity in T. gondii and is subsequently required for parasite internalization. Moreover, we show that disruption of the AMA1 gene results in upregulation of AMA1 and RON2 homologues that cooperate to support residual invasion. Our study highlights a considerable complexity and molecular plasticity in the architecture of the MJ ...
HZI researchers redefine the invasion mechanism of Salmonella.. Bacteria of the genus Salmonella cause most food-borne illnesses. The bacteria attach to cells of the intestinal wall and induce their own ingestion by cells of the intestinal epithelium. Up …
Annually 163 mio. people are affected by bacillary dysentery, an acute inflammatory bowel disease, caused by Shigella bacteria. Shigella have the ability to invade the colonic epithelium in humans, thereby causing an acute mucosal inflammation. The invasive phenotype is encoded on a virulence plasmid. The expression of the so-called invasion genes is controlled by a virulence factor VirF. The translation of the virF mRNA depends on the activity of a tRNA modifying enzyme - the tRNA-guanine transglycosylase (TGT). TGT-mutants of Shigella are almost unable to penetrate host cells. In the first part of this work, the pathogenicity factor genes ipaA, ipgB2, ospD1, spa15, and ipgE, which are required at different points of the Shigella invasion mechanism, were cloned into several plasmid vectors and expressed in E. coli. In case of IpaA, OspD1, and IpgB2 only insoluble protein was obtained while in case of IpgE a purification protocol could be successfully established. Purified IpgE was identified ...
Im not going to go into confusing in depth number calculations and percentages instead Ill give you a simple rundown on whats going on. In BM 1 mastery is giving us about a .75% increase to overall dps whereas crit is a just a hair more than a 1% flat dps increase for each point. In SV mastery gets 1% on magical damage, but doesnt apply towards auto shots, kill shot, or pet dps numbers. Crit however gives 1% to all of these. So feel free to reforge into some crit over mastery right now, even if you didnt have mastery on anything you still get 8% because thats the baseline to start anyhow. I recommend playing around with reforging crit and mastery numbers and testing on the dummy to see how your own numbers are stacking up. Its easy to just read online about whos doing what and copy them, but doing a little of your own testing will help you see for yourself how its affecting you. ...
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http://www.mmo-champion.com/talent/?paladin=05203351020020320000000000000000000000000000000000000553201002030205200055300000 yea its kind of far fetched but +spell dmg from stam and ap and +30% crit heal and the healing crit HoTs for 30% of the crit heal hello big crit heals?
Prof. Lili Chen from Taiwan Ocean University paid a visit to Institute of Hydrobiology, Chinese Academy of Science (IHB) on April 25th, 2017. During his visit, he gave an oral presentation with the title of Study on the early morphogenesis stage of shrimp white spot syndrome virus (WSSV). Prof. Chen introduced that WSSV outbroke in the 1990s, causing serious economic losses to the worlds shrimp aquaculture. Her study focused on the early morphogenesis stage of WSSV. By investigating the interaction between viral protein and receptor, her team found the receptors of WSSV entry and the receptor binding protein. Based on these studies, she developed a kind of protein inhibitor which could specifically bind the receptor protein. After adding the protein inhibitor to the feed of shrimp, the mortality of shrimp infected with WSSV effectively decreased. In addition, Prof. Chen also made a brief introduction to the genome size, structure, morphology and invasion mechanism of WSSV. Prof. Chen, ...
Crit 4 Crit . My last piece was totally based ona stupid theory which i have devloped and Im proud of it. Tell me what do u think about this one P...
The C1 complex (complement component 1, C1) is a protein complex involved in the complement system. It is the first component ... Active C1s splits C4 and then C2, producing C4a, C4b, C2a and C2b. The classical pathway C3-convertase (C4bC2b complex) is ... 2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease. New York: Garland ... The antibodies IgM or certain subclasses of IgG complexed with antigens are able to initiate the complement system: a single ...
MASP-2 is activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. MASP1 (protein) Mannan-binding ... MASP-2 is involved in the complement system. MASP-2 is very similar to the C1s molecule, of the classical complement pathway, ... The Ra-reactive factor (RARF) is a complement-dependent bactericidal factor that binds to the Ra and R2 polysaccharides ... Petersen SV, Thiel S, Jensenius JC (2001). "The mannan-binding lectin pathway of complement activation: biology and disease ...
The classical pathway C5 convertase is composed of the fragments of complement proteins, C4b, C2a produced by cleavage mediated ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... In these respects, the mode of action of C5 is completely analogous to that of the other components of complement. The C5 step ...
Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or even a bacterial enzyme leads to formation of C3a ... C4a and C2a are released. C4a is an anaphylatoxin. C3 convertases are unstable (half-life 10 - 20 min) - respectively they are ... DAF protects host cells from damage by autologous complement. DAF acts on C2b and Bb and dissociates them rapidly from C4b and ... Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ...
The ship carries a complement of Dassault Rafale M and E‑2C Hawkeye aircraft, EC725 Caracal and AS532 Cougar helicopters for ... In June 2011 two US Navy C-2A(R) Greyhounds were assigned to French Navy to conduct operational carrier on-board delivery (COD ... In event of war CdG is expected to operate close to full complement of 40 aircraft. CdG air group took part in combat ... The figure equated to nearly 60 percent of the carrier's total complement.[74] ...
Historically, the larger fragment of C2 was named C2a, but it is now referred to as C2b. In invertebrates without an adaptive ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...
C2a, and C2b). C4a and C2b form C4bC2b, also known as C3 convertase. The lectin pathway is activated when pattern-recognition ... 12th European Meeting on Complement in Human Disease12th European Meeting on CHD12th European Meeting on Complement in Human ... C3a is one of the proteins formed by the cleavage of complement component 3; the other is C3b. C3a is a 77 residue ... Anaphylatoxins are small complement peptides that induce proinflammatory responses in tissues. C3a is primarily regarded for ...
... whereas older sources refer to the larger fragment of C2 as C2a, making the C3 convertase C4b2a). The smaller fragment, C2a (or ... Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical ... "Entrez Gene: C2 complement component 2". Krishnan V, Xu Y, Macon K, Volanakis JE, Narayana SV (2009). "The structure of C2b, a ... Johnson CA, Densen P, Hurford RK, Colten HR, Wetsel RA (May 1992). "Type I human complement C2 deficiency. A 28-base pair gene ...
... and C2a remaining in association with C4b; the C4b-C2a complex of the two proteins then exhibits a further system-associated ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar A, ... Complement component 4 (C4), in humans, is a protein involved in the intricate complement system, originating from the human ... All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a ...
Together, MBL, C4b and C2a are known as the C3 convertase. C3 is cleaved into its a and b subunits, and C3b binds the ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ... "/"self turned nonself" type pathogen pattern are also identified and destroyed (e.g. by complement fixation or other cytotoxic ...
After flying the Grumman C-1A Trader aircraft for over 26 years, VRC-40 completed a transition to the C-2A in 1986, marking the ... Instead, it prepares five separate sea going detachments with a two-plane complement while maintaining ashore "Homeguard" to ... VRC-40, homeported at NS Norfolk, operates the Grumman C-2A Greyhound and reports to Commander, Airborne Early Warning Wing, U. ...
MASP-1 and MASP-2 are activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. In f, two smaller MBL- ... The lectin pathway or lectin complement pathway is a type of cascade reaction in the complement system, similar in structure to ... Additional resources on Endothelial Injury Syndrome Classical complement pathway Alternative complement pathway Mannan-binding ... Historically, the larger fragment of C2 was called C2a but some publications now refer to it as C2b in keeping with the ...
Some sources designate the larger and smaller fragments as C2a and C2b respectively[13][14][15][16][17][18][19][20][21] while ... complement factor B, and complement factor I, as well as deletion of complement factor H-related 3 and complement factor H- ... Complement deficiencyEdit. Main article: Complement deficiency. It is thought that the complement system might play a role in ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...
Zipfel, P. F., Hallström, T., & Riesbeck, K. (2013). Human complement control and complement evasion by pathogenic microbes- ... mille tulemusena moodustuvad C2a, C2b, C4a ja C4b. C2a ja C4b kombineeruvad ning moodustub C3-konvertaas C4bC2a. Sama ... 1,0 1,1 1,2 1,3 Rus, H., Cudrici, C., & Niculescu, F. (2005). The role of the complement system in innate immunity. Immunologic ... 7,0 7,1 Lambris, J. D., Ricklin, D., & Geisbrecht, B. V. (2008). Complement evasion by human pathogens. Nature Reviews. ...
