Complement c3d. Medical search

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Antibodies produced by a single clone of cells.

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

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

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

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

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

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

Established cell cultures that have the potential to propagate indefinitely.

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

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

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

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

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

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

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

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

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

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

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

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

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

Proteins prepared by recombinant DNA technology.

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

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

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

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

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

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

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

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

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

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

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

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

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

Proteins found in any species of bacterium.

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

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

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

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

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

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

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

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

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

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

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

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

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

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

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

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

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

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

Glycoproteins found on the membrane or surface of cells.

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

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

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

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

The rate dynamics in chemical or physical systems.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Immunoglobulins produced in a response to BACTERIAL ANTIGENS.

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

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

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

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

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

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

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

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

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

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

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

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

Immunohistochemical analysis of arterial wall cellular infiltration in Buerger's disease (endarteritis obliterans). (1/194)

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

Complement activation and expression of membrane regulators in the middle ear mucosa in otitis media with effusion. (2/194)

The aetiopathogenesis of chronic otitis media with effusion (OME) in children is not yet fully understood. OME is characterized by metaplasia of the epithelium and accumulation of sticky, glue-like effusion in the middle ear containing different mediators of inflammation, including activation fragments of the complement system. Here we examined whether the fluid phase complement activation is reflected in the middle ear mucosa and how the mucosa is protected against the cytolytic activity of complement. Mucosal biopsies from 18 middle ears of children with a history of chronic OME were taken. The biopsies were analysed by immunofluorescence microscopy after staining for complement fragments iC3b/C3c, C3d and C9, and regulators membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55) and protectin (CD59). There was a strong staining for iC3b/C3c, and a weaker one for C3d and C9 on the surface of the middle ear epithelial cells of OME patients but not in controls without OME. MCP was expressed on the hyperplastic three to four outer cell layers of the epithelium, while CD59 was expressed throughout the middle ear mucosa. The results suggest a strong ongoing complement activation and consequent inflammation in the middle ear cavity. Unrestricted complement damage of the epithelial lining is prevented by the strong expression of MCP and CD59. (+info)

C6 produced by macrophages contributes to cardiac allograft rejection. (3/194)

The terminal components of complement C5b-C9 can cause significant injury to cardiac allografts. Using C6-deficient rats, we have found that the rejection of major histocompatibility (MHC) class I-incompatible PVG.R8 (RT1.A(a)B(u)) cardiac allografts by PVG.1U (RT1.A(u)B(u)) recipients is particularly dependent on C6. This model was selected to determine whether tissue injury results from C6 produced by macrophages, which are a conspicuous component of infiltrates in rejecting transplants. We demonstrated that high levels of C6 mRNA are expressed in isolated populations of macrophages. The relevance of macrophage-produced C6 to cardiac allograft injury was investigated by transplanting hearts from PVG. R8 (C6-) donors to PVG.1U (C6-) rats which had been reconstituted with bone marrow from PVG.1U (C6+) rats as the sole source of C6. Hearts grafted to hosts after C6 reconstitution by bone marrow transplantation underwent rejection characterized by deposition of IgG and complement on the vascular endothelium together with extensive intravascular aggregates of P-selectin-positive platelets. At the time of acute rejection, the cardiac allografts contained extensive perivascular and interstitial macrophage infiltrates. RT-PCR and in situ hybridization demonstrated high levels of C6 mRNA in the macrophage-laden transplants. C6 protein levels were also increased in the circulation during rejection. To determine the relative contribution to cardiac allograft rejection of the low levels of circulating C6 produced systemically by macrophages, C6 containing serum was passively transferred to PVG.1U (C6-) recipients of PVG.R8 (C6-) hearts. This reconstituted the C6 levels to about 3 to 6% of normal values, but failed to induce allograft rejection. In control PVG.1U (C6-) recipients that were reconstituted with bone marrow from PVG.1U (C6-) donors, C6 levels remained undetectable and PVG.R8 cardiac allografts were not rejected. These results indicate that C6 produced by macrophages can cause significant tissue damage. (+info)

Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and differential regulation by heparin. (4/194)

The human factor H-related proteins FHR-3 and FHR4 are members of a family of proteins related to the complement factor H. Here, we report that the two proteins bind to the C3d region of complement C3b. The apparent K(A) values for the interactions of FHR-3 and FHR-4 with C3b are 7.5 x 10(6) M(-1) and 2.9 x 10(6) M(-1), respectively. Binding studies performed with C3b-coated pneumococci confirmed the results obtained with the biosensor system. A C-terminal construct of factor H showed similar binding characteristics. The interaction of FHR-3, but not of FHR4, with opsonised pneumococci was inhibited by heparin. (+info)

Tracing uptake of C3dg-conjugated antigen into B cells via complement receptor type 2 (CR2, CD21). (5/194)

Electron microscopy was used to study the internalization and delivery of ligands for complement receptor type 2 (CR2, CD21) to endocytic compartments of B-lymphoblastoid Raji cells. Opsonized antigen was mimicked with purified C3dg conjugated to colloidal gold. C3dg-gold bound specifically to the cell surface in a time-dependent manner, and preincubation of the cells with a monoclonal antibody blocking the CR2 ligand-binding site completely inhibited any C3dg-gold binding. Notably, the binding of C3d-gold was confined to cell surface protrusions, eg, microvilli. C3dg-gold was apparently internalized through coated pits located at the bases of microvilli and could be traced to different compartments of the endocytic pathway. The morphologic characteristics and intracellular distribution of these multivesicular or multilaminar structures were compatible with those of compartments known to harbor major histocompatibility complex (MHC) class II molecules. Immunolabeling showed that the internalized C3dg-gold colocalized with MHC class II in these structures. These data provide the first ultrastructural evidence that complement-coated antigens are endocytosed by antigen-nonspecific B cells by CR2 and are delivered to the compartments in which peptide loading for antigen presentation occurs. They support the notion that CR2 may play a role in antigen presentation by B cells regardless of B-cell receptor specificity. (Blood. 2000;95:2617-2623) (+info)

Structure at 1.44 A resolution of an N-terminally truncated form of the rat serum complement C3d fragment. (6/194)

Complement component C3 plays a key role in the complement-mediated immune defence, and occupies a central position within the complement cascade system. One of its degradation products, C3dg, was purified from rat serum and crystallised in two different crystal forms as N-terminally truncated fragment. Despite the truncation and the lack of a significant portion of the N-terminus as compared to C3d, the structure of the fragment is highly similar to that of recombinant human C3d (Nagar et al., Science 280 (1998) 1277-1281). Structural details of the reactive site have been obtained, suggesting a possible mode of thioester bond formation between Cys-1010 and Gln-1013 and thioester bond cleavage in the transacylation reaction involving His-1126. The truncation at the N-terminus of C3d leads to the exposure of a surface of the molecule that favours dimerisation, so that in both crystal forms, the fragment is present as a dimer, with monomers related by a two-fold axis. (+info)

Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2. (7/194)

After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC. (+info)

Structure-guided identification of C3d residues essential for its binding to complement receptor 2 (CD21). (8/194)

A vital role for complement in adaptive humoral immunity is now beyond dispute. The crucial interaction is that between B cell and follicular dendritic cell-resident complement receptor 2 (CR2, CD21) and its Ag-associated ligands iC3b and C3dg, where the latter have been deposited as a result of classical pathway activation. Despite the obvious importance of this interaction, the location of a CR2 binding site within C3d, a proteolytic limit fragment of C3dg retaining CR2 binding activity, has not been firmly established. The recently determined x-ray structure of human C3d suggested a candidate site that was remote from the site of covalent attachment to Ag and consisted of an acidic residue-lined depression, which accordingly displays a significant electronegative surface potential. These attributes were consistent with the known ionic strength dependence of the CR2-C3d interaction and with the fact that a significant electropositive surface was apparent in a modeled structure of the C3d-binding domains of CR2. Therefore, we have performed an alanine scan of all of the residues within and immediately adjacent to the acidic pocket in C3d. By testing the mutant iC3b molecules for their ability to bind CR2, we have identified two separate clusters of residues on opposite sides of the acidic pocket, specifically E37/E39 and E160/D163/I164/E166, as being important CR2-contacting residues in C3d. Within the second cluster even single mutations cause near total loss of CR2 binding activity. Consistent with the proposed oppositely charged nature of the interface, we have also found that removal of a positive charge immediately adjacent to the acidic pocket (mutant K162A) results in a 2-fold enhancement in CR2 binding activity. (+info)

