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 sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.
Complement 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.
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).
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.
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.
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.
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.
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.
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 minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
The 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).
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 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).
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 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.
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.
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 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).
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
A 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 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 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 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 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).
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.
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.
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 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.
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.
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.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
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.
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
A 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.
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.
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.
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
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.
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).
Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
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.
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
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.
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.
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.
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.
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).
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)
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.
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.
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.
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.
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.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
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.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
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.
The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.
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.
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.
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.
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.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
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 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.
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.
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 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.
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.
Antibodies produced by a single clone of cells.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
The rate dynamics in chemical or physical systems.
Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.
The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.
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).
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
A 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 cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
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.
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).
Proteins prepared by recombinant DNA technology.
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).
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.
Elements of limited time intervals, contributing to particular results or situations.
Proteins found in any species of bacterium.
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.)
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
The 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 common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
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.
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.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A 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.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
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.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or 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.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
A 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).
Transport proteins that carry specific substances in the blood or across cell membranes.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
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.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
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.
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.
A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.
Glycoproteins found on the membrane or surface of cells.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
Serum proteins with an electrophoretic mobility that falls between ALPHA-GLOBULINS and GAMMA-GLOBULINS.
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)
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.
Polysaccharides consisting of mannose units.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
The sum of the weight of all the atoms in a molecule.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
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.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)
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.
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.
Immunoelectrophoresis in which a second electrophoretic transport is performed on the initially separated antigen fragments into an antibody-containing medium in a direction perpendicular to the first electrophoresis.
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.
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.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
A 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.
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.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.
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.
A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues.
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.
Polysaccharide isolated from the edible mushroom LENTINULA EDODES. The exact composition is unknown.
A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p100 precursor protein and is important for maturation of B-LYMPHOCYTES and adaptive HUMORAL IMMUNITY.
Physiologically inactive substances that can be converted to active enzymes.
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.
Inflammation of any part of the KIDNEY.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
An immunologic deficiency state characterized by an extremely low level of generally all classes of gamma-globulin in the blood.
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.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
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.
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.
Procedures, such as TISSUE CULTURE TECHNIQUES; mathematical models; etc., when used or advocated for use in place of the use of animals in research or diagnostic laboratories.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.
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 genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
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).
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
A species of motile, free-living, gram-negative bacteria that occur in the soil. They are aerobic or microaerophilic and are sometimes capable of nitrogen fixation.
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.
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.
A plant genus of the family NELUMBONACEAE. The common name of lotus is also for LOTUS and NYMPHAEA.
Presence of warmth or heat or a temperature notably higher than an accustomed norm.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
"Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2". J Clin Invest 116: 1425- ... Watford WT, Ghio AJ, Wright JR (2000). "Complement-mediated host defense in the lung". Am J Physiol Lung Cell Mol Physiol 279: ... Watford WT, Wright JR, Hester CG, Jiang H, Frank MM (2001). "Surfactant Protein A Regulates Complement Activation". J Immunol ... Alvarez-Dominguez C, Carrasco-Marin E, Leyva-Cobian F (1993). "Role of Complement Component Clq in Phagocytosis of Listeria ...
... alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with the ... Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene. DAF ... conversion of C2 to C2b, thereby preventing formation of the C4b2a C3-convertase, and interaction of DAF with C3b of the ... thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. Thus, by limiting the amplification ...
Medicus RG, Götze O, Müller-Eberhard HJ (1976). "Alternative pathway of complement: Recruitment of precursor properdin by the ... This characteristic distinguishes the C5 step, along with the C2 step, as potentially rate-limiting in the complement reaction ... or the alternative pathway (C3bBbC3b) of complement system. Two fluid phase C5 convertases have been described: the classical ... and C3b produced by cleavage mediated by the classical pathway C3 convertase (C4bC2a). The formation of the alternative pathway ...
The MASPs cleave C4 and C2, resulting in C3 convertase formation. The alternative pathway of complement activation is typically ... The classical pathway of complement activation is initiated when the C1 complex, made up of C1r and C1s serine proteases, ... Other than the alternative pathway, which is constantly active, C3a formation is triggered by pathogenic infection. ... C1q mediates the classical pathway by activating the C1 complex, which cleaves C4 and C2 into smaller fragments (C4a, C4b, C2a ...
In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 ... One form of C3-convertase, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. It catalyzes the ... Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are ... The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase. C3bBb is deactivated in steps. First, the ...
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... The cleavage of C4 and C2 is mediated by serine proteases. In the classical pathway, this is by sequential proteolytic ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... C3 convertase formation can occur in three different pathways: the classical, lectin, and alternative pathways. Cleavage of ...
C4a C2 Mannan-binding lectin pathway MASP1 / MASP2 Mannan-binding lectin Alternative complement pathway Factor B Factor D ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... divided by pathway) Classical complement pathway C1Q complex - C1R / C1S C4 - ... Treg differentiation JAK-STAT signaling pathway TGF beta signaling pathway TLR signalling pathway Cell adhesion molecules ...
This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in ... "Production and interferon-gamma-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line ... Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the ... components of the alternative-pathway C3 convertase of complement". The Biochemical Journal. 253 (3): 667-75. doi:10.1042/ ...
Alternative pathwayEdit. Main article: Alternative complement pathway. The alternative pathway is continuously activated at a ... Here, for consistency, we shall call all large fragments of complement b, so the larger fragment of C2 will be designated C2b. ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... Reaction Cascade of the Complement System: Classical, Alternative and Lectin Pathway, Amplification Loop, Terminal Pathway, and ...
... amongst other complement proteins and factors, leading to regulation of the alternative pathway of complement in particular. ... such as complement factor H-related genes, as well as in other complement proteins (e.g. factor I, C2/factor B, and C3) have ... Its principal function is to regulate the alternative pathway of the complement system, ensuring that the complement system is ... which are involved in dampening the effects of the alternative pathway of complement. A rare functional coding change, p.R1210C ...
Additional resources on Endothelial Injury Syndrome Classical complement pathway Alternative complement pathway Mannan-binding ... 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 ... In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The ...
The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the ... "Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus ... The alternative pathway of the complement system is an innate component of the immune system's natural defense against ... The C5-convertase of the alternative pathway consists of (C3b)2BbP (sometimes referred to as C3b2Bb). After the creation of C5 ...
... inactivate the complement component. Given the C3 is constantly being turned over in the alternative pathway and its ability to ... This activated C1 complex cleaves C4 and C2 forming a C4bC2b complex that covalently bonds to the surface of the microbe and ... This cleavage can occur via three mechanisms (classical pathway, alternative pathway and lectin pathway) that ultimately lead ... In the alternative pathway, C3, present in the blood stream, spontaneously cleaves at low rates into C3b and C3a. If a microbe ...
... protein associated with pattern recognition molecules of the complement system and regulating the lectin pathway of complement ... hence preventing cleavage of C4 and C2 mannan-binding lectin lectin pathway Degn SE, Hansen AG, Steffensen R, Jacobsen C, ... MASP-1, MASP-3 and MAp44 are alternative splice products of the MASP1 gene. MAp44 has been suggested to act as a competitive ... inhibitor of lectin pathway activation, by displacing MASP-2 from MBL, ...
... participates in all three of the complement pathways (classical, alternative, and lectin); the alternative pathway is " ... It interacts with protein C2; the same protease invoked earlier, C1s, then cleaves C2 into two parts, termed C2a and C2b, with ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar A, ... All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a ...
Most cases are associated with the dysregulation of the alternative complement pathway. DDD is associated with deposition of ... inherited complement deficiencies (esp C2 deficiency), scleroderma, Celiac disease. The histomorphologic differential diagnosis ... It is believed to be associated with the classical complement pathway. Also called recently as 'C3 nephropathy' The preferred ... immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway ( ...
... the classical complement pathway, the alternative complement pathway, and the lectin pathway. The alternative pathway accounts ... Here, for consistency, we shall call all large fragments of complement b, so the larger fragment of C2 will be designated C2b. ... Accordingly, the alternative complement pathway is one element of innate immunity.[citation needed] Once the alternative C3 ... Alternative Complement Pathway) Inflammation - by attracting macrophages and neutrophils. (Lectin pathway) Most of the proteins ...
... alternative pathway MeSH D12.776.124.486.274.860.387.500.374 - complement c3 convertase, alternative pathway MeSH D12.776. ... complement c2 MeSH D12.776.124.486.274.150.500 - complement c2a MeSH D12.776.124.486.274.150.750 - complement c2b MeSH D12.776. ... alternative pathway MeSH D12.776.124.486.274.860.387.750 - complement c3-c5 convertases, classical pathway MeSH D12.776.124.486 ... classical pathway MeSH D12.776.124.486.274.860.387.750.750 - complement c5 convertase, classical pathway MeSH D12.776.124.486. ...
The purine nitrogenous bases are characterized by their single amino group (NH2), at the C6 carbon in adenine and C2 in guanine ... Several groups are working on alternative "extra" base pairs to extend the genetic code, such as isoguanine and isocytosine or ... In order to understand how life arose knowledge is required of chemical pathways that permit formation of the key building ... which are called base complements, connect the two strands of the helix and are often compared to the rungs of a ladder. The ...
437.4 metres (1,435 ft)), then canal C-2 to Ingonish II (El. 436 metres (1,430 ft)) reservoirs, and on to canal C-3 which ... Wreck Cove is one of the two pathways Nova Scotia Power uses to meet this NERC requirement. Nova Scotia Power must maintain ... Wreck Cove makes up half of that hydro capacity, making it a key provider of reliable, renewable energy needed to complement ... NERC/NPCC requires electric utilities to have their largest single energy production source covered by an alternative source in ...
In organisms with two complements of the mutation, the protein is entirely absent from the cell membrane, and these critical ... 284 (1): C2-15. doi:10.1152/ajpcell.00417.2002. PMID 12475759. "Cystic Fibrosis Research Directions". National Institute of ... ATP binding, and the hydrolysis that follows, drives the alternative exposure of the cargo binding site, ensuring a ... in which the anion permeation pathway is closed off. The CFTR is found in the epithelial cells of many organs including the ...
Xu, Y., Narayana, S. V, & Volanakis, J. E. (2001). Structural biology of the alternative pathway convertase. Immunological ... Zipfel, P. F., Hallström, T., & Riesbeck, K. (2013). Human complement control and complement evasion by pathogenic microbes- ... C1r ja C1s-i aktivatsioonile koos C1s esteraasi formuleerumisega järgneb C4 ja C2 lõhustumine, mis vabastab väikseid peptiide ... 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 ...
... including the lack of other employment alternatives, the lower profitability of alternative crops in official crop substitution ... Cocaine is addictive due to its effect on the reward pathway in the brain. After a short period of use, there is a high risk ... This is due to the extra chiral center at C-2. This process occurs through an oxidation, which regenerates the pyrrolinium ... as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose. It has been ...
Many of the specifics of this pathway are still being investigated. It is not yet known if Dab1 is phosphorylated as a result ... Francis PJ, Hamon SC, Ott J, Weleber RG, Klein ML (May 2009). "Polymorphisms in C2, CFB and C3 are associated with progression ... These different isoforms result from variations in alternative splicing. The transcript of type I VLDLR (VLDLR-I) is composed ... "A neuronal VLDLR variant lacking the third complement-type repeat exhibits high capacity binding of apoE containing ...
Nevertheless, an alternative model has been proposed reinforced by certain experimental data. According to this model, ... Modulation alters CPG neuron complement by switching neurons between networks and fusing formerly separate networks into larger ... Cunningham ET, Sawchenko PE (February 2000). "Dorsal medullary pathways subserving oromotor reflexes in the rat: implications ... C2) to release more transmitter and strengthen its network synapses. Application of serotonergic antagonists prevents the ...
