Complement c4b. Medical search

A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.

A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.

The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.

The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.

A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.

The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.

The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.

The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.

The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.

Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).

A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.

A 206-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.

A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).

A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.

Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.

A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).

A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.

A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.

Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.

A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.

Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.

A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.

Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.

Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.

A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.

The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.

Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.

An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).

The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.

The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.

Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.

Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.

A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.

Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.

Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.

Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.

Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.

A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.

A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.

A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).

Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.

GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.

Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.

The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.

Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)

Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.

The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.

An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).

Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.

An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.

The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.

The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.

A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.

A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).

A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.

Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.

Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.

A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.

A serine protease that cleaves multiple COMPLEMENT C5 into COMPLEMENT C5A (anaphylatoxin) and COMPLEMENT C5B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. It is the complex of ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) with an additional COMPLEMENT C3B, or C3bBb3b.

The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.

A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.

A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).

An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.

The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.

Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.

A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.

A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts.

A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.

An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.

Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.

Antibodies produced by a single clone of cells.

The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.

Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.

Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)

Established cell cultures that have the potential to propagate indefinitely.

The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.

Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.

Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.

Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.

A specific mannose-binding member of the collectin family of lectins. It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY.

Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.

Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).

Proteins prepared by recombinant DNA technology.

An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.

Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.

Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.

Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.

Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).

Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).

Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

Plasmids containing at least one cos (cohesive-end site) of PHAGE LAMBDA. They are used as cloning vehicles.

In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.

Proteins found in any species of bacterium.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.

A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.

Transport proteins that carry specific substances in the blood or across cell membranes.

Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.

A group of inherited disorders of the ADRENAL GLANDS, caused by enzyme defects in the synthesis of cortisol (HYDROCORTISONE) and/or ALDOSTERONE leading to accumulation of precursors for ANDROGENS. Depending on the hormone imbalance, congenital adrenal hyperplasia can be classified as salt-wasting, hypertensive, virilizing, or feminizing. Defects in STEROID 21-HYDROXYLASE; STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; 3-beta-hydroxysteroid dehydrogenase (3-HYDROXYSTEROID DEHYDROGENASES); TESTOSTERONE 5-ALPHA-REDUCTASE; or steroidogenic acute regulatory protein; among others, underlie these disorders.

The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.

An individual in which both alleles at a given locus are identical.

Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

Biologically active substances whose activities affect or play a role in the functioning of the immune system.

Elements of limited time intervals, contributing to particular results or situations.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.

The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.

Glycoproteins found on the membrane or surface of cells.

The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.

The sum of the weight of all the atoms in a molecule.

The rate dynamics in chemical or physical systems.

Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.

The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.

Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.

The presence of proteins in the urine, an indicator of KIDNEY DISEASES.

Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.

The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.

Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.

A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.

A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.

Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.

A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

A plasma protein that circulates in increased amounts during inflammation and after tissue damage.

The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.

A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)

Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.

Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.

Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.

A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.

Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.

A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

A mass spectrometric technique that is used for the analysis of large biomolecules. Analyte molecules are embedded in an excess matrix of small organic molecules that show a high resonant absorption at the laser wavelength used. The matrix absorbs the laser energy, thus inducing a soft disintegration of the sample-matrix mixture into free (gas phase) matrix and analyte molecules and molecular ions. In general, only molecular ions of the analyte molecules are produced, and almost no fragmentation occurs. This makes the method well suited for molecular weight determinations and mixture analysis.

A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.

Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.

Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.

The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.

A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.

A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.

A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.

A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.

Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.

Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.

A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.

Immunoglobulins produced in a response to BACTERIAL ANTIGENS.

The systematic study of the complete complement of proteins (PROTEOME) of organisms.

Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.

A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.

The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).

Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.

A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.

A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.

Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.

Immunohistochemical analysis of arterial wall cellular infiltration in Buerger's disease (endarteritis obliterans). (1/363)

PURPOSE: The diagnosis of Buerger's disease has depended on clinical symptoms and angiographic findings, whereas pathologic findings are considered to be of secondary importance. Arteries from patients with Buerger's tissue were analyzed histologically, including immunophenotyping of the infiltrating cells, to elucidate the nature of Buerger's disease as a vasculitis. METHODS: Thirty-three specimens from nine patients, in whom Buerger's disease was diagnosed on the basis of our clinical and angiographic criteria between 1980 and 1995 at Nagoya University Hospital, were studied. Immunohistochemical studies were performed on paraffin-embedded tissue with a labeled streptoavidin-biotin method. RESULTS: The general architecture of vessel walls was well preserved regardless of the stage of disease, and cell infiltration was observed mainly in the thrombus and the intima. Among infiltrating cells, CD3(+) T cells greatly outnumbered CD20(+) B cells. CD68(+) macrophages or S-100(+) dendritic cells were detected, especially in the intima during acute and subacute stages. All cases except one showed infiltration by the human leukocyte antigen-D region (HLA-DR) antigen-bearing macrophages and dendritic cells in the intima. Immunoglobulins G, A, and M (IgG, IgA, IgM) and complement factors 3d and 4c (C3d, C4c) were deposited along the internal elastic lamina. CONCLUSION: Buerger's disease is strictly an endarteritis that is introduced by T-cell mediated cellular immunity and by B-cell mediated humoral immunity associated with activation of macrophages or dendritic cells in the intima. (+info)

Deficiency of human complement protein C4 due to identical frameshift mutations in the C4A and C4B genes. (2/363)

The complement protein C4, encoded by two genes (C4A and C4B) on chromosome 6p, is the most polymorphic among the MHC III gene products. We investigated the molecular basis of C4 deficiency in a Finnish woman with systemic lupus erythematosus. C4-specific mRNA was present at low concentrations in C4-deficient (C4D) patient fibroblasts, but no pro-C4 protein was detected. This defect in C4 expression was specific in that synthesis of two other complement proteins was normal. Analysis of genomic DNA showed that the proposita had both deleted and nonexpressed C4 genes. Each of her nonexpressed genes, a C4A null gene inherited from the mother, a C4A null gene, and a C4B null gene inherited from the father, all contained an identical 2-bp insertion (TC) after nucleotide 5880 in exon 29, providing the first confirmatory proof of the C4B pseudogene. This mutation has been previously found only in C4A null genes. Although the exon 29/30 junction is spliced accurately, this frameshift mutation generates a premature stop at codon 3 in exon 30. These truncated C4A and C4B gene products were confirmed through RT-PCR and sequence analysis. Among the possible genetic mechanisms that produce identical mutations is both genes, the most likely is a mutation in C4A followed by a gene conversion to generate the mutated C4B allele. (+info)

Interaction between protein S and complement C4b-binding protein (C4BP). Affinity studies using chimeras containing c4bp beta-chain short consensus repeats. (3/363)