B cells express complement receptor CR2 (CD21) to bind to iC3b, C3dg, or C3d. This additional binding makes the B cells 100- to ... Microbes may activate the complement system directly and complement component C3b bind to microbes. After C3b is degraded into ... "C3d of complement as a molecular adjuvant: Bridging innate and acquired immunity". Science. 271 (5247): 348-350. doi:10.1126/ ... Frank K, Atkinson JP (2001). "Complement system." In Austen KF, Frank K, Atkinson JP, Cantor H. eds. Samter's Immunologic ...

https://en.wikipedia.org/wiki/Co-stimulation

Complement factor I can further cleave iC3b into a protein fragment known as C3d. Robbins Basic Pathology 8th ed 2007. R Cotran ... iC3b is produced when complement factor I cleaves C3b. Complement receptors on white blood cells are able to bind iC3b, so iC3b ... iC3b is a protein fragment that is part of the complement system, a component of the vertebrate immune system. ... Unlike intact C3b, iC3b cannot associate with factor B, thus preventing amplification of the complement cascade through the ...

https://en.wikipedia.org/wiki/IC3b

Leivo I, Engvall E (1986). "C3d fragment of complement interacts with laminin and binds to basement membranes of glomerulus and ...

https://en.wikipedia.org/wiki/Laminin,_alpha_1

In this way, the complement system participates in the adaptive immune response. C3d, a cleavage product of C3, recognizes ... Complement proteins involved in innate opsonization include C4b, C3b and iC3b. In the alternative pathway of complement ... C1q association eventually leads to the recruitment of complement C4b and C3b, both of which are recognized by complement ... Opsonins of the innate immune system largely comprise complement proteins, though interaction between complement proteins and ...

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

... is the receptor for EBV and for C3d, C3dg and iC3b. Complement components may activate B cells through CD21. CD21 is part of a ... Complement decay-accelerating factor (Antigen CD55) belongs to the Cromer blood group system and is associated with Cr(a), Dr(a ... Complement receptor type 1 (C3b/C4b receptor) (Antigen CD35) belongs to the Knops blood group system and is associated with Kn( ... Sushi domains exist in a wide variety of complement and adhesion proteins. The structure is known for this domain; it is based ...

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

2000). "Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and ... Complement factor H-related protein 4 is a protein that in humans is encoded by the CFHR4 gene. GRCh38: Ensembl release 89: ... "Entrez Gene: CFHR4 complement factor H-related 4". Hageman GS, Hancox LS, Taiber AJ, et al. (2007). "Extended Haplotypes in the ... Diaz-Guillen MA, Rodriguez de Cordoba S, Heine-Suner D (Jul 1999). "A radiation hybrid map of complement factor H and factor H- ...

https://en.wikipedia.org/wiki/CFHR4

2000). "Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and ... "Entrez Gene: CFHR3 complement factor H-related 3". Zipfel PF, Skerka C (1994). "Complement factor H and related proteins: an ... Complement factor H-related protein 3 is a protein that in humans is encoded by the CFHR3 gene. GRCh38: Ensembl release 89: ... 2000). "Complement factor H: sequence analysis of 221 kb of human genomic DNA containing the entire fH, fHR-1 and fHR-3 genes ...

https://en.wikipedia.org/wiki/CFHR3

CD21, complement receptor 2, can bind fragments of C3 that have covalently attached to glycoconjugates by complement activation ... The CD19/CD21 complex arises from C3d binding to CD21; however, CD19 does not require CD21 for signal transduction. CD81, ... While colligated with the BCR, the CD19/CD21 complex bound to the antigen-complement complex can decrease the threshold for B ... CD19 has been shown to interact with: CD81 CD82 Complement receptor 2 VAV2 Mutations in CD19 are associated with severe ...

https://en.wikipedia.org/wiki/CD19

These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 ... It remains entirely possible that the disease is due to e.g. an unusual interaction between immune complexes, complement ...

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

February 2011). "Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement". ... Moreover, the complement inhibitory activities of factor H, and other complement regulators, are often used by pathogens to ... Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large (155 ... Variation in other genes of the regulators of complement activation locus, such as complement factor H-related genes, as well ...

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

Factor I can cleave C3b into C3c and C3d, the latter of which plays a role in enhancing B cell responses. In the alternative ... Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement ... "Entrez Gene: C3 complement component 3". Sahu A, Lambris JD (Apr 2001). "Structure and biology of complement protein C3, a ... Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease cleaves ...

https://en.wikipedia.org/wiki/Complement_component_3

Fearon DT (July 1985). "Human complement receptors for C3b (CR1) and C3d (CR2)". The Journal of Investigative Dermatology. 85 ( ... 1989). "Immunoregulatory functions of complement: structural and functional studies of complement receptor type 1 (CR1; CD35) ... complement receptor 2 is the C3d receptor. Factor H, another immunoregulatory protein, also maps to this location. The ... complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1". The Journal ...

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

Complement receptor type 2 (CR2), also known as complement C3d receptor, Epstein-Barr virus receptor, and CD21 (cluster of ... 1987). "A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32". J. ... CR2 is involved in the complement system. It binds to iC3b (inactive derivative of C3b), C3dg, or C3d. B cells express CR2 ... 1991). "Epstein Barr virus/complement C3d receptor is an interferon alpha receptor". EMBO J. 10 (4): 919-26. doi:10.1002/j.1460 ...

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

CR2 CCP modules complexed with C3d (pdb:1ghq)). Complement has been implicated in many diseases associated with inflammation ... Complement control protein are proteins that interact with components of the complement system. The complement system is ... Complement proteins protect against malignant cells- both by direct complement attack and through initiation of Complement- ... Complement C3b/C4b Receptor 1, CR1 (CD35) Complement Regulator of the Immunoglobulin Superfamily, CRIg Soluble complement ...

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

... complement c3c MeSH D12.776.124.486.274.250.260.750 - complement c3d MeSH D12.776.124.486.274.350 - complement c4 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. ... complement c5b MeSH D12.776.124.486.274.550 - complement c6 MeSH D12.776.124.486.274.650 - complement c7 MeSH D12.776.124.486. ...

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

Second, up to 20% of patients with CAD have IgG on the RBC surface in addition to C3d.[non-primary source needed] Thermal ... Role of Complement and Potential New Targets for Therapy". BioMed Research International. Hindawi Limited. 2015: 363278. doi: ... Role of Complement and Potential New Targets for Therapy". BioMed Research International. Hindawi Limited. 2015. 363278-1- ...

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

this specification is complemented by additional documents defining interfaces to specific embedding environments such as the ... jfbastien; rossberg-chromium; kripken; titzer; s3ththompson; sunfishcode; lukewagner; flagxor; enricobacis; c3d; binji; ... c3d; binji; andrewosh, GitHub. WebAssembly/design. To learn how to add open license text to Wikipedia articles, please see this ...