Nucleophilic attack on C2 generates a tetrahedral intermediate, with loss of the double bond in the dioxygen unit and bonds to ... Müller W, Hanauske-Abel H, Loos M (October 1978). "Biosynthesis of the first component of complement by human and guinea pig ... the complete cDNA-derived amino acid sequence and evidence for alternative splicing of RNA transcripts". Proceedings of the ... "Activation of the hypoxia-inducible factor-pathway and stimulation of angiogenesis by application of prolyl hydroxylase ...
Analysis of complement C1 inhibitor levels may play a role in diagnosis. C4 and C2 are complementary components. There are ... Dendorfer A, Wolfrum S, Wagemann M, Qadri F, Dominiak P (May 2001). "Pathways of bradykinin degradation in blood and plasma of ... can be used as an alternative, as it also contains C1 inhibitor. Other treatment modalities can stimulate the synthesis of C1 ... Measure: serum complement factor 4 (C4), C1 inhibitor (C1-INH) antigenic protein, C1 inhibitor (C1-INH) functional level if ...
The LRVs would complement the Infantry Squad Vehicles (ISVs), electrified versions of Stryker ICVDs (Infantry Carrier Vehicle ... 14 January 2020) Army Chief Seeks 'Minimally Manned' Vehicles, Joint C2 LRPF, ITN, IBCS, FARA, FLRAA, and "We need a joint ... Analysis of alternatives (AoA). Phase II award-2020-2023 Steve Trimble (24 July 2020) U.S. Army Upgrades Vision For Future ... and specify pathways for technology development'; Buy into the 'fail fast' mentality; '6.3-funded projects to produce knowledge ...
G-protein coupled receptor signaling pathway. • cell surface receptor signaling pathway. • movement of cell or subcellular ... Alternative splicing has been observed for this gene and three variants have been found.[7] The N-terminal fragment of CD97 ... Decay accelerating factor (DAF/CD55), a regulatory protein of the complement cascade, interacts with the first and second EGF- ... 8 C2,8 40.22 cM. Start. 83,723,251 bp[2]. End. 83,741,326 bp[2]. ... is independently regulated of the canonical Wnt pathway". ...
All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. ... Media related to Complement membrane attack complex at Wikimedia Commons. *Complement+Membrane+Attack+Complex at the US ... The membrane attack complex (MAC) or terminal complement complex (TCC) is a structure typically formed on the surface of ... Reid K. B. M., The complement system, in: B. D. Hames and D. M. Glover (eds.), Molecular Immunology, Oxford: IRL Press, 1988, ...
Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2.. Selander B1, Mårtensson U ... Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2 ... Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2 ... Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2 ...
C2.. C3.. 3.1.2 The alternative complement pathway.. 3.1.3 The lectin pathway. ...
... which can be activated by three pathways: classical (CP), lectin (LP) and alternative (AP). The CP and LP are mainly initiated ... which can be activated by three pathways: classical (CP), lectin (LP) and alternative (AP). The CP and LP are mainly initiated ... In fact, several T. cruzi molecules are known to interfere in the initiation of all three pathways and in the assembly of C3 ... In this context, the complement, as one of the first line of host defense against infection was shown to play an important role ...
Initial complement: activates the classical pathway, in which it breaks c4 into multiple parts (c4a=small c4b= big). ... Innate immunity: alternative pathway. activator- contact of microbial cell wall with C3 ...
Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. ... Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. ... The existence of an MBL-dependent C2 bypass mechanism for alternative pathway-mediated C3 activation was clearly demonstrated ... specific antibodies to CO supported C3 deposition through classical and alternative pathways. MBL-dependent C2 bypass ...
"Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2". J Clin Invest 116: 1425- ... Watford WT, Ghio AJ, Wright JR (2000). "Complement-mediated host defense in the lung". Am J Physiol Lung Cell Mol Physiol 279: ... Watford WT, Wright JR, Hester CG, Jiang H, Frank MM (2001). "Surfactant Protein A Regulates Complement Activation". J Immunol ... Alvarez-Dominguez C, Carrasco-Marin E, Leyva-Cobian F (1993). "Role of Complement Component Clq in Phagocytosis of Listeria ...
The C2-deficient serum demonstrated that A. baumannii can activate the alternative pathway. None of the isolates bound FH. ... Flow cytometry was utilized to determine whether complement regulator factor H (FH) was bound by A. baumannii, and to assay C3 ... and C2-deficient serum was used to examine its activation of the alternative pathway. ... Many gram-negative bacteria are directly killed by complement, but we hypothesized that A. baumannii would be resistant to ...
... of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin ... of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin ... mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement ... mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement ...
... factor B serves a function analogous to C2 and is a very similar protein; and factor D serves a function analogous to that of ... we studied the role of the C1-INH in inhibition of the alternative complement pathway. In the alternative complement pathway, ... as an inhibitor of the alternative complement pathway. C1-INH prevented lysis, induced by the alternative complement pathway, ... Because the alternative complement pathway has many features in common with the classical complement pathway, and because many ...
2012). Alternative complement pathway of channel catfish (Ictalurus punctatus): molecular characterization, mapping and ... expression analysis of factors Bf/C2 and Df. Fish and Shellfish Immunology 32:186-195. doi:10.1016/j.fsi.(2011).11.012. ... Jiang, C., Zhang, J. R., Yao, J., Liu, S. K., Li, Y., Song, L., Li, C., Wang, X. Z., and Liu, Z. J. (2015). Complement ... 2010). Alternative splicing in teleost fish genomes: Same-species and cross-species analysis and comparisons. Molecular ...
... complement C2 and complement factor B, which, respectively, have analogous roles in the classical and alternative pathways of ... Complement B/C2 (IPR011360). Short name: Compl_C2_B Overlapping homologous superfamilies *von Willebrand factor A-like domain ... in non-mammalian species are often more or less equally related to mammalian C2 and B and may be designated as complement B/C2 ... New structural motifs on the chymotrypsin fold and their potential roles in complement factor B.. EMBO J. 19 164-73 2000 ...
Binding of CRP to these substrates activates the classical complement pathway leading to their uptake by phagocytic cells. ... C2 and C3 with little consumption of C5-9. Surface bound CRP reduces deposition of and generation of C5b-9 by the alternative ... Binding of CRP to these substrates activates the classical complement pathway leading to their uptake by phagocytic cells. ... Regulation of complement activation by C-reactive protein Immunopharmacology. 1999 May;42(1-3):23-30. doi: 10.1016/s0162-3109( ...
Mouse Crry/p65 is a regulator of the alternative pathway of complement activation. Eur. J. Immunol. 1993. 23:1381-1384. View ... Deposition was dependent on C1q, C2, and factor B, consistent with initial activation of the classical pathway followed by ... Preferential inactivation of the C5 convertase of the alternative complement pathway by factor I and membrane cofactor protein ... This pattern is consistent with engagement of the classical pathway followed by amplification through the alternative pathway. ...
Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. J. Clin. Invest. 116:1425- ... the C4 and C2 bypass pathway) (11-13). The alternative pathway is constitutively active at low levels through the spontaneous ... the C4 and C2 bypass pathway). The alternative pathway amplification loop serves to generate more C3b deposition on the virus. ... pathway and the C4 and C2 bypass pathways (11-13) of complement activation (Fig. 1E). ...
Activate C4 and C2. 8 Describe the alternative pathway of complement activation ... What is the key enzyme of complement activation where all three pathways converge? ... to determine whether deficiencies or abnormalities in the complement system are causing, or contributing to, a patients ...
Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. Selander, Barbro LU ; ... Genetic analysis of complement C1s deficiency associated with systemic lupus erythernatosus highlights alternative splicing of ... Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway Moller-Kristensen, Mette ; ...
Which complement component is found in both the classic and alternative pathways? ...
In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 ... One form of C3-convertase, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. It catalyzes the ... Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are ... The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase. C3bBb is deactivated in steps. First, the ...
C3 is a key component of the complement system since classical and alternative activation pathways merge at the C3 activation ... Genetically controlled deficiencies of certain complement components occur relatively frequently, for example, C2 and C9. ... Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are ... severe bacterial infections revealing the central role of C3 in complement activation via the classical or alternative pathway ...
alternative pathway. C4BP. C4b-binding protein. CPB. cardiopulmonary bypass. CP. classical pathway. CR. complement receptor. FB ... Through activation of C2 and C4, both pathways lead to the assembly of C3 convertase complexes, which cleave the abundant ... Activation of complement by the alternative pathway as a factor in the pathogenesis of periodontal disease. Lancet 308: 1001- ... The spectrum of complement alternative pathway-mediated diseases. Immunol. Rev. 223: 300-316. ...
... complement explanation free. What is complement? Meaning of complement medical term. What does complement mean? ... Looking for online definition of complement in the Medical Dictionary? ... participate in the classical pathway; the alternative pathway lacks components C1, C2, and C4 but adds factor b, factor d, and ... alternate complement pathway, alternative complement pathway. the sequence in which complement components C3 and C5 to C9 are ...
alternate complement pathway, alternative complement pathway. the sequence in which complement components C3 and C5 to C9 are ... participate in the classical pathway; the alternative pathway lacks components C1, C2, and C4 but adds factor b, factor d, and ... the classic and alternative pathways. See Alternative pathway, Classic pathway, Complement activation Medtalk noun A set of ... Complement activation occurs by two different sequences, the classical pathway and the alternative pathway. All of the " ...
Hui K, Magnadottir B, Schifferli J, Inal J. CRIT peptide interacts with factor B and interferes with alternative pathway ... In a haemolytic assay using C2-deficient serum, CRIT-H17 interfered with AP complement activation. .. ... We suggest that MEP-1 acts together with the MOG proteins to repress fem-3 mRNA and that it also functions in other pathways to ... Schulz H, Pellicioli E, Thony Meyer L. New insights into the role of CcmC, CcmD and CcmE in the haem delivery pathway during ...
The complement system plays an important part in defense against pyogenic organisms. ... The complement system is part of the innate immune system. ... C2, C4), the alternative pathway (C3, factor B, properdin), and ... The complement cascade consists of 3 separate pathways that converge in a final common pathway. The pathways include the ... Zipfel PF, Heinen S, Jozsi M, Skerka C. Complement and diseases: defective alternative pathway control results in kidney and ...
... or C2. These results suggested that activation of the alternative pathway of complement might be involved in the observed ... permits activation of the alternative pathway but inhibits activation of the classical complement pathway. Sera in the presence ... The results are consistent with a role for the alternative pathway of complement in the inhibition of growth of rat primary ... prevents activation of both the alternative and classical complement pathways. [Ethylenebis(oxyethylenenitrilo)]tetraacetic ...
... the results using factor-B deficient serum and the influence of the alternative complement pathway from the results using C2- ... In another embodiment, the isolated human antibody mediates complement activation by the alternative pathway. ... shows FACS analysis of Mab-mediated deposition of C3 using C2-depleted (A) and Factor B-depleted (B) human serum as complement ... We performed ELISAs to determine if the Mabs could activate the human complement pathways and deposit C3 on PPS-3. We coated ...
CFH not only controls activity of the alternative complement pathway but of the other complement pathways, as well, as its ... this one containing the gene for complement component 1 and complement factor B (C2/CFB). The five SNPs in three genes acted in ... C3 is the key complement protein that mediates complement activation in all pathways of complement activation. Its endogenous ... Factor H is involved in the regulation of the alternative complement pathway and may influence any of the above activities. If ...