Human C4b-binding protein (C4BP) is a regulator of the complement system and plays an important role in the regulation of the anticoagulant protein C pathway. C4BP can bind anticoagulant protein S, resulting in a decreased cofactor function of protein S for activated protein C. C4BP is a multimeric protein containing several identical alpha-chains and a single beta-chain (C4BPbeta), each chain being composed of short consensus repeats (SCRs). Previous studies have localized the protein S binding site to the NH2-terminal SCR (SCR-1) of C4BPbeta. To further localize the protein S binding site, we constructed chimeras containing C4BPbeta SCR-1, SCR-2, SCR-3, SCR-1+2, SCR-1+3, and SCR-2+3 fused to tissue-type plasminogen activator. Binding assays of protein S with these chimeras indicated that SCR-2 contributes to the interaction of protein S with SCR-1, since the affinity of protein S for SCR-1+2 was up to 5-fold higher compared with SCR-1 and SCR-1+3. Using an assay that measures protein S cofactor activity, we showed that cofactor activity was decreased due to binding to constructs that contain SCR-1. SCR-1+2 inhibited more potently than SCR-1 and SCR-1+3. SCR-3 had no additional effect on SCR-1, and therefore the effect of SCR-2 was specific. In conclusion, beta-chain SCR-2 contributes to the interaction of C4BP with protein S. (+info)

Consumption of C4b-binding protein (C4BP) during in vivo activation of the classical complement pathway. (4/363)

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

Some anticardiolipin antibodies recognize a combination of phospholipids with thrombin-modified antithrombin, complement C4b-binding protein, and lipopolysaccharide binding protein. (5/363)

The standard enzyme-linked immunosorbent assay (ELISA) for anticardiolipin antibodies (ACA) detects a heterogenous group of antibodies against cardiolipin on its own, beta2-glycoprotein I (beta2GPI), and, potentially, other phospholipid-binding plasma proteins from bovine or human origin. In an attempt to identify new proteic targets of ACA, we selected 6 patients who possessed cofactor-dependent ACA but no antibody to human or bovine beta2GPI detectable in the beta2GPI-ELISA. Three of these samples proved to recognize beta2GPI in combination with cardiolipin, but not beta2GPI directly immobilized on gamma-irradiated polystyrene or agarose beads. In the other cases, the component required for ACA binding was purified from adult bovine serum or plasma by means of ammonium sulfate precipitation and chromatography on Phenyl-Sepharose, diethyl aminoethyl (DEAE)-cellulose, heparin-Ultrogel, and Sephacryl S-300 columns. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis coupled to N-terminal amino acid microsequencing identified the cofactors of patients no. 4, 5, and 6 ACA as lipopolysaccharide binding protein (LBP), complement C4b-binding protein (C4BP), and the thrombin-antithrombin (AT) complex, respectively. Adsorption of each of these cofactor preparations with cardiolipin liposomes led to suppression of ACA reactivity, concomitant with the loss of bands from SDS gels corresponding to sequenced material. Bacterial lipopolysaccharide (which forms high-affinity complexes with LBP) specifically neutralized the cofactor activity of the LBP preparation in a concentration-dependent manner. Bovine serum and plasma, as well as the C4BP preparation, optimally supported the binding of a rabbit anti-C4BP antiserum to immobilized cardiolipin. The binding of a rabbit anti-AT antiserum to solid-phase cardiolipin was sustained by the thrombin-AT preparation and bovine serum, but neither by bovine plasma nor by native AT, thus reproducing the behavior of patient no. 6 ACA. Taking advantage of the restricted recognition by the latter ACA of a cofactor from bovine origin appearing upon clotting, we studied the generation of such activity in human plasma supplemented with bovine AT or bovine prothrombin before clotting. In these conditions, patient no. 6 antibody binding to cardiolipin required the addition of bovine AT, whereas addition of bovine prothrombin alone was ineffective. We therefore concluded that those ACA targeted bovine AT once it has been modified/cleaved by thrombin. These findings underline the wide heterogeneity of ACA and the links that may exist between various coagulation pathways, inflammation and the complement system. (+info)

A cluster of positively charged amino acids in the C4BP alpha-chain is crucial for C4b binding and factor I cofactor function. (6/363)

C4b-binding protein (C4BP) is a regulator of the classical complement pathway, acting as a cofactor to factor I in the degradation of C4b. Computer modeling and structural analysis predicted a cluster of positively charged amino acids at the interface between complement control protein modules 1 and 2 of the C4BP alpha-chain to be involved in C4b binding. Three C4BP mutants, R39Q, R64Q/R66Q, and R39Q/R64Q/R66Q, were expressed and assayed for their ability to bind C4b and to function as factor I cofactors. The apparent affinities of R39Q, R64Q/R66Q, and R39Q/R64Q/R66Q for immobilized C4b were 15-, 50-, and 140-fold lower, respectively, than that of recombinant wild type C4BP. The C4b binding site demonstrated herein was also found to be a specific heparin binding site. In C4b degradation, the mutants demonstrated decreased ability to serve as factor I cofactors. In particular, the R39Q/R64Q/R66Q mutant was inefficient as cofactor for cleavage of the Arg937-Thr938 peptide bond in C4b. In contrast, the factor I mediated cleavage of Arg1317-Asn1318 bond was less affected by the C4BP mutations. In conclusion, we identify a cluster of amino acids that is part of a C4b binding site involved in the regulation of the complement system. (+info)

Analysis of human C4A and C4B binding to an immune complex in serum. (7/363)

Previous studies using isolated complement proteins have shown that more C4A than C4B binds to certain types of immune complexes. However, the in vivo binding of the C4 isoforms to an immune complex has not been investigated in detail and may differ from events when measured with the isolated proteins. We report here the binding of C4A and C4B to an immune complex of bovine serum albumin (BSA) anti-BSA as it occurs in serum. We found that when using the isolated C4 proteins more C4A than C4B bound to the complex, but in serum similar amounts of C4A and C4B were found to bind. Furthermore, these results were not explainable by a difference in activity between isoforms. In an attempt to explain these results a number of unexpected observations were noted. First C4A, but not C4B, bound specifically to a yet unidentified 38-kD serum protein. Second, when both covalent and non-covalent binding was assessed, we found that as serum concentration increased there followed a concomitant decrease in covalent binding and C4B was more affected than C4A. The potential biological significance of these findings is discussed. (+info)

Upregulation of ICAM-1 on cardiomyocytes in jeopardized human myocardium during infarction. (8/363)

OBJECTIVE: Impaired perfusion of the myocardium induces a local inflammatory response. In animal models, there is ample evidence that polymorphonuclear leucocytes (PMNs) infiltrating infarcted myocardium contribute significantly to infarct size. METHODS: To explore a possible role for PMNs in the tissue damage of human myocardial infarction, we investigated localization of intercellular adhesion molecule-1 (ICAM-1) and CD66b (previously clustered as CD67), a marker of degranulation of human PMNs, in relation to deposition of complement in tissue specimens of infarcted and healthy parts of the heart obtained from 20 patients, who had died following acute myocardial infarction. RESULTS: ICAM-1 was transiently expressed by endothelium and for a longer period (few days) on myofibers of infarcted myocardium. This expression only occurred in parts that stained positive for complement. PMN infiltration exclusively occurred in areas with ICAM-1 expression, but not every ICAM-1-positive area contained PMN infiltrates. CD66b was found in PMNs but was also fixed to the plasma membrane of myofibers that stained positive for complement and ICAM-1. CONCLUSION: These findings indicate that, in infarcted human myocardium, PMNs are degranulated, possibly upon interaction with ICAM-1 and activated complement. (+info)

... or C4B-C4B) and 31% trimodular configuration (equally split between LLL as C4A-C4A-C4B or LSS as C4A-C4B-C4B). Regarding C4 ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar A, ... C4b and C2a, from their complex (whereupon C4b can bind another protein C2, and conduct these steps again). Because C4b is ... Law SK, Dodds AW, Porter RR (August 1984). "A comparison of the properties of two classes, C4A and C4B, of the human complement ...