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

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

The structure of the complex between complement receptor CR2 and its ligand complement fragment C3d. *DOI: 10.2210/pdb3OED/pdb ... A crystal structure of the complex between human complement receptor 2 and its ligand C3d.. van den Elsen, J.M., Isenman, D.E. ... Complement receptor type 2. C, D. 135. Homo sapiens. Mutation(s): 0 Gene Names: C3DR, CR2. ... Complement C3. A, B. 310. Homo sapiens. Mutation(s): 1 Gene Names: C3, CPAMD1. ...

https://www.rcsb.org/structure/3OED

Previous crystallographic studies of Efb-C bound to its cognate subdomain of human C3 (C3d) identified Arg-131 and Asn-138 … ... defines a novel three-helix bundle motif that regulates complement activation. ... Only the C3d molecule of the wild-type Efb-C/C3d complex is shown in panel A. The C3d molecules of the N138A and R131A mutants ... The RMSD of C3d (B) and Efb-C (C) were measured with respect to the minimized C3d and Efb-C of each one of the complexes, ...

https://pubmed.ncbi.nlm.nih.gov/18687868/?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=31

Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking. J Mol Biol. 2010 ... Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking. ... Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking. ...

https://connects.catalyst.harvard.edu/Profiles/display/25902383

Additionally, the antigen-bound C3d fragment interacts with complement receptor 2 (CR2; also known as CD21) on B cells and ... X-ray Crystal Structure of C3d: A C3 Fragment and Ligand for Complement Receptor 2 ... X-ray Crystal Structure of C3d: A C3 Fragment and Ligand for Complement Receptor 2 ... X-ray Crystal Structure of C3d: A C3 Fragment and Ligand for Complement Receptor 2 ...

https://science.sciencemag.org/content/280/5367/1277

The final degradation product of the third (C3) component of complement, C3d, is a natural adjuvant. The adjuvant properties of ... The classic mechanism of enhancement of the immune response involves interaction of C3d with its natural ligand, complement ... Toapanta, Franklin Ramiro (2006) Immune Enhancement Mechanisms by the Complement Protein C3d. Doctoral Dissertation, University ... fused to C3d inefficiently induced IgG class switch in MHC II-/- mice. This demonstrated that C3d requires CD4+ T-cells to ...

http://d-scholarship.pitt.edu/8756/

Multimeric Interactions between Complement Factor H and Its C3d Ligand Provide New Insight on Complement Regulation. J MOL BIOL ... Multimeric Interactions between Complement Factor H and Its C3d Ligand Provide New Insight on Complement Regulation ... Multimeric Interactions between Complement Factor H and Its C3d Ligand Provide New Insight on Complement Regulation. ... Activation of Q to C3b signals the start of the alternative complement pathway. The C-terminal short complement regulator (SCR ...

http://discovery.ucl.ac.uk/129555/

Key to all of these, however, is the complement system.. In certain disease states, immune complexes may initiate complement- ... C3d Immune Complexes. 123015. C3d Immune Complexes. ug Eq/mL. 10864-7. ... This activation of complement may begin a series of potentially destructive events, including cell lysis, the production of ... For the measurement of C3d-bound circulating immune complexes (CIC) present in human plasma or serum. ...

https://www.labcorp.com/test-menu/29286/

C3d is involved in the regulation of many aspects of the immune response including antigen processing and presentation. The C3d ...

https://www.immbio.hu/hu/cabcos-2/adatbazis/45-c3d-complement

Gulati SM, Agarwal V, Sharma V, Saha K. C3 complement components & their breakdown product (C3d) in patients of thromboangiitis ... C3 complement components & their breakdown product (C3d) in patients of thromboangiitis obliterans. ...

https://imsear.searo.who.int/handle/123456789/18559

papers/detection-of-complement-c3d-coated-cells-in-a/452076. ... Detection of complement (c3d) coated cells in a newborn due to ... The direct antiglobulin test was moderately positive using polyspecific antiglobulin reagent and monospecific anti-C3d, but ...

https://www.meta.org/papers/detection-of-complement-c3d-coated-cells-in-a/452076

... shows that Jurkat human T cells have a molecule that reacts with both anti-CR2 antibodies and the third component of complement ... Characterization of the EBV/C3d Receptor on the Human Jurkat T Cell Line: Evidence for a Novel Transcript J Immunol. 1993 Jun ...

https://pubmed.ncbi.nlm.nih.gov/8390533/

X-ray crystal structure of C3d : A C3 fragment and ligand for complement receptor 2. / Nagar, Bhushan; Jones, Russell G.; ... Fingerprint Dive into the research topics of X-ray crystal structure of C3d: A C3 fragment and ligand for complement receptor ... X-ray crystal structure of C3d: A C3 fragment and ligand for complement receptor 2. Science. 1998;280(5367):1277-1281. ... Additionally, the antigen-bound C3d fragment interacts with complement receptor 2 (CR2; also known as CD21) on B cells and ...

https://researchers.mq.edu.au/en/publications/x-ray-crystal-structure-of-c3d-a-c3-fragment-and-ligand-for-compl

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). ... C3dg/C3d. B cell, follicular dendritic cell. Co-receptor for B-cell signaling ... encoded search term (Pediatric Complement Receptor Deficiency) and Pediatric Complement Receptor Deficiency What to Read Next ...

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

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). ... CR2 binds C3dg, and C3d is present on B cells and dendritic cells (see the Table 1). CR2 associates with CD19 forming a CR2- ... The complement system exerts many of its effects through complement receptors (CRs). Of the 8 plasma membrane receptors for ...

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

Both domain 19 and domain 20 of factor H are involved in binding to complement C3b and C3d. Mol. Immunol. 47: 1686-1691. ... complement factor H. CFHR. complement factor H-related. CIC. circulating immune complex. CIC-FH. circulating immune complexes ... Study of FH binding to C3(H2O), C3c, and C3d. The binding of FH to C3(H2O), C3c, and C3d was tested in presence of purified IgG ... Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement. Proc. Natl. Acad. ...

https://www.jimmunol.org/content/189/7/3528

Complement C3d receptor 2 (CR2) is the main receptor for complement protein C3d and plays an important role in adaptive immune ... Association of complement C3d receptor 2 genotypes with the acquisition of HIV infection in a trial of recombinant glycoprotein ...

https://phgkb.cdc.gov/PHGKB/phgHome.action?action=forward&dbsource=huge&id=183446

Fingerprint Dive into the research topics of DNA epitope vaccine containing complement component C3d enhances anti-amyloid-β ... DNA epitope vaccine containing complement component C3d enhances anti-amyloid-β antibody production and polarizes the immune ... DNA epitope vaccine containing complement component C3d enhances anti-amyloid-β antibody production and polarizes the immune ... DNA epitope vaccine containing complement component C3d enhances anti-amyloid-β antibody production and polarizes the immune ...

https://augusta.pure.elsevier.com/en/publications/dna-epitope-vaccine-containing-complement-component-c3d-enhances-

... a serine protease that cleaves the central complement protein C3, and generates the major cleavage fragment C3b. ... In the presence of complement regulatory molecules C3b may be further degraded sequentially to iC3b, C3c, C3dg and C3d. C3d is ... The complement pathway generates a C3 convertase, a serine protease that cleaves the central complement protein C3, and ... All Quidel complement components are tested for functional activity in a standard lytic or applicable functional assay and for ...

http://www.quidel.com/research/complement-proteins/c3d-protein

Complement activation and acute phase proteins were measured in blood samples and broncho-alveolar lavage. Plasma C3d levels ... There was complement activation in response to respirable dust, more so among cases than in the control group. It is concluded ... Plasma C3d levels of young farmers correlate with respirable dust exposure levels during normal work in swine confinement ...

http://www.ilo.org/dyn/cisdoc2/cismain.listdocs?p_lang=en&p_bsubject=584

Complement C3. A, C, E, G. 297. Homo sapiens. Mutation(s): 1 Gene Names: C3, CPAMD1. ... but loss of these side chains did not completely disrupt Ehp/C3d binding. This suggested the presence of a second C3d-binding ... Further molecular level details of the Ehp/C3d interaction were revealed by solving the 2.7-A crystal structure of an Ehp.C3d ... This inhibition was directly related to Ehp/C3d binding and was more potent than that seen for Efb-C. An altered conformation ...