BF is a component of the alternative pathway of complement, whereas C2 is a component of the classical pathway. Both variants ... Complement Factor H, the Complement Alternative Pathway and AMD. Factor H is the main soluble inhibitor of the "alternative ... 6. The Complement System and AMD.. Three complement pathways can be distinguished by the "triggers" that activate them. 1) ... uncontrolled regulation of the alternative pathway of complement, plays a central role in the pathobiology of AMD. At this ...
... a major inhibitor of the alternative complement pathway, have been associated with the risk for developing AMD. ... and complement component 2 (C2). These genes were screened for genetic variation in two independent cohorts comprised of ~900 ... Complement Regulatory Gene Variants as Predictive Tests for Age-Related Macular Degeneration (AMD) Description of Technology: ... NIH researchers and their collaborators have now extended this work to two other regulatory genes of this pathway, Factor B (BF ...
No significant diet-family interaction for the regulation of LC-PUFA biosynthesis pathways could be detected by microarray ... the combination of our transcriptomic data with an analysis of plasmatic immune parameters revealed a stimulation of complement ... The expression of several genes involved in the LC-PUFA and cholesterol biosynthetic pathways was found to be up-regulated in ... fish fed VD, suggesting a stimulation of the lipogenic pathways. ... Determination of the alternative pathway of plasma complement ...
  • Lectin pathway activation of C3 is known to involve target recognition by mannan-binding lectin (MBL) or ficolins and generation of classical pathway C3 convertase via cleavage of C4 and C2 by MBL-associated serine protease 2 (MASP-2). (nih.gov)
  • In fact, several T. cruzi molecules are known to interfere in the initiation of all three pathways and in the assembly of C3 convertase, a key step in the activation of complement. (frontiersin.org)
  • Moreover, T. cruzi promotes secretion of plasma membrane-derived vesicles from host cells, which prevent the activity of C3 convertase C4b2a and thereby may hinder complement. (frontiersin.org)
  • Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system. (frontiersin.org)
  • At physiologic concentrations, it is a downregulator of the alternative pathway convertase. (rupress.org)
  • One form of C3-convertase, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. (wikipedia.org)
  • In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 (C3b) and factor B (Bb). (wikipedia.org)
  • The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase. (wikipedia.org)
  • First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having decay-accelerating factor (DAF) activity. (wikipedia.org)
  • Through activation of C2 and C4, both pathways lead to the assembly of C3 convertase complexes, which cleave the abundant plasma protein C3 into an anaphylatoxin fragment (C3a) and the opsonin C3b. (jimmunol.org)
  • for example, the proteins factor H and factor I inhibit the formation of the enzyme C3 convertase of the alternative pathway. (medscape.com)
  • Two fluid phase C5 convertases have been described: the classical pathway enzyme, C4b2boxy3b and the cobra venom factor-dependent C5 convertase, CVFBb. (wikipedia.org)
  • The formation of the alternative pathway C5 convertase (C3bBbC3b) starts by spontaneous cleavage of C3 protein exposing previously hidden thioester bond. (wikipedia.org)
  • Factor B then binds to C3b and is cleaved by a plasma serine protease Factor D. The C3bBb complex (= alternative pathway C3 convertase) remains attached to the cell-surface. (wikipedia.org)
  • This complex might interact with another C3b and thus form the alternative pathway C5 convertase.CVFBb is a noncovalent association product of CVF3 and the complement fragment Bb. (wikipedia.org)
  • The modified C5 convertase, C4b2boxy3b, contains C2b that is derived from C2 oxidized by iodine. (wikipedia.org)
  • The target of C5 convertase is complement protein C5. (wikipedia.org)
  • The complement component C5 can be also activated by fluid phase C5 convertase. (wikipedia.org)
  • For these functions to be executed, the complement system requires activation that is marked by the formation of the C3 convertase complex on the surface of target cells. (rupress.org)
  • This convertase cleaves large quantities of C3 into C3b, the main effector of complement, and C3a, a potent mediator of inflammation released into the medium. (rupress.org)
  • MBL-associated serine proteases MASP1 and MASP1 can cleave C2 and C4 in place of the C1 complex, leading to the formation of C3 convertase and the subsequent cascade. (wikipathways.org)
  • The Alternative pathway relies on the spontaneous hydrolysis of C3 and the cleavage of factor B (CFB) by factor D (CFD), which form an alternative C3 convertase stabilized by factor P (CFP). (wikipathways.org)
  • Additional copies of the cleavage product C3B are recruited to the complex, resulting in an alternative C5 convertase, which cleaves C5 and contributes C5B to the formation of the Membrane Attack Complex. (wikipathways.org)
  • MBL or ficolin activation of mannose-associated serine proteases (MASP) results in cleavage of C2 and C4 similar to the C1 complex, with subsequent production of C3 convertase and complement cascade activation resembling the classic pathway. (aacrjournals.org)
  • Generated C3b binds Bb, a cleavage fragment of factor B, and properdin, resulting in the formation of the alternative pathway C3 convertase. (aacrjournals.org)
  • Binding of additional C3b to the alternative pathway C3 convertase renders it capable of C5 cleavage, and forms the basis for the amplification loop of the alternative pathway. (aacrjournals.org)
  • Additionally, C3b generated by alternative pathway C3 convertase can attach to target surfaces and bind Bb, forming a C3 convertase that amplifies downstream complement proteins locally at the target surface. (aacrjournals.org)
  • Both the classical and the lectin pathway share the identical C3 and C5 convertase complexes formed after cleavage of C4 by either activated C1s (classical pathway) or activated MASP-2 (lectin pathway) (see 1) and subsequent cleavage and activation of C4b-bound C2 through activated C1s or MASP-2 (see 2). (asmscience.org)
  • More C3b is formed through the alternative pathway (AP) via the formation of alternative C3 convertase C3bBb. (biomedcentral.com)
  • This convertase, the alternative pathway C3-convertase, although only produced in small amounts, can cleave multiple C3 proteins into C3a and C3b. (wikipedia.org)
  • The addition of properdin forms the complex C3bBbP, a stable compound which can bind an additional C3b to form alternative pathway C5-convertase. (wikipedia.org)
  • The C5-convertase of the alternative pathway consists of (C3b) 2 BbP (sometimes referred to as C3b 2 Bb). (wikipedia.org)
  • After the creation of C5 convertase (either as (C3b) 2 BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). (wikipedia.org)
  • The formation of a C3 convertase can also be prevented when a plasma protease called complement factor I cleaves C3b into its inactive form, iC3b. (wikipedia.org)
  • Sequential activation of C4 and C2 enables the formation of C4b2b, which is the classical-pathway-derived C3 convertase. (asm.org)
  • On the bacterial surface, C3b binds factor B and presents factor B for cleavage by factor D. The resultant C3bBb complex is the alternative-pathway-derived C3 convertase. (asm.org)
  • The C3 convertase generated from either pathway can cleave C3 into C3a and C3b. (asm.org)
  • The DAF inhibitory effect on EAC14 or EAC43 was not overcome by supplying an excess of C2 or factor B, but the alternative pathway C3 convertase could be assembled in the presence of Ni++, or nonphysiological concentrations of Mg++, which enhances the binding affinity of factor B for C3b. (rupress.org)
  • 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)
  • The alternative pathway (AP) C3 convertase C3bBb is formed when factor B (fB) combines with C3b, after which fB is activated by factor D (fD) ( Figure 1A ). (embopress.org)
  • Alternative pathway c2 convertase, complement deficiencies in c3. (safeembrace.org)
  • The three pathways of activation all generate homologous variants of the protease C3-convertase . (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)
  • The C1-complex cleaves C2 and C4, which then form C3 convertase (C4b2a). (sinobiological.com)
  • The generation of C5 convertase is the end of the classical pathway. (sinobiological.com)
  • The MBL-associated serine proteases, MASP-1, and MASP-2, are activated and cleave C4 and C2, which then form the C3 convertase as in the classical pathway. (sinobiological.com)
  • 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)
  • Ligand binding by C1q and MBL results in the sequential activation of C4 and C2 to form the classical and lectin pathway C3-convertase. (justia.com)
  • Activated MASP2 in MBL-MASP2 complex cleaves C4 and C2 and generates C3 convertase (C4bC2a). (jci.org)
  • On a complement-activating surface, C3b binds Bb (produced by factor D-mediated cleavage of factor B) and generates C3bBb (the alternative pathway's C3 convertase). (jci.org)
  • Reconstitution of undiluted serum with C1q (70 mg/l, not shown) or D (1 mg/l) together with P (25 mg/l) did not promote C3 deposition, showing that the CO antigen did not activate complement in the absence of recognition proteins. (nih.gov)
  • The complement consists of at least 35 or more plasma proteins and cell surface receptors/regulators, which can be activated by three pathways: classical (CP), lectin (LP), and alternative (AP). (frontiersin.org)
  • Because the alternative complement pathway has many features in common with the classical complement pathway, and because many proteins of that pathway function in a manner analogous to proteins of the classical pathway, we studied the role of the C1-INH in inhibition of the alternative complement pathway. (rupress.org)
  • This family contains two mammalian proteins, complement C2 and complement factor B, which, respectively, have analogous roles in the classical and alternative pathways of complement activation. (ebi.ac.uk)
  • These proteins are composed of three regions, an N-terminal three-module complement control protein domain, a von Willebrand factor A domain, and a C-terminal serine protease domain. (ebi.ac.uk)
  • Briefly, they are activated by cleavage and function as the serine protease components of the C3/C5 convertases, which play similar roles in these pathways although composed of different proteins. (ebi.ac.uk)
  • Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case-letter suffixes, e.g. (thefreedictionary.com)
  • We suggest that MEP-1 acts together with the MOG proteins to repress fem-3 mRNA and that it also functions in other pathways to control development more broadly. (labome.org)
  • Genes that encode the proteins of complement components or their isotypes are distributed throughout different chromosomes, with 19 genes comprising 3 significant complement gene clusters in the human genome. (medscape.com)
  • The important components of this system are various cell membrane-associated proteins such as complement receptor 1 (CR1), complement receptor 2 (CR2), and decay accelerating factor (DAF). (medscape.com)
  • Complement, a part of the innate immune system, is composed of more than 30 plasma- and cell membrane-bound proteins that function cooperatively in antimicrobial and inflammatory reactions. (psychiatryadvisor.com)
  • A second set of initiating proteins, the ficolins, interact with acetylated sugars and proceed as in the mannose-binding lectin (MBL) pathway. (psychiatryadvisor.com)
  • Although deficiencies in complement components are rare, defects in the proteins that regulate complement are far more common. (psychiatryadvisor.com)
  • However, the decline in worldwide supplies of marine oils and fish meal [ 1 ] has led the industry and several research initiatives to investigate the possibility of using plant proteins and vegetable oils as alternatives to marine fishery-derived proteins and oils. (biomedcentral.com)
  • Various proteins of the complement system interact specifically with platelets, which, in turn, activates them and promotes thrombosis. (rupress.org)
  • Complement is a multi-component system that involves several plasma and cell-expressed proteins, and has been conserved throughout evolution. (rupress.org)
  • Also, C3b on the cell surface participates in the serial activation of complement proteins (C5-C9) that polymerize and form the C5b-9 complex, also known as the membrane attack complex. (rupress.org)
  • Several negative regulatory proteins exist to prevent uncontrolled activation of the complement system and widespread tissue damage. (rupress.org)
  • Several proteins of the complement system, including C3 and C5-C9, were shown to potentiate thrombin-induced platelet secretion and aggregation ( 4 ). (rupress.org)
  • Also, treatment of platelets with sublytic concentrations of C5b-9 caused transient membrane depolarization ( 6 ), granule secretion ( 7 ), generation of procoagulant platelet microparticles ( 8 ), and translocation of phosphatidylserine to the outer membrane leaflet ( 9 , 10 ) Collectively, these studies make the case that the complement system may serve as a link between inflammation and thrombosis, and reveal specific interactions between complement proteins and platelets. (rupress.org)
  • Lysozyme, some milk proteins, such as alpha lactalbumin, and low molecular-weight ligands, such as citrates and phosphates, are known to have high affinity binding sites for calcium (4), and may therefore act as inhibitors of complement indirectly, by chelating the divalent ions required for complement activation. (mcmaster.ca)