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

Surface bound C4b acts as a receptor for the binding of C2. The binding of C2 and C4b results in C2 being cleaved by C1s into ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ... The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune ... Activation of the complement pathway through the classical, lectin or alternative complement pathway is followed by a cascade ...

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

... is a kind of the Complement component 4 protein that in humans is encoded by the C4B gene. This gene encodes the basic form of ... Complement component 4 Complement component 4A HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency ... "Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases". Front Immunol. 12: 739430. doi: ... "Entrez Gene: Complement component 4B (Chido blood group)". Retrieved 2012-01-27. Zhou D, Rudnicki M, Chua GT, Lawrance SK, Zhou ...

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

"Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases". Front Immunol. 12: 739430. doi: ... Complement component 4 Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency ... Complement C4-A is a kind of the Complement component 4 protein that in humans is encoded by the C4A gene. This gene encodes ... "Importance of the alpha 3-fragment of complement C4 for the binding with C4b-binding protein". FEBS Letters. 271 (1-2): 131-6. ...

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

C1q mediates the classical pathway by activating the C1 complex, which cleaves C4 and C2 into smaller fragments (C4a, C4b, C2a ... 12th European Meeting on Complement in Human Disease12th European Meeting on CHD12th European Meeting on Complement in Human ... C3a is one of the proteins formed by the cleavage of complement component 3; the other is C3b. C3a is a 77 residue ... Anaphylatoxins are small complement peptides that induce proinflammatory responses in tissues. C3a is primarily regarded for ...

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

C4b and C3bi from plasma complement. The extracellular domain of the receptors contains a lectin-like complement-binding domain ... Recognition by complement receptors is not enough to cause internalisation without additional signals. In macrophages, the CR1 ... Complement coated targets are internalised by 'sinking' into the phagocyte membrane, without any protrusions. Mannose and other ... Among these are receptors that recognise the Fc part of bound IgG antibodies, deposited complement or receptors, that recognise ...

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

Blom, Anna M.; Villoutreix, Bruno O.; Dahlbäck, Björn (2004). "Complement inhibitor C4b-binding protein-friend or foe in the ... "High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding ... Dahlbäck, Björn (1991). "Protein S and C4b-Binding Protein: Components Involved in the Regulation of the Protein C ...

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

In the classical pathway, C4 binds to Ig-associated C1q and C1r2s2 enzyme cleaves C4 to C4b and 4a. C4b binds to C1q, antigen- ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...

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

1987). "A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32". J. ... Complement receptor type 2 (CR2), also known as complement C3d receptor, Epstein-Barr virus receptor, and CD21 (cluster of ... homology with the receptor for fragments C3b and C4b of the third and fourth components of complement". Proc. Natl. Acad. Sci. ... Complement receptor 2 interacts with CD19, and, on mature B cells, forms a complex with CD81 (TAPA-1). The CR2-CD19-CD81 ...

https://en.wikipedia.org/wiki/Complement_receptor_2

... (C4BP) is a protein complex involved in the complement system where it acts as inhibitor. C4BP has an ... Complement+C4b-Binding+Protein at the US National Library of Medicine Medical Subject Headings (MeSH) v t e (Articles with ... C4BP accelerates decay of C3-convertase and is a cofactor for serine protease factor I which cleaves C4b and C3b. C4BP binds ... A number of bacterial and fungal pathogens capture human C4BP and use it to prevent binding of C4b, which allows them to ...

https://en.wikipedia.org/wiki/C4b-binding_protein

In lieu of the membrane attack complex, complement proteins (particularly C3b and C4b) are deposited on red blood cells. This ... Binding of antibodies to red blood cells activates the classical pathway of the complement system. If the complement response ... Jaffe, C J; Atkinson, J P; Frank, M M (1976-10-01). "The role of complement in the clearance of cold agglutinin-sensitized ... Detection of antibodies (cold or warm) and /or complement system on RBC from the patient is a direct Coombs antiglobulin test. ...

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

... duttonii acquire complement regulators C4b-binding protein and factor H". Infection and Immunity. 74 (7): 4157-63. doi:10.1128/ ...

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

The C1 complex (complement component 1, C1) is a protein complex involved in the complement system. It is the first component ... Active C1s splits C4 and then C2, producing C4a, C4b, C2a and C2b. The classical pathway C3-convertase (C4bC2b complex) is ... 2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease. New York: Garland ... The antibodies IgM or certain subclasses of IgG complexed with antigens are able to initiate the complement system: a single ...

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

... , also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. Complement ... either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein ... Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement ... Whaley K (March 1980). "Biosynthesis of the complement components and the regulatory proteins of the alternative complement ...

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

DAF regulates the complement system on the cell surface. It recognizes C4b and C3b fragments that are created during activation ... Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene. ... DAF contains four complement control protein (CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2 ... Binding of DAF to human HIV-1 when the virons are budding from the surface of infected cells protects HIV-1 from complement ...

https://en.wikipedia.org/wiki/Decay-accelerating_factor

Porins are also recognized by TLR2, they bind complement factors (C3b, C4b, factor H, and C4bp (complement factor 4b-binding ... fHbp protects meningococci from complement-mediated death in human serum experiments, but has also been shown to protect ... Porins are also an important factor for complement inhibition for both pathogenic and commensal species. Porins are important ... and complement deficiency. The incubation period is short, from 2 to 10 days. In susceptible individuals, N. meningitidis may ...

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

DAF protects host cells from damage by autologous complement. DAF acts on C2b and Bb and dissociates them rapidly from C4b and ... C4b-binding protein inhibits the haemolytic function of cell-bound C4b. C4b-binding protein and C3b inactivator control the C3 ... complement receptor 1 (CR1), C4b-binding protein and Factor H. Convertase assembly is suppressed by the proteolytic cleavage of ... Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or even a bacterial enzyme leads to formation of C3a ...

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

Complement proteins involved in innate opsonization include C4b, C3b and iC3b. In the alternative pathway of complement ... C1q association eventually leads to the recruitment of complement C4b and C3b, both of which are recognized by complement ... In both cases C1q activates complement, resulting in the cells being marked for phagocytosis by C3b and C4b. C1q is an ... The C1 complement complex can also interact with the Fc region of IgG and IgM immune complexes activating the classical ...