https://www.rcsb.org/structure/2NOJ

Structure of Complement Receptor 2 in Complex with Its C3d Ligand. By Gerda Szakonyi, Joel M. Guthridge, Dawei Li, Kendra Young ...

https://science.sciencemag.org/content/292/5522

Complement receptor type 2. Complement receptor type 2, Cr2 (Complement C3d receptor) (CD antigen CD21) ... Complement receptor type 2Imported. ,p>Information which has been imported from another database using automatic procedures.,/p ... tr,A0A0A6YWU7,A0A0A6YWU7_MOUSE Complement receptor type 2 (Fragment) OS=Mus musculus OX=10090 GN=Cr2 PE=1 SV=1 ...

https://www.uniprot.org/uniprot/A0A0A6YWU7

Antibodies to the C3d fragment of complement component 3. US20010011171 *. Apr 3, 2001. Aug 2, 2001. Alchas Paul G.. ... Methods of treating complement-associated disorders with anti-C5a antibodies. US9226901. Sep 25, 2013. Jan 5, 2016. Locl Pharma ... Methods of treating complement-associated disorders with anti-C5a antibodies. US9498444. Jul 1, 2015. Nov 22, 2016. Locl Pharma ... Compositions and methods for increasing the serum half-life of a therapeutic agent targeting complement c5. ...

http://www.google.com/patents/US6146361?dq=6,654,957

The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological ... complement inhibitor CFH. Can associate with lipoproteins and may play a role in lipid metabolism. ... Complement C3dg fragment (PRO_0000005913). 2. EBI-21988278,EBI-21988425. Complement C3d fragment (PRO_0000005915). 3. EBI- ... "Dimerization of complement factor H-related proteins modulates complement activation in vivo.". Goicoechea de Jorge E., Caesar ...

https://www.uniprot.org/uniprot/P36980

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

Anti-C3d antibody conjugates and methods of detecting complement activation. US9650447. May 13, 2011. May 16, 2017. The Regents ... Targeting complement factor H for treatment of diseases. US9259488. Feb 17, 2015. Feb 16, 2016. The Regents Of The University ... Complement receptor 2 (CR2) targeting groups. US20050222030 *. Mar 10, 2005. Oct 6, 2005. Anthony Allison. Modified annexin ... A nucleic acid sequence complement of any nucleic acid sequence refers to the nucleic acid sequence of the nucleic acid strand ...

http://www.google.com/patents/US7635680?dq=6,411,947

1380 CR2; complement C3d receptor 2 933 CD22; CD22 molecule 2208 FCER2; Fc fragment of IgE receptor II 100133941 CD24; CD24 ... 1378 CR1; complement C3b/C4b receptor 1 (Knops blood group) 1379 CR1L; complement C3b/C4b receptor 1 like 948 CD36; CD36 ... complement component (3b/4b) receptor 1 K04011 CR1; complement component (3b/4b) receptor 1 K06259 CD36; CD36 antigen K06475 ... 728 C5AR1; complement C5a receptor 1 2204 FCAR; Fc fragment of IgA receptor 7070 THY1; Thy-1 cell surface antigen 4035 LRP1; ...

https://www.genome.jp/kegg-bin/get_htext?hsa04090+4486

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

Complement C3d receptor 2 antibody. *Complement C3d receptor antibody. *Complement component (3d/Epstein Barr virus) receptor 2 ... Receptor for complement C3Dd, for the Epstein-Barr virus on human B-cells and T-cells and for HNRPU. Participates in B ... Belongs to the receptors of complement activation (RCA) family.. Contains 15 Sushi (CCP/SCR) domains. ...

https://www.abcam.com/cd21-antibody-bu32-ab54253.html

B) An mAb to C3d labeled with Alexa Fluor 647 binds to the IAM. (C) Overlay of A and B. C3d deposition is limited to the IAM. ... An mAb against C3d was used as a marker of complement activation. Unexpectedly, this mAb reacted with unsensitized, ionophore- ... Complement, complement activation and anaphylatoxins in human ovarian follicular fluid. Clin. Exp. Immunol. 1990. 82:359-362. ... Complement receptors 1 and 3 are expressed on the plasma membrane of the egg (29). Complement is visualized as part of a highly ...

https://www.jci.org/articles/view/23213

The C-terminal short complement regulator (SCR)-20 domain of factor H (FH), the major serum regulator of C3b, possesses a binding site for C3d, a 35-kDa physiological fragment of C3b. (ucl.ac.uk)
The complement pathway generates a C3 convertase, a serine protease that cleaves the central complement protein C3, and generates the major cleavage fragment C3b. (quidel.com)
Further cleavage forms the C3d fragment. (els.net)
Iida K, Nadler L, Nussenzweig V. Identification of the membrane receptor for the complement fragment C3d by means of a monoclonal antibody. (springer.com)
They linked an antibody fragment that recognizes a post-ischemic neoepitope (the vehicle) to a complement inhibitor-naming it B4Crry- and tested it in a murine stroke model. (eurekalert.org)
We utilized CR2-Crry, which is the soluble rodent-specific complement inhibitor (sCrry) linked to a complement receptor 2 (CR2) targeting moiety that directs sCrry to sites of C3b-fragment (iC3b/C3dg/C3d) deposition. (arvojournals.org)
Growth control of activated murine B-cells by the C3d-fragment of human complement. (springer.com)
PMID 17022693 ] Determination of complement factor H functional polymorphisms (V62I, Y402H, and E936D) using sequence-specific primer PCR and restriction fragment length polymorphisms. (snpedia.com)
Importantly, C3d fragment of C3 has been found responsible for the binding to UspA1/A2. (avhandlingar.se)
The latter fragment is the critical first protein that combines with C6, C7, C8, and multiple C9 proteins to form the MAC, the terminal, pore-forming complement protein complex responsible for lysis of cells and pathogens. (aacrjournals.org)

CR2 binds C3dg, and C3d is present on B cells and dendritic cells (see the Table 1). (medscape.com)
In the presence of complement regulatory molecules C3b may be further degraded sequentially to iC3b, C3c, C3dg and C3d. (quidel.com)

The C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) defines a novel three-helix bundle motif that regulates complement activation. (nih.gov)
The adjuvant properties of this protein have been studied using several antigens fused to C3d. (pitt.edu)
To determine the ability of this protein to enhance the humoral immune response in mice with different genetic backgrounds, inbred and outbred mice were immunized with C3d conjugated antigens. (pitt.edu)
Complement C3d receptor 2 (CR2) is the main receptor for complement protein C3d and plays an important role in adaptive immune responses. (cdc.gov)
C3b is an opsonin and also a required protein to create the main convertases that drives the complement cascade. (quidel.com)
Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 (cluster of differentiation 35) is a protein that in humans is encoded by the CR1 gene. (wikipedia.org)
The protein mediates cellular binding to particles and immune complexes that have activated complement. (wikipedia.org)
In 5'-3' order the genes in this region are: membrane cofactor protein - CR1 - complement receptor type 2 - decay-accelerating factor - C4-binding protein. (wikipedia.org)
Using FACS to simultaneously evaluate viability, acrosomal status, and complement deposition, we found that complement activation was initiated by C-reactive protein (CRP) and was C1q, C2, and factor B dependent. (jci.org)
2014) Complement factor H related hybrid protein deregulates complement in dense deposit disease. (els.net)
Complement control protein are proteins that interact with components of the complement system. (wikipedia.org)
Increasing complement activation, achieved by genetic removal of the complement regulatory protein decay-accelerating factor, enhances murine T cell immunity and accelerates allograft rejection. (springer.com)
Synthesis of complement protein C3 in the kidney is an important mediator of local tissue injury. (springer.com)
C3 is the most abundant protein of the complement system with serum protein levels of about 1.3 mg/ml. (acris-antibodies.com)
There was increased binding of the classical pathway mediators immunoglobulin G (IgG) and C-reactive protein (CRP) to unencapsulated S. pneumoniae , indicating that the capsule could inhibit classical pathway complement activity by masking antibody recognition of subcapsular antigens, as well as by inhibiting CRP binding. (asm.org)
Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. (biomedcentral.com)
Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. (biochemj.org)