In February 2018, Petrel, with a US Navy team aboard, located and mapped the wreckage of a C-2A Greyhound aircraft that crashed ... For each expedition, Petrel invites local historians, scientists, and observers to complement the project crew. The team, while ... CS1 maint: discouraged parameter (link) "U.S. Navy mapped the wreckage of C-2A Greyhound that crashed into the Ocean". ...
The C1a and C2a subdomains are homologous and form an intramolecular 'dimer' that forms the active site. This structure ... "Mechanism of human immunodeficiency virus-induced complement expression in astrocytes and neurons". Journal of Virology. 76 (7 ...
For eight days, SH-60 Seahawk helicopters and C-2A Greyhound aircraft of the Ronald Reagan CSG helped deliver more than 519,000 ... Complement:. *Ship's company: 3,532. *Air wing: 2,480. Sensors and processing systems:. *SPS-48E 3-D air search radar ... "Search Ends For Sailors in C-2A Crash". navy.mil. 23 November 2017. Archived from the original on 25 November 2017. Retrieved ... On 22 November, a C-2A Greyhound cargo plane of VRC-30 with 11 crew and passengers aboard crashed into the Philippine Sea 145 ...
A Grumman C-2A Greyhound appears in the 2003 film Tears of the Sun. A SEAL team performs a parachute jump from it to begin a ... In Fascist Italy in the 1930s, aviation-themed films were used as propaganda tools to complement the massed flights led by ...
Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement. *DOI: 10.2210/pdb2ODP/pdb ... The crystal structure of c2a, the catalytic fragment of classical pathway c3 and c5 convertase of human complement.. Krishnan, ... Complement C2. A. 509. Homo sapiens. Mutation(s): 1 Gene Names: C2, hCG_43694. EC: 3.4.21.43. ... Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic ...
C2b and C2a. C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase. ... Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two ... C2b and C2a. C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase. ... Complement C2a fragmentAdd BLAST. 510. Amino acid modifications. Feature key. Position(s). DescriptionActions. Graphical view. ...
ELISA for the measurement of Human Complement C2 in Human Cell culture supernatant, Saliva, Milk, Serum, Plasma, Cerebral ... Human Complement C2 ELISA Kit is a Sandwich (quantitative) ... C2a, a serine protease, then combines with complement factor 4b ... Defects in C2 are the cause of complement component 2 deficiency (C2D) [MIM:217000]. A deficiency of the complement classical ... Cynomolgus C2 detected with complement C2 human ELISA kit (ab154132). Average Good 4/5 (Ease of Use) ...
Prevents Complement Attack. antigen/antibody. complex. C1QG. C7. C3. C8A. C4A. C4B. C5. H2O. DAF. C9. C1QA. C8B. C1R. C2A. C6. ... C2A. C4B. C5 convertase. C5B. C1QB. C1QG. C1QA. C1R. C1S. C1 complex. C8G. H2O. Osmotic lysis. MASP1. C3B. CFBb. Classical ... The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an ... Pathway:Human:Complement Activation Classical]] moved to [[Pathway:Homo sapiens:Complement Activation Classical]]: Renaming ...
C2A. H2O. C3. C8A. C1QA. C4B. C1R. C1S. C1QB. C7. C2. C4B. C3B. C3 convertase. C2A. C4B. C5 convertase. C5B. C1QB. C1QG. C1QA. ... The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an ... Pathway:Human:Complement Activation Classical]] moved to [[Pathway:Homo sapiens:Complement Activation Classical]]: Renaming ... gpml file for [[Human:Complement_Activation_Classical]]. External references DataNodes. View all...", "View last 5...") style ...
The enzymatic fragment of C2 is referred to as C2b in this review; the same fragment is sometimes designated as C2a in ... Complement beyond microbial defense. The past decade revealed a new perception of complement that reaches beyond the ... Complement can also be therapeutically engaged for the killing of tumor cells via complement-dependent cytotoxicity; for ... Beneficial effects of complement inhibition with soluble complement receptor 1 (TP10) during cardiac surgery: is there a gender ...
At least 30 different complement proteins act sequentially to produce a wide ranges of activities, from cell lysis to ... The complement system is a collection of blood and cell surface proteins that is a major primary defense and a clearance ... Why C2 left C2a on membrane? Non-senses!! ... when complement has been activated to separate in a-form and b- ... The complement system has four major antimicrobial functions.. Lysis - Polymerization of specific activated complement ...
5) C1 cleaves C2 C2a +C2b. 6) C3 convertase (C4b2a) splits C3 into C3a+C3b (important part: where converges). I) C3b ( ... Cannot tell cells apart, only groups/types (gram+/-) all have same gene to recognize patterns, same complement of receptors ( ... What are the three pathways to activate the complement system? What does each need to start? ... 1)recognition by tissue macrophages and complement. 2) macrophage cytokines production (tissue cell sentries). 3) other cells ...
Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement. ... Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement. ... Complement component C2a. 2ica. CD11a (LFA1) I-domain complexed with BMS-587101 aka 5-[(5S, 9R)-9-(4-cyanophenyl)-3-(3,5- ... Integrin I domain of complement receptor 3 in complex with C3d. 4mmx. Integrin AlphaVBeta3 ectodomain bound to the tenth domain ...
... promotes release of C2a from C4b2a by physically interfering with C4b and C2a association. ... encoded search term (Complement-Related Disorders) and Complement-Related Disorders What to Read Next on Medscape. Related ... Table 3. Proteins of the Human Complement (C) System, Lectin Pathway *Table 4. Proteins of the Human Complement (C) System, C3 ... Table 1. Proteins of the Human Complement (C) System, Classical Pathway* *Table 2. Proteins of the Human Complement (C) System ...
Complement C2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene ... Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or ... Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or ... C2b and C2a. C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase. *CO2_HUMAN, ...
binding to complement receptors (opsonization and clearance of immune complexes) *promote phagocytosis ... What are the functions and ligands of complement receptor 3 and 4 (CR3 and CR4) ... Which cell is an exception to all human cells have inhibitors to complement? ...
Complement cascade (Homo sapiens) * Initial triggering of complement (Homo sapiens) * Conversion of C2 into C2a and C2b (Homo ... Lectin pathway of complement activation (Homo sapiens) * Activation of MASPs (Homo sapiens) * MBL2,FCN:activated MASPs: ...
Complement cascade (Homo sapiens) * Initial triggering of complement (Homo sapiens) * Conversion of C2 into C2a and C2b (Homo ... Classical antibody-mediated complement activation (Homo sapiens) * Activation of C1r (Homo sapiens) * Antigen:IgG:C1Q:2x ... Regulation of Complement cascade (Homo sapiens) * Antigen:IgG:C1Q:2xActivated C1R:SERPING1:2xActivated C1S:SERPING1 dissociates ...
... whereas older sources refer to the larger fragment of C2 as C2a, making the C3 convertase C4b2a). The smaller fragment, C2a (or ... Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical ... "Entrez Gene: C2 complement component 2". Krishnan V, Xu Y, Macon K, Volanakis JE, Narayana SV (2009). "The structure of C2b, a ... Johnson CA, Densen P, Hurford RK, Colten HR, Wetsel RA (May 1992). "Type I human complement C2 deficiency. A 28-base pair gene ...
Some sources designate the larger and smaller fragments as C2a and C2b respectively[13][14][15][16][17][18][19][20][21] while ... complement factor B, and complement factor I, as well as deletion of complement factor H-related 3 and complement factor H- ... Complement deficiencyEdit. Main article: Complement deficiency. It is thought that the complement system might play a role in ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...
This pathway depends on the association of complement cleavage product C2a with mycobacteria. Identification of this method of ...
C2b and C2a. C2a, a serine protease, then combines with complement factor 4b to generate the C3 or C5 convertase. ... Defects in C2 are the cause of complement component 2 deficiency (C2D) [MIM:217000]. A deficiency of the complement classical ... Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two ... Patients with complement component 2 deficiency are also reported to have recurrent or invasive infections. ...
... complement component 2) for ICC/IF, WB. Anti-Complement C2 pAb (GTX105404) is tested in Human samples. 100% Ab-Assurance. ... Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or ... CO2 antibody, DKFZp779M0311 antibody, C2 antibody, complement C2 antibody, complement component C2 antibody, C3/C5 convertase ... complement component 2. Background. Component C2 is a serum glycoprotein that functions as part of the classical pathway of the ...