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

Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 (cluster of differentiation 35) is a protein that in ... LHR-A binds preferentially to the complement component C4b: LHR-B and LHR-C bind to C3b and also, albeit with a lower affinity ... Membrane cofactor protein is a widely distributed C3b/C4b binding regulatory glycoprotein of the complement system; decay- ... 1989). "Immunoregulatory functions of complement: structural and functional studies of complement receptor type 1 (CR1; CD35) ...

https://en.wikipedia.org/wiki/Complement_receptor_1

In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b-binding ... Protein S does not bind to the nascent complement complex C5,6,7 to prevents it from inserting into a membrane. This is a ... Dahlbäck B (2007). "The tale of protein S and C4b-binding protein, a story of affection". Thromb. Haemost. 98 (1): 90-6. doi: ... Griffin JH, Gruber A, Fernández JA (1992). "Reevaluation of total, free, and bound protein S and C4b-binding protein levels in ...

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

... and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution". The Journal ... cells from complement-mediated damage. CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for ... there are several different kinds of regulatory proteins that disrupt the complement activation process: Complement Receptor 1 ... The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, ...

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

C3, C4A, C4B, C4B-1, C5, FBLN1, FBLN2 Allergy Anaphylatoxin receptors Anaphylaxis Complement system Inflammation Immune system ... that are produced as part of the activation of the complement system. Complement components C3, C4 and C5 are large ... Gennaro R, Simonic T, Negri A, Mottola C, Secchi C, Ronchi S, Romeo D (February 1986). "C5a fragment of bovine complement. ... C3a works with C5a to activate mast cells, recruit antibody, complement and phagocytic cells and increase fluid in the tissue, ...

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

September 2009). "Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement ... C2a and C4b are used to create C3 convertase, a complex that will then be able to cleave C3 into C3a and C3b. However, MASP-1 ... MASP-1 is a serine protease that functions as a component of the lectin pathway of complement activation. The complement ... "The role of MASP-1/3 in complement activation". In Lambris JD, Holers VM, Ricklin D (eds.). Complement Therapeutics. Advances ...

https://en.wikipedia.org/wiki/MASP1_(protein)

"Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes ... Yang Z, Qu X, Yu CY (August 2001). "Features of the two gene pairs RD-SKI2W and DOM3Z-RP1 located between complement component ... are present between complement component genes factor B and C4 in the class III region of the HLA". Genomics. 53 (3): 338-47. ...

https://en.wikipedia.org/wiki/SKIV2L

Complement C3b/C4b Receptor 1, CR1 (CD35) Complement Regulator of the Immunoglobulin Superfamily, CRIg Soluble complement ... Complement control protein are proteins that interact with components of the complement system. The complement system is ... Complement proteins protect against malignant cells- both by direct complement attack and through initiation of Complement- ... Convertases, specifically the C3 convertases C3b.Bb and C4b.2a, are the enzymes that drive complement activation by activating ...

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

"Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes ... 1996). "Complete sequence of the complement C4 gene from the HLA-A1, B8, C4AQ0, C4B1, DR3 haplotype". Immunogenetics. 43 (4): ... "Entrez Gene: STK19 serine/threonine kinase 19". Yu CY (1991). "The complete exon-intron structure of a human complement ... 1998). "Four ubiquitously expressed genes, RD (D6S45)-SKI2W (SKIV2L)-DOM3Z-RP1 (D6S60E), are present between complement ...

https://en.wikipedia.org/wiki/STK19

... of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. The protein ... The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system. The encoded ... CD46 complement regulatory protein also known as CD46 (cluster of differentiation 46) and Membrane Cofactor Protein is a ... This gene is found in a cluster on chromosome 1q32 with other genes encoding structural components of the complement system. At ...

https://en.wikipedia.org/wiki/CD46

Because primate erythrocytes express complement receptor 1 (CR1) on their surface and having binding specificity to C4b, C3b, ... which activate the classical pathway of the complement system. The cascade begins to work from C1 to C3b through C4b, C3b being ... London: Mosby, ISBN 0-7234-2918-9. Frank K, Atkinson JP (2001). "Complement system." In Austen KF, Frank K, Atkinson JP, Cantor ... Bala Subramanian V, Liszewski MK, Atkinson JP (2000). "The complement system and autoimmunity." In Lahita RG, Chiorazzi N, ...

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

... in the major histocompatibility complex III close to the Complement component 4 genes C4A and C4B, the Tenascin X gene TNXB and ... In the chicken and quail, there is only a single CYP21 gene, which locus is located between complement component C4 and TNX ... Sweeten TL, Odell DW, Odell JD, Torres AR (January 2008). "C4B null alleles are not associated with genetic polymorphisms in ... Yu CY (1999). "Molecular genetics of the human MHC complement gene cluster". Experimental and Clinical Immunogenetics. 15 (4): ...

https://en.wikipedia.org/wiki/21-Hydroxylase

2005). "Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/ ... "Entrez Gene: CFHR1 complement factor H-related 1". Zipfel PF, Skerka C (1994). "Complement factor H and related proteins: an ... Complement factor H-related protein 1 is a protein that in humans is encoded by the CFHR1 gene. GRCh38: Ensembl release 89: ... 2000). "Complement factor H: sequence analysis of 221 kb of human genomic DNA containing the entire fH, fHR-1 and fHR-3 genes ...

https://en.wikipedia.org/wiki/CFHR1

Together, MBL, C4b and C2a are known as the C3 convertase. C3 is cleaved into its a and b subunits, and C3b binds the ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ... binding the C4b subunit and releasing C4a into the bloodstream; similarly, binding of C2 causes release of C2b. ...

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

Sweeten TL, Odell DW, Odell JD, Torres AR (January 2008). "C4B null alleles are not associated with genetic polymorphisms in ... Yu CY (1998). "Molecular genetics of the human MHC complement gene cluster". Exp Clin Immunogenet. 15 (4): 213-30. doi:10.1159/ ... C4A and C4B. Each C4 gene contains 41 exons and has a dichotomous size variation between approximately 22 kb and 16 kb, with ... "Dancing with complement C4 and the RP-C4-CYP21-TNX (RCCX) modules of the major histocompatibility complex". Prog Nucleic Acid ...

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

... complement c4 MeSH D12.776.124.486.274.350.250 - complement c4a MeSH D12.776.124.486.274.350.260 - complement c4b MeSH D12.776. ... complement factor i MeSH D12.776.124.486.274.920.662 - complement c4b-binding protein MeSH D12.776.124.486.274.930 - complement ... complement c1 MeSH D12.776.124.486.274.050.270 - complement c1q MeSH D12.776.124.486.274.050.280 - complement c1r 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. ...

https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D12.776.124)

The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. This activated C1 ... or a C5 convertase when bound to C4b and C2b (C4b2b3b complex) or when an additional C3b molecule binds to the C3bBb complex ( ... C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the ... The key to the success of the complement system in clearing antigens is regulating the effects of C3b to pathogens alone and ...

https://en.wikipedia.org/wiki/C3b

... the MASP protein functions to cleave the blood protein C4 into C4a and C4b. The C4b fragments can then bind to the surface of ... The complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin ... The subsequent complement cascade catalyzed by C3-convertase results in creating a membrane attack complex, which causes lysis ... In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), ...

https://en.wikipedia.org/wiki/Mannan-binding_lectin

It is thought that cleavage of C2 by C1s, while bound to C4b, results in a conformational rotation of C2b whereas the released ... Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical ... "Entrez Gene: C2 complement component 2". Krishnan V, Xu Y, Macon K, Volanakis JE, Narayana SV (2009). "The structure of C2b, a ... Complement+2 at the US National Library of Medicine Medical Subject Headings (MeSH) v t e (Articles with short description, ...

https://en.wikipedia.org/wiki/Complement_component_2

The classical pathway C5 convertase is composed of the fragments of complement proteins, C4b, C2a produced by cleavage mediated ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... In these respects, the mode of action of C5 is completely analogous to that of the other components of complement. The C5 step ...

https://en.wikipedia.org/wiki/C5-convertase

It can also recruit complement regulators such as Factor H, C4b-binding protein, factor H-like binding protein, and vitronectin ... It also secretes proteases to degrade complement proteins such as C3. It can bind to thrombin that decreases the fibrin ... They also bind to several human proteins such as complement proteins, thrombin, fibrinogen, and plasminogen using surface ...

