Complement c4a. 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.

Deficiency of human complement protein C4 due to identical frameshift mutations in the C4A and C4B genes. (1/96)

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)

Analysis of human C4A and C4B binding to an immune complex in serum. (2/96)

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)

Possible mechanism for in vitro complement activation in blood and plasma samples: futhan/EDTA controls in vitro complement activation. (3/96)

BACKGROUND: Ongoing in vitro complement (C) activation in citrate or EDTA plasma has prevented an accurate analysis of C-activation products generated in vivo. The aim of this study was to characterize handling and storage conditions required to prevent in vitro C activation in blood and plasma samples collected with Futhan/EDTA. METHODS: Biotrak(TM) RIAs were used to quantitatively measure C3a and C4a in blood and/or plasma samples from healthy individuals (controls) and from liver transplant patients. Blood samples were routinely drawn into either EDTA (1 g/L) tubes or into tubes containing both EDTA (1 g/L) and Futhan (0.1 g/L) and immediately centrifuged at 2000g for 15 min at 4 degrees C. RESULTS: In controls, C4a, but not C3a, in fresh samples (time 0) was higher in EDTA plasma than in Futhan/EDTA plasma (n = 20; P = 0.002). Futhan/EDTA prevented C3a and C4a generation in blood and plasma samples held at room temperature (22-23 degrees C) for 1 h and in plasma held for 24 h at 4 degrees C or -70 degrees C. The mean C3a concentration (1.76 mg/L; n = 19) at time 0 in EDTA plasma samples from liver transplant patients was significantly higher than for controls (0.34 mg/L; n = 11). In these patients, the mean C3a in EDTA samples increased to 13.8 mg/L after 60 min at room temperature, but there was no change in the C3a concentration of an EDTA plasma from a control. In the patients, C3a concentrations were lower in Futhan/EDTA plasma than in EDTA at time 0 and after 60 min at room temperature (1.40 and 2.02 mg/L, respectively). The mean patient C4a was 4.02 mg/L in EDTA plasma at time 0 vs 0.24 mg/L for controls; it increased to 16.9 mg/L after 60 min at room temperature compared with 0.76 mg/L for controls. The mean patient C4a was 0.83 mg/L in Futhan/EDTA plasma at time 0 vs 0.1 mg/L for controls. Neither patient nor control C4a concentrations increased vs time in Futhan/EDTA. CONCLUSION: The combination of Futhan (0.1 g/L) and EDTA (1 g/L) eliminates in vitro C activation. (+info)

Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules in caucasians. The load of RCCX genetic diversity on major histocompatibility complex-associated disease. (4/96)

The complement component C4 genes located in the major histocompatibility complex (MHC) class III region exhibit an unusually complex pattern of variations in gene number, gene size, and nucleotide polymorphism. Duplication or deletion of a C4 gene always concurs with its neighboring genes serine/threonine nuclear protein kinase RP, steroid 21-hydroxylase (CYP21), and tenascin (TNX), which together form a genetic unit termed the RCCX module. A detailed molecular genetic analysis of C4A and C4B and RCCX modular arrangements was correlated with immunochemical studies of C4A and C4B protein polymorphism in 150 normal Caucasians. The results show that bimodular RCCX has a frequency of 69%, whereas monomodular and trimodular RCCX structures account for 17.0 and 14.0%, respectively. Three quarters of C4 genes harbor the endogenous retrovirus HERV-K(C4). Partial deficiencies of C4A and C4B, primarily due to gene deletions and homoexpression of C4A proteins, have a combined frequency of 31.6%. This is probably the most common variation of gene dosage and gene size in human genomes. The seven RCCX physical variants create a great repertoire of haplotypes and diploid combinations, and a heterozygosity frequency of 69.4%. This phenomenon promotes the exchange of genetic information among RCCX constituents that is important in homogenizing the structural and functional diversities of C4A and C4B proteins. However, such length variants may cause unequal, interchromosomal crossovers leading to MHC-associated diseases. An analyses of the RCCX structures in 22 salt-losing, congenital adrenal hyperplasia patients revealed a significant increase in the monomodular structure with a long C4 gene linked to the pseudogene CYP21A, and bimodular structures with two CYP21A, which are likely generated by recombinations between heterozygous RCCX length variants. (+info)

Deficient APC-cofactor activity of protein S Heerlen in degradation of factor Va Leiden: a possible mechanism of synergism between thrombophilic risk factors. (5/96)

In protein S Heerlen, an S-to-P (single-letter amino acid codes) mutation at position 460 results in the loss of glycosylation of N458. This polymorphism has been found to be slightly more prevalent in thrombophilic populations than in normal controls, particularly in cohorts of patients having free protein S deficiency. This suggests that carriers of the Heerlen allele may have an increased risk of thrombosis. We have now characterized the expression in cell cultures of recombinant protein S Heerlen and investigated the anticoagulant functions of the purified recombinant protein in vitro. Protein S Heerlen was synthesized and secreted equally well as wild-type protein S by transiently transfected COS-1 cells. The recombinant protein S Heerlen interacted with conformation-dependent monoclonal antibodies and bound C4b-binding protein to the same extent as wild-type protein S. Protein S Heerlen displayed reduced anticoagulant activity as cofactor to activated protein C (APC) in plasma-based assays, as well as in a factor VIIIa-degradation system. In contrast, protein S Heerlen functioned equally well as an APC cofactor in the degradation of factor Va as wild-type protein S did. However, when recombinant activated factor V Leiden (FVa:Q506) was used as APC substrate, protein S Heerlen was found to be a poor APC cofactor as compared with wild-type protein S. These in vitro results suggest a possible mechanism of synergy between protein S Heerlen and factor V Leiden that might be involved in the pathogenesis of thrombosis in individuals carrying both genetic traits. (Blood. 2000;96:523-531) (+info)

Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE). (6/96)

The aim of the present study was to investigate the prevalence of C4 and C2 deficiencies and to characterize genomic alterations in C4 genes in a large cohort of 125 unselected patients with SLE. We determined the protein concentration and functional activity of C2 and C4, as well as the C4 phenotype. C4 genotyping included Taq 1 restricted fragment lengh polymorphism (RFLP) analysis and polymerase chain reaction using sequence-specific primers (SSP-PCR). Type I C2 deficiency was diagnosed by PCR. Overall, 79.2% of the patients exhibited abnormalities of the C4 genes including deletion, non-expression, gene conversion and duplication. Among C4-deficient patients (n = 66, 52.8% prevalence), 41.0% of the patients exhibited a C4A deficiency and 59.0% a C4B deficiency. Half of the C4 deficiencies were due to a gene deletion. There was a strong association between C4A and C4B gene deletion and the presence of the DRB1*03 allele. Among the silent C4A genes, only two cases were related to a 2-bp insertion in exon 29 of the C4A gene. A gene conversion was demonstrated in eight patients (6.4%). One patient had a homozygous C4A deficiency. Three (2.4%) patients presented with a heterozygous type I C2 deficiency and none with homozygous deficiency. Our results argue against a specific role for C4A gene deficiency in determining disease susceptibility among patients with SLE that are C4-deficient. (+info)

Characterization of a de novo conversion in human complement C4 gene producing a C4B5-like protein. (7/96)

Complement C4 is a highly polymorphic protein essential for the activation of the classical complement pathway. Most of the allelic variation of C4 resides in the C4d region. Four polymorphic amino acid residues specify the isotype and an additional four specify the Rodgers and Chido determinants of the protein. Rare C4 allotypes have been postulated to originate from recombination between highly homologous C4 genes through gene conversions. Here we describe the development of a de novo C4 hybrid protein with allotypic and antigenic diversity resulting from nonhomologous intra or interchromosomal recombination of the maternal chromosomes. A conversion was observed between maternal C4A3a and C4B1b genes producing a functional hybrid gene in one of the children. The codons determining the isotype, Asp(1054), Leu(1101), Ser(1102), Ile(1105) and His(1106), were characteristic of C4B gene, whereas the polymorphic sites in exon and intron 28 were indicative of C4A3a sequence. The protein produced by this hybrid gene was electrophoretically similar to C4B5 allotype. It also possesses reversed antigenicity being Rodgers 1, 2, 3 and Chido-1, -2, -3, 4, -5, and -6. Our case describes the development of a rare bimodular C4B-C4B haplotype containing a functional de novo C4 hybrid gene arisen through gene conversion from C4A to C4B. Overall the data supports the hypothesis of gene conversions as an ongoing process increasing allelic diversity in the C4 locus. (+info)

Determining the one, two, three, or four long and short loci of human complement C4 in a major histocompatibility complex haplotype encoding C4A or C4B proteins. (8/96)

The complex genetics of human complement C4 with unusually frequent variations in the size and number of C4A and C4B, as well as their neighboring genes, in the major histocompatibility complex has been a hurdle for accurate epidemiological studies of diseases associated with C4. A comprehensive series of novel or improved techniques has been developed to determine the total gene number of C4 and the relative dosages of C4A and C4B in a diploid genome. These techniques include (1) definitive genomic restriction-fragment-length polymorphisms (RFLPs) based on the discrete duplication patterns of the RCCX (RP-C4-CYP21-TNX) modules and on the specific nucleotide changes for C4A and C4B isotypes; (2) module-specific PCR to give information on the total number of C4 genes by comparing the relative quantities of RP1- or TNXB-specific fragments with TNXA-RP2 fragments; (3) labeled-primer single-cycle DNA polymerization procedure of amplified C4d genomic DNA for diagnostic RFLP analysis of C4A and C4B; and (4) a highly reproducible long-range-mapping method that employs PmeI-digested genomic DNA for pulsed-field gel electrophoresis, to yield precise information on the number of long and short C4 genes in a haplotype. Applications of these vigorously tested techniques may clarify the roles that human C4A and C4B gene-dosage variations play in infectious and autoimmune diseases. (+info)

Complement peptide C5a, C4a, and C3a receptors". Pharmacol. Rev. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID 23383423. ... Complement 3 (C3) through its interaction with factors B and D (adipsin) generates C3a. In the human body, C3a is rapidly ...