The origin and evolution of the complement system. *The evolution of complement begins with an ancestor to protease inhibitor a ... C2 can then attach to C4b, and is then cleaved by C1 into C2a and C2b. C2b and C4b then form the second serine protease in the ... Model for the evolution of the complement system Any model for the origin of the complement system must begin with the ... The complement system - Behes largest error in chapter 6 is choosing the complement system as an example of how evolution ...
... complement protein homologous to complement C3 of the mammalian complement system." Journal of Immunology 133(6): 3242-3249. ... C2 can then attach to C4b, and is then cleaved by C1 into C2a and C2b. C2b and C4b then form the second serine protease in the ... The origin and evolution of the complement system. *The evolution of complement begins with an ancestor to protease inhibitor a ... Model for the evolution of the complement system Any model for the origin of the complement system must begin with the ...
The C1 complex (complement component 1, C1) is a protein complex involved in the complement system. It is the first component ... Active C1s splits C4 and then C2, producing C4a, C4b, C2a and C2b. The classical pathway C3-convertase (C4bC2b complex) is ... 2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease. New York: Garland ... The antibodies IgM or certain subclasses of IgG complexed with antigens are able to initiate the complement system: a single ...
Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or ... Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. ...
Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or ... Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. ...
... of the vertebrate complement system. SpBf is composed of motifs typical of the Bf/C2 protein family. Expression of Sp152 ( ... Diversity of complement factor B/C2 in the common carp (Cyprinus carpio): three isotypes of B/C2-A expressed in different ... The sea urchin complement homologue, SpC3, functions as an opsonin.. *Lori A. Clow, David A. Raftos, Paul S. Gross, L Courtney ... Echinoderm immunity and the evolution of the complement system.. *Paul S. Gross, Walid Z. Al-Sharif, Lori A. Clow, L Courtney ...
Indeed, it now seems clear that complement first evolved as part of the innate immune system, where it still plays an important ... Although first discovered as an effector arm of the antibody response, complement can also be activated early in infection in ... This activity was said to complement the antibacterial activity of antibody, hence the name. ... Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria ...
Initial triggering of complement (Danio rerio) * Conversion of C2 into C2a and C2b (Danio rerio) * Homologues of C2a [ ... C4b:C2a:C3b [plasma membrane] (Danio rerio) * Cell surface:C4b:C2a [plasma membrane] (Danio rerio) * Homologues of C2a [ ... C4b:C2a:C3b [plasma membrane] (Danio rerio) * Cell surface:C4b:C2a [plasma membrane] (Danio rerio) * Homologues of C2a [ ... C4b:C2a:C3b [plasma membrane] (Danio rerio) * Cell surface:C4b:C2a [plasma membrane] (Danio rerio) * Homologues of C2a [ ...
This pathogen salvages the catalytic complement fragment C2a of the classical pathway C3 convertase and uses it to then deposit ... Complement, complement activation and anaphylatoxins in human ovarian follicular fluid. Clin. Exp. Immunol. 1990. 82:359-362. ... Complement receptors 1 and 3 are expressed on the plasma membrane of the egg (29). Complement is visualized as part of a highly ... The purpose of complement activation on AR spermatozoa may be to coat the IAM with opsonins. Complement fragments on ...
C5 convertase is also formed by the Classical Pathway when C3b binds C4b and C2a. C5a is an important chemotactic protein, ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells ... The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and ...
Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ... Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ... Since convertases mediate nearly all complement effector functions, they are ideal targets for therapeutic complement ... Since convertases mediate nearly all complement effector functions, they are ideal targets for therapeutic complement ...
  • The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. (wikipathways.org)
  • The complement system is a collection of blood and cell surface proteins that is a major primary defense and a clearance component of innate and adaptive immune responses. (virology.ws)
  • At least 30 different complement proteins act sequentially to produce a wide ranges of activities, from cell lysis to augmentation of the adaptive response. (virology.ws)
  • Activation of inflammation - Several peptides produced by proteolytic cleavage of complement proteins bind to vascular endothelial cells and lymphocytes. (virology.ws)
  • Opsonization - Certain complement proteins can bind to virions. (virology.ws)
  • Phagocytic cells with receptors for these complement proteins can then engulf the virus particles and destroy them. (virology.ws)
  • Some complement proteins can disrupt these complexes and facilitate their clearance from the circulatory system. (virology.ws)
  • Unfortunately the nomenclature of the complement proteins is confusing, because they were named as they were discovered, not according to their function (see illustration below of the classical pathway). (virology.ws)
  • The complement system as understood today is a multimolecular system composed of more than 32 proteins and consisting of serum proteins, serosal proteins, and cell membrane receptors that bind to complement fragments. (medscape.com)
  • The complement system consists of 7 serum and 9 membrane regulatory proteins, 1 serosal regulatory protein, and 8 cell membrane receptors that bind complement fragments. (medscape.com)
  • The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver , and normally circulating as inactive precursors ( pro-proteins ). (wikipedia.org)
  • Over 30 proteins and protein fragments make up the complement system, including serum proteins , and cell membrane receptors . (wikipedia.org)
  • Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes . (wikipedia.org)
  • The complement system is made up of a large number of distinct plasma proteins that react with one another to opsonize pathogens and induce a series of inflammatory responses that help to fight infection. (nih.gov)
  • A number of complement proteins are proteases that are themselves activated by proteolytic cleavage. (nih.gov)
  • In this way, the activation of a small number of complement proteins at the start of the pathway is hugely amplified by each successive enzymatic reaction, resulting in the rapid generation of a disproportionately large complement response. (nih.gov)
  • First, it generates large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement. (nih.gov)
  • Second, the small fragments of some complement proteins act as chemoattractants to recruit more phagocytes to the site of complement activation, and also to activate these phagocytes. (nih.gov)
  • Complement is a member of the innate immune system and is comprised of both soluble proteins and membrane-bound receptors that are activated following invasion of foreign pathogens. (frontiersin.org)
  • Deposition of complement proteins on the bacteria was monitored by Western blotting. (asm.org)
  • The complement system is a series of proteins that act in a defined sequence (Fig. 1 ) to promote immune clearance by opsonizing or killing microorganisms and augmenting the inflammatory response. (asm.org)
  • The nonactivated complement proteins are indicated above and to the right of the wide arrows, and the arrows pointing from them show the product that is released during activation. (asm.org)
  • To elucidate the molecular basis for complement resistance by BrkA, in this study we have attempted to determine which step in the complement cascade is affected by BrkA by monitoring the deposition of complement proteins on the surface of strains either expressing or not expressing BrkA. (asm.org)
  • The human complement system comprises a family of proteins that are essential to the human immune response against infections ( 1 ). (frontiersin.org)
  • Kirjavainen V, Jarva H, Biedzka Sarek M, Blom A, Skurnik M, Meri S. Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein. (labome.org)
  • The complement system consists of a number of small proteins found in the blood, normally circulating as inactive zymogens . (wikidoc.org)
  • Binding of the encoded protein to complement proteins accelerates their decay, thereby disrupting the cascade and preventing damage to host cells. (nih.gov)
  • The complement system that is a collection of proteins produced in the liver and circulate the whole body attacking pathogenic microbes. (start-seeking.ru)
  • The decreased expression of complement regulatory proteins (CRP) seems to play an important role in RA activity, and is associated with worsening of the clinical symptoms. (scielo.br)
  • rheumatoid arthritis, complement system proteins, complement activation. (scielo.br)
  • The complement system (CS) is composed of receptors and regulators bound to the cell membrane and different plasma proteins that interact with cells and mediators of the immune system ( Figure 1 ). (scielo.br)
  • Two additional human serum proteins structurally related to complement factor H. Evidence for a family of factor H-related genes. (embl-heidelberg.de)
  • We identify and characterize two human serum proteins with an apparent molecular mass of 24 and 29 kDa, which are antigenically related to complement factor H. These proteins represent differently glycosylated forms and are encoded by the same mRNA. (embl-heidelberg.de)
  • In addition, SCR3-4 of h24 and h29 display homology to SCR19-20 of human complement factor H. The relatedness of structural elements of the factor H-related proteins h24, h29, h37, and h42 and of factor H, suggests a function common to these proteins and indicates the existence of a gene family consisting of factor H and at least two factor H-related genes. (embl-heidelberg.de)