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

... complex also creates byproducts like C3b and C4b which are important components for the efficient function of the complement ... As well as endocytic PRRs, phagocytes furthermore express opsonin receptors such as Fc receptor and complement receptor 1 (CR1 ... or they can facilitate the formation of the Complement membrane attack complex (MAC) by being deposited on the cell surface of ... Should the microbe be coated with opsonising antibodies or C3b complement, the co-stimulation of endocytic PRR and opsonin ...

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

The system also complements the school curriculum, where in many cases, students in Years 9 and 10 and 11 are in the same ... If the student chooses to not attend the detention, then they receive a C4b, which means it is 1 hour instead of 30 minutes. A ...

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

Besides complement particles C1q and C3b which help to opsonize the apoptotic cells, also thrombospondin, pentraxins (C- ... Among soluble inhibitors there are factor H, C1 inhibitor, C4b-binding protein, factor I, S protein or clusterin, the membrane- ... Non-apoptotic cells also express complement inhibitors, preventing the assembly of C3 convertase or the lytic pore. ... components of complement pathways (e.g. C1q, C3b) and other molecules found in extracellular space. Collectins (e.g. mannose- ...

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

... while serum levels of complement C4b (C4b), fibronectin (FN), and prolidase (PEPD) were detected using the ELISA method among ... We found significantly higher levels of serum C4b and PEPD (P = 0.018, P = 0.003), and significantly lower levels of serum FN ( ... On the other hand, a significant positive correlation was found between C4b and globulin, CRP, PEPD, as well as between PEPD ... A significant negative correlation was found between C4b and albumin, prealbumin. ...

https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-14-52/figures/3

C4A and C4B) in the genome. Although these genes differ only in 5 nucleotides, the encoded C4A and C4B proteins are ... The reliable, single-step analysis provides the determination of the copy number of the C4A and C4B genes applying a wide range ... This report describes a novel real-time PCR method for single-step quantification of C4A and C4B genes. The developed technique ... A novel quantitative real-time PCR (qPCR) technique was developed for rapid and accurate quantification of the C4A and C4B ...

https://bmcgenomdata.biomedcentral.com/articles/10.1186/1471-2156-7-1/figures/2

Of the 8 plasma membrane receptors for complement, only deficiencies of CR3 and CR4 due to CD18 deficiency have been described ... The complement system exerts many of its effects through complement receptors (CRs). ... C3b/C4b. RBC, polymorphonuclear cell, macrophage, B cell, follicular dendritic cell. Immune adherence, phagocytosis ... encoded search term (Pediatric Complement Receptor Deficiency) and Pediatric Complement Receptor Deficiency What to Read Next ...

https://emedicine.medscape.com/article/886248-medication

Factor I is a serine protease which inactivates complement components C3b ... Complement Factor I is a member of the peptidase S1 family present in the blood plasma. Factor I is an 88kD protein consisting ...

https://labstore.ru/en/catalog/antitela-3/complement-factor-i-c3bc4b-inactivator-cfi-if-igg-mouse-polyclonal/50-mkg/

Complement C4b-Binding Protein * Eye Proteins * Membrane Glycoproteins * NF-kappa B p50 Subunit ... Most of the novel genes are expressed in retinal tissue and could be involved in the pathogenesis of AMD (i.e., complement, ...

https://pubmed.ncbi.nlm.nih.gov/32277175/

The variola virus overcomes human viral clearance by inactivation of complement components C3b and C4b. ... The variola virus overcomes human viral clearance by inactivation of complement components C3b and C4b.. Tudor Toma([email protected] ... engineered the smallpox inhibitor of complement enzymes (SPICE) - a homologue of the vaccinia virulence factor, vaccinia virus ... complement control protein (VCP). When they compared VCP and SPICE and they found that SPICE was nearly 100-fold more potent ...

https://www.the-scientist.com/research-round-up/smallpox-repays-the-complement-53245

Immunologic studies have identified abnormalities such as decreased plasma concentrations of the C4B complement protein. Such ...

https://www.medscape.com/answers/912781-193663/which-patient-groups-have-the-highest-prevalence-of-autism-spectrum-disorder-asd

Here, we show that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice, a lupus-prone murine ... Generally, complement cascade products of C3b, C5b, C4b are involved in opsonization for pathogens. And evidence suggests that ... 3d) and the classical complement pathway (KEGG term the complement and coagulation cascades, Fig. 2c). In the above category ... Nayak, A., Pednekar, L., Reid, K. B. & Kishore, U. Complement and non-complement activating functions of C1q: A prototypical ...

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

C4b. Name: complement component 4B (Chido blood group). Synonyms: Ss, C4. Type: Gene ...

https://www.mmrrc.org/catalog/sds.php?mmrrc_id=39242

KSHV Kaposin to classical/Lectin pathway of complement cascade, C4b breakdown. N01528 KSHV Kaposin to alternative pathway of ... Kaposis sarcoma-associated herpes virus complement control protein: KCP--complement inhibition and more. ...

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

... complement receptor 2) and C3d receptor, binds C3d and iC3b. ... CD35, also known as CR1, binds C3b, iC3b, C4b, and iC4b. CD21/ ... CD21, also known as CR2 (complement receptor 2) and C3d receptor, binds C3d and iC3b. It is also a receptor of Epstein-Barr ... CD21 binds C3d, iC3b, and EBV; CD35 binds C3b, iC3b, C4b, and iC4b. Cell Type B cells, Dendritic cells Biology Area Cell ...

https://www.biolegend.com/de-de/products/pe-cyanine7-anti-mouse-cd21-cd35-cr2-cr1-antibody-6228

Complement C4b-Binding Protein Medicin och livsvetenskap 54% * Islets of Langerhans Medicin och livsvetenskap 47% ... Outside in: Roles of complement in autophagy. King, B. C., Kulak, K., Colineau, L. & Blom, A. M., 2021 juli 1, I: British ... Complement in metabolic disease: metaflammation and a two-edged sword. King, B. C. & Blom, A. M., 2021, I: Seminars in ... before moving to Sweden and starting to work with the complement system. I am currently studying novel roles of complement ...