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

Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... The C5a receptor also known as complement component 5a receptor 1 (C5AR1) or CD88 (Cluster of Differentiation 88) is a G ... Complement component 5a for binding mechanism GRCh38: Ensembl release 89: ENSG00000197405 - Ensembl, May 2017 GRCm38: Ensembl ... Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, Woodruff TM, Ruitenberg MJ (April 2015). "The Complement ...

https://en.wikipedia.org/wiki/C5a_receptor

Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... Complement+C5a at the US National Library of Medicine Medical Subject Headings (MeSH) (Webarchive template wayback links, ... C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b ...

https://en.wikipedia.org/wiki/Complement_component_5a

C4A-C4A, or C4B-C4B) and 31% trimodular configuration (equally split between LLL as C4A-C4A-C4B or LSS as C4A-C4B-C4B). ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar A, ... Law SK, Dodds AW, Porter RR (August 1984). "A comparison of the properties of two classes, C4A and C4B, of the human complement ... 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

Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... 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

Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... bacteria-induced complement activation also causes the formation of complement component 3a (C3a) by cleavage from complement ... Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM (Mar 2013). "C5L2: a controversial receptor of complement anaphylatoxin, C5a ... interaction of bacteria with blood plasma components to activate the complement cascade which then cleave C5a from Complement ...

https://en.wikipedia.org/wiki/Formyl_peptide_receptor_1

Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... The receptor binds to complement component C3a, although there is limited evidence that this receptor also binds C4a in lesser ... The C3a receptor also known as complement component 3a receptor 1 (C3AR1) is a G protein-coupled receptor protein involved in ... Sayegh ET, Bloch O, Parsa AT (August 2014). "Complement anaphylatoxins as immune regulators in cancer". Cancer Medicine. 3 (4 ...

https://en.wikipedia.org/wiki/C3a_receptor

It's a complement component G protein-coupled receptor, of class A (rhodopsin-like). The anaphylatoxins C3a, C4a, and C5a are ... Complement peptide C5a, C4a, and C3a receptors". Pharmacol. Rev. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID 23383423. Ohno ... "Complement Peptide Receptors: C5a2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Cain SA, Monk PN (2002). "The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg ...

https://en.wikipedia.org/wiki/C5AR2

Activated C1s cleaves C4 into C4a and C4b. The newly formed C4b cannot stay activated as a highly reactive thioester bond is ... 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

C4a and C5a) that are produced as part of the activation of the complement system. Complement components C3, C4 and C5 are ... C3, C4A, C4B, C4B-1, C5, FBLN1, FBLN2 Allergy Anaphylatoxin receptors Anaphylaxis Complement system Inflammation Immune system ... coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as ... C4a is the least active anaphylatoxin. Although some drugs (morphine, codeine, synthetic ACTH) and some neurotransmitters ( ...

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

1994). "Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the ... "The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21 ... "Characterisation of the novel gene G11 lying adjacent to the complement C4A gene in the human major histocompatibility complex ... 1996). "Complete sequence of the complement C4 gene from the HLA-A1, B8, C4AQ0, C4B1, DR3 haplotype". Immunogenetics. 43 (4): ...

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

Complement C4-A is a kind of the Complement component 4 protein that in humans is encoded by the C4A gene. This gene encodes ... Complement component 4 Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency ... Media related to C4A at Wikimedia Commons Human C4A genome location and C4A gene details page in the UCSC Genome Browser. v t e ... "Entrez Gene: C4A complement component 4A (Rodgers blood group)". Dawkins RL, Uko G, Christiansen FT, Kay PH (Sep 1983). "Low C4 ...

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

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

C4A and C4B. Each gene contains 41 exons and has a dichotomous size variation between approximately 22 kb and 16 kb, with the ... Complement component 4 Complement component 4A HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency ... Complement component 4B (Chido blood group) is a kind of the Complement component 4 protein that in humans is encoded by the ... "Entrez Gene: Complement component 4B (Chido blood group)". Retrieved 2012-01-27. Zhou D, Rudnicki M, Chua GT, Lawrance SK, Zhou ...

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

... mechanism for this interaction is increased complement factor C3 deposition onto synaptosomes as a consequence of increased C4A ... Genes in the Complement Component 4 (C4) locus of the major histocompatibility complex (MHC), which encode for complement ... Specifically, complement factors C1q and C3 have been found to have a role in microglia-mediated synaptic pruning. Carriers of ... The fact that some of these complement factors are involved in signaling during synaptic pruning also seems to suggest that ...

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

"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

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)

... 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 ... Yu CY (1999). "Molecular genetics of the human MHC complement gene cluster". Experimental and Clinical Immunogenetics. 15 (4): ... "Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man". ...

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

C4a and C2a are released. C4a is an anaphylatoxin. C3 convertases are unstable (half-life 10 - 20 min) - respectively they are ... Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or even a bacterial enzyme leads to formation of C3a ... DAF protects host cells from damage by autologous complement. DAF acts on C2b and Bb and dissociates them rapidly from C4b and ... Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ...

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

... 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 c3a MeSH D12.776.124.486.274.024.260 - complement c4a MeSH D12.776.124.486.274.024.270 - complement c5a MeSH D12.776 ... 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 complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin ... 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 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

Antibodies are produced against the RBCs, which leads to complement activation. Complement fragments, such as C3a, C4a and C5a ... Cases may also arise with complement alone or with IgA, IgM or a combination of these three antibody classes and complement. ... IgM is a potent activator of the classical complement pathway, thus, AIHA involving IgM is characterized by complement-mediated ... When these RBCs return to central regions, they are damaged by complement. Patients may present with one or both types of ...

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

... histamine-inducers Complement proteins C3a, C4a, and C5a work by triggering histamine release from mast cells and basophil ...