  • Complements are essential proteins. (labpedia.net)
  • Complement makes 10% of the serum proteins. (labpedia.net)
  • The complement system found in the blood of mammals is composed of heat labile substances (proteins) that combine with antibodies or cell surfaces. (atwebpages.com)
  • Within the blood are several small proteins that play an important role in the complement system. (iahealth.net)
  • These proteins can be found on every human cell and prevent for complement to occur to these cells. (iahealth.net)
  • Cell debris, virus, bacteria, antibody-antigen complexes and more items are not protected by these proteins and are subject to the complement system. (iahealth.net)
  • Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. (pubmedcentralcanada.ca)
  • Innate complement control mechanisms include complement regulatory proteins expressed on all serum-exposed cells, each of which intervenes at key points in the cascade, thereby protecting cell membranes against autologous complement damage. (pubmedcentralcanada.ca)
  • Complement system is a group of more than 23 proteins that interacts with each other to opsonize the pathogen and induces a series of inflammatory responses that helps to generate immune response against that pathogen. (periobasics.com)
  • The principal participants in this system are 11 proteins designated C1 through C9, B, and D . Term complement means to augment the effect of other complements of immune system. (periobasics.com)
  • It is composed of plasma and membrane proteins that complement antibody-mediated immunity through activation by three pathways. (lecturio.com)
  • Complement proteins C1-9 are named after C as complement and numbers in order of activation, except that C4 is activated before C2. (lecturio.com)
  • Serum sickness is an example of immune complex clearance by complement proteins. (lecturio.com)
  • The complement protein fragments with the lowest number attach to the target and act to activate other proteins. (lecturio.com)
  • C5 convertase (C2aC4bC3b) involved in classical pathway is assembled of two proteins, C4b and C2a , and additional C3b molecules. (pathwaymaps.com)
  • 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. (sinobiological.com)
  • 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. (sinobiological.com)
  • Some complement proteins bind to immunoglobulins or to membrane components of cells. (sinobiological.com)
  • Others are proenzymes that, when activated, cleave one or more other complement proteins and initiate an amplifying cascade of further cleavages. (sinobiological.com)
  • In HAE types I and II, complement proteins C2 and C4 are low. (mastattack.org)
  • Complement proteins are mercenaries produced regularly by the liver cells and employed in fighting infections in the body. (atgventure.com)
  • Complement proteins are enzymatic in nature and circulate in the body in inactive form. (atgventure.com)
  • The binding of antibodies (IgG or IgM) to the antigens which are mainly bacteria ( i.e antigen-antibody complex) trigger the activation of complement proteins, mainly: C1 and C4 and subsequently lead to the activation of other complement proteins in a cascade reaction. (atgventure.com)
  • Activations of complement proteins in this pathway require the binding of Mannan-Binding Lectins (MBL) to mannose (sugar) on the surfaces of microorganisms. (atgventure.com)
  • The complement proteins (C3b) bind to the antigens and present it to phagocytes which engulfs and digest them. (atgventure.com)
  • Complement proteins such as C5b, C6, C7 and C8 and C9 assembles at the membrane of cells to form "Membrane-attack complex (MAC)" which creates pores on the membrane of target cells and subsequently leading to their disruption. (atgventure.com)
  • The complement system or complement cascade as it is also known is a complex system of multiple proteins involved in inflammation and immunological response. (vetsci.co.uk)
  • It is a triggered enzyme cascade and there are more than 20 different proteins in the complement cascades, with most being enzymes or pro-enzymes. (vetbook.org)
  • Complement acts as a danger‐sensing system in the innate immune system, and its activation initiates a strong inflammatory response and cleavage of the proteins C3 and C5 by proteolytic enzymes, the convertases. (embopress.org)
  • Activation of the proteolytic complement cascade triggers cleavage of the homologous 185-200 kDa proteins C3, C4, and C5 ( Supplementary Figure S1 ). (embopress.org)
  • The complement system consists of a series of cleavage reactions, whereby complement proteins are split off into fragments, and in certain steps bond to other complement fractions. (metabolichealing.com)
  • The complement system is a part of the immune system, consists of a series of proteins that interact with one another in a highly regulated manner, in order to eliminate pathogens. (microbeonline.com)
  • Complements are soluble proteins and glycoproteins mostly produced by hepatocytes . (microbeonline.com)
  • Later on, it was discovered that the lytic action of complement was due to the interactions of a complex group of proteins. (microbeonline.com)
  • Up to C5, activation involves prote- The term 'complement' refers to the ability of olytic cleavage, liberating smaller fragments these proteins, to complement (augment) the from C2 through C5 except for C2, where for effects of other components of the immune historical reasons the larger fragment that re- system (e. (gurmeeteater.ee)
  • Type III hypersensitivity reactions occur when IgG and IgM antibodies bind to soluble proteins rather than cell surface molecules as in type II hypersensitivity reactions forming immune complexes that can deposit in tissues, leading to complement activation, inflammation, neutrophil influx and mast cell degranulation. (musicmarkup.info)
  • Complement proteins promote the solubilization of these complexes and their clearance by phagocytes. (aurignacien.com)
  • Synthesis of proteases specifically against complement proteins degrades complement components. (aurignacien.com)
  • C3b has most important opsonizing activity Inflammation - by attracting macrophages and neutrophils Membrane attack - by rupturing cell wall of bacteria Overview[ edit ] Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes. (rhein-main-verzeichnis.info)
  • The C-terminal fragment C2a consisting of a serine protease (SP) and a von Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3 convertase, C4b2a. (rcsb.org)
  • Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the alternative pathway C3 convertase, C3bBb. (rcsb.org)
  • C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase. (uniprot.org)
  • Activated cleavage products C2A and C4B combine to form C3 convertase, which cleaves C3. (wikipathways.org)
  • C2b is the smallest , enzymatically active fragment which is incorporated into the C3 convertase in this pathway, C4b2b (NB: some sources now refer to the larger fragment of C2 as C2b, making the C3 convertase C4b2b, whereas older sources refer to the larger fragment of C2 as C2a, making the C3 convertase C4b2a). (wikipedia.org)
  • In the first phase, a series of specific interactions leads to formation of intrinsic complement proteinase, termed C3 convertase. (medscape.com)
  • Depending on the nature of complement activators, the classic pathway, the alternative pathway, or the more recently discovered lectin pathway is activated predominantly to produce C3 convertase. (medscape.com)
  • C5 convertase is also formed by the Classical Pathway when C3b binds C4b and C2a. (technologynetworks.com)
  • Our models enable functional characterization of purified convertase enzymes and provide a platform for the identification and development of specific convertase inhibitors for treatment of complement-mediated disorders. (frontiersin.org)
  • Convertase enzymes fulfill a central role in the complement cascade as they cleave C3 and C5, which mediate nearly all complement effector functions. (frontiersin.org)
  • In its activated form, C4b becomes a subunit of the C3 convertase, which is an enzymatic complex that activates C3 of the classical and lectin complement activation pathways. (adipogen.com)
  • C4b and C2a bind to form C3-convertase. (adipogen.com)
  • The remaining α chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. (adipogen.com)
  • C2a and C4b combine to produce C3 convertase (C3 activating enzyme). (atwebpages.com)
  • 1 , 2 Although IgG1-acetylcholine receptor (AChR) complexes can modulate AChRs by cross-linking and accelerating degradation as well as functionally blocking AChRs, it is the activation of complement through successive stimulation of C3 and C5 convertase that ultimately results in a membrane attack complex with lysis of the post-synaptic muscle endplate. (pubmedcentralcanada.ca)
  • C4b and C2a form together C4b2a, which is known as the C3 convertase . (lecturio.com)
  • Most of C4b attaches to the target cells while only a few binds to C2a to form C3 convertase. (lecturio.com)
  • C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. (bireme.br)
  • C1r cleaves and activates C1s , which translates the activation of the Complement component C1 complex into complement activation via cleavage of C4 and C2 to form a C3 convertase (C2aC4b) . (pathwaymaps.com)
  • Together C2a and C4b forms the classical C3 convertase. (labhos.com)
  • C3 is then cleaved by the C3 convertase, and forms C5 convertase in association with C4b and C2a. (sinobiological.com)
  • The protein C2a combines with newly cleaved protein C4a to generate a C3 convertase, C2aC4b. (epinex.cf)
  • Proteolysis of C4 is also triggered via recognition of microbial carbohydrates in the lectin pathway (LP). C4b combines with C2 and subsequent cleavage of C2 to C2a results in generation of the LP/CP C3 convertase C4b2a. (embopress.org)