https://portal.research.lu.se/sv/persons/ben-king

Recombinant Human Complement receptor type 1 (CR1), partial , CSB-EP005932HU , CusabioAlternative Name(s): C3b/C4b receptor CD_ ... Recombinant Human Complement receptor type 1 (CR1), partial , CSB-EP005932HU Cusabio Human Recombinants ...

https://joplink.net/recombinant-mouse-egf-containing-fibulin-like-extracellular-matrix-protein-1-efemp1-csb-mp007450mo/

The complement component C4 with the isotypes C4A and C4B is an effector protein of the immune system, and differences in the ...

https://www.researchgate.net/profile/Femke-Anouska-Heinsen

Approximately 60% is bound non-covalently to complement component C4b binding protein β-chain (C4BP), whereas the remaining 40 ... Dahlback B. Inhibition of protein C cofactor function of human and bovine protein S by C4b-binding protein. J Biol Chem 1986; ... Dahlback B. The tale of protein S and C4b-binding protein, a story of affection. Thromb Haemost 2007; 98: 90-6. Links ... Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation ...

https://www.stoptheclot.org/news/article137/

Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules ... Pulsed field gel electrophoresis identifies a high degree of variability in the number of tandem 21-hydroxylase and complement ... the C4B gene, and the 5 end of the functional CYP21 gene [27]. ...

https://www.wikigenes.org/e/gene/e/1590.html

We found that inhalation of GMA-SS welding fume was associated with activation of complement (C2, C3, C1QA-C, C4B), type 1 ...

http://www2a.cdc.gov/nioshtic-2/BuildQyr.asp?s1=welding&f1=%2A&Startyear=&Adv=0&terms=1&D1=10&EndYear=&Limit=10000&sort=&PageNo=28&RecNo=271&View=f&

C4b-Binding Protein C4b-C3b Inactivator Cofactor C4bC3bINA-Cofactor Complement 4b Binding Protein Complement C3b-C4b ... Complement C3b Inactivator Proteins [D12.776.124.486.274.920.325] * Complement C4b-Binding Protein [D12.776.124.486.274.920.662 ... It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE ( ... It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE ( ...

https://meshb-prev.nlm.nih.gov/record/ui?ui=D050716

complement C3b/C4b receptor.... ENSG00000198336. 4635. MYL4. myosin light chain 4 [Sourc.... ...

https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/DESCARTES_FETAL_INTESTINE_ERYTHROBLASTS.html

However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on ... MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on ...

https://www.frontiersin.org/articles/10.3389/fphy.2018.00130/full

Complement activity is antigen specific. Complement fixation results in all of the following. Activation of C3b, Immune ... C5b joins C6, C7, C8, and C9 to form the membrane attack complex,activated C1 activates C2 and C4,activated C2a and C4b ... Complement. Effects of complement activation. Interference with viral replication, bacterial cell lysis, opsonization and ... Complement component C3, in the classical pathway, is split by ________.. C2aC4b Which of the following occurs first, setting ...

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

Learn about the three pathways lead to complement activation and some of their key inhibitors. ... C4b binds C2, which is subsequently cleaved by C1s. This results in the release of C2b and C2a. C2a remains associated with C4b ... C4b binds C2, which is subsequently cleaved by C1s. This results in the release of C2b and C2a. C2a remains associated with C4b ... Inhibitors of the complement syste. The complement cascade is tightly controlled to protect host cells from indiscriminate ...

https://www.abcam.com/pathways/complement-cascade-and-its-inhibitors

Complement factor I binds C4BP (Homo sapiens) * C4-binding protein:C4b [plasma membrane] (Homo sapiens) * C4b-binding protein [ ... C4b-binding protein binds C4b (Homo sapiens) * C4-binding protein:C4b [plasma membrane] (Homo sapiens) * C4b-binding protein [ ... Complement factor I inactivates C4BP-bound C4b (Homo sapiens) * C4b-binding protein [plasma membrane] (Homo sapiens) * C4BPA [ ... Complement cascade (Homo sapiens) * Regulation of Complement cascade (Homo sapiens) * C4b binding protein binds C4bC2a (Homo ...

https://reactome.org/content/detail/R-HSA-981625

Fixation of complement results in C3b and/or C4b components on the RBC membrane, which may lead to phagocytosis by macrophages ... Lytic components of complement C5-C9 generally do not form on these cells, and intravascular hemolysis by complement is less ... Complement levels in hemolysis. In chronic cold agglutinin disease, complement tends to be depleted. Thus, the hemolysis is ... Association of complement fixation with temperature. In vivo, the IgM antibody attaches to RBCs and causes them to agglutinate ...

https://emedicine.medscape.com/article/135327-overview

BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the ... BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the ... The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity. Basmarke-Wehelie, Rahma; ...

https://orbilu.uni.lu/browse?type=author&value=Jurkowski%2C+Wiktor+40021149

... including the binding of several complement factors to fragments C3b and C4b [ (PUBMED:2751824) ]. The sushi domain is also ... Crystal Structure of Complement C3b in Complex with Factor B. 2yby. Structure of domains 6 and 7 of the mouse complement ... Structure of complement regulator Factor H mutant, T1184R.. 3rj3. Complement components factor H CCP19-20 (S1191L mutant) and ... Vaccinia Complement Protein in Complex with Heparin. 1srz. Solution structure of the second complement control protein (CCP) ...

https://smart.embl.de/smart/do_annotation.pl?DOMAIN=CCP&START=1462&END=1519&E_VALUE=4.81e-1&TYPE=SMART&BLAST=CGVPDSSLVNYANFSCLEGTDFLKQCSISCVPPAKLQGLNPWLTCLEDGLWSLPEVYC

CD21, also known as CR2 (complement receptor 2) and C3d receptor, binds C3d and iC3b. (biolegend.com)
It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a). (nih.gov)
Complement C6 then binds to C5b to form the complex C5b6 [ 7 ]. (frontiersin.org)
C4b binds C2, which is subsequently cleaved by C1s. (abcam.com)
The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE , to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE). (bvsalud.org)
Once this occurs, a complement protein termed C1 (which comprises a single C1q subunit, two C1r subunits and two C1s subunits) binds to adjacent Fc domains in the antibody-antigen complex. (pharmacy180.com)
A further complement protein, C2, binds to this membrane complex to give C4b2. (pharmacy180.com)
C4b then binds to C2, and also, via a very unusual type of reactive thioester bond, to any local macromolecule, such as the antigen- antibody complex itself, or to the membrane in the case of a cell-bound antigen. (pediagenosis.com)