The following product was used in this experiment: Complement Polyclonal Antibody from Thermo Fisher Scientific, catalog # RAHU-C. (thermofisher.com)
Antibody and complement in transplant vasculopathy. (springer.com)
Formalin-Fixed, Paraffin-Embedded Human Placenta tissue stained with Complement C3c Antibody Cat. (acris-antibodies.com)
Formalin-Fixed, Paraffin-Embedded Human skin biopsy (4 μm) from lesion of the early pemphigus vulgaris (without blister formation), stained with anti-C3d antibody (DB 106) shows strong positive intraepidermal intercellular immunostaining. (acris-antibodies.com)
We conclude that constrained scattering modelling makes useful contributions to our understanding of antibody and complement structure and function. (royalsocietypublishing.org)
Complement C3 antibody LS-C653323 is a PE-conjugated mouse monoclonal antibody to human Complement C3. (lsbio.com)
Complement C3 antibody was raised against purified human C3d (neoantigen). (lsbio.com)
Eculizumab is a monoclonal antibody that targets a key component of the complement pathway named C5, and blocks its activation. (clinicaltrials.gov)
Since its discovery, the complement system has been primarily considered an effector of innate immunity with the ability to "complement" antibody-mediated clearance of foreign pathogens, dispose of dead cells, and cause inflammatory states ( 12 ). (aacrjournals.org)

The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens. (medscape.com)
CD21 (complement receptor 2, CR2) deficiency has been first described in 2012 by Thiel et al. (springer.com)
Complement receptor 2 (CR2/CD21) is an important receptor that amplifies Blymphocyte activation by bridging the innate and adaptive immune systems. (embl-heidelberg.de)
Human complement receptor 2 (CR2/CD21) as a receptor for DNA: implications for its roles in the immune response and the pathogenesis of systemic lupus erythematosus (SLE). (doktori.hu)
CD21, also known as CR2 (complement receptor 2) and C3d receptor, binds C3d and iC3b. (biolegend.com)

Activation of Q to C3b signals the start of the alternative complement pathway. (ucl.ac.uk)
Following binding of C1q to gp41 of HIV, the classical pathway of complement activation is initiated ( 1 ), while the lectin-dependent activation is initiated by the interaction of gp120 and gp41 with the mannan-binding lectin ( 2 ). (jimmunol.org)
The alternative pathway of complement is a powerful and evolutionarily old defence system of innate immunity that recognises and destroys invading infectious microbes and also targets and eliminates modified self cells. (els.net)
For survival in an immunocompetent host, pathogenic microbes provide strategies to interfere with alternative pathway activation at their surface and they evade complement immune recognition. (els.net)
C3 is continuously activated by the alternative complement pathway and attaches to surfaces in the form of C3b in a random manner. (els.net)
A powerful amplification reaction results in surface deposition of C3b (opsonization) and formation of C5 convertases, followed by the induction of the lytic complement pathway and cell lysis. (els.net)
The immune cell-derived, alternative pathway complement components activate spontaneously, yielding local, but not systemic, production of C3a and C5a. (springer.com)
The present invention relates to methods and materials for modulating the complement alternative pathway (CAP), the complement classical pathway (CCP), the. (patents.com)
A rare defect of the complement classical pathway. (abcam.com)
Association between polymorphisms of complement pathway genes and age-related macular degeneration in a Chinese population. (snpedia.com)
Atkinson C, He S, Morris K, Qiao F, Casey S, Goddard M, and Tomlinson S . (2010) Targeted complement inhibitors protect against post-transplant cardiac ischemia and reperfusion injury and reveal an important role for the alternative pathway of complement activation . (musc.edu)
Elvington A, Atkinson C, Zhu H, Yu J, Takahashi K, Stahl GL, Kindy MS, and Tomlinson S . (2012) The alternative complement pathway propagates inflammation and injury in murine ischemic stroke . (musc.edu)
Marshall KM, He S, Zhong Z, Atkinson C, and Tomlinson S . (2014) Dissecting the complement pathway in hepatic injury and regeneration with a novel protective strategy . (musc.edu)
Elvington M, Schepp-Berglind J, and Tomlinson S . (2015) Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of DSS-induced colitis . (musc.edu)
Recent laboratory studies have identified that an important pathway of inflammation called the 'complement pathway' may play an important role in how Antineutrophil Cytoplasmic Autoantibodies (ANCA) cause damage to the blood vessels. (clinicaltrials.gov)
MBL or ficolin activation of mannose-associated serine proteases (MASP) results in cleavage of C2 and C4 similar to the C1 complex, with subsequent production of C3 convertase and complement cascade activation resembling the classic pathway. (aacrjournals.org)
Additionally, C3b generated by alternative pathway C3 convertase can attach to target surfaces and bind Bb, forming a C3 convertase that amplifies downstream complement proteins locally at the target surface. (aacrjournals.org)

Enhanced infection is completely abolished by a mAb specific for the ligand-binding site of CD11b (i.e., α-chain of complement receptor 3, receptor for iC3b), proving the importance of complement receptor 3 in this process. (jimmunol.org)
The capsule impaired bacterial opsonization with C3b/iC3b by both the alternative and classical complement pathways and also inhibited conversion of C3b bound to the bacterial surface to iC3b. (asm.org)
Cleavage of serum IgG by the enzyme IdeS reduced C3b/iC3b deposition on all of the strains, but there were still marked increases in C3b/iC3b deposition on unencapsulated TIGR4 and D39 strains compared to encapsulated strains, suggesting that the capsule inhibits both IgG-mediated and IgG-independent complement activity against S. pneumoniae . (asm.org)

Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking. (harvard.edu)
Difference in the clustering of complement receptor type 1 (CR1) on polymorphonuclear leukocytes and erythrocytes: effect on immune adherence. (medscape.com)
Wakabayashi M, Ohi H, Tamano M, Onda K, Fujita T, Tomino Y. Acquired loss of erythrocyte complement receptor type 1 in patients with diabetic nephropathy undergoing hemodialysis. (medscape.com)

Although a cocrystal structure of a complex between C3d and the ligand-binding domains of CR2 has been published, several aspects of this structure, including the position in C3d of the binding interface, remained controversial because of disagreement with biochemical data. (rcsb.org)
The classic mechanism of enhancement of the immune response involves interaction of C3d with its natural ligand, complement receptor 2 (CR2). (pitt.edu)
Structure of complement receptor 2 in complex with its C3d ligand. (springer.com)

For the measurement of C3d-bound circulating immune complexes (CIC) present in human plasma or serum. (labcorp.com)
In certain disease states, immune complexes may initiate complement-mediated damage of various organs and tissues. (labcorp.com)
In primates, CR1 serves as the main system for processing and clearance of complement opsonized immune complexes. (wikipedia.org)
After generation of pathogen-specific antibodies, complement contributes in the clearance of immune complexes and pathogen elimination. (frontiersin.org)
Correlation between plasma C3d, circulating immune complexes, and clinical activity. (semanticscholar.org)
A cell line (Raji) without MBIg but with receptors for IgG Fc, C3-C3b, and C3d was selected for use in studying the binding mechanism of soluble immune complexes to cell surface membrane. (rupress.org)
Immune complexes containing complement bind to Raji cells only via receptors for complement, namely receptors for C3-C3b and C3d. (rupress.org)
Binding of immune complexes containing complement to cells is much greater than that of complexes without complement. (rupress.org)
Immune complexes bound to cells via receptors for complement can be partially released from the cell surface by addition of normal human serum as well as isolated human C3 or C3b. (rupress.org)