  • It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. (nih.gov)
  • C5 convertase, generated by the alternative, classical, or lectin pathway, initiates the activation of late components of the complement system to form membrane attack complex (MAC) and ultimately kills the pathogen. (microbeonline.com)
  • Two of the cleavage products -- C4b and C2a -- form a new protease ( C3 convertase , aka C4b2a ) which cleaves C3 into C3a and C3b. (studentreader.com)
  • Activated C1s also cleaves C2 and the larger fragment of C2 binds to the surface-attached C4b forming C4b,C2a, the C3/C5 convertase of the classical pathway. (complementtech.com)
  • Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. (uniprot.org)
  • A deficiency of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. (abcam.com)
  • The protein encoded by this gene is part of the classical pathway of the complement system, acting as a multi-domain serine protease. (wikipedia.org)
  • Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. (genecards.org)
  • Among its related pathways are Complement and coagulation cascades and Immune response Lectin induced complement pathway . (genecards.org)
  • Binding of factor H to C3b increases its inactivation by factor I. Properdin stabilizes it, preventing its inactivation by factors H and I. The alternate pathway does not result in a truly nonspecific activation of complement because it requires specific types of compounds for activation. (medscape.com)
  • Three biochemical pathways activate the complement system: the classical complement pathway , the alternative complement pathway , and the lectin pathway . (wikipedia.org)
  • The classical complement pathway typically requires antigen-antibody complexes for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous C3 hydrolysis, foreign material, pathogens, or damaged cells. (wikipedia.org)
  • This pathway depends on the association of complement cleavage product C2a with mycobacteria. (sciencemag.org)
  • It is the first component of the classical complement pathway and is composed of the subcomponents C1q, C1r and C1s. (wikipedia.org)
  • Activation of the C1 complex initiates the classical complement pathway. (wikipedia.org)
  • The antibodies IgM or certain subclasses of IgG complexed with antigens are able to initiate the complement system: a single pentameric IgM can initiate the pathway, while several monomeric IgG molecules are needed. (wikipedia.org)
  • This in turn cleaves and activates the next zymogen in the complement pathway. (nih.gov)
  • The classical pathway can be initiated by the binding of C1q, the first protein in the complement cascade, directly to the pathogen surface. (nih.gov)
  • Finally, the alternative pathway can be initiated when a spontaneously activated complement component binds to the surface of a pathogen. (nih.gov)
  • The alternative pathway is activated by distinct carbohydrate or lipid motifs on pathogens or altered self molecules, leading to recruitment of C3 and factor B. Mannan-binding lectin (MBL) is one of five different lectin pathway-specific carbohydrate recognition molecules in man that associate with lectin pathway-specific serine proteases to drive complement activation. (frontiersin.org)
  • MBL shares a high degree of structural homology with C1, the multimolecular complex that initiates the classical activation pathway of complement. (frontiersin.org)
  • These studies show that BrkA inhibits the classical pathway of complement activation and prevents accumulation of deposited C4. (asm.org)
  • Antigen-antibody complexes on the surface of a microorganism can activate the classical pathway of complement, a part of the acquired immune system (Fig. 1 ), by providing a binding site for C1. (asm.org)
  • Both the classical and alternative pathways of complement activation are represented, although details are given only for the classical pathway. (asm.org)
  • Interestingly, B. pertussis does not activate the alternative pathway of complement ( 7 ). (asm.org)
  • Chronic indwelling catheters have been reported to be associated with membranoproliferative glomerulonephritis (MPGN) via the activation of the classical complement pathway in association with bacterial infections such as coagulase negative staphylococcus. (hindawi.com)
  • The underlying etiologies of MPGN comprise a spectrum of conditions including infection, monoclonal gammopathy, autoimmune or rheumatologic disease, and dysregulation of the alternative complement pathway. (hindawi.com)
  • The classical complement pathway typically requires antibodies for activation (specific immune response), while the alternative and mannose-binding lectin pathways can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). (wikidoc.org)
  • Once bound to the target surface, C4b becomes an essential non-enzymatic subunit of the classical pathway C3 cleaving enzyme (C4b,C2a). (emdmillipore.com)
  • The complement system is a part of the larger immune system and three biochemical pathways are present: the classical complement pathway, the alternative pathway, and the mannose-binding lectin pathway. (adipogen.com)
  • C4 plays a central role in the activation of the classical pathway of the complement system. (adipogen.com)
  • factor B a complement component that participates in the alternative complement pathway. (thefreedictionary.com)
  • Antibody-mediated damage at the neuromuscular junction in myasthenia gravis (MG) is largely because of concomitant activation of the classical complement pathway. (pubmedcentralcanada.ca)
  • The binding of antibody to its antigen triggers the complement system through the so-called classical pathway. (periobasics.com)
  • A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. (bireme.br)
  • Complement activation by the classical pathway commonly begins with the formation of soluble antigen-antibody complexes (immune complexes) or with the binding of antibody (Immunoglobulins such as IgG1 and IgM ) to antigen on a suitable target, such as a bacterial cell. (pathwaymaps.com)
  • C4 is a component of the classical complement pathway and is split by activated C1s to C4a and C4b. (labhos.com)
  • The complement system has four major function, including lysis of infectious organisms, activation of inflammation, opsonization and immune clearance.There are three different complement pathways, the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway. (sinobiological.com)
  • The classic complement pathway is triggered when antibody-antigen complex interact with C1-complex, which consists of C1q, two molecules of C1r, and two molecules of C1s. (sinobiological.com)
  • The alternative complement pathway begins with the activation of C3 and requires factor B and factor D. All three pathways merge at C3, which is then converted into C3a and C3b. (sinobiological.com)
  • 3. Describe the Alternative Pathway of the complement cascade if it was NOT activated by random cleavage on the surface of a microbe. (wikidot.com)
  • 15. What are the difference between the Lectin Complement Pathway and the Classical Complement Pathway? (wikidot.com)
  • Deficiencies of an early component of the classical complement pathway (C1q, C1r, C1s, C2, C4) have been associated with lupus like autoimmune conditions. (mastattack.org)
  • There are three types of complement cascade, the classical and alternative pathways and the Mannan-binding lectin pathway. (vetsci.co.uk)
  • However in the alternative pathway the complement cascade does not require that an antibody binds to the antigen. (vetsci.co.uk)
  • This is the lytic pathway of complement function and can be initiated via either C3bB¯b3b or C4b2¯b3b. (vetbook.org)
  • The complement immune response consists of 3 pathways: the lectin pathway, the alternative pathway and the classical pathway. (metabolichealing.com)
  • The primary immune constituents of the lectin pathway are complements C4 and C2. (metabolichealing.com)
  • Both mold exposure and Lyme disease are associated with higher C4a levels ( R ). CFS/ME is associated with higher C4a levels ( R ). The significance of an elevation of C4a in these conditions is associated with activation of the lectin pathway of the complement immune system, the involvement of MASP-1, MASP-2, and MBL. (metabolichealing.com)
  • Controls the classical pathway of complement activation. (nih.gov)
  • A single, unique beta-chain encoded by this gene assembles with seven identical alpha-chains into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. (nih.gov)
  • The lectin pathway of complement activation is when mannose-binding lectin (MBL) and ficolins recognize and bind to carbohydrates on the pathogen surface. (wordpress.com)
  • In the classical pathway of complement, the F(c) of an antigen-antibody complex binds to the C1q component of C1. (studentreader.com)
  • The lectin pathway of complement is identical to the classical pathway, except the lectin pathway begins with mannose-binding protein instead of C1. (studentreader.com)
  • the noglobulin G (IgG) (IgG1, IgG2, IgG3 not system makes up an effective host im- IgG4) activate or fix complement via the clas- mune defense long before specific host sical pathway. (gurmeeteater.ee)
  • C1s is a subunit of the C1 complex which is the first complement component in the cascade referred to as the classical pathway of complement. (complementtech.com)
  • The alternative activation pathway and complement component C3 are critical. (rhein-main-verzeichnis.info)
  • This pathway can proceed on The complement component C3 is. (rhein-main-verzeichnis.info)
  • Reaction Cascade of the Complement System: Classical complement pathway The classical and alternative complement pathways The classical pathway is triggered by activation of the C1-complex. (rhein-main-verzeichnis.info)
  • The C1-complex now binds to and splits C2 and C4 producing C2a and C4b. (adipogen.com)
  • Binds C5 for cleavage by C2a. (atwebpages.com)