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

MASP-1 and MASP-2 are activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. In f, two smaller MBL- ... C4a and C2b act as potent cytokines, with C4a causing degranulation of mast cells and basophils and C2b acting to increase ... Classical complement pathway Alternative complement pathway Mannan-binding lectin Wallis R, Mitchell DA, Schmid R, Schwaeble WJ ... The lectin pathway or lectin complement pathway is a type of cascade reaction in the complement system, similar in structure to ...

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

Classical complement pathway C1Q complex - C1R / C1S C4 - C4a C2 Mannan-binding lectin pathway MASP1 / MASP2 Mannan-binding ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... see complement proteins section) Collectins Mannan-binding lectin (MBL) Surfactant protein A (SP-A) Surfactant protein D (SP-D ... Complement receptor of the immunoglobulin family) Anaphylatoxin receptors C3a receptor C5a receptor (CD88) C5AR2 Fc receptor Fc ...

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

MASP-2 is activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. MASP1 (protein) Mannan-binding ... MASP-2 is involved in the complement system. MASP-2 is very similar to the C1s molecule, of the classical complement pathway, ... The Ra-reactive factor (RARF) is a complement-dependent bactericidal factor that binds to the Ra and R2 polysaccharides ... Petersen SV, Thiel S, Jensenius JC (2001). "The mannan-binding lectin pathway of complement activation: biology and disease ...

https://en.wikipedia.org/wiki/MASP2_(protein)

September 2009). "Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement ... MASP-2 is then able to cleave C4 into proteins C4a and C4b. MASP-1 is also responsible for creating C3 convertase by cleaving ... 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)

Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... binding the C4b subunit and releasing C4a into the bloodstream; similarly, binding of C2 causes release of C2b. Together, MBL, ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ... "/"self turned nonself" type pathogen pattern are also identified and destroyed (e.g. by complement fixation or other cytotoxic ...

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

The system also complements the school curriculum, where in many cases, students in Years 9 and 10 and 11 are in the same ... Upon reaching a C4a, the student is removed from the classroom and given an after-school School punishment 30 mins. If the ...

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

Complement component 4 Complement component 4A Complement component 4B Price P, Witt C, Allcock R, et al. (February 1999). "The ... C4A(Null), DR3, DQ2.5. The entire haplotype, A1-Cw7-B8-TNFB*1-C4A(Null)-DR3-DQ2, is increased in patients and the genetic ... Closer to DR3, C4A is null in B8-DR3 haplotype. In 1972, a link between "HLA A1,8" (current:HLA A1-B8) active chronic hepatitis ... Other genes in the region, C4A-null and TNF may be associated with autoimmune hepatitis. The appearance of anti-nuclear ...

https://en.wikipedia.org/wiki/HLA_A1-B8-DR3-DQ2

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 ... the RCCX modules of the human MHC leading to the presence of a CYP21B gene and a tenascin TNXB/TNXA-RP2 recombinant between C4A ...

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

C4 (complement 4) produces a null allele at on locus C4AQ. This locus in part of the HLA A1-B8-DR3-DQ2 haplotype (markers are ... C4A(Null), DR3, DQ2.5. While type 1 diabetes shows an extended association on the HLA A1-B8-DR3-DQ2 haplotype, the association ...

https://en.wikipedia.org/wiki/HLA_A1-B8_haplotype

Long PCR detection of the C4A null allele in B8-C4AQ0-C4B1-DR3 Grant SF, Kristjansdottir H, Steinsson K, Blondal T, Yuryev A, ... Determination of the structural basis for selective binding of Epstein-Barr virus to human complement receptor type 2 Martin DR ...

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

Their data suggested this because the results showed that the structural variants of C4 express the C4A protein at different ... This study found that the association is caused partly by the complement component 4 (C4) genes and therefore implying that ... "Schizophrenia risk from complex variation of complement component 4". Nature. 530 (7589): 177-83. Bibcode:2016Natur.530..177.. ... levels and this difference in higher C4A protein expressions were associated with higher rates of schizophrenia development. ...

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

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

Description: A sandwich quantitative ELISA assay kit for detection of Human Complement Component 4a (C4a) in samples from serum ... Description: A sandwich quantitative ELISA assay kit for detection of Human Complement Component 4a (C4a) in samples from serum ... Description: A sandwich quantitative ELISA assay kit for detection of Mouse Complement Component 4a (C4a) in samples from serum ... Description: A sandwich quantitative ELISA assay kit for detection of Mouse Complement Component 4a (C4a) in samples from serum ...

https://elisareagents.com/rat-c4acomplement-component-4a-elisa-kit/

C4A kills bacteria and boosts immunity, but too much can damage tissues and trigger allergic reactions. Learn what high levels ... What is C4A?. C4A is part of a "complement" group. The term complement means it is able to kill bacteria and contributes to ... High & Low C4A Levels (Complement C4A) & Mold Illness. Written by Joe Cohen, BS , Reviewed by Genius Labs Science Team , Last ... C4A Test. You can request that your doctor test your C4A. Conventional doctors will look at high or low C4A levels and not ...

https://selfhack.com/blog/c4a/

Learn about the three pathways lead to complement activation and some of their key inhibitors. ... C1s cleaves C4 present in the plasma releasing C4a and C4b. C4b binds C2, which is subsequently cleaved by C1s. This results in ... Inhibitors of the complement syste. The complement cascade is tightly controlled to protect host cells from indiscriminate ... The complement system is a heat-labile component of blood that confers bactericidal properties. The functions of complement ...