Simultaneous interaction of the antigen and C3d with the surface immunoglobulin M (sIgM) and CR2 on the surface of B-cells triggers two signaling pathways that cross-talk and synergize in cell activation. (pitt.edu)
It has been shown that CR1 can act as a negative regulator of the complement cascade, mediate immune adherence and phagocytosis and inhibit both the classic and alternative pathways. (wikipedia.org)
Its activation is required for both classical and alternative complement activation pathways. (thermofisher.com)
C3 and C4, mainly produced by the liver, are the major plasma proteins of the immune system complement pathways. (thermofisher.com)
The complement system is an important part of the humoral response in innate immunity, consisting of three different pathways. (acris-antibodies.com)
The third complement component, C3, is central to the classical, alternative and lectin pathways of complement activation. (acris-antibodies.com)
Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. (abcam.com)
A more integrated approach addressing upstream and downstream pathways in addition to those attributable to complement activation are critical for the successful treatment of MAP. (biomedcentral.com)
All three complement activation pathways converge at C3 cleavage. (arvojournals.org)
The UspA2 has been demonstrated to inhibit both the classical and the alternative pathways of the complement. (avhandlingar.se)
The complement cascade comprises the classic, alternative, and MBL pathways. (aacrjournals.org)

The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH. (uniprot.org)
We propose that this localized deposition of complement fragments aids in the fusion process between the spermatozoa and egg, in a role akin to that of complement in immune adherence. (jci.org)
Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. (springer.com)
We conclude that two fragments of the C3 molecule, that is, C3b and C3d, can function as opsonins if the phagocyte has the appropriate membrane receptors. (rupress.org)
It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. (biochemj.org)

abstract = "Activation and covalent attachment of complement component C3 to pathogens is the key step in complement-mediated host defense. (edu.au)

Upon exposure of human spermatozoa to autologous serum or follicular fluid, we unexpectedly observed that acrosome-reacted spermatozoa activated the complement cascade efficiently through C3 but not beyond. (jci.org)
Emerging evidence over the last decade unexpectedly identified the complement cascade as a common thread in this process. (jci.org)
Emerging evidence over the past 15 years supports the concept that the complement cascade, traditionally considered a component of innate immunity, unexpectedly regulates kidney IR injury, T cell and humoral alloimmunity that underlie transplant rejection, and progressive kidney injury that results in late graft failure. (jci.org)
The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. (frontiersin.org)
Complement cascade is activated immediately after encountering the pathogen. (frontiersin.org)
Unfortunately, the lack of coherence in complement proteins nomenclature and the complexity of the enzymatic cascade render complement one of the "most complicated and incomprehensible" parts of immunology and is frequently avoided by students and scientists. (frontiersin.org)
Activation products of the complement cascade contain neo-epitopes that are not present in the individual native components. (acris-antibodies.com)
Monoclonal antibodies detecting neo-epitopes have been used for direct quantification of activation at different steps in the complement cascade. (acris-antibodies.com)
As a fundamental component of innate immunity, the complement cascade ( Fig. 1 ) contains some of the most powerful proinflammatory molecules in the body, including most notably the anaphylatoxins C3a and C5a. (aacrjournals.org)
The contribution of the complement cascade to acute inflammation is well established, as is the continuous activation and consumption of complement proteins in chronic inflammatory states ( 7 , 8 ). (aacrjournals.org)
Nevertheless, emerging literature examining the mechanistic relationship between inflammation and cancer ( 4 , 9 , 10 ) has almost completely omitted the role of the complement cascade. (aacrjournals.org)

Inhibition of complement activation by EDTA also prevents enhanced infection, further demonstrating the role of complement in virus uptake and productive infection. (jimmunol.org)
Terminal complement inhibition decreases early acute humoral rejection in sensitized renal transplant recipients. (springer.com)
Medof ME, Kinoshita T, Nussenzweig V. Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. (springer.com)
article he co-authored with Dr. Stephen Tomlinson and other researchers at the Medical University of South Carolina about complement inhibition and stroke. (eurekalert.org)
They also found that B4Crry has a short circulatory half-life but a prolonged (35-hour) tissue half-life--features that ensure that complement inhibition will be restricted to affected brain tissue and not impact systemic serum complement activation. (eurekalert.org)
These results suggest that hyperglycemia inhibited humoral effector recruitment, anaphylatoxin generation, and complement-mediated opsonization of S. aureus , suggesting that hyperglycemic inhibition of complement effectors may contribute to the increased risk and severity of S. aureus infections in diabetic patients. (hindawi.com)
Hyperglycemic inhibition of complement-mediated opsonization resulted in decreased phagocytosis efficiency by euglycemic neutrophils, such that neutrophil function was not directly inhibited by excess glucose. (hindawi.com)
Overall, these data show that the S. pneumoniae capsule affects multiple aspects of complement- and neutrophil-mediated immunity, resulting in a profound inhibition of opsonophagocytosis. (asm.org)
Inhibition experiments showed that receptors for C3-C3b and receptors for C3d are distinct and that receptors for C3-C3b and C3d are different from receptors for IgG Fc. (rupress.org)
Integrated within these studies is the development and characterization of various site-targeted strategies for complement inhibition. (musc.edu)

Our study shows that Jurkat human T cells have a molecule that reacts with both anti-CR2 antibodies and the third component of complement, C3. (nih.gov)
Monoclonal antibodies to complement componenets without the need of their prior purification. (acris-antibodies.com)
2004 . Novel monoclonal antibodies against C3 interfering with complement activation: description of fine specificity and applications to various immunoassays. (acris-antibodies.com)
In recent years, a greater range of proteins have been successfully studied by scattering, including antibodies of adaptive immunity and the complement proteins of innate immunity. (royalsocietypublishing.org)
An immune recognition system consisting of natural antibodies sees stressed, non-functioning cells and assumes they're about to die and release their own damaging toxins, so it activates the complement system to start clearing out the damaged cells. (eurekalert.org)
When combined with our LIFECODES LSA ™ Single Antigen Kits, the assay offers a simple method for the detection of complement binding to HLA antibodies. (immucor.com)

Measurements of serum complement components C3 and C4 are useful in the diagnosis and monitoring of immune complex disease. (thermofisher.com)
Unencapsulated strains were more susceptible to neutrophil phagocytosis after incubation in normal serum, normal serum treated with IdeS, complement-deficient serum, and complement-deficient serum treated with IdeS or in buffer alone, suggesting that the capsule inhibits phagocytosis mediated by Fcγ receptors, complement receptors, and nonopsonic receptors. (asm.org)

Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma. (medscape.com)
Structure, function and cellular expression of complement anaphylatoxin receptors. (medscape.com)
Hyperglycemia decreased the influx of IgG and complement components into the peritoneum in response to S. aureus infection and decreased anaphylatoxin generation. (hindawi.com)
6 mM glucose) inhibit complement effectors against S. aureus including opsonization and anaphylatoxin generation [ 13 ]. (hindawi.com)
Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. (abcam.com)

A soluble form of hemagglutinin (sHA) fused to C3d inefficiently induced IgG class switch in MHC II-/- mice. (pitt.edu)
Complement is a group of about 50 soluble and cell surface proteins that represent a crucial component of both the innate and adaptive immune systems. (musc.edu)

Surface plasmon resonance studies showed that native FH binds C3d in two stages. (ucl.ac.uk)

Convertases, specifically the C3 convertases C3b.Bb and C4b.2a, are the enzymes that drive complement activation by activating C3b, a central component of the complement system. (wikipedia.org)
The receptor for EB virus is also the receptor for the C3d component of the complement system. (lymphomation.org)

Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. (frontiersin.org)
Differences in complement activation, as defined by the systemic C3d/C3 ratio, between AMD stages were evaluated using general linear modeling. (arvojournals.org)

Effector functions of the complement system, one of the main components of natural immunity, include opsonization leading to enhanced phagocytosis and lysis of microbes. (jimmunol.org)
The role of membrane receptors for C3b and C3d in phagocytosis. (rupress.org)
The Streptococcus pneumoniae capsule is vital for virulence and may inhibit complement activity and phagocytosis. (asm.org)

We conclude that the physiological interaction between FH and C3d is not a simple 1:1 binding stoichiometry between the two proteins that is often assumed. (ucl.ac.uk)
The complement system is tightly regulated by a network of proteins known as "regulators of complement activation (RCA)" that help distinguish target cells as "self" or "non-self. (wikipedia.org)
A subset of this family of proteins, complement control proteins (CCP), are characterized by domains of conserved repeats that direct interaction with components of the complement system. (wikipedia.org)
Results of studies published since 2002 reveal that T cells and antigen-presenting cells (APCs) produce complement proteins. (springer.com)
X-ray and neutron-scattering techniques characterize proteins in solution and complement high-resolution structural studies. (royalsocietypublishing.org)
We also discuss the applications to the large multi-domain proteins of the complement system, most notably its major regulator factor H, which is important in age-related macular degeneration and renal diseases. (royalsocietypublishing.org)
The present thesis is concentrated on discussing two properties of M. catarrhalis, - binding and inactivation of alpha1-anticnymotrypsin (ACT) and complement component 3 (C3) for which M. catarrhalis outer membrane proteins "ubiquitous surface proteins" (Usp) A1/A2 are responsible. (avhandlingar.se)
Thus, the recent finding that complement proteins C3, C4, and C5a may aid tumor growth through immunosuppression ( 11 ) is unexpected and suggests an insidious and previously unrecognized relationship between the complement system and cancer. (aacrjournals.org)

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)
Complement deficiency or blockade attenuates T cell-mediated autoimmunity and delays allograft rejection in mice. (springer.com)
Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:120700]. (abcam.com)

Key to all of these, however, is the complement system. (labcorp.com)
The complement system exerts many of its effects through complement receptors (CRs). (medscape.com)
Complement is a major innate immune surveillance system. (jimmunol.org)
The complement system is a part of the innate immune response, acting as a first line of defense against pathogens and participating in immune surveillance and homeostasis. (jimmunol.org)
C3d is an opsonin and deposits on the surface of cells targeted by the complement system. (quidel.com)
Dysregulation of the complement system has been implicated, but molecular mechanisms are incompletely understood. (frontiersin.org)
We used a custom-made single nucleotide polymorphism (SNP) genotyping assay consisting of 98 SNPs in 18 genes that encode components of the complement system. (frontiersin.org)
This is, as far as we are aware, the first candidate gene in the complement system with an association to a clinically relevant PE subphenotype, severe PE. (frontiersin.org)
The result highlights a potential role for the complement system in the pathogenesis of PE and may help in defining prognostic and therapeutic subgroups of preeclamptic women. (frontiersin.org)
On the basis of its central relevance in immunity targeting, the complement system by specific therapeutic agents is a promising approach to treat autoimmune diseases and inflammatory disorders. (els.net)
Most CCPs prevent activation of the complement system on the surface of host cells and protect host tissues against damage caused by autoimmunity. (wikipedia.org)
Other CCPs prevent the activity of terminal effectors of the complement system, CD59 for example blocks oligomerization of the complement peptide C9 stalling the formation of the Membrane Attack Complex (MAC). (wikipedia.org)
Efforts to develop therapeutics that target the interactions between the RCA network, CCPs, and components of the complement system have led to the development of successful drugs including Eculizumab. (wikipedia.org)
Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. (frontiersin.org)
Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. (frontiersin.org)
Complement system represents a major part of the innate immunity. (frontiersin.org)
After that, for a long time, complement system has been considered as a supportive part of the innate immunity and received relatively little attention from the immunologists. (frontiersin.org)
Complement component C3 plays a central role in the activation of complement system. (thermofisher.com)
Complement: a key system for immune surveillance and homeostasis. (springer.com)
OBJECTIVE To test the hypothesis that the complement system may be activated in patients with type II diabetes and CAD. (diabetesjournals.org)
An RIA system was used for measurement of urinary albumin levels, and the plasma C3d concentrations were measured by ELISA. (diabetesjournals.org)
CONCLUSIONS Activation of the complement system may play a role in the development of macrovascular disease in type II diabetes. (diabetesjournals.org)
A team of investigators at the Medical University of South Carolina (MUSC) has developed a novel therapy for ischemic (clot-caused) stroke and has shown in a preclinical model that it locally inhibits complement at and around the stroke core but does not inhibit functioning of the complement system in other areas of the body. (eurekalert.org)
The complement system is a component of both innate and adaptive immune responses and its dual role in both injury and recovery has made it a challenging target for potential stroke therapies. (eurekalert.org)
These in vitro results suggested that the complement system, a major contributor to innate immune host defenses against S. aureus [ 14 - 16 ], was significantly inhibited by hyperglycemic conditions in responding to S. aureus . (hindawi.com)
Research in the laboratory is focused on the biology of the complement system, and how it modulates an inflammatory response and shapes adaptive immunity. (musc.edu)

also called neoepitopes) that trigger deposition of complement C3d on the outer cell membrane. (eurekalert.org)

The findings support the need for design and testing of complement inhibitors in humans. (springer.com)
These findings contribute to the discussion on the pathogenesis of AMD in relation to complement activation and might suggest refinement in patient selection and the optimum window of treatment with complement inhibitors. (arvojournals.org)
Holers VM, Rohrer B, and Tomlinson S . (2013) CR2-mediated targeting of complement inhibitors: bench-to-bedside using a novel strategy for site-specific complement modulation . (musc.edu)

The final degradation product of the third (C3) component of complement, C3d, is a natural adjuvant. (pitt.edu)
Most previous studies stressed the importance of the C3d-CR2 interaction for the adjuvant effect. (pitt.edu)
We have engineered a DNA epitope vaccine that expresses 3 self-B cell epitopes of Aβ 42 (3Aβ 1-11 ), a non-self T helper (Th) cell epitope (PADRE), and 3 copies of C3d (3C3d), a component of complement as a molecular adjuvant, designed to safely reduce CNS Aβ. (elsevier.com)
C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. (springer.com)

This gene is a member of the regulators of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. (wikipedia.org)
In mice, CR1 is an alternatively spliced variant of the complement receptor 2 (CR2) gene. (wikipedia.org)
In this study, we determined the potential linkage of severe PE to the most central complement gene, C3 . (frontiersin.org)
1992) Analysis of the human regulators of complement activation (RCA) gene cluster with yeast artificial chromosomes (YACs). (els.net)
Expansion of the complement receptor gene family. (springer.com)
Genetic variants of complement factor H gene are not associated with premature coronary heart disease: a family-based study in the Irish population. (snpedia.com)
Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration. (snpedia.com)
PMID 18421087 ] Multiple gene polymorphisms in the complement factor h gene are associated with exudative age-related macular degeneration in chinese. (snpedia.com)

Because the multimers involve the C-terminus of FH, which is bound to host cell surfaces, our results provide new insight on FH regulation during excessive complement activation, both in the fluid phase and at host cell surfaces decorated by C3d. (ucl.ac.uk)
C3d is involved in the regulation of many aspects of the immune response including antigen processing and presentation. (immbio.hu)
Involved in complement regulation. (uniprot.org)

Holers VM (2014) Complement and its receptors: new insights into human disease. (els.net)

This review discusses recent advances in the understanding of the role of complement in physiology and pathology. (frontiersin.org)
Role of complement in the induction of immunological responses. (springer.com)
The team conducted a series of experiments to clarify the role of complement in stroke since it contributes to both neurodegenerative and neuroregenerative processes. (eurekalert.org)
A further area of study is the dual role of complement in liver injury and regeneration, important in the context of liver resection or small-for-size transplant. (musc.edu)