  • The serum Cp system consist of at least 19 proteins, mostly in pre-activated enzymatic forms, activated in a multi-step cascade reaction via either the classical or alternative pathways. (mcmaster.ca)
  • Complement is the term used to describe a group of serum proteins that are critically important in our defense against infection. (primaryimmune.org)
  • The complement system consists of more than 30 proteins, present in blood and tissues, as well as other proteins anchored on the surfaces of cells. (primaryimmune.org)
  • Complement proteins in the circulation are not activated until triggered by an encounter with a bacterial cell, a virus, an immune complex, damaged tissue or other substance not usually present in the body. (primaryimmune.org)
  • The circulating proteins have been grouped into three activation pathways, based on the types of substances and proteins that initiate the activation. (primaryimmune.org)
  • This unit describes several assay methods that can be used to determine the functional status of the classical pathway of complement and to quantitate its component proteins. (currentprotocols.com)
  • These can be used to measure the concentrations of most circulating complement proteins and to evaluate the functional status of C1‐esterase inhibitor. (currentprotocols.com)
  • The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. (wikipathways.org)
  • The contribution of the complement cascade to acute inflammation is well established, as is the continuous activation and consumption of complement proteins in chronic inflammatory states ( 7 , 8 ). (aacrjournals.org)
  • Thus, the recent finding that complement proteins C3, C4, and C5a may aid tumor growth through immunosuppression ( 11 ) is unexpected and suggests an insidious and previously unrecognized relationship between the complement system and cancer. (aacrjournals.org)
  • The latter fragment is the critical first protein that combines with C6, C7, C8, and multiple C9 proteins to form the MAC, the terminal, pore-forming complement protein complex responsible for lysis of cells and pathogens. (aacrjournals.org)
  • The complement system that is a collection of proteins produced in the liver and circulate the whole body attacking pathogenic microbes. (start-seeking.ru)
  • These kits allow for the analysis of activation of key proteins and specific pathways of the complement system in serum, plasma, and other biological fluids. (quidel.com)
  • Depleted sera are well suited for the detection and quantitation of hemolytically active complement proteins. (quidel.com)
  • 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 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)
  • conversely, higher levels of complement proteins were detected in plasma from patients than those in healthy subjects. (biomedcentral.com)
  • Our iTRAQ proteome study identified decreased and increased levels of 31 and 2 complement and complement-related proteins, respectively, in lung cancer tissues, of which the reduced levels of 10 components were further confirmed using quantitative RT-PCR and western blotting. (biomedcentral.com)
  • Serum complement is a group of globulin proteins that act as enzymes. (wbccount.org)
  • 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)
  • 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)
  • 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)
  • Each of these pathways uses different proteins. (medscape.com)
  • 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 lectin pathway is a type of cascade reaction in the complement system, similar in structure to the classical complement pathway, [ 1 ] in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade. (meddic.jp)
  • 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)
  • The complement system involves a group of proteins that play a role in host defense against infection. (google.com)
  • The inflammatory response is triggered by way of the cascade, in which low molecular weight peptides are cleaved from complement proteins. (google.com)
  • The attachment of complement proteins, C3b/C4b to microbial membranes or immune complexes, a process commonly known as opsonization, facilitates the binding of opsonized material to cell receptors. (google.com)
  • Several genes encoding complement system proteins are associated with age-related macular degeneration (AMD). (arvojournals.org)
  • We evaluated whether alterations in plasma proteins responsible for complement activation and regulation are also independentlyassociated with advanced AMD. (arvojournals.org)
  • 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)
  • Later on, it was discovered that the lytic action of complement was due to the interactions of a complex group of proteins. (microbeonline.com)
  • Complements are soluble proteins and glycoproteins mostly produced by hepatocytes. (microbeonline.com)
  • Complements are essential proteins. (labpedia.net)
  • Complement makes 10% of the serum proteins. (labpedia.net)
  • We determined bacterial survival rate and CS protein deposition in the presence of purified proteins, specific component depleted sera and NHS treated with the chelating agents EDTA (inhibits all three activation pathways) or EGTA (inhibits the Classical and Lectin Pathways). (bvsalud.org)
  • In this Review, I discuss immune and nonimmune functions of complement proteins and the tumor-promoting effect of complement activation. (jci.org)
  • The complement system is part of the innate immune response that is responsible for the opsonization of cell surfaces, generation of potent anaphylatoxins, and direct killing of invasive pathogens and altered self-cells ( 7 ). (frontiersin.org)
  • 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)
  • Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. (asm.org)
  • Complement component 3, often simply called C3, is a protein of the immune system. (wikipedia.org)
  • The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. (thefreedictionary.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • The complement system is part of the innate immune system. (medscape.com)
  • In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). (medscape.com)
  • New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. (medscape.com)
  • In addition, the combination of our transcriptomic data with an analysis of plasmatic immune parameters revealed a stimulation of complement activity associated with an immunodeficiency in the fish fed VD, and different inflammatory status between the two half-sibfamilies. (biomedcentral.com)
  • The complement system, an important component of innate immunity, is the most widely accepted pathogenic pathway of the immune system implicated in AMD. (molvis.org)
  • The primary functions of the complement system are to protect from infection, to remove particulate substances, (like damaged or dying cells, microbes or immune complexes) and to help modulate adaptive immune responses. (primaryimmune.org)
  • As part of the innate immune system, complement acts immediately to start the process of removal and resolution of the problem. (primaryimmune.org)
  • Complement works with the inflammatory cells of the innate immune system and those of adaptive or acquired immunity. (primaryimmune.org)
  • The Classical Pathway (CP) is activated primarily by immunoglobulins (antibodies, including autoantibodies) that are bound to antigens - either in the fluid phase as soluble immune complexes, or on cell membrane surfaces or other tissues. (primaryimmune.org)
  • C2 and C4 also participate in the LP. The LP is thought to be the most evolutionarily primitive of the complement pathways and the first to react before the adaptive immune response occurs. (primaryimmune.org)
  • Specifically, the immune-related differentially expressed genes (IRDEGs), which belong to the KEGG (Kyoto encyclopedia of genes and genomes) pathways, such as the complement and coagulation cascades, chemokine signalling pathways and toll-like receptor signalling pathways were mainly observed at 24 h post-infection. (biomedcentral.com)
  • The rapid and significant response of the S. marmoratus immune signalling pathways following C. irritans infection may be associated with their involvement in the immune process. (biomedcentral.com)
  • The complement system provides a fundamental component of the body's immune response to invading microorganisms. (asmscience.org)
  • This chapter highlights the various roles of the complement system in the orchestration of the immune response towards microbial infections, gives examples of microbial strategies to evade complement-mediated clearance, and discusses how acquired and inherited complement deficiencies may predispose an organism to infectious disease. (asmscience.org)
  • The alternative pathway of the complement system is an innate component of the immune system 's natural defense against infections. (wikipedia.org)
  • In the presence of antibody and complement, pneumococci attach to erythrocytes in a process called immune adherence (IA), which facilitates their delivery to, and eventual phagocytosis by, macrophages. (asm.org)
  • In contrast, in nine patients with immune complex-mediated membranoproliferative glomerulonephritis, glomerular samples contained mainly immunoglobulins and complement factors C3 and C4. (elsevier.com)
  • Quidel MicroVue Products are a well-established name in Immune System Monitoring, assays for the assessment of complement activation, as well as biochemical bone markers. (quidel.com)
  • Diagnostic kits and controls for assessment of two types of circulating immune complexes (CIC), diagnosis of hereditary angioedema (HAE) and measurement of total classical pathway activity. (quidel.com)
  • The classical pathway (CP) is activated by surface‐bound immune complexes, resulting in cleavage of C4 and thereby generation of C4b ( Figure 1A ). (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)
  • Ehrlich introduced the term "complement" as part of his larger theory of the immune system. (wikipedia.org)
  • 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)
  • 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)
  • As a functional bridge between innate and adaptive immunity, the complement system plays critical roles in tumour progression and immune responses. (biomedcentral.com)
  • 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)
  • This pathway is activated by viruses, fungi, bacteria, parasites, cobra venom, immunoglobulin A, and polysaccharides and forms an important part of the defense mechanism independent of the immune response. (medscape.com)
  • 43 Complement component 2 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. (malacards.org)
  • An important gene associated with Complement Component 2 Deficiency is C2 (Complement C2), and among its related pathways/superpathways are Immune response Lectin induced complement pathway and Staphylococcus aureus infection . (malacards.org)
  • 20 Complement component 2 deficiency (C2D) is a genetic condition that affects the immune system. (malacards.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 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)
  • It has been demonstrated that the lectin pathway is integral in the protection from opportunistic fungi such as candida, as well as certain bacteria and viruses ( R ). The activation of MBL is necessary for the completion of lectin activation and pathogenic removal, as well as the recruitment of the adaptive immune responders, T and B-cell lymphocytes. (metabolichealing.com)
  • Among the myriad immune-modulatory effects of 1,3 beta glucans, they have shown to activate the lectin pathway ( R ). This research may be significant for individuals dealing with suspected lectin pathway activation, such as in Lyme disease, mold, CIRS and CFS/ME. (metabolichealing.com)
  • 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)
  • What role if any do other polysaccharides play in the complement immune system? (metabolichealing.com)
  • Moreover, patients with immune deficiencies, hypertension, diabetes, coronary heart disease, and kidney disease often have altered activation of these pathways, either due to underlying disease or to medications, and may be more susceptible to SARS-CoV-2 infection. (cdc.gov)
  • 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)
  • Complement receptors CR1 and CR2 are active in the immune response and autoimmune diseases. (google.com)
  • Complement is active in immune defenses, especially antibody mediated events by way of the "classical pathway. (google.com)
  • The classical pathway begins with the formation of antigen-antibody complex (immune complex). (microbeonline.com)
  • urther analysis of the immune system included complement and immunoglobulins. (docplayer.net)
  • valuation and Diagnosis Analysis of the immune system was performed including immunoglobulins and complement. (docplayer.net)
  • The Complement System (CS) plays an important role in the immune response against leptospirosis and can be activated by the Alternative and Lectin Pathways (Innate Immunity) and by the Classical Pathway (Acquired Immunity). (bvsalud.org)
  • The complement system, an essential component of the innate immune system, plays a critical role as a defense mechanism against invading pathogens, primes adaptive immune responses, and helps remove immune complexes and apoptotic cells. (justia.com)
  • While the complement system plays a critical role in many protective immune functions, complement activation is a significant mediator of tissue damage in a wide range of autoimmune and inflammatory disease processes. (justia.com)