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

Additionally, proteases may activate the complement cascade associated with C3a, C4a, and C5a, which are considered ... The complement cascade hyperreacts, producing large amounts of C1. C1-INH is then consumed in attempts to prevent the ... Zingale LC, Castelli R, Zanichelli A, Cicardi M. Acquired deficiency of the inhibitor of the first complement component: ...

https://www.medscape.com/answers/135208-52728/what-is-the-pathophysiology-of-angioedema-with-urticaria

... complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. ... complement component 3 Rn00566466_m1 C4a 24233 complement component 4a Rn00709527_m1 ... complement component 1, subcomponent s Rn00594278_m1 C3 24232 ...

https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-8-138/tables/2

... complement-dependent anaphylaxis, where C3a, C4a, and C5a peptides (also called anaphylatoxins) can activate mast cells, ... basophils, and macrophages, leading to the release of inflammatory mediators [10,11]. Blood levels of C3, C4a, and C5 correlate ...

https://www.mdpi.com/1422-0067/22/9/4935/htm

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

... while patients with high C4A levels also displayed high levels of IL-1beta in cerebrospinal fluid. C4A levels also correlated ... Publication: "Cerebrospinal fluid concentration of complement component 4A is increased in first-episode schizophrenia". ... The same team has now developed a method to measure C4A levels in cerebrospinal fluid. In two independent cohorts, they ... "After checking for genetic risk variants, we still observed elevated levels of C4A," says Jessica Gracias Lekander, a doctoral ...

https://www.eurekalert.org/news-releases/970151

... and anaphylatoxins derived from split complement components (C3a, C4a, and C5a) [10]. These cause MC exocytosis by directly ...

http://ispub.com/IJAAI/6/1/10898

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). ... C3a, C4a, and C5a (CD88) receptors. Receptors for C3a and C5a have been identified; whether a distinct receptor for C4a is ... The complement system exerts many of its effects through complement receptors (CRs). Of the 8 plasma membrane receptors for ...

https://www.staging.medscape.com/answers/886248-191646/what-is-pediatric-complement-receptor-3-cr3-and-4-cr4-deficiency

Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules ... The suppression effect of DNA sequences within the C4A region on the transcription activity of human CYP21. Chang, S.F., Cheng ... Pulsed field gel electrophoresis identifies a high degree of variability in the number of tandem 21-hydroxylase and complement ... All patients with the G424S mutation presented CYP21P and C4A gene deletions and human leukocyte antigen DR17 on the same ...

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

If your doctor cannot or will not order the C4A test, you can order it yourself through Life Extension. Search for "Complement ... The complement system (C4A) is a group of proteins that move freely through your bloodstream. The proteins work with your ... Twice a year I make sure to have the good old basic blood work done alone with a C4A test. I personally feel that the C4A lab ... C4a has become the inflammatory marker of greatest significance looking at innate immune responses in those with exposure to ...

https://hybridrastamama.com/need-to-detox-from-mold-exposure-heres-how-i-did-it/?replytocom=240060

Complement C4a Entry term(s). C4a Complement C4a, Complement Complement 4a Complement Component 4a Complement, C4a Component 4a ... Complément C4a Entry term(s):. C4a Complement. C4a, Complement. Complement 4a. Complement Component 4a. Complement, C4a. ... Complement C4a - Preferred Concept UI. M0024379. Scope note. The smaller fragment formed when complement C4 is cleaved by ... The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of ...

https://decs.bvsalud.org/en/ths/resource/?id=24578

Complement C4a measurement (procedure). Code System Preferred Concept Name. Complement C4a measurement (procedure). ...

https://phinvads.cdc.gov/vads/ViewCodeSystemConcept.action?oid=2.16.840.1.113883.6.96&code=104356003

Kaninchen Polyklonal Complement C4 Antikörper AA 1450-1723 für ICC, IHC, IP, WB. Order anti-Complement C4 Antikörper ... complement 4, complement component 4A, complement component 4B (Chido blood group), C4B, C4A, C4a, C4, C4b Pathways ... Details zu Complement C4 (verbergen) Target Complement C4 (C4) (Complement 4 (C4)) Andere Bezeichnung Complement Component 4 ( ... complement C4B (Chido blood group), complement C4A (Rodgers blood group), complement component 4A (Rodgers blood group), ...

https://www.antikoerper-online.de/antibody/6995381/anti-Complement+4+C4+AA+1450-1723+antibody/

Description: A sandwich ELISA kit for quantitative measurement of Human C4a (Complement Component 4a) in samples from Serum, ... Description: A sandwich CLIA kit for quantitative measurement of Human C4a (Complement Component 4a) in samples from Serum, ... Description: A sandwich ELISA kit for detection of Complement Component 3a from Human in samples from blood, serum, plasma, ... Description: A sandwich ELISA kit for detection of Complement Component 4 from Human in samples from blood, serum, plasma, cell ...

https://biologiayctma.com/transcriptomics-for-understanding-plant-growth-and-useful-biology/

Query Trace: Hepatitis and C4A[original query] Immunogenetics of complement in mixed cryoglobulinaemia. Clinical and ...

https://phgkb.cdc.gov/PHGKB/searchSummary.action?firstQuery=Hepatitis+and+C4A&Mysubmit=Search

Low copy numbers of complement C4 and C4A deficiency are risk factors for myositis, its subgroups and autoantibodies. Zhou, ...