HIV-1 infection of human lymphocytes and monocytes/macrophages is greatly enhanced by opsonization of the virus with complement ( 3 , 4 , 5 ). (jimmunol.org)
Our observation that complement opsonization of HIV causes a distinctively productive infection of DCs has not yet been documented. (jimmunol.org)

Previous crystallographic studies of Efb-C bound to its cognate subdomain of human C3 (C3d) identified Arg-131 and Asn-138 of Efb-C as key residues for its activity. (nih.gov)
A ) Cartoon representation of the cocrystal (PDB accession code 2GOX) between human C3d (pale blue) and wild-type Efb-C (spectrum). (nih.gov)
The x-ray crystal structure of human C3d solved at 2.0 angstroms resolution reveals an α-α barrel with the residues responsible for thioester formation and covalent attachment at one end and an acidic pocket at the other. (sciencemag.org)
Quidel's purified human complement components are useful in a wide variety of immunochemical and research applications. (quidel.com)
Receptor for complement C3Dd, for the Epstein-Barr virus on human B-cells and T-cells and for HNRPU. (abcam.com)
In the present study, we demonstrate that macrophage-tropic HIV-1 opsonized by complement and limited amounts of anti-HIV-IgG causes up to 10-fold higher productive infection of human monocyte-derived dendritic cells than HIV treated with medium or HIV opsonized by Ab only. (jimmunol.org)
Lane 1 : Complement C3 isolated from Human plasma. (acris-antibodies.com)
In the present work we studied the expression of membrane-bound Ig (MBIg) as well as receptors for IgG Fc and complement on nine human lymphoblastoid cell lines. (rupress.org)
Recognizes human complement component 3d (C3d) neoantigen at ~33kD. (lsbio.com)

Complement regulators existing in the fluid phase and on the cell membrane determine the fate of the newly formed C3b molecule. (els.net)

These results suggested that C3d enhances the immune responses by CR2-dependent and CR2-independent mechanisms. (pitt.edu)

To inhibit these processes, the team developed a novel therapeutic agent to inhibit complement activation locally at sites where cells express DAMPs (or neoepitopes). (eurekalert.org)
They found that B4Crry would bind to hypoxic (oxygen-deprived) cells and inhibit complement activation but did not bind to normally oxygenated cells. (eurekalert.org)
Pre-treatment with ibrutinib did not inhibit complement activation or complement-mediated lysis. (haematologica.org)

He JQ , Wiesmann C and von Lookeren Campagne M (2008) A role of macrophage complement receptor CRIg in immune clearance and inflammation. (els.net)
Complement has been implicated in many diseases associated with inflammation and autoimmunity. (wikipedia.org)
Atkinson C, Mosely E, Varela JC, Stoica S, Large S, Goddard M, and Tomlinson S . (2009) Complement dependent inflammation and Injury in a murine model of brain dead donor hearts . (musc.edu)

Association of complement C3d receptor 2 genotypes with the acquisition of HIV infection in a trial of recombinant glycoprotein 120 vaccine. (cdc.gov)
CR2ligands include complement C3d and Epstein-Barr virus glycoprotein 350/220. (embl-heidelberg.de)

To study the levels of complement activation in different disease stages of AMD and the influence of genetic polymorphisms in complement genes. (arvojournals.org)
In addition, we evaluated the influence of 18 genetic AMD polymorphisms in complement genes and their effect on complement activation. (arvojournals.org)
Two polymorphisms in CFH (rs10922109 and rs570618) and one in CFB (rs116503776) were significantly associated with complement activation. (arvojournals.org)

Two types of receptors for complement could be detected on the cell lines studied, one for C3-C3b and one for C3d. (rupress.org)

To determine the importance of the C3d-CR2 interaction for enhancement of the immune response in vivo, mice deficient in CR2 (CR2-/-) were immunized with antigens fused to C3d. (pitt.edu)
Contrary to the predicted, CR2-/- mice immunized with antigens fused to C3d, developed almost similar humoral immune responses than wild-type mice. (pitt.edu)

This activation of complement may begin a series of potentially destructive events, including cell lysis, the production of anaphylatoxins, leukocyte stimulation, and activation of macrophages. (labcorp.com)
Complement was discovered at the end of the nineteenth century and described as a "factor" or "principle" capable to induce bacterial lysis. (frontiersin.org)

PMID 18806293 ] Analysis of rare variants in the complement component 2 (C2) and factor B (BF) genes refine association for age-related macular degeneration (AMD). (snpedia.com)
PMID 17591627 ] Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes. (snpedia.com)

Elvington M, Huang Y, Morgan BP, Qiao F, van Rooijen N, Atkinson C, and Tomlinson S . (2012) A targeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer . (musc.edu)

No significant changes in the overall structure could be detected between the three complexes, suggesting that the mutations do not induce any significant conformational changes at the Efb-C/C3d interface. (nih.gov)
Gros P , Milder FJ and Janssen BJ (2008) Complement driven by conformational changes. (els.net)

Our results show that while these mutations do not drastically affect the structure of the Efb-C/C3d recognition complex, they have significant adverse effects on both the thermodynamic and kinetic profiles of the resulting complexes. (nih.gov)
B ) Aligned backbone traces of the crystallized C3d complexes with Efb-C wild type (blue) as well as mutants R131A (green) and N138A (red). (nih.gov)
Size distribution analyses of mixtures of SCR-16/20 or FH with C3d by analytical ultracentrifugation in 50 and 137 mM NaCl buffer revealed a range of discrete peaks, showing that multimeric complexes had formed at physiologically relevant concentrations. (ucl.ac.uk)
Overlay experiments indicated that C3d formed multimeric complexes with FH. (ucl.ac.uk)
X-ray scattering showed that the maximum dimension of the C3d complexes with SCR-16/20 at 29 nm was not much longer than that of the unbound SCR-16/20 dimer. (ucl.ac.uk)

We now report a cocrystal structure of a CR2(SCR1-2):C3d complex at 3.2 angstrom resolution in which the interaction interfaces differ markedly from the previously published structure and are consistent with the biochemical data. (rcsb.org)
In order to characterize more completely the physical and chemical driving forces behind this important interaction, we employed in this study a combination of structural, biophysical, and computational methods to analyze the interaction of C3d with Efb-C and the single-point mutants R131A and N138A. (nih.gov)
The structure supports a model whereby the transition of native C3 to its functionally active state involves the disruption of a complementary domain interface and provides insight into the basis for the interaction between C3d and CR2. (sciencemag.org)

In general, consecutive AMD disease stages showed increasing levels of complement activation, especially in individuals with a genetic burden in complement genes. (arvojournals.org)

Biopsies were screened for the presence of complement deposition, specifically C4d and C3d. (ahajournals.org)

Anatomy15

Organisms10

Diseases16

Chemicals and Drugs101

Analytical, Diagnostic and Therapeutic Techniques and Equipment25

Phenomena and Processes48

Disciplines and Occupations2

Information Science3

Health Care1

Immunohistochemical analysis of arterial wall cellular infiltration in Buerger's disease (endarteritis obliterans). (1/194)

Complement activation and expression of membrane regulators in the middle ear mucosa in otitis media with effusion. (2/194)

C6 produced by macrophages contributes to cardiac allograft rejection. (3/194)

Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and differential regulation by heparin. (4/194)

Tracing uptake of C3dg-conjugated antigen into B cells via complement receptor type 2 (CR2, CD21). (5/194)

Structure at 1.44 A resolution of an N-terminally truncated form of the rat serum complement C3d fragment. (6/194)

Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2. (7/194)

Structure-guided identification of C3d residues essential for its binding to complement receptor 2 (CD21). (8/194)

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