  • The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. (meta.org)
  • In addition to being a component of innate immunity and an ancient defense mechanism against invading pathogens, complement activation also participates in the adaptive immune response, inflammation, hemostasis, embryogenesis, and organ repair and development. (jci.org)
  • The classical pathway is primarily activated by the binding of C1 to antigen-antibody complexes containing the immunoglobulins IgM or IgG. (thefreedictionary.com)
  • complement fixation the combining of complement with the antigen-antibody complex , rendering the complement inactive, or fixed. (thefreedictionary.com)
  • Ehrlich's term for the thermolabile substance, normally present in serum, that is destructive to certain bacteria and other cells sensitized by a specific complement-fixing antibody. (thefreedictionary.com)
  • The classical pathway is triggered by interaction of the Fc portion of an antibody (immunoglobulin [Ig] M, IgG1, IgG2, IgG3) or C-reactive protein with C1q. (medscape.com)
  • The alternative pathway is activated in an antibody-independent manner. (medscape.com)
  • Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)
  • The classical pathway is typically activated by antibody. (psychiatryadvisor.com)
  • The alternative and lectin pathways are evolutionarily older than the classical pathway and do not require antibody for activation. (psychiatryadvisor.com)
  • The classical pathway is activated mainly by antigen-antibody complexes (IgG or IgM mostly) starting with C1q, C1r, C1s, C4 and C2, and eventually leading to the activation of C3 by cleavage into C3a and C3b. (mcmaster.ca)
  • Alternative pathway activation was observed during complement component C3 conversion in the presence of ethylene - glycol -bis-(beta-amino-ethyl- ether)N,N'-tetracetic-acid, while classical complement components C1, C4 and C2 were decreased in serum free of antibody. (cdc.gov)
  • Encapsulated meningococci expressing a Hep 2 (GlcNAc)→KDO 2 →lipid A LOS without an α-chain demonstrated enhanced sensitivity to 50% NHS (98% killed at 30 min) mediated through the antibody-dependent classical complement pathway. (asm.org)
  • Since its discovery, the complement system has been primarily considered an effector of innate immunity with the ability to "complement" antibody-mediated clearance of foreign pathogens, dispose of dead cells, and cause inflammatory states ( 12 ). (aacrjournals.org)
  • The mechanism of complement activation that does not involve activation of the C1, C4, C2 pathway by antigen-antibody complexes, and begins with the activation of C3. (rxpgonline.com)
  • Data are presented as the percent neutralization by a given complement-deficient or antibody-deficient serum compared to wild-type C57BL/6 serum. (asm.org)
  • Classic complement activation starts when an immunoglobulin (Ig) M or IgG antibody binds with the C1 q subcomponent of C1. (wbccount.org)
  • Acquired complement deficiency occurs with diseases that are associated with increased antibody/antigen complexes. (wbccount.org)
  • Unlike the classical and alternative pathways, the lectin pathway does not use or recognize an antibody. (metabolichealing.com)
  • In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. (meddic.jp)
  • 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)
  • Complement response to an invasion by a foreign particle can also embody an antibody independent mechanism which is known as the "alternative pathway. (google.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)
  • Complement activation is triggered by an antibody when it is bound to the antigen. (microbeonline.com)
  • Classical pathway , activated by antigen-antibody reaction, Alternative pathway , activated on microbial cell surfaces, and Mannose binding Lectin pathway , activated by a plasma lectin that binds to mannose residues on microbes. (microbeonline.com)
  • Hence, the antibody activates the complement system only when bound to an antigen. (microbeonline.com)
  • The complement system can be activated by antigen-associated antibody. (meta.org)
  • A ) The classical pathway is initiated by a complement-fixing antibody binding to an antigen on targeted cells. (jci.org)
  • Complement 1 inhibitor (C1-INH) * is a critically important protein that controls activation of multiple plasma mediator pathways ( 1 ). (rupress.org)
  • Complement regulatory protein genes in channel catfish and their involvement in disease defense response. (auburn.edu)
  • Strongylocentrotus purpuratus (Purple sea urchin) has an atypical factor B with a five-module complement control protein domain. (ebi.ac.uk)
  • 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)
  • 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)
  • Infections are prominent in many complete complement deficiencies, and the kinds of infections are determined by the function of the deficient protein in host defense. (psychiatryadvisor.com)
  • A wide range of diseases are therefore associated with abnormalities or deficiencies in complement and depend on the specific protein that is abnormal. (psychiatryadvisor.com)
  • C3 is the central protein of all three complement pathways and plays a critical role in the opsonization of pathogens. (psychiatryadvisor.com)
  • The same authors did, however, note a significant increase in fat content and a decrease in plasma cholesterol concentrations for sea bass fed with plant protein, suggesting altered regulation of lipid metabolic pathways. (biomedcentral.com)
  • Patients with complement deficiencies encounter clinical problems that depend on the role of the specific complement protein in normal function. (primaryimmune.org)
  • Properdin makes it possible for the amplification loop of the alternative pathway to set up a very efficient mechanism for putting lots of C3b onto the surface of the activating cells, protein complexes or particles in the immediate vicinity of the activation site. (primaryimmune.org)
  • The pathway is triggered when the C3b protein directly binds a microbe . (wikipedia.org)
  • CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating activity and is able to bind preferentially to C3b at host surfaces. (wikipedia.org)
  • The classical pathway can be triggered by natural immunoglobulin M antibodies bound to the C polysaccharide of the pneumococcal cell wall or by the acute-phase-reactant C-reactive protein, which can bind the phosphocholine on the pneumococcal teichoic and lipoteichoic acids ( 28 ). (asm.org)
  • PspC binds complement activation regulatory protein factor H, which promotes factor I-mediated cleavage of C3b, hence abrogating C3b's opsonic activity ( 11 , 19 , 30 ). (asm.org)
  • Each complement protein has been tested for functional purity in standard hemolytic assays and for biochemical purity by SDS-polyacrylamide gel electrophoresis. (quidel.com)
  • The concentration of each complement protein, except for Factor D and C3a, is approximately 1.0 mg/mL. (quidel.com)
  • Except for the C3-dpl, C3/C4-dpl and the C4-deficient guinea pig sera, a specific complement protein has been removed immunochemically from each depleted human serum reagent. (quidel.com)
  • Complement can develop very similarly to an acute-phase reactant protein. (wbccount.org)
  • C-reactive protein (CRP, not shown) leads to classic pathway activation analogous to lectin pathway activation by MBL and ficolins. (medscape.com)
  • 73 Complement C2 is a protein that in humans is encoded by the C2 gene. (malacards.org)
  • Mannan-binding lectin (MBL, also called mannose-binding protein) is a protein belonging to the collectin family that is produced by the liver and can initiate the complement cascade by binding to pathogen surfaces. (meddic.jp)
  • The association of each complement protein with AMD was assessed using logistic regression analysis controlling for age, gender, smoking, body mass index and seven AMD genotypes. (arvojournals.org)
  • We found that transgenic (tg) mice stably expressing a bacterial artificial chromosome (BAC)-derived human complement receptor type 2 (CR2/CD21) gene demonstrate B cell specific hCR2 protein expression, normal B cell development and no changes in B cell subpopulations. (usda.gov)
  • C3 deposition onto wells coated with O antigen-specific BO, CO, and DO following incubation in PNHS or C2-deficient serum. (nih.gov)
  • The serum was used at a final concentration of 20% and was studied with or without reconstitution of the alternative pathway. (nih.gov)
  • C1-INH prevented lysis, induced by the alternative complement pathway, of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes in human serum. (rupress.org)
  • It inhibited the binding of both factors B and C3 to PNH and rabbit erythrocytes and blocked the ability of factor B to restore alternative-pathway function in factor B-depleted serum. (rupress.org)
  • Removal of C1-INH from serum, in the presence of Mg-EGTA with an anti-C1-INH immunoabsorbant, markedly increased alternative-pathway lysis. (rupress.org)
  • Many gram-negative bacteria are directly killed by complement, but we hypothesized that A. baumannii would be resistant to serum killing. (nih.gov)
  • A serum bactericidal assay assessed the resistance of seven A. baumannii isolates to serum killing, and C2-deficient serum was used to examine its activation of the alternative pathway. (nih.gov)
  • The C2-deficient serum demonstrated that A. baumannii can activate the alternative pathway. (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)
  • The alternative pathway (APC) utilizes active sites (such as are present on zymosan, yeast, cobra venom, most gram-negative bacteria, sheep erythrocytes and human cells deficient in the expression of membrane regulatory molecules) in the presence of properdin, serum factors B and D, to activate C3. (mcmaster.ca)
  • Methods: Complement activation were compared after incubation of purified adult porcine islets in 20% human serum with or without complement inhibitors, C1 esterase inhibitor (C1E-inh), anti-factor B, and purified human factor H. Intraportal porcine ITx was performed in diabetic NHPs to which cobra venom factor (CVF), factor H, or none of complement inhibitor was administered during the peritransplant period. (elsevierpure.com)
  • Neutralization of insect cell- and mammalian cell-derived DENV-2 by mouse serum is mediated by the lectin pathway. (asm.org)
  • A and C) Neutralization of C6/36 cell-derived (A) or Vero cell-derived (C) DENV-2 in the presence of 10% (vol/vol) complement-deficient serum. (asm.org)
  • 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)
  • Kinetic studies revealed that opsonization of peptidoglycan, as well as C3-C9 consumption by peptidoglycan, proceeded at a slower rate via the alternative pathway (C2-deficient serum) than when the classical pathway was present (normal serum). (umn.edu)
  • Neither sera depleted of terminal complement components by treatment with inulin or cobra venom factor nor human serum deficient in C8 supported phagocytosis of the tested strains. (meta.org)
  • Dose-dependent restoration of the opsonic activity of factor B-depleted serum was accomplished by purified human factor B but not by human C2. (meta.org)
  • Thus the complement system works in both innate and acquired immunity. (microbeonline.com)
  • Once activated, several relevant complement functions are generated which include opsonization and phagocytosis of particles or microorganisms and cell lysis. (frontiersin.org)
  • Nevertheless, the parasite uses a sequence of events in order to escape from complement-mediated lysis. (frontiersin.org)
  • Surface bound CRP reduces deposition of and generation of C5b-9 by the alternative pathway and deposition of C3b and lysis by the lectin pathway. (nih.gov)
  • Both pathways result in cleavage of C5 and formation of the membrane attack complex , which in its final state creates a pore in the cell wall and causes cell lysis. (thefreedictionary.com)
  • Complement has many functions, including promoting phagocytosis of pathogens by acting as an opsonin, inducing lysis of bacteria or susceptible cells and generatinginflammation by products formed during complement activation. (psychiatryadvisor.com)
  • CD59 on hematologic cells is required to prevent unregulated complement lysis. (psychiatryadvisor.com)
  • This step unifies the two pathways and proceeds uniformly thereafter to the formation of (C5b-9) membrane attack complexes (MAC), capable of inserting into biological membranes and producing cell lysis and death. (mcmaster.ca)
  • As a gram-positive bacterium, the pneumococcus has a thick and rigid cell wall that protects it from lysis by the complement membrane attack complex. (asm.org)
  • When incorporated into the membrane of rabbit erythrocytes, human DAF inhibited their lysis by human complement. (rupress.org)
  • Activation of complements leads to inflammation and localize the antigen or cause lysis. (labpedia.net)
  • Activation of any of these three pathways results in the formation of inflammatory mediators (C3 and C5a) and the membrane attack complex (MAC), which causes cellular lysis. (justia.com)
  • MBL-dependent C2 bypass activation could be particularly important in various inherited and acquired complement deficiency states. (nih.gov)
  • Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)
  • A North African study of molecular basis of complement factor I deficiency in atypical hemolytic and uremic syndrome patients suggested that the Ile357Met mutation may be a founding effect. (medscape.com)
  • Are you sure your patient has a complement deficiency? (psychiatryadvisor.com)