https://pesquisa.bvsalud.org/saudepublica/?lang=pt&q=au:Rider,+Lisa+G

C4a, C3b and C4b. Nominally these complement fragments contribute to the elimination of pathogens through multiple biological ... The complement system in COVID-19. The complement system is an essential component of the innate immune system [65, 75, 109, ... The case of complement activation in COVID-19 multiorgan impact. Kidney Int 2020; 98: 314-322. doi:10.1016/j.kint.2020.05.013. ... complement activation promoted systemic inflammation, rather than suppressing viral replication. Dysregulated complement ...

https://openres.ersjournals.com/content/6/4/00405-2020

C4a. 17. 34809092 to 34823454 14362. -. protein coding gene. complement component 4A (Rodgers blood group). ... complement component 2 (within H-2S). Tssr147691. 17. 34882004 to 34882080 76. -. TSS region. transcription start site region ...

https://phenome.jax.org/markers/search?searchterm=17%3A34761151-34961165

Complement. Complement are serum proteins which when activated react in an orderly manner with each other to cause immunologic ... The activated C1 cleaves C4 to form C4a and C4b; C4a is released into the body fluid while C4b attaches to the red cell ... IgG is capable of fixing complement with order of efficacy being IgG3, IgG1 and IgG2. IgG4 cannot bind complement in the ... IgM is highly efficient in binding complement. A single molecule of IgM can bind complement while two molecules of IgG (lgG ...

https://www.jaypeedigital.com/eReader/chapter/9789350901847/ch1

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

Three novel single-nucleotide polymorphisms of complement component 4 gene (C4A) in Chinese Holstein cattle and their ... serum MBL-Clevels and complement activity. Vet. Immunol. Immunop., 148: 311-319.. Search in Google Scholar ...

https://sciendo.com/it/article/10.2478/aoas-2013-0043

human Complement C4a des Arg Correlate -EIA Kit 5 x 96 Well 901-059 Price:. 1,830.00. ... human Complement C4a des Arg Correlate -EIA Kit 96 Well 900-059 Price:. 528.00. ... human Complement C3a des Arg Correlate -EIA Kit 5 x 96 Well 901-058 Price:. 1,830.00. ... human Complement C3a des Arg Correlate -EIA Kit 96 Well 900-058 Price:. 528.00. ...

https://genoprice.com/aspnet_client/acatalog/Catalog_Kits_401.html

A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions ... The activated C1s subunits cleave C4 into C4b and C4a; the latter can diffuse away and serve as a leucocyte activator. The C4b ... ACTIVATION OF THE CLASSICAL COMPLEMENT PATHWAY. A complement cascade similar to that of the alternative pathway can be ... A further complement protein, C2, binds to this membrane complex to give C4b2. The C1s subunit then enzymically cleaves the ...

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

Unravelling the nature of postexertional malaise in ME/CFS: the role of elastase, complement C4a and interleukin-1β 2010, Nijs ... complement C4a and... Thread by: Sly Saint, Oct 23, 2022, 9 replies, in forum: ME/CFS research ...

https://www.s4me.info/tags/2010/

Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Complement Component 4a (C4a) in serum, plasma and other biological fluids. (elisareagents.com)
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Rat Complement Component 4a (C4a) in samples from serum, plasma and other biological fluids with no significant corss-reactivity with analogues from other species. (elisareagents.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)
A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions. (pharmacy180.com)
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)
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)
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)
Complement is an ancient component of our innate immune system that was initially discovered in the 19th century and named for its ability to complement antibody in the lysis of cells. (downhouse.software)

The C3a receptor binds C3a and C4a. (medscape.com)
Complement C6 then binds to C5b to form the complex C5b6 [ 7 ]. (frontiersin.org)
A further complement protein, C2, binds to this membrane complex to give C4b2. (pharmacy180.com)
A neutrophil binds to a C3b-coated immunological complex by means of the C3b-specific type I complement receptor. (microbiologynote.com)
In Alzheimer's, the CR1 (complement receptor 1) gene is a top GWAS candidate, and this receptor binds to complement C3, which is a gene highly expressed in aging tissues. (infino.me)

Description: A sandwich quantitative ELISA assay kit for detection of Human Complement Component 4a (C4a) in samples from serum, plasma or other biological fluids. (elisareagents.com)
The complement system is a heat-labile component of blood that confers bactericidal properties. (abcam.com)
A few years ago, researchers at Karolinska Institutet could show in an experimental model that the elimination of synapses is increased in schizophrenia patients and can be linked to the gene coding for complement component 4A (C4A), a protein involved in immune signalling. (eurekalert.org)
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)
The molecular basis for the difference in immune hemolysis activity of the Chido and Rodgers isotypes of human complement component C4. (aai.org)
A label-free quantification analysis of the MS data using PEAKS7 software found that four plasma proteins of apolipoprotein C-1, gelsolin, sex hormone-binding globulin (SHBG), and complement component C4-A were significantly overexpressed in GC patients. (elsevier.com)
The C3b complement component coats immune complexes with opsonin. (microbiologynote.com)
CR1 (left) is complement receptor 1, a major component of the innate immune response. (infino.me)