I am currently studying novel roles of complement proteins, with focuses on C3 and CD59 and how they affect cellular function in various systems, with particular focus within the pancreatic islet. (lu.se)
The complex between complement system proteins C5b and C6 is the cornerstone for the assembly of the membrane attack complex (MAC, also known as C5b6789 n ). (frontiersin.org)
The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. (embl.de)
These modules have been identified more than 140 times in over 20 proteins, including 12 proteins of the complement system. (embl.de)
The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. (medlineplus.gov)
Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed. (medlineplus.gov)

engineered the smallpox inhibitor of complement enzymes (SPICE) - a homologue of the vaccinia virulence factor, vaccinia virus complement control protein (VCP). (the-scientist.com)
Approximately 60% is bound non-covalently to complement component C4b binding protein β-chain (C4BP), whereas the remaining 40% is free [ 3 ]. (stoptheclot.org)
Activation of all three pathways converges on the cleavage of complement protein C3 into C3b and C3a [ 6 ]. (frontiersin.org)
The sushi domain is also known as the complement controle protein (CCP) module or the short consensus repeat (SCR). (embl.de)
Three-dimensional structure of a complement control protein module in solution. (embl.de)
The complement control protein (CCP) modules (also known as short consensus repeats) are defined by a consensus sequence within a stretch of about 60 amino acid residues. (embl.de)
C4b-binding protein is a regulatory protein of the Complement Cascade that possesses decay-accelerating activity. (athensresearch.com)
C4b-binding protein has been investigated for its role in Alzheimer's Disease, Psoriasis, as well as autoimmune diseases including Rheumatoid Arthritis, and different types of Cancer. (athensresearch.com)
The CFI gene provides instructions for making a protein called complement factor I. This protein helps regulate a part of the body's immune response known as the complement system. (medlineplus.gov)
The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. (medlineplus.gov)
The unregulated activity of the complement system decreases blood levels of another complement protein called C3, reducing the immune system's ability to fight infections. (medlineplus.gov)
The CFI gene mutations identified in this disorder result in an abnormal or nonfunctional version of complement factor I. The defective protein allows uncontrolled activation of the complement system. (medlineplus.gov)
The overactive complement system attacks certain kidney cells, which damages the kidneys and leads to a loss of protein in the urine (proteinuria). (medlineplus.gov)
The classical pathway can additionally lead to complement protein deposition on insoluble antibody- antigen immune complexes circulating within blood, and in doing so promote the clearance of such potentially harmful complexes by Kupffer cells of the liver. (pharmacy180.com)
Efdamrofusp alfa is a novel bispecific decoy receptor fusion protein that acts independent through neutralizing both C3b/C4b and VEGF. (hcplive.com)
The study, " A novel bispecific fusion protein targeting C3b/C4b and VEGF in Patients with nAMD: A Randomized, Open-label Phase 1b Study ," was published in the American Journal of Ophthalmology . (hcplive.com)
Note that, in the absence of antibody, many of the molecules that activate the complement system are carbohydrate or lipid in nature (e.g. lipopolysaccharides, mannose), suggesting that the system evolved mainly to recognize bacterial surfaces via their non-protein features. (pediagenosis.com)
Total Protein S is comprised of Free Protein S and Protein S bound to a complement protein, C4B-BP. (nicholsinstitute.com)

C2a remains associated with C4b to form the classical pathway C3 convertase (C4b2a). (abcam.com)

Of the 8 plasma membrane receptors for complement, only deficiencies of CR3 and CR4 due to CD18 deficiency have been described, known as leukocyte adhesion deficiency (LAD) type 1 . (medscape.com)
At least 10 mutations in the CFI gene have been identified in people with complement factor I deficiency, a disorder characterized by immune system dysfunction. (medlineplus.gov)
This condition, which may also occur in people with complement factor I deficiency, is characterized by kidney malfunction that can be serious or life-threatening. (medlineplus.gov)
Ponce-Castro IM, Gonzalez-Rubio C, Delgado-Cervino EM, Abarrategui-Garrido C, Fontan G, Sanchez-Corral P, Lopez-Trascasa M. Molecular characterization of Complement Factor I deficiency in two Spanish families. (medlineplus.gov)
Increased frequency of complement C4B deficiency in rheumatoid arthritis. (cdc.gov)

Most of the novel genes are expressed in retinal tissue and could be involved in the pathogenesis of AMD (i.e., complement, inflammation, and lipid pathways). (nih.gov)
We found that inhalation of GMA-SS welding fume was associated with activation of complement (C2, C3, C1QA-C, C4B), type 1 interferon pathways and increased expression of monocyte and lymphocyte chemotactic genes such as CCL2, CCL7 and CCL8. (cdc.gov)
MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on cell surfaces, as a response of the immune system in fighting pathogens. (frontiersin.org)
The versatile response of the complement system emerges from its three pathways known as alternative, classical, and lectin, that are either constitutively active in the fluid phase (alternative and classical pathway [ 3 - 5 ]) or initiate upon sensing danger-associated molecular patterns on pathogens (classical and lectin pathways). (frontiersin.org)
Learn about the three pathways lead to complement activation and some of their key inhibitors. (abcam.com)
the classical pathway initiated by antibodies bound to the surface of foreign bodies and the alternative and lectin pathways that provide an antibody-independent mechanism for complement activation, induced by the presence of bacteria and other micro-organisms. (abcam.com)
The presence of two complement pathways provides for rapid (alternative) and specific (classical) activation of a key defence mechanism, and offers greater protection against the development of microbial resistance mechanisms. (pharmacy180.com)
Complement activation plays an important role in local and remote tissue injury associated with gastrointestinal ischemia-reperfusion (GI/R). The role of the classical and lectin complement pathways in GI/R injury was evaluated using C1q-deficient (C1q KO), MBL-A/C-deficient (MBL-null), complement factor 2- and factor B-deficient (C2/fB KO), and wild-type (WT) mice. (aai.org)

Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma. (medscape.com)
Structure, function and cellular expression of complement anaphylatoxin receptors. (medscape.com)
The complement system exerts many of its effects through complement receptors (CRs). (medscape.com)

As part of the innate immunity, the complement system orchestrates a cascade of biochemical reactions that result in pathogen elimination and in activation of the adaptive immune response [ 1 , 2 ]. (frontiersin.org)
Subsequently, continued propagation leads to the terminal cascade by cleavage of complement C5 to form C5b and C5a. (frontiersin.org)
C1 is the first molecule in the classical complement cascade and comprises C1q and two molecules of C1r and C1s respectively. (abcam.com)
A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions. (pharmacy180.com)

The complement system is a heat-labile component of blood that confers bactericidal properties. (abcam.com)
C3 (MW 180 000), the central component of all complement reac- tions, split by its convertase into a small (C3a) and a large (C3b) fragment. (pediagenosis.com)

Correlations between serum C4b, PEPD and some biochemical parameters. (biomedcentral.com)
Using this method, the beta chains of both complement C3 and C4 were found to decrease in serum from hepatitis C patients with cirrhosis, a change not observed previously by 2-DE. (ox.ac.uk)

The solution structure of the 16th CCP module from human complement factor H has been determined by a combination of 2-dimensional nuclear magnetic resonance spectroscopy and restrained simulated annealing. (embl.de)
Circulating in plasma, it aids in the control of fluid-phase and surface-associated activation of C3 and C5 and serves as a cofactor to Factor 1 in the proteolytic degradation of C4b. (athensresearch.com)
The mutations result in abnormal, nonfunctional, or absent complement factor I. (medlineplus.gov)
Variation near complement factor I is associated with risk of advanced AMD. (medlineplus.gov)
Characterization of mutations in complement factor I (CFI) associated with hemolytic uremic syndrome. (medlineplus.gov)
complement factor D [Source:HGNC Symbol. (gsea-msigdb.org)
Similar increments in complement factors C3b/c and C4b/c, tumour necrosis factor-α and neutrophil elastase, but not endotoxins, were found in both groups as indicators of a systemic inflammatory response. (vumc.nl)