  • Most of the genetically determined deficiencies of the complement system are inherited as autosomal recessive traits, with the exception of C1 esterase inhibitor, which is inherited as an autosomal dominant trait, and properdin deficiency, which is inherited as an X-linked recessive trait. (psychiatryadvisor.com)
  • A complete deficiency of a complement component is rare, and partial deficiencies are rarely of any clinical significance. (psychiatryadvisor.com)
  • A deficiency in the negative regulators of complement leads to excessive complement activation, as observed in paroxysmal nocturnal hemoglobinuria (PNH) and atypical or familial hemolytic uremic syndrome (HUS). (rupress.org)
  • A deficiency in any component of the classical pathway is associated with an increased risk of immunological disease and recurrent bacterial infections. (asmscience.org)
  • People with complement component 2 deficiency have a significantly increased risk of recurrent bacterial infections, specifically of the lungs (pneumonia), the membrane covering the brain and spinal cord (meningitis), and the blood (sepsis), which may be life-threatening. (malacards.org)
  • These infections most commonly occur in infancy and childhood and become less frequent in adolescence and adulthood.Complement component 2 deficiency is also associated with an increased risk of developing autoimmune disorders such as systemic lupus erythematosus (SLE) or vasculitis. (malacards.org)
  • Between 10 and 20 percent of individuals with complement component 2 deficiency develop SLE. (malacards.org)
  • Females with complement component 2 deficiency are more likely to have SLE than affected males, but this is also true of SLE in the general population.The severity of complement component 2 deficiency varies widely. (malacards.org)
  • Complement Component 2 Deficiency, also known as c2 deficiency , is related to enterocolitis and complement deficiency . (malacards.org)
  • 12 A complement deficiency that is characterized by recurrent bacterial infections, has material basis in autosomal recessive inheritance of mutation in the C2 gene. (malacards.org)
  • 72 Complement component 2 deficiency: A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. (malacards.org)
  • Patients with complement component 2 deficiency are also reported to have recurrent invasive infections. (malacards.org)
  • A recombinant human dnase , creation of glass splinters if forms the alternative pathway c2 complement receptor deficiency imiglucerase. (wisc.edu)
  • 1 Diagnosis of complete deficiency of C2 Lennart ruedsson MD/PhD, Section of Microbiology, Immunology and Glycobiology Dept of Laboratory Medicine, Lund University, Lund, he patient was a 14-year-old girl who has healthy parents and a healthy 11-year-old sister. (docplayer.net)
  • urther analysis with measurement of individual components in the classical pathway (C1q, C2 and C4) revealed complete deficiency of C2. (docplayer.net)
  • Increased susceptibility for bacterial infections is seen in several types of complement deficiency. (docplayer.net)
  • Complete deficiency of C2 as diagnosed here is rare, found in about 1/ individuals. (docplayer.net)
  • Analysis of complement function is the way to detect this deficiency. (docplayer.net)
  • hen all pathways show normal activity as in this case, the suspicion of complement deficiency can be ruled out and the diagnostic could focus on other explanations. (docplayer.net)
  • 3 Diagnosis of complete deficiency of C2 Lennart ruedsson MD/PhD, Section of Microbiology, Immunology and Glycobiology Dept of Laboratory Medicine, Lund University, Lund, A girl of 8 years of age had a sudden onset of febrile illness with headache and was taken to hospital. (docplayer.net)
  • Complete deficiency of C2 is associated with increased susceptibility for infections with encapsulated bacteria such as pneumococci and also increased risk to develop SL. (docplayer.net)
  • C1-INH is a known inhibitor of kinin generating (kallikrein), fibrinolytic (plasmin), and contact activation (intrinsic) pathway of the coagulation cascade (factor XIIa, XIIf, and factor XIa) ( 1 , 6 - 9 ). (rupress.org)
  • Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. (asm.org)
  • activation of the alternative pathway triggers a cascade involving C3 and factors B and D and properdin. (thefreedictionary.com)
  • A role for the complement cascade was not suspected in the disease until the genetic association was made, but since then much work has cemented the idea that the macula is destroyed by complement-stimulated inflammatory and/or angiogenic processes. (alzforum.org)
  • Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.com)
  • The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)
  • If you visualize a trident, the three tines represent the different initiation routes, while the handle represents the lytic mechanism by which this cascade ultimately destroys the threat, no matter which activation pathway started the response. (primaryimmune.org)
  • These factors include the absence of bactericidal antibodies against meningococci ( 17 , 18 , 45 ), deficiencies in the complement cascade ( 13 ), and the presence of blocking immunoglobulin A antibodies that inhibit the bactericidal activity of human sera ( 19 ). (asm.org)
  • The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. (wikipathways.org)
  • As a fundamental component of innate immunity, the complement cascade ( Fig. 1 ) contains some of the most powerful proinflammatory molecules in the body, including most notably the anaphylatoxins C3a and C5a. (aacrjournals.org)
  • Nevertheless, emerging literature examining the mechanistic relationship between inflammation and cancer ( 4 , 9 , 10 ) has almost completely omitted the role of the complement cascade. (aacrjournals.org)
  • The complement cascade comprises the classic, alternative, and MBL pathways. (aacrjournals.org)
  • The complement activation is tightly regulated by membrane-bound and fluid-phase regulatory components to avoid runaway activation of the enzymatic cascade that could lead to excess host tissue damage, inflammation, and depletion of complement components. (asmscience.org)
  • Here, we review the genetic architecture of AMD, considering the contribution of both common and rare alleles to susceptibility, and we explore the possible mechanistic links between photoreceptor degeneration and the alternative complement pathway, a cascade that has emerged as the most potent genetic driver of this disorder. (cdc.gov)
  • In conclusion, on the basis of these and previous results, it appears that DAF plays a central role in preventing the amplification of the complement cascade on host cell surfaces. (rupress.org)
  • 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)
  • The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
  • ACE2 serves as an endogenous inhibitor of inflammatory signals associated with four major regulator systems: the renin-angiotensin-aldosterone system (RAAS), the complement system, the coagulation cascade, and the kallikrein-kinin system (KKS). (cdc.gov)
  • As part of the body's natural defenses, the complement system operates as a biological cascade in which one component activates successive components. (google.com)
  • Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. (asm.org)
  • In the lectin pathway (LP), microbial carbohydrates are recognized by mannose-binding lectin (MBL) or ficolins in complex with MBL-associated serine proteases (MASP). (jimmunol.org)
  • The lectin pathway is initiated by the binding of mannose-binding lectin to certain sugars, which are often present on the cell surfaces of pathogens, and joins the classical pathway at the level of C3. (psychiatryadvisor.com)
  • The Lectin pathway involves mannose-binding lectin (MBL) binding the surface of the pathogen instead of C1Q. (wikipathways.org)
  • Complement can be deposited on pneumococci through activation of the classical and alternative pathways, whereas the mannose-binding lectin pathway seems to play a relatively minor role ( 8 , 36 ). (asm.org)
  • Instead, the lectin pathway can use polysaccharides, ficolin, collectin or mannose binding lectin (MBL) to create adhesive bonds in order to bind pathogens. (metabolichealing.com)
  • The lectin pathway starts with mannose-binding lectin or ficolin binding to certain sugars. (meddic.jp)
  • In this pathway, mannose-binding lectin binds to mannose, glucose or other sugars with 3- and 4-OH groups placed in the equatorial plane, in terminal positions on carbohydrate or glycoprotein components of microorganisms including bacteria such as Salmonella , Listeria , and Neisseria strains. (meddic.jp)
  • C1q and mannose-binding lectin (MBL) are the structurally related recognition molecules of the classical and lectin pathways, respectively. (justia.com)
  • It catalyzes the proteolytic cleavage of C3 into C3a and C3b, generated during activation through the classical pathway as well as the lectin pathway. (wikipedia.org)
  • The proteolytic cleavage of C5 is the only known enzymatic event in assembly of the cytolytic membrane attack complex of complement. (wikipedia.org)
  • Upon binding of C1q to an inciting stimulus, C1r catalyzes breakage of a C1s ester bond, resulting in its activation and subsequent cleavage of C2 and C4 into their respective "a" and "b" fragments. (aacrjournals.org)
  • This pathway exhibits a unique "tickover" effect whereby low-level C3 cleavage occurs continuously. (aacrjournals.org)
  • Although the complement system is part of the body's innate, relatively nonspecific defense against pathogens, its role is hardly primitive or easily understood. (medscape.com)
  • The complement system is a key component of innate immunity implicated in the neutralization and clearance of invading pathogens. (biomedcentral.com)
  • The alternative pathway is one of three complement pathways that opsonize and kill pathogens. (wikipedia.org)
  • The result of classical and alternative pathway activation results in the elimination of pathogens, called opsonization. (metabolichealing.com)
  • Complement activation and inflammation occur in AD, possibly because of Aβ production. (alzforum.org)
  • at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check. (medscape.com)
  • Complement is often associated with unregulated inflammation, and many mechanisms exist for downregulation of complement activation. (psychiatryadvisor.com)
  • Inflammation and thrombosis are two responses that are linked through a number of mechanisms, one of them being the complement system. (rupress.org)
  • c3 may be lost in urine in nephrotic syndrome Complement component 3 has been shown to interact with Factor H. Deficiencies in C3 lead to genetic infections, usually fatal to the newborn. (wikipedia.org)
  • Complement deficiencies are said to comprise between 1 and 10% of all primary immunodeficiencies. (medscape.com)
  • [ 3 ] A registry of complement deficiencies has been established as a means to promote joint projects on treatment and prevention of diseases associated with defective complement function. (medscape.com)
  • This article outlines some of the disease states associated with complement deficiencies and their clinical implications. (medscape.com)
  • Complement pathways and deficiencies. (medscape.com)
  • Deficiencies in complement predispose patients to infection via 2 mechanisms: (1) ineffective opsonization and (2) defects in lytic activity (defects in MAC). (medscape.com)
  • Specific complement deficiencies are also associated with an increased risk of developing autoimmune disease, such as SLE. (medscape.com)
  • There are deficiencies of each of the individual components of complement. (primaryimmune.org)
  • he symptoms of increased susceptibility for infections may have many different causes and among these are complement deficiencies. (docplayer.net)
  • C1, C2, and C4 deficiencies are associated with pyogenic infections and rheumatologic disorders, particularly systemic lupus erythematosus. (cancertherapyadvisor.com)
  • Independent of MBL, specific antibodies to CO supported C3 deposition through classical and alternative pathways. (nih.gov)
  • Complement Components and Antibodies. (rupress.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)
  • When Complement is activated, it increases vascular permeability which helps delivering antibodies and white blood cells (WBCs) to the area where the antigen complex is found. (wbccount.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)
  • The ability of peptidoglycan to activate C3-C9 was significantly reduced when normal and C2-deficient sera were preabsorbed with peptidoglycan at 2 degrees C suggesting that antibodies to peptidoglycan may be involved in activation of both the classical and alternative complement pathways. (umn.edu)
  • Find the latest research on antibodies and complement activation here. (meta.org)
  • Recently, it has been shown to be an inhibitor of the mannan-binding lectin pathway of complement activation, inhibiting mannan-binding lectin-associated serine proteases (MASPs) in that pathway ( 10 ). (rupress.org)
  • The structures of the von Willebrand factor A and serine protease domains from human complement factor B ( P00751 ) have been analysed [ PMID: 15016353 , PMID: 10637221 ]. (ebi.ac.uk)
  • Although the activation and amplification of the three pathways differ initially, they commonly cleave C3 into C3a and C3b, resulting in terminal formation of the MAC. (aacrjournals.org)
  • Binding of MBL also activates MASPs that directly cleave C3 without activation of C4 and C2 (the C4 and C2 bypass pathway). (asm.org)