The C3a, C4a, and C5a components are referred to as anaphylatoxins, causing smooth muscle contraction, histamine release from mast cells, and enhanced vessel permeability [ 2 , 3 ]. (selfhack.com)
can also be activated non-immunologically by polybasic molecules such as compound 48/80, substance P, and anaphylatoxins derived from split complement components (C3a, C4a, and C5a) [ 10 ]. (ispub.com)
The C3a, C4a, and C5a complement split products are anaphylatoxins that cause localised mast-cell lysis and an increase in local vascular permeability. (microbiologynote.com)
The anaphylatoxins generated during the complement cascade attract neutrophils and mast cells to the site of immunoglobulin (IC) deposition. (microbiologynote.com)
The anaphylatoxins, C3a, C5a (and, to a lesser extent, C4a), function to induce contraction of the smooth muscle and then an increase in vascular permeability of the capillaries. (downhouse.software)

There are three general pathways by which the body increases C4a: The Alternative Pathway, The Lectin Pathway, and The Classical Pathway. (selfhack.com)
Learn about the three pathways lead to complement activation and some of their key inhibitors. (abcam.com)
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)
Activation of all three pathways converges on the cleavage of complement protein C3 into C3b and C3a [ 6 ]. (frontiersin.org)
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)
In summary, complement can be activated through three somewhat distinct pathways, each one converging at a C3 Convertase. (downhouse.software)
In heart disease, activation of the complement cascade appears to play a central role in the formation of atherosclerotic plaques , and incidentally many of the genes in the 2009 meta-analysis point to atherosclerosis pathways in the literature. (infino.me)

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 pathway involving complement components C3, factor B, factor D, and properdin that, in the presence of a stabilizing activator surface such as microbial polysaccharide, generates the alternative pathway C3 convertase C3bBb. (roitt.com)

C4A is an activation protein, which means it also activates the other complement proteins to increase in level [ 1 ]. (selfhack.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)
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)
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)
Disease is amplified by activation of the complement system and secretion of inflammatory cytokines. (michaelcarrolllab.com)
Immunoglobulins: Types and Functions and the complement system Complement system Serum glycoproteins participating in the host defense mechanism of complement activation that creates the complement membrane attack complex. (lecturio.com)
Additional activation of the complement system's membrane-attack mechanism can potentially contribute to tissue damage. (microbiologynote.com)
In addition, complement activation can cause platelet aggregation, and the subsequent release of clotting factors can result in the production of microthrombi. (microbiologynote.com)
The presence of ICs in the tissues initiates complement activation via the classical pathway. (microbiologynote.com)
Activation of the complement also results in the deposition of C3b on ICs and adjacent tissue cells. (microbiologynote.com)
Succinate to inhibit complement activation. (theloganguards.com)
The objectives of this study were to monitor the complement activation products C3a, C4a, Bb, and C5b-9 prior to, during, and after correction of DKA. (elsevier.com)
Activation of the classical complement pathway starts with binding of an activating substance to the Cl molecule, which activates the Cl sub-units, resulting in cleavage of C4 to C4b releasing C4a in the process. (immbio.hu)

Precision of the determination of the C4A and C4B gene number. (biomedcentral.com)
The pro-inflammatory cytokines IL-1beta and IL-6 have previously been shown to be elevated in schizophrenia, and the researchers performed new experiments in which they could show that these cytokines stimulate the expression of the C4A gene, while patients with high C4A levels also displayed high levels of IL-1beta in cerebrospinal fluid. (eurekalert.org)
Deletion of the C4A gene was independently associated with increased incidences of encephalopathy and early death. (duke.edu)
Previously when we looked at the 2009 meta analysis by the Church lab of 27 different aging gene expression datasets, we found many genes linked to the complement cascade were enriched, along with several genes associated with mitochondrial function and Reactive Oxygen Species (ROS) cleanup. (infino.me)
Complement 1Q binding protein - this gene has been shown to bind and inhibit complement C1Q, 3 genes of which are present in the aging dataset (in addition to complement C3 and C4A). (infino.me)

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)

C1 is the first molecule in the classical complement cascade and comprises C1q and two molecules of C1r and C1s respectively. (abcam.com)
Subsequently, continued propagation leads to the terminal cascade by cleavage of complement C5 to form C5b and C5a. (frontiersin.org)
And stimulates the complement cascade and hence an inflammatory reaction. (theloganguards.com)
We would need to find connections to the complement cascade and mitochondrial function. (infino.me)
The complement system is the cascade of inflammation that fires off when your body sees and recognizes an outside invader. (newsinnutrition.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)
What are the cell sources and regulation of the complement system in the brain? (michaelcarrolllab.com)

Finally, we also present evidence showing that the apparent m.w. difference between the alpha-chains of the C4A and C4B isotypes is not due to differences in protein glycosylation. (aai.org)

The antibodies that activate the classical complement pathway are IgM and IgG. (pharmacy180.com)
and lectin complement pathway). (lecturio.com)
None of us should be surprised about the mitochondrial connections, but the complement pathway hyperactivation is interesting. (infino.me)

Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and. (s4me.info)
Platelet factors (platelet count and beta-thromboglobulin), coagulation factors (thrombin-antithrombin III complex and fibrinopeptide A), fibrinolysis factors (alpha 2-plasmin inhibitor complex and alpha 2-plasmin inhibitor), complement factors (C3a, C4a), free hemoglobin, and granulocyte elastase were measured at the beginning and end of the study. (fujita-hu.ac.jp)
There were no significant differences between Group F and Group B in platelet count, C3a, C4a and granulocyte elastase, although these indices were significantly lower in Groups F and B when compared to Group C. Therefore, FUT-175 appears to reduce blood-foreign surface reaction and diminishes cellular adhesion to the inner surface of the cardiopulmonary bypass circuit. (fujita-hu.ac.jp)