  • Cleavage of C5 requires complement fragment C3b which binds C5 and renders it susceptible to cleavage by the C4b,2a complex. (qmul.ac.uk)
  • The C1qrs complex binds with the C4b and C2b subcomponents, releasing C4a and C2a. (vetsci.co.uk)
  • It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. (nih.gov)
  • C2a binds C4b forming the C4b2a complex whereas C2b goes away. (microbeonline.com)
  • C4b then binds C2, which is cleaved by C1s to C2a and C2b forming the C4b2b complex. (wordpress.com)
  • It is thought that cleavage of C2 by C1s, while bound to C4b, results in a conformational rotation of C2b whereas the released C2a fragment may retain most of its original structure. (wikipedia.org)
  • In such a cascade, an active complement enzyme generated by cleavage of its zymogen precursor then cleaves its substrate, another complement zymogen, to its active enzymatic form. (nih.gov)
  • Investigations into the role of complement in ischemia/reperfusion (I/R) injury have identified common effector mechanisms that depend on the production of C5a and C5b-9 through the cleavage of C3. (frontiersin.org)
  • Less clear however is the mechanism of complement activation that leads to the cleavage of C3 in ischemic tissues and to what extent the potential trigger mechanisms are organ dependent - an important question which informs the development of therapies that are more selective in their ability to limit the injury, yet preserve the other functions of complement where possible. (frontiersin.org)
  • In most cases, the smaller fragment resulting from cleavage of a Complement component is designated 'a' and the larger fragment designated 'b' (e.g. (pathwaymaps.com)
  • C2a is the larger cleavage fragment) [1] . (pathwaymaps.com)
  • As a protease it has very restricted specificity, cleaving only C3b or C4b in the presence of a cofactor such as Complement factor H ( Factor H ). Cleavage of C3b by Factor I yields iC3b , a major opsonin [12] . (pathwaymaps.com)
  • Smaller fragments resulting from complement cleavage, C3a and C5a , called anaphylatoxins, bind to their cognate receptors ( CR3aR and CR5aR ) on the surface of mast cells and blood basophils and induce degranulation, upon release of histamine and other biologically active mediators [3] . (pathwaymaps.com)
  • Both provide a path to the cleavage of C3 which is a central event in complement activation. (vetsci.co.uk)
  • The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. (wikipathways.org)
  • The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
  • The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, inflammation to attract additional phagocytes, and activation of the cell-killing membrane attack complex . (wikipedia.org)
  • What does activation of the complement cascade result in? (brainscape.com)
  • The complement system activates through a triggered-enzyme cascade. (nih.gov)
  • Schematic overview of the complement cascade. (nih.gov)
  • In the early phases of an infection, the complement cascade can be activated on the surface of a pathogen through any one, or more, of the three pathways shown in Fig. 2.8 . (nih.gov)
  • Upon exposure of human spermatozoa to autologous serum or follicular fluid, we unexpectedly observed that acrosome-reacted spermatozoa activated the complement cascade efficiently through C3 but not beyond. (jci.org)
  • There are three different pathways that initiate the complement cascade, namely the classical, alternative, and the lectin pathways. (frontiersin.org)
  • In this study we characterized the step in the complement cascade where BrkA acts, using three strains: a wild-type strain, a strain containing an insertional disruption of brkA , and a strain containing two copies of the brkA locus. (asm.org)
  • The complement cascade. (asm.org)
  • Complement recognizes microbes or damaged host cells and subsequently triggers an enzymatic cascade that mainly serves to (a) label target cells for phagocytosis by immune cells, (b) produce chemoattractants, and (c) directly kill target cells via pore formation ( 2 ). (frontiersin.org)
  • The complement cascade begins via specific recognition of target cells in the classical (CP) and lectin (LP) pathways. (frontiersin.org)
  • The complement system is a biochemical cascade which helps clear pathogens from an organism. (wikidoc.org)
  • This gene encodes a glycoprotein involved in the regulation of the complement cascade. (nih.gov)
  • Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade (PubMed:7525274). (nih.gov)
  • the amplification convertases of the complement cascade. (genetex.com)
  • The 'complement cascade' is constitutive and non-specific but it must be activated in order to function. (atwebpages.com)
  • Once initiated, a cascade of events (the 'complement cascade') ensues, providing the functions listed above. (atwebpages.com)
  • A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. (bireme.br)
  • The complement system is known as a cascade because of the triggering and amplification of further components of the system. (vetsci.co.uk)
  • The whole complement cascade can be triggered in its entirety in a matter of microseconds. (vetsci.co.uk)
  • During the activation process the smaller 'a' subcomponent peptides which are formed, mediate many of the other effects caused by the complement cascade, for example acting as chemoattractants. (vetsci.co.uk)
  • The complement cascade (aka complement system or just complement ) has seven functions -- shown in the table below -- all of which are essential to the immune system. (studentreader.com)
  • The first complement cascade function discovered, cell lysis begins with pores forming in the cell membrane, and ends with fluid rushing into and bursting the cell (an event called hypotonic cell death ). (studentreader.com)
  • Anaphylatoxins C3a, C4a and C5a are small peptides produced during the complement cascade, and induce inflammation. (studentreader.com)
  • Complement System 7 The complement system includes serum and activate or inhibit reactions in the cascade. (gurmeeteater.ee)
  • One molecule 2 so far identified in the complement system, of IgM or two molecules of IgG can initiate 13 participate in the cascade itself, seven the process. (gurmeeteater.ee)
  • The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. (rcsb.org)
  • The recent crystal structure of complement protein component C2a reveals an interface between its VWA and serine protease domains that could not exist in the zymogen C2. (mblwhoilibrary.org)
  • The hublike organization of complement and its cell surface-directed action ( Fig. 1 ), involving some 50 constituents such as pattern-recognition molecules (PRM), protein components, proteases, regulators, and cell surface receptors, is essential for adjusting the complement response to different triggers ( Fig. 2A ). (jimmunol.org)
  • Complement C2 is a protein that in humans is encoded by the C2 gene. (wikipedia.org)
  • C2 (Complement C2) is a Protein Coding gene. (genecards.org)
  • Full length native complement component C2 protein isolated from human plasma. (abcam.com)
  • Recombinant protein encompassing a sequence within the center region of human Complement C2. (genetex.com)
  • The C1 complex (complement component 1, C1) is a protein complex involved in the complement system. (wikipedia.org)
  • Using FACS to simultaneously evaluate viability, acrosomal status, and complement deposition, we found that complement activation was initiated by C-reactive protein (CRP) and was C1q, C2, and factor B dependent. (jci.org)
  • Bordetella pertussis produces a 73-kDa protein, BrkA (Bordetella resistance to killing), which inhibits the bactericidal activity of complement. (asm.org)
  • Meri T, Blom A, Hartmann A, Lenk D, Meri S, Zipfel P. The hyphal and yeast forms of Candida albicans bind the complement regulator C4b-binding protein. (labome.org)
  • A complement protein attacking an invader. (wikidoc.org)
  • Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE): An autosomal recessive disease characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease. (nih.gov)
  • Solution structure of the fifth repeat of factor H: a second example of the complement control protein module. (embl-heidelberg.de)
  • Molecular cloning of a human serum protein structurally related to complement factor H. (embl-heidelberg.de)
  • Human C4 is the most polymorphic protein of the complement system. (adipogen.com)
  • CD46 molecule, complement regulatory protein ( MCP ) is a cofactor for the Factor I -mediated degradation of C3b and C4b deposited on host cells [13] . (pathwaymaps.com)
  • out, a electroneutrally employed protein on the domain of this carcinogenesis is congenital through the complex GlycoVis( Hossler P. After the complement of the incontinentia to the cancer, the modification of N-glycosylation activates. (erik-mill.de)
  • The important protein components of complement are number C1 to C9 (they are numbered in their order of discovery however and not their order of action as you will see later). (vetsci.co.uk)
  • C4b-binding protein has a regulatory role in the coagulation system also, mediated through the beta-chain binding of protein S, a vitamin K-dependent protein that serves as a cofactor of activated protein C. The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. (nih.gov)
  • In this paper, a mouse model is proposed to test whether a recombinant fusion protein consisting of CR2 and a region of Crry (CR2-Crry) is able to specifically inhibit the local complement activation induced by EV71 infection, and to observe whether this treatment strategy can alleviate or even cure the neurogenic inflammation. (biomedcentral.com)
  • The contributions of antibodies to the disease are initiated by their direct binding to their respective antigens and involve immune complex formation, deposition, and activation of complement and Fc receptors (FcRs). (biomedcentral.com)
  • Phagocytes have large numbers of iC3b receptors (complement receptors) which give opsonisation when engaged. (vetbook.org)