  • When the carbohydrate-recognising heads of MBL bind to specifically arranged mannose residues on the surface of a pathogen, MASP-1 and MASP-2 are activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. (meddic.jp)
  • C1r and C1s are proteases which help to cleave C4 and C2. (microbeonline.com)
  • Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. (thefreedictionary.com)
  • The Alternative Pathway (AP) is initiated by fragments of the complement component C3. (primaryimmune.org)
  • Increased plasma levels of the complement activation fragments Bb and C5a are independently associated with advanced AMD. (arvojournals.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)
  • In this review, we aim to present an overview on the strategies used by T. cruzi in order to circumvent the activation of complement and, consequently, its biological effects. (frontiersin.org)
  • What are the results of the activation of complement? (brainscape.com)
  • 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)
  • The expression of several genes involved in the LC-PUFA and cholesterol biosynthetic pathways was found to be up-regulated in fish fed VD, suggesting a stimulation of the lipogenic pathways. (biomedcentral.com)
  • Functional classification analysis of DE genes revealed dynamic changes in ion binding (such as DSG1 ) between AH and CS, proliferation and apoptotic processes (such as BAG3 , HLA-DQA1 , and UGT2B17 ) and complement activation (such as C7 ) between AH or RS and CS. (biomedcentral.com)
  • Our results suggest that both nutrients (VFAs) and particle sizes can alter expression of genes involved in cell proliferation/apoptosis process and complement complex. (biomedcentral.com)
  • Notably, the subsequent association of common and rare alleles at or near several additional complement genes ( CFH , C2/CFB , C3 , CFI , and C9) has had a significant impact of the formation of pathomechanistic hypotheses, with the cumulative evidence both from human genetics but also from histopathological studies highlighting a major role of the alternative complement pathway as a driver of AMD [ 9 - 21 ]. (cdc.gov)
  • Moreover, benefiting from the discovery of likely potent coding mutations in genes encoding complement components, we explore how these mutations might impede specific functions and discuss the potential contribution of aspects of this pathway to AMD pathogenesis. (cdc.gov)
  • 2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. (guidetopharmacology.org)
  • DNA samples were genotyped for seven single nucleotide polymorphisms in six genes previously shown to be associated with AMD: CFB, CFH, C2, C3, CFI, and the LOC387715/HTRA1 gene region. (arvojournals.org)
  • These complement components form the final membrane attack complex (MAC). (thefreedictionary.com)
  • In addition, all three complement pathways result in the formation of the membrane attack complex, which is vital to bactericidal activity. (psychiatryadvisor.com)
  • The Terminal Pathway (TP) is the final set of steps in the complement activation process that forms a membrane lesion or hole (membrane attack complex or MAC) that kills susceptible bacteria or other cells that activate complement on their surfaces. (primaryimmune.org)
  • Activation of the alternative pathway is tightly controlled by membrane associated complement regulatory components and the competition of the main fluid phase antagonists factor B and factor H for binding C3b or hydrolsed C3. (asmscience.org)
  • Decay-accelerating factor (DAF), extracted from the stroma of human erythrocytes, was purified to homogeneity and incorporated into the membrane of sheep red cell complement intermediates, where its functional properties were analyzed. (rupress.org)
  • The presence of DAF in the membrane of EA did not affect the deposition of C1 and C4, but as few as 10(2) DAF molecules per cell profoundly inhibited the assembly of C3 and C5 convertases of both the classical and alternative pathways. (rupress.org)
  • Taken together, the experimental evidence suggests that DAF interacts directly with membrane-bound C3b or C4b and prevents subsequent uptake of C2 and factor B. DAF can function only within the cell membrane. (rupress.org)
  • 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)
  • Activation of the complement system via classical, lectin, or alternative pathways generates anaphylatoxins (C3a and C5a) and membrane attack complex (C5b-9) and opsonizes targeted cells. (jci.org)
  • Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. (frontiersin.org)
  • In saliva of Lutzomyia longipalpis , the main vector of visceral leishmaniasis in the Americas, different molecules with antihemostatic properties have been characterized, such as the vasodilator Maxadilan ( 2 , 3 ), the anticoagulant Lufaxin ( 4 ), the endonuclease Lundep ( 5 ), and, recently, the inhibitor of the classical pathway of the complement system SALO ( 6 ). (frontiersin.org)
  • What is the main fxn of the complement system? (brainscape.com)
  • It plays a central role in the complement system and contributes to innate immunity. (wikipedia.org)
  • C3 plays a central role in the activation of the complement system. (wikipedia.org)
  • 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)
  • 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)
  • The complement system plays an important part in defense against pyogenic organisms. (medscape.com)
  • These findings underscore the duality of the complement system. (medscape.com)
  • Knowledge about the complement system is expanding. (medscape.com)
  • An intricate system regulates complement activity. (medscape.com)
  • It participates in the complement system ending with cell death. (wikipedia.org)
  • Two of the convertases are physiological complement enzymes, associate to the cell-surface and mediate the classical pathway (C4b2b3b, or C4b2a3b depending on source) or the alternative pathway (C3bBbC3b) of complement system. (wikipedia.org)
  • The complement system is composed of three pathways: the classical pathway, the alternative pathway, and the lectin pathway (Figure 1). (psychiatryadvisor.com)
  • In this paper, we show that the converse is also true: activated platelets can activate the complement system. (rupress.org)
  • Activation of the complement system proceeded to its final stages, which was marked by the increased generation of the anaphylotoxin C3a and the C5b-9 complex. (rupress.org)
  • Using heterologous cells expressing P-selectin, we found that P-selectin alone is sufficient to activate the complement system, marked by increases in C3b deposition, C3a generation, and C5b-9 formation. (rupress.org)
  • In summary, we have found that platelets are capable of activating the complement system, and have identified P-selectin as a receptor for C3b capable of initiating complement activation. (rupress.org)
  • The complement system mediates cell-cell interactions in many physiological processes, such as hematopoiesis, organogenesis, and in reproduction ( 1 ). (rupress.org)
  • Here, we show that upon activation, platelets activate the complement system, which proceeds to its final stages marked by the formation of the C5b-9 complex. (rupress.org)
  • We have also identified P-selectin expressed on activated platelets as a receptor for C3b, thus linking thrombosis and local activation of the complement system on platelets. (rupress.org)
  • Age-related macular degeneration (AMD) is the leading cause of permanent vision loss among the elderly in many industrialized countries, and the complement system plays an important role in the pathogenesis of AMD. (molvis.org)
  • Its interaction with the Complement system (Cp) system has so far been found to be indirect, by an inhibition of PMN response towards complement derived chemotaxins. (mcmaster.ca)
  • A unique feature of the AP is the presence of the only positive regulator in the complement system, Properdin. (primaryimmune.org)
  • Dysregulation of the complement system has been implicated in several diseases and pathologies. (wikipedia.org)
  • Three biochemical pathways activate the complement system: the classical complement pathway , the alternative complement pathway , and the lectin pathway . (wikipedia.org)
  • The clinical and experimental evidences for complement-cancer relationships are solid, whereas an epidemiological study reporting the imbalance of complement system in patients is still lacking. (biomedcentral.com)
  • The opposite associations between the levels of complement and complement-related components in lung cancer tissues and plasma from patients that have been repeatedly reported by independent publications may indicate the prevalence of an imbalance in the complement system of lung cancer patients. (biomedcentral.com)
  • Consistent with the conflicting roles of the complement system in tumour formation, the levels of complement components in plasma and cancer tissues from patients with lung cancer seem to be paradoxical. (biomedcentral.com)
  • The complement system is important for destroying foreign cells and isolating "foreign" antigens . (wbccount.org)
  • There are also alternative pathways for the activation of this system. (wbccount.org)
  • These tests assess the overall function of the entire complement system. (wbccount.org)
  • The complement system is overly activated and the complement components are "consumed" or used up. (wbccount.org)
  • If the presence of these complexes is chronic, the complement system is overly activated and the complement components are consumed or used up. (wbccount.org)
  • Certain characteristic COVID-associated skin, sensory, and central nervous system manifestations may also be linked to viral activation of the RAAS, complement, coagulation, and KKS pathways. (cdc.gov)
  • The complement system functions to promote the inflammatory response, to modify the membranes of infectious organisms, and also to identify pathogenic material for removal. (google.com)
  • The early step of complement system varies in different pathways. (microbeonline.com)
  • HC-PS1 and HC-PS3 were found to inhibit complement activation through both the classical and alternative pathways with 50% inhibition concentrations of 0.272â -â 0.318 mg/mL without interfering with the coagulation system. (bvsalud.org)
  • Preliminary mechanism studies indicated that both HC-PS1 and HC-PS3 inhibited the activation of the complement system by interacting with C2, C4, and C5. (bvsalud.org)
  • The results suggest that HC-PS1 and HC-PS3 could be valuable for the treatment of diseases associated with the excessive activation of the complement system. (bvsalud.org)
  • valuation and Diagnosis Analysis of complement function with the Complement system screen ieslab showed no activity for the classical pathway and the lectin pathway but normal activity for the alternative pathway. (docplayer.net)
  • The present invention provides peptide compounds that regulate the complement system and methods of using these compounds. (justia.com)
  • No. 14/536,073, entitled "Peptide Compounds to Regulate the Complement System," filed Nov. 7, 2014, which is a division of U.S. application Ser. (justia.com)
  • No. 13/809,371, entitled "Peptide Compounds to Regulate the Complement System," filed May 23, 2013 now U.S. Pat. (justia.com)
  • No. 8,906,845 issued Dec. 9, 2014, which is a §371 of PCT/US2011/044791 entitled "Peptide Compounds to Regulate the Complement System," filed Jul. (justia.com)
  • 21, 2011, which claims priority to U.S. Provisional Application No. 61/366,204 entitled "Peptide Compounds to Regulate the Complement System," filed Jul. (justia.com)
  • While the complement system is a vital host defense against pathogenic organisms, its unchecked activation can cause devastating host cell damage. (justia.com)
  • Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. (asm.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)
  • The results are consistent with a role for the alternative pathway of complement in the inhibition of growth of rat primary mammary carcinomas observed after treatment with absorbed sera. (aacrjournals.org)
  • Inhibition of complement factor B, a key regulator of the alternative pathway, is implicated as a potential therapeutic intervention for AMD. (molvis.org)
  • The results suggest that inhibition of liver factor B mRNA by factor B ASOs would reduce systemic alternative complement pathway activation and has potential to be used as a novel therapy for AMD. (molvis.org)
  • Complement inhibition during the peritransplant period may be beneficial for the survival of islet grafts. (elsevierpure.com)
  • Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. (rupress.org)
  • In the classical pathway (CP), this is mainly mediated by binding of the C1 complex, consisting of the PRM C1q and the proteases C1r and C1s, to Ig patches on the pathogen. (jimmunol.org)
  • Complement activation by CRP may help limit the inflammatory response by providing opsonization with minimal generation of C5a and C5b-9. (nih.gov)
  • Immunoglobulin G functioned as the major heat-stable opsonic factor and both the classical and alternative pathways participated in opsonization. (umn.edu)
  • Studies were conducted to determine the requirements for immunoglobulin and complement in opsonization of Bacteroides fragilis and Bacteroides thetaiotaomicron. (meta.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)
  • A method and a package for identifying single nucleotide polymorphisms in complement receptor is useful in identifying individual susceptibility to a disease. (google.com)
  • The susceptibility and severity of autoimmune disease is determined by genotyping or phenotyping an individual for complement receptor. (google.com)