C4a activates Neutrophils, which increases inflammation and free radicals [ 4 ]. (selfhack.com)

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)

By using purified C4A and C4B isolated from individual donors known serologically to possess only one of the C4 isotypes, we examined the molecular basis for the differences in their respective hemolytic activities. (aai.org)
It was found that the C4B:C4A hemolytic activity ratio was approximately 4:1. (aai.org)
Hydrocortisone depresses hemolytic complement in male and female mice. (theloganguards.com)

As such, they are distinctly innate mediators of immunity and are specifically capable of fixing complement on their bacterial targets. (downhouse.software)

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)
Low copy numbers of complement C4 and C4A deficiency are risk factors for myositis, its subgroups and autoantibodies. (bvsalud.org)

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. (bvsalud.org)

The complement system exerts many of its effects through complement receptors (CRs). (medscape.com)

Immunological complexes activate the complement system's variety of immune effector molecules, resulting in Type III hypersensitivity reactions. (microbiologynote.com)

The DR3 haplotype and C4A deletion may reflect the same underlying mechanism of susceptibility in that the DR3 haplotype is in linkage disequilibrium with other C4A null alleles. (duke.edu)

Complement will lead to direct cell death via pore formation (MAC complex formation), it will recruit leukocytes to the area of infection via chemotaxis, and will facilitate phagocytosis of pathogens via complement receptor-mediated endocytosis. (downhouse.software)

The term complement means it is able to kill bacteria and contributes to immune defenses. (selfhack.com)

We demonstrate the presence of complement factor b (bf) and complement c3 in uterine luminal fluid collected from estrogen-stimulated immature and. (theloganguards.com)

In two independent cohorts, they observed elevated C4A levels in first-episode psychosis patients that a few years later would develop schizophrenia. (eurekalert.org)
Does "too much" expression of C4A promote loss of synapses leading to schizophrenia? (michaelcarrolllab.com)

These give rise to two C4 isotypes, designated C4A and C4B, which can be distinguished by charge and apparent m.w. differences in their respective alpha-chains and by the presence or absence of the Chido/Rodgers blood group antigens. (aai.org)

C4A is often elevated in chronic inflammation. (selfhack.com)
Reveals complement-mediated inflammation in chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (clippers). (theloganguards.com)

METHODS: Human leukocyte antigen (HLA) class II and complement C4 genotypes were determined by means of molecular genetic techniques for 243 black children born to HIV-1-infected mothers in New York City and San Francisco. (duke.edu)
And activity of steroid sulfatase complementing dehydroepiandrosterone sulfate uptake and intracrine steroid activations in human adipose tissue. (theloganguards.com)

It's been observed that C4A levels can be increased in people with Lyme disease [ 5 ]. (selfhack.com)
Some researchers are looking at C3A and C4A levels to diagnose Lyme disease [ 6 ]. (selfhack.com)
One must realize, however, that C3A and C4A and general markers, and will never be able to diagnose Lyme disease specifically (see images above). (selfhack.com)

Immunoglobulins (IgG, IgM) and CRP can also increase C4a (they can be high in infections). (selfhack.com)

In the present study, we investigated the association between complement system status at the time of admission and clinical outcomes in COVID-19 patients. (iimmun.ru)
It is the nexus of the complement system. (newsinnutrition.com)
The complement system continues to be activated. (newsinnutrition.com)

C4A levels also correlated with markers of synapse density. (eurekalert.org)

C3a, C4a, or C5a) capable of directly triggering mast cell degranulation. (roitt.com)

whether a distinct receptor for C4a is present is unclear (see Table 1). (medscape.com)

Conventional doctors will look at high or low C4A levels and not mention anything. (selfhack.com)
C4A levels may be decreased with mold avoidance (anecdotal) and antibiotic treatments [ 6 ]. (selfhack.com)
The same team has now developed a method to measure C4A levels in cerebrospinal fluid. (eurekalert.org)
After checking for genetic risk variants, we still observed elevated levels of C4A," says Jessica Gracias Lekander, a doctoral student at the Department of Physiology and Pharmacology, Karolinska Institutet, and first author of the study. (eurekalert.org)
We also found that complement parameter levels in COVID-19 patients who died or were admitted to ICU were significantly lower than in non-ICU COVID-19 patients. (iimmun.ru)

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Organisms10

Diseases16

Chemicals and Drugs101

Analytical, Diagnostic and Therapeutic Techniques and Equipment25

Phenomena and Processes48

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Health Care1

Deficiency of human complement protein C4 due to identical frameshift mutations in the C4A and C4B genes. (1/96)

Analysis of human C4A and C4B binding to an immune complex in serum. (2/96)

Possible mechanism for in vitro complement activation in blood and plasma samples: futhan/EDTA controls in vitro complement activation. (3/96)

Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules in caucasians. The load of RCCX genetic diversity on major histocompatibility complex-associated disease. (4/96)

Deficient APC-cofactor activity of protein S Heerlen in degradation of factor Va Leiden: a possible mechanism of synergism between thrombophilic risk factors. (5/96)

Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE). (6/96)

Characterization of a de novo conversion in human complement C4 gene producing a C4B5-like protein. (7/96)

Determining the one, two, three, or four long and short loci of human complement C4 in a major histocompatibility complex haplotype encoding C4A or C4B proteins. (8/96)

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