  • This complex then stimulates phagocytosis by binding phagocytices' complement receptors. (studentreader.com)
  • A Complement C2 specific antibody has been precoated onto 96-well plates and blocked. (abcam.com)
  • Standards or test samples are added to the wells and subsequently a Complement C2 specific biotinylated detection antibody is added and then followed by washing with wash buffer. (abcam.com)
  • Immunofluorescence analysis of methanol-fixed A431, using Complement C2(GTX105404) antibody at 1:200 dilution. (genetex.com)
  • This activity was said to ' complement ' the antibacterial activity of antibody , hence the name. (nih.gov)
  • Although first discovered as an effector arm of the antibody response, complement can also be activated early in infection in the absence of antibodies. (nih.gov)
  • Herein, we present a patient with PNH that received eculizumab, a humanized monoclonal antibody that blocks activation of the terminal complement at C5, before and immediately following allogeneic peripheral stem cell transplantation. (thefreelibrary.com)
  • 1 , 3 , 5 Animal models became resistant to the induction of EAMG when circulating complement was either depleted by cobra venom toxin or functionally inhibited by the administration of a monoclonal C5 antibody or soluble C1 receptor. (pubmedcentralcanada.ca)
  • Immune complexes can activate complement deposition on the antibody portion of the immune complexes leading to further activation of phagocytic and hematopoietic cells that clear the immune complexes from the circulation. (lecturio.com)
  • Formation of an antigen-antibody complex induces conformational changes in the Fc part of the IgM molecule that expose a binding site for the Complement component C1 . (pathwaymaps.com)
  • Complement, an important aspect of porcine immunology , is so called because it complements the function of antibody. (vetbook.org)
  • Complement activation is triggered by an antibody when it is bound to the antigen. (microbeonline.com)
  • Hence, the antibody activates the complement system only when bound to an antigen. (microbeonline.com)
  • In 1899, Paul Ehrlich renamed the heat sensitive component complement defining it as "the activity of blood serum that completes the action of antibody. (microbeonline.com)
  • We propose that this localized deposition of complement fragments aids in the fusion process between the spermatozoa and egg, in a role akin to that of complement in immune adherence. (jci.org)
  • Various cell types express surface membrane glycoproteins that react with one or more of the fragments of C3 produced during complement activation and degradation. (labpedia.net)
  • Complement fragments named opsonins, i.e. (pathwaymaps.com)
  • Complement fragments interact with each another to form functional complexes. (pathwaymaps.com)
  • A complex of complement fragments C4b, C2a and C2b. (qmul.ac.uk)
  • Complement has sev- mains bound to the complex is termed C2a, eral main effects: the smaller fragments are by the letter 'a' 1. (gurmeeteater.ee)
  • Complement component 3 (C3) occupies a central position because of the manifold biological activities of its activation fragments, including the major fragment, C3b, which anchors the assembly of convertases effecting C3 and C5 activation. (uab.edu)
  • The smaller fragment, C2a (or C2b, depending on the source) is released into the fluid phase. (wikipedia.org)
  • The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. (labome.org)
  • The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. (bvsalud.org)
  • Here we consider recent evidence for each of the three major pathways of complement activation (classical, lectin, and alternative) as mediators of I/R injury, and in particular highlight the role of lectin molecules that increasingly seem to underpin the injury in different organ models and in addition reveal unusual routes of complement activation that contribute to organ damage. (frontiersin.org)
  • Cite this article as: Fagbohun, S.O., "IMMUNOLOGY: UNDERSTANDING THE COMPLEMENT SYSTEM," in ATG Ventures , 09/03/2019, https://atgventure.com/immunology-understanding-the-complement-system/ . (atgventure.com)
  • Activated C1 cleaves C2 into C2a and C2b. (genecards.org)
  • Upon binding via C1q, C1r is activated to become a protease that cleaves C1s to a form that activates (cleaves) both C2 and C4 to C2a/b and C4a/b. (atwebpages.com)
  • C1 cleaves C2 into C2a and C2 b d. (wikidot.com)
  • MASP-1 cleaves complement C4 and C2 into C4b2a. (metabolichealing.com)
  • MASP-2 cleaves complement C4 into C4a and C4b, and Complement C2 into C2a and C2b, respectively. (metabolichealing.com)
  • Activated C1s enzyme cleaves complement component C4 releasing C4a and initiating covalent attachment of C4b to the activating surface. (complementtech.com)
  • Abcam's Complement C2 Human in vitro ELISA (Enzyme-Linked Immunosorbent Assay) kit is designed for the quantitative measurement of Complement C2 in CSF, plasma, serum, saliva, and cell culture supernatants. (abcam.com)
  • Although often overlooked as a defense of the respiratory tract, complement levels in this location are normally 10 to 20% of that found in serum and increase during inflammation ( 21 ). (asm.org)
  • Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. (bireme.br)
  • More than 20 types of complements are present in serum, found circulating normally in human body in inactive forms (called as zymogens or proenzymes) . (microbeonline.com)
  • In prezenta ionilor de Mg 2+ , C4b leaga C2 care este clivat, la randul sau, in doua fragmente: cel mare, C2a, ramane legat pe C4b si constituie complexul C4b2a, denumit convertaza C3, iar cel mic, C2b, este eliberat in plasma. (lamedic.ro)
  • C4b2a is the widely used short‐hand nomenclature for the C4b-C2a complex in the complement field, and similar nomenclature is used for the remaining complexes in the following). (embopress.org)
  • The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's cell membrane . (wikipedia.org)
  • The complement system can be recruited and brought into action by antibodies generated by the adaptive immune system . (wikipedia.org)
  • In the early 20th century, this controversy was resolved when it became understood that complement can act in combination with specific antibodies, or on its own in a non-specific way. (wikipedia.org)
  • Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria by antibodies and allows antibodies to kill some bacteria. (nih.gov)
  • Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss. (labome.org)
  • 05). The results of our study suggest that anti-beta2GPI antibodies may play a role in GMT formation, and this process might involve complement activation. (labome.org)
  • These are called complement because it complements the antibacterial activity of some of the antibodies. (labpedia.net)
  • The following example shows the role of Antibodies and complement in the process of Bacteriolysis and Agglutination. (labpedia.net)
  • Antibodies depend on complement for many of their biological activities. (vetsci.co.uk)
  • Because IgM has multiple F(c)s, it is more effective than other antibodies at activating complement. (studentreader.com)
  • In recent years, the complement system has been associated with a growing number of immunological and inflammatory conditions that include degenerative diseases, cancer, and transplant rejection. (jimmunol.org)
  • It becomes evident that excessive activation or insufficient control of complement activation on host cells can cause an immune imbalance that may fuel a vicious cycle between complement, inflammatory cells, and tissue damage that exacerbates clinical complications. (jimmunol.org)
  • Although the exact involvement of complement needs to be carefully investigated for each disease, therapeutic modulation of complement activity emerges as an attractive target for upstream inhibition of inflammatory processes. (jimmunol.org)
  • This review provides an update about the functional and collaborative capabilities of complement, highlights major disease areas with known complement contribution, and indicates the potential for complement as a focal point in immunomodulatory strategies for treating inflammatory diseases. (jimmunol.org)
  • Given the classic perception of complement as defense system against microbial intruders, it may appear surprising that this ancient pillar of innate immunity was identified as a contributor in various inflammatory pathologies. (jimmunol.org)
  • In the worst case, a vicious cycle between tissue damage, complement activation, and immune attack perpetually re-creates inflammatory stimulators rather than resolving them. (jimmunol.org)
  • In view of this upstream position in inflammatory homeostasis, there is growing interest in understanding the role of complement in pathological processes and in exploiting complement targets for therapeutic modulation ( 3 , 4 ). (jimmunol.org)
  • Fortunately, our knowledge about the functions of complement in health and disease has much improved, and new discoveries have revealed a fascinating cross-talk network that ties complement closely into the immune-inflammatory network ( 1 , 5 ). (jimmunol.org)
  • The past decade revealed a new perception of complement that reaches beyond the elimination of pathogens and includes key functions in immune surveillance, homeostasis, and mediation of inflammatory responses ( 1 , 2 ). (jimmunol.org)
  • however, dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. (frontiersin.org)
  • Unwanted complement activation on the body's own cells is a key pathological driver in a wide spectrum of immune diseases including autoimmune, inflammatory, and degenerative diseases ( 3 - 5 ). (frontiersin.org)
  • In addition, surface bound C4b has opsonic and immune adherence activities which are mediated via binding to the CR1 (CD35) complement receptor which is found on a variety of inflammatory cells. (emdmillipore.com)