  • 5. The method of claim 4 wherein said complement receptor is CR1. (google.com)
  • No. 60/106,643 filed Nov. 2, 1998 entitled "Genetic Polymorphism in a Complement Receptor. (google.com)
  • The present invention relates generally to compounds and methods for identifying polymorphism in a cellular receptor, and more particularly, to compounds and methods for identifying and typing single nucleotide polymorphisms that code for a complement receptor and applying these polymorphisms to delineation of disease susceptibility and severity. (google.com)
  • Complement receptor 1 (CR1) is important in increasing phagocytosis. (labpedia.net)
  • 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)
  • 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)
  • Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. (hindawi.com)
  • When complement is activated, it also increases very important processes that occur during a normal inflammatory response. (wbccount.org)
  • Complement components are increased following the onset of various acute or chronic inflammatory diseases or acute tissue damage. (wbccount.org)
  • Complements are activated only during inflammatory reactions. (microbeonline.com)
  • Once complement is activated, its components participate in virtually every aspect of the inflammatory response. (labpedia.net)
  • More specifically, the invention relates to peptide compounds that can regulate complement activation and can be used therapeutically in the prevention and treatment of complement-mediated diseases, such as inflammatory, autoimmune and pathogenic diseases. (justia.com)
  • The activated C1 complex cleaves C2 and C4. (wikipathways.org)
  • This then acts similarly to C1 esterase and cleaves C2 and C4 to form C2aC4b, which is the C3 esterase that cleaves C3 to form C3b. (medscape.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)
  • C1r and C1s assemble on C1q, C1r cleaves and activates C1s, and activated C1s cleaves C4 and C2 into C4b and C2a, respectively. (jci.org)
  • C ) In the alternative pathway, small amounts of hydrolyzed plasma C3 [C3(H2O)] bind to factor B, which forms the C3(H2O)Bb complex with help from factor D. C3(H2O)Bb cleaves additional plasma C3 to generate highly active C3b, which binds to cell the surface. (jci.org)
  • The classic pathway is activated by the Fc portion of immunoglobulins bound to antigen, apoptotic cells, Gram-negative bacteria, and viruses. (aacrjournals.org)
  • The affinity of factor B to bind C3b is higher on "activating "surfaces, and the half-life of C3bB, C3Bb, and C3Bb(C3b)n complexes, significantly increased by the action of properdin, allows the alternative pathway amplification loop to be formed. (asmscience.org)
  • 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)
  • And preserved, this compound complexes with fadd and activates ras and rac pathways generate the small water drops in the production of medicines in multidose containers. (safeembrace.org)
  • Here again, these complexes serve to act as complement activators. (wbccount.org)
  • Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. (nih.gov)
  • Binding of CRP to these substrates activates the classical complement pathway leading to their uptake by phagocytic cells. (nih.gov)
  • C1 activates C4, which activates C2 and so on to C9. (wbccount.org)
  • Factor B, factor D, and properdin (factor P) are specific components of the alternative pathway of complement activation. (asmscience.org)
  • In vitro measurements of fluid phase markers of complement activation C4d and Bb and the terminal pathway marker SC5b-C9 in normal and genetically deficient sera were used to study the mechanisms of human complement activation. (biomedcentral.com)
  • 2009) Structure-activity relationships for substrate-based inhibitors of human complement factor B. (guidetopharmacology.org)
  • Absorbed plasmas were depleted of the third component of complement (C3) (other complement components defined similarly) and C5 but not C1, C4, or C2. (aacrjournals.org)
  • They also found two SNPs in a second complement-related locus, this one containing the gene for complement component 1 and complement factor B (C2/CFB). (alzforum.org)
  • These 3 pathways converge at the component C3. (medscape.com)
  • C5 is activated by CVFBb in the presence of complement component C6 and the C5b6 complex is formed. (wikipedia.org)
  • A protease component of the alternative complement pathway. (guidetopharmacology.org)
  • Except for the specifically depleted component, the classical and alternative pathways are intact. (quidel.com)
  • In 1899, Paul Ehrlich renamed the heat-sensitive component "complement. (wikipedia.org)
  • Amino Acid Sequence of the Anaphylatoxin from the fifth Component of Porcine Complement," J. Biol. (freepatentsonline.com)
  • C3 makes up the majority of the component of complement. (wbccount.org)
  • Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration. (opensnp.org)
  • Activation of the classical and alternative pathways leads to a common terminal pathway from C5 to C9. (thefreedictionary.com)
  • MBL bound to CO, but not to BO and DO, and efficiently supported C3 deposition in the absence of C2, C4, or MASP-2. (nih.gov)
  • Flow cytometry was utilized to determine whether complement regulator factor H (FH) was bound by A. baumannii, and to assay C3 deposition on cells. (nih.gov)
  • In vitro measurements of C3 deposition on SPIO NW using sera genetically deficient for various components of the classical pathway (CP), lectin pathway (LP) or alternative pathway (AP) components were used to study mechanisms of mouse complement activation. (biomedcentral.com)
  • Using PspA and/or PspC isogenic mutants and complement-deficient mouse sera, we demonstrated that absence of PspA allows greater deposition of C1q and thus increased classical-pathway-mediated C3 deposition. (asm.org)
  • In the absence of both PspA and PspC, there is also a major increase in C1q-independent C3 deposition through the alternative pathway. (asm.org)
  • The latter was observed even though absence of PspC alone did not have a major effect on alternative-pathway-dependent complement deposition. (asm.org)
  • The enhanced complement C3 deposition realized in the absence of PspA alone and in the absence of PspA and PspC resulted in both greatly increased IA to human erythrocytes and improved transfer of pneumococci from erythrocytes to phagocytes. (asm.org)
  • It has been shown that C3 deposition on wild-type pneumococci is dependent on activation by the classical pathway ( 8 ). (asm.org)
  • Several pneumococcal components have been shown to interfere with complement deposition. (asm.org)
  • MBL binding to the virion surface initiates lectin pathway activation resulting in deposition of C4b and C3b. (asm.org)
  • The alternative pathway amplification loop serves to generate more C3b deposition on the virus. (asm.org)
  • In this context, the complement, as one of the first line of host defense against infection was shown to play an important role in recognizing T. cruzi metacyclic trypomastigotes and in controlling parasite invasion. (frontiersin.org)
  • An important step during T. cruzi infection is when intracellular trypomastigotes are release to bloodstream where they may be target by complement. (frontiersin.org)
  • Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. (asm.org)
  • These data provide new insight into how PspA and PspC act in synergy to protect pneumococci from complement-dependent clearance during invasive infection. (asm.org)
  • Complement alternative pathway genetic variation and Dengue infection in the Thai population. (opensnp.org)
  • In mouse sera, SPIO NW triggered the complement activation via the LP, whereas the AP contributes via the amplification loop. (biomedcentral.com)
  • Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. (asm.org)
  • Results implicate ongoing activation of the alternative complement pathway in AMD pathogenesis. (arvojournals.org)
  • Complement activation end products and their receptors mediate cell-cell interactions that regulate several biological functions in the extravascular tissue. (jci.org)
  • We investigated C3 activation in C2-deficient human sera and in sera with other defined defects of complement to assess other mechanisms through which MBL might recruit complement. (nih.gov)
  • Sera from 3 C2-deficient patients were used in the kinetic experiments. (nih.gov)
  • A major mechanism inhibiting or preventing the multiplication of meningococci in the blood is the complement-mediated bactericidal activity of human sera ( 17 , 39 ). (asm.org)
  • In human sera the LP together with the direct enhancement of the AP turnover was responsible for the complement activation. (biomedcentral.com)
  • There were important differences and similarities in the complement activation by SPIO NW in mouse versus human sera. (biomedcentral.com)
  • The ability of human sera depleted of immunoglobulin or of components of complement to promote the phagocytosis and intracellular killing of the two strains of Bacteroides by human leukocytes was measured in vitro under anaerobic conditions. (meta.org)
  • Beyond the genetics lesson, could the role of complement in AMD also have something to teach us about AD? (alzforum.org)
  • Compared to glomeruli from five control patients, we found that all of the glomeruli from patients with DDD contain components of the alternative pathway and terminal complement complex. (elsevier.com)
  • Our study shows that in addition to fluid-phase dysregulation of the alternative pathway, soluble components of the terminal complement complex contribute to glomerular lesions found in DDD. (elsevier.com)
  • Smith, Richard J.H. / Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway . (elsevier.com)
  • Using publicly available databases, we jointly compared the levels of complement components in plasma and lung cancer tissues. (biomedcentral.com)
  • Complement components are mainly synthesized by the liver and secreted into the blood. (biomedcentral.com)
  • The total complement, sometimes labeled CH 50 , is made up of nine major components, C1 through C9. (wbccount.org)
  • The liver is the site of synthesis of many of the complement components. (wbccount.org)
  • Jules Bordet (1895) identified complements as heat-sensitive components in the blood, bearing non-specific antimicrobial activity. (microbeonline.com)
  • C2-C5 have two components, a and b . (microbeonline.com)
  • The results indicate that immunoglobulin and components of the alternative comed in this study. (meta.org)
  • We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. (rupress.org)
  • phyl thus represents a possible target gene of the Raf pathway during eye development, controlling the fates of a novel subset of photoreceptors. (labome.org)
  • Last year, four independent research groups reported a linkage between polymorphisms in the complement factor H (CFH) gene to age-related macular degeneration (AMD), the most common cause of blindness in people over 60. (alzforum.org)
  • One possibility is that the variants affect complement factor H gene expression. (alzforum.org)
  • Thus, the NMD pathway serves both as a silencer of genomic noise and a regulator of gene expression. (pubmedcentralcanada.ca)
  • Genetic variants of complement factor H gene are not associated with premature coronary heart disease: a family-based study in the Irish population. (snpedia.com)
  • Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration. (snpedia.com)
  • PMID 18421087 ] Multiple gene polymorphisms in the complement factor h gene are associated with exudative age-related macular degeneration in chinese. (snpedia.com)
  • PMID 18515590 ] Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy. (snpedia.com)
  • This variant is associated with reduced risk of age-related macular degeneration when inherited with the E318D variant of the C2 gene as part of haplotype 10. (guidetopharmacology.org)
  • C2D is caused by mutations in the C2 gene and is inherited in an autosomal recessive fashion. (malacards.org)
  • MASP-1, MASP-3 and MAp44 are alternative splice products of the MASP1 gene, while MASP-2 and MAp19 are alternative splice products of the MASP-2 gene. (meddic.jp)
  • Although recognized primarily as an important part of innate immunity, complement has adopted additional functions in different organisms. (rupress.org)
  • What is the key enzyme of complement activation where all three pathways converge? (brainscape.com)
  • PMID 17591627 ] Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes. (snpedia.com)
  • Age related macular degeneration (AMD) is now believed to be caused, at least in part, by complement mediated attack on ocular tissues . (wikipedia.org)
  • Association of polymorphisms in C2, CFB and C3 with exudative age-related macular degeneration in a Korean population. (opensnp.org)
  • Complement factor B polymorphism 32W protects against age-related macular degeneration. (opensnp.org)
  • In the classical pathway of complement activation, C1q, C4b, and C3b are all able to bind to the Fc portion of IgG or IgM. (meta.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)
  • While research has not yet demonstrated its specific complement effects, a mushroom hericium erinaceus, aka Lion's mane possesses one of the highest polysaccharide concentrations. (metabolichealing.com)
  • The lectin pathway is activated by carbohydrate recognition molecules that bind to polysaccharide on the surface of a pathogen. (asmscience.org)
  • Ethylenebis(oxyethylenenitrilo)]tetraacetic acid, by chelating calcium but not magnesium, permits activation of the alternative pathway but inhibits activation of the classical complement pathway. (aacrjournals.org)