18 Genetic or pharmacologic blockade of the complement pathway can prevent synaptic stripping and alleviate multiple age- and inflammation-related disorders. (nature.com)
Mannan-binding lectin (MBL) and MBL-associated serine proteases (MASPs) are involved in the initial step of the lectin pathway of complement activation. (abcam.com)
Following these cleavage events, complement pathway activation continues as in the classical pathway. (abcam.com)
Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjögren's Syndrome. (cdc.gov)
The antibodies that activate the classical complement pathway are IgM and IgG. (pharmacy180.com)
The functions of the classical complement pathway are similar to those described for the alternative pathway, i.e. opsonization, leucocyte activation and membrane lysis of target cells. (pharmacy180.com)

Activation of complement can be started either via adaptive or innate immune recognition. (pediagenosis.com)
Nevertheless, excessive complement activation can cause unpleasant side-effects (see Fig. 36). (pediagenosis.com)

Difference in the clustering of complement receptor type 1 (CR1) on polymorphonuclear leukocytes and erythrocytes: effect on immune adherence. (medscape.com)
Wakabayashi M, Ohi H, Tamano M, Onda K, Fujita T, Tomino Y. Acquired loss of erythrocyte complement receptor type 1 in patients with diabetic nephropathy undergoing hemodialysis. (medscape.com)

The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens. (medscape.com)

However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to several complement-mediated autoimmune diseases. (frontiersin.org)

Precision of the determination of the C4A and C4B gene number. (biomedcentral.com)

The C4b covalently associates with the antibody-antigen complex on the surface of a microbial membrane and can serve as an opsonin. (pharmacy180.com)

In May 28 Proceedings of the National Academy of Sciences , Ariella Rosengard and colleagues from University of Pennsylvania School of Medicine , Philadelphia show that variola overcomes the human immune response by expressing a highly efficient inhibitor of human complement ( Proc Natl Acad Sci USA 2002, 10.1073/pnas.112220499). (the-scientist.com)
Case studies report benefit from treatment with rituximab or the complement inhibitor eculizumab. (medscape.com)

Several inherited deficiencies in the complement system occur in humans. (studystack.com)

The variola virus overcomes human viral clearance by inactivation of complement components C3b and C4b. (the-scientist.com)
When they compared VCP and SPICE and they found that SPICE was nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. (the-scientist.com)
SPICE was also more human complement-specific than VCP. (the-scientist.com)

I completed my PhD within the field of cancer immunotherapy, working with cytotoxic T cells, before moving to Sweden and starting to work with the complement system. (lu.se)
Long-term use of anti-VEGF therapies for nAMD may activate the complement system, which can further stimulate the formation of CNV or geography atrophy (GA). (hcplive.com)

C3b and C4b bind to CR1, which is present on various phagocytes and also on erythrocytes and B cells. (medscape.com)

The instigation of an immune response via C5b6 is also detrimental to host-cells unless complement is properly regulated at the terminal stage [ 14 ]. (frontiersin.org)
The functions of complement include the attraction of inflammatory cells, opsonization to promote phagocytosis, immune complex clearance and direct microbial killing through the formation of the membrane attack complex (MAC). (abcam.com)

Both low (2 mg) and high-dose (4 mg) regimens of efdamrofusp alfa were well-tolerated and all enrolled patients completed the treatment and all scheduled visits, with similar safety as other intravitreal anti-VEGF agents and complement inhibitors. (hcplive.com)

Anatomy15

Organisms10

Diseases16

Chemicals and Drugs101

Analytical, Diagnostic and Therapeutic Techniques and Equipment25

Phenomena and Processes48

Disciplines and Occupations2

Information Science3

Health Care1

Immunohistochemical analysis of arterial wall cellular infiltration in Buerger's disease (endarteritis obliterans). (1/363)

Deficiency of human complement protein C4 due to identical frameshift mutations in the C4A and C4B genes. (2/363)

Interaction between protein S and complement C4b-binding protein (C4BP). Affinity studies using chimeras containing c4bp beta-chain short consensus repeats. (3/363)

Consumption of C4b-binding protein (C4BP) during in vivo activation of the classical complement pathway. (4/363)

Some anticardiolipin antibodies recognize a combination of phospholipids with thrombin-modified antithrombin, complement C4b-binding protein, and lipopolysaccharide binding protein. (5/363)

A cluster of positively charged amino acids in the C4BP alpha-chain is crucial for C4b binding and factor I cofactor function. (6/363)

Analysis of human C4A and C4B binding to an immune complex in serum. (7/363)

Upregulation of ICAM-1 on cardiomyocytes in jeopardized human myocardium during infarction. (8/363)

Complement C3

Complement C4

Complement C4a

Complement C3a

Complement C1q

Complement C5a

Complement Activation

Complement C4b

Complement C5

Complement C3b

Complement System Proteins

Complement C6

Complement C3c

Complement C3d

Complement C2

Complement C9

Receptors, Complement

Complement C1s

Complement Membrane Attack Complex

Complement C1r

Complement Inactivator Proteins

Complement C7

Complement C3-C5 Convertases

Complement Factor B

Complement Pathway, Alternative

Complement Pathway, Classical

Complement C8

Complement C1

Receptors, Complement 3b

Complement Factor H

Complement C5b

Complement C2a

Receptor, Anaphylatoxin C5a

Complement Activating Enzymes

Complement Inactivating Agents

Complement Hemolytic Activity Assay

Complement C1 Inactivator Proteins

Receptors, Complement 3d

Anaphylatoxins

Complement Fixation Tests

Complement Factor D

Complement Factor I

Complement C4b-Binding Protein

Complement C3b Inactivator Proteins

Antigens, CD55

Complement C3-C5 Convertases, Classical Pathway

Complement C2b

Antigens, CD59

Cobra Venoms

Antigen-Antibody Complex

Steroid 21-Hydroxylase

Complement C3-C5 Convertases, Alternative Pathway

Complement C1 Inhibitor Protein

Immunoglobulin G

Hemolysis

Complement C3 Convertase, Alternative Pathway

Complement C5 Convertase, Classical Pathway

Molecular Sequence Data

Complement C3 Convertase, Classical Pathway

Antigens, CD46

Opsonin Proteins

Blood Proteins

Lupus Erythematosus, Systemic

Complement C5 Convertase, Alternative Pathway

Phagocytosis

Amino Acid Sequence

Complement Pathway, Mannose-Binding Lectin

Properdin

Complement C5a, des-Arginine

Mice, Inbred C57BL

Macrophage-1 Antigen

Protein Binding

Neutrophils

Base Sequence

Kidney Glomerulus

Serum

Glomerulonephritis, Membranoproliferative

Immunoglobulin M

Schistosoma

Genetic Complementation Test