  • Once complement is activated, its components participate in virtually every aspect of the inflammatory response. (labpedia.net)
  • Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. (adipogen.com)
  • The complement system plays a pivotal role in the inflammatory response. (biomedcentral.com)
  • Inappropriate or excessive activation of the complement system results in a severe inflammatory reaction or numerous pathological injuries. (biomedcentral.com)
  • Previous studies have revealed that EV71 infection can induce complement activation and an inflammatory response of the CNS. (biomedcentral.com)
  • Complements are activated only during inflammatory reactions. (microbeonline.com)
  • The ultimate goal for complement activation is C3b deposition on the target cell membrane followed by the membrane attack complex (MAC) responsible for opsonization . (lecturio.com)
  • The terminal sequence of complement activation involves Complement components C5b , C6 , C7 , C8 , and C9 , which interact sequentially to form a macromolecular structure called Membrane attack complex . (pathwaymaps.com)
  • These are the terminal complement components that form the membrane-attack complex. (wordpress.com)
  • Since convertases mediate nearly all complement effector functions, they are ideal targets for therapeutic complement inhibition. (frontiersin.org)
  • A unique feature of convertases is their covalent attachment to target cells, which effectively confines complement activation to the cell surface. (frontiersin.org)
  • Screening of well-characterized complement-binding molecules revealed that differential inhibition of AP C3 convertases (C3bBb) and C5 convertases [C3bBb(C3b) n ] is possible. (frontiersin.org)
  • Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents complement damage (PubMed:28657829). (nih.gov)
  • CD55 molecule decay accelerating factor for complement ( DAF ) inhibits the assembly of the complement system C3/C5 convertases by complex formation with C4b and C3b [10] , [11] . (pathwaymaps.com)
  • Finally, implications for metastability of complement convertases are discussed. (mblwhoilibrary.org)
  • Activation of complements leads to inflammation and localize the antigen or cause lysis. (labpedia.net)
  • Due to its destructive potential the complement system is heavily regulated but when activated it works largely by forming pore complexes as well as triggering acute inflammation and by promoting phagocytosis by macrophages and neutrophils. (vetbook.org)
  • CR2-Crry-mediated targeting complement inhibition will alleviate the local inflammation and provide an effective treatment for the severe neurological diseases associated with EV71 infection. (biomedcentral.com)
  • Lysis - Polymerization of specific activated complement components on a foreign cell or enveloped virus leads to the formation of pores. (virology.ws)
  • why human immune system has three complement pathways when all of them ultimately converge in cell lysis? (virology.ws)
  • A group of mice deficient in complement C3, the breakdown products of which bind to CR2, are also infected with EV71 virus. (biomedcentral.com)
  • Along with C3a and C5b67, C5a also is a chemoattractant an activator of white blood cells -- it induces monocytes and neutrophils to bind capillaries' vascular endothelium, extravasate out of the capillaries and migrate to tissue where complement has been activated. (studentreader.com)
  • A novel short consensus repeat-containing molecule is related to human complement factor H. (embl-heidelberg.de)
  • One molecule of IgM can activate complement but activation of IgG is with the help of cross linking 2 molecules. (periobasics.com)
  • As might be expected, there are many regulatory mechanisms to prevent uncontrolled complement activation. (nih.gov)
  • The components of the complement system can be found throughout the body in fluids, providing the body with a systemic means of protection. (vetsci.co.uk)
  • Complement receptor 1 (CR1) is important in increasing phagocytosis. (labpedia.net)
  • Yet it has become evident that complement not only acts as a sensor of pathogens but also recognizes diseased and damaged host cells, and it closely collaborates with other immune and defense systems to eliminate potential danger ( 1 , 2 ). (jimmunol.org)
  • Kupffer cells and other macrophage cell types help clear complement-coated pathogens. (technologynetworks.com)
  • Complement is also part of the innate immune defenses and provides a defense against pathogens that have not previously infected the host by recognizing repeating structures such as lipopolysaccharide (LPS) found on the surface of bacteria. (asm.org)
  • Complement resistance is common among respiratory pathogens. (asm.org)
  • Vascular endothelial growth factor receptor-1, interleukin-6 and TNF-alpha are all released by complement activation leading to angiogenesis with the formation of new blood vessels . (lecturio.com)
  • Opsonization of organisms and immune vation of complement components occurs complexes for clearance by phagocyto- via three main pathways. (gurmeeteater.ee)
  • Patients' T lymphocytes show increased complement activation causing surface deposition of complement and the generation of soluble C5a. (nih.gov)
  • Complement component C3 is cleaved by: A. C3b The classical and alternative pathways meet at complement component: A. C3. (rhein-main-verzeichnis.info)
  • A number of proteolytic activation steps follow which lead to deposition of C4b, C2a, C3b, and C5b on the bacterium. (asm.org)
  • These contain a non‐catalytic substrate contacting subunit (C3b or C4b) in complex with a protease subunit (Bb or C2a). (embopress.org)
  • Ehrlich and Morgan termed this factor complement. (medscape.com)
  • The purple sea urchin, Strongylocentrotus purpuratus, possesses a non-adaptive immune system including elements homologous to C3 and factor B (Bf) of the vertebrate complement system. (semanticscholar.org)
  • Coelomocytes express SpBf, a homologue of factor B, the second component in the sea urchin complement system. (semanticscholar.org)
  • Diversity of complement factor B/C2 in the common carp (Cyprinus carpio): three isotypes of B/C2-A expressed in different tissues. (semanticscholar.org)
  • Two diverged complement factor B/C2-like cDNA sequences from a teleost, the common carp (Cyprinus carpio). (semanticscholar.org)
  • Complement has been argued to have a component or factor in certain disease. (iahealth.net)
  • Complement factor I ( Factor I )), or by trivial names. (pathwaymaps.com)
  • Factor I is a major regulator of complement. (pathwaymaps.com)
  • functionally the larger peptide of Complement Factor 2( C2) had coiled C2a. (ersichtlich.de)
  • as the larger concentration of Complement Factor 2( C2) were deleted C2a. (erik-mill.de)
  • Research has found Lion's Mane is capable of inhibiting reverse transcriptase of HIV retrovirus ( R ), as well as increasing the expression of the antioxidant genes Nrf2 and gamma glutamyl cysteine (which activates glutathione directly) ( R ). Lion's mane also has neuroprotective and neurotrophic effects, by acting to increase NGF (nerve growth factor) ( R ). Does lion's mane activate the complement immune system? (metabolichealing.com)
  • Echinoderm immunity and the evolution of the complement system. (semanticscholar.org)
  • The effects of these polysaccharides have far-reaching possibilities for various aspects of the human immune system, including those relating to innate, complement immunity. (metabolichealing.com)
  • The human complement system is an important component of innate immunity. (uab.edu)
  • Third, the terminal complement components damage certain bacteria by creating pores in the bacterial membrane. (nih.gov)
  • C5 is cleaved into C5a/b that initiates the assembly of the terminal complement components. (wordpress.com)
  • Ehrlich, therefore, named this heat-labile component "complement," because it is something in the blood that "complements" the cells of the immune system. (wikipedia.org)
  • A decrease in deposition on the bacteria of C4, C3, and C9 corresponded with decreased complement sensitivity. (asm.org)
  • Complement system is a major effector of the humoral branch of the immune system, acting to protect the host from microorganisms such as bacteria. (pathwaymaps.com)
  • Complement system can be activated by immune complexes and immunologic molecules like endotoxins. (periobasics.com)
  • Immune complexes trigger complement activation by binding C1. (vetbook.org)
  • In addition, complement helps make immune complexes more soluble. (studentreader.com)
  • Indeed, it now seems clear that complement first evolved as part of the innate immune system , where it still plays an important role. (nih.gov)
  • Complement activation was monitored by enzyme-linked immunosorbent assay (ELISA) or Western blotting. (asm.org)
  • Ehrlich believed that each antigen-specific amboceptor has its own specific complement, whereas Bordet believed that there is only one type of complement. (wikipedia.org)
  • 12 , 13 Both DAF and, another complement regulator, CD59, appear to be concentrated at neuromuscular junctions and both can be upregulated by muscle cells. (pubmedcentralcanada.ca)
  • Only IgM and IgG can activate complement. (periobasics.com)
  • Only IgM and certain IgG subclasses can activate complement this way. (vetbook.org)
  • The bound C3b activates the next complement component C5, which again splits up into the subcomponents C5a and C5b upon activation. (vetsci.co.uk)
  • It inhibits complement activation at the yeast surface and, in addition, mediates adhesion of C. albicans to host endothelial cells. (labome.org)
  • Serpin peptidase inhibitor clade G member 1 ( C1 inhibitor ) inhibits activated C1r and C1s and thus regulates complement activation [9] . (pathwaymaps.com)
  • Which pathways trigger the role of complement in ischaemia/reperfusion injury? (frontiersin.org)
  • What are the two most important functions of complement? (brainscape.com)