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.
Complement Pathway, Alternative
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 C3-C5 Convertases
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.
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.
Complement Factor B
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.
Complement C3 Convertase, Alternative Pathway
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.
Complement System Proteins
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 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.
Complement Pathway, Classical
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.
Proprotein Convertase 2
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.
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).
Proprotein Convertase 1
Complement Activating Enzymes
Complement Inactivator Proteins
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 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 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.
Complement Factor H
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
A 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).
Complement Factor D
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.
Proprotein Convertase 5
Complement Membrane Attack Complex
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 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).
Complement C3b Inactivator Proteins
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.
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.
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.
Receptors, Complement 3b
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.
Complement C3 Nephritic Factor
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.
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.
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
Complement Factor I
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.
Complement C3-C5 Convertases, Alternative Pathway
Complement Inactivating Agents
Complement Hemolytic Activity Assay
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.
Complement C5 Convertase, Alternative Pathway
Receptors, Complement 3d
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.
Receptor, Anaphylatoxin C5a
Complement C4b-Binding Protein
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.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Complement C1 Inactivator Proteins
Complement C3 Convertase, Classical Pathway
Neuroendocrine Secretory Protein 7B2
Amino Acid Sequence
Complement C5 Convertase, Classical Pathway
Complement Fixation Tests
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.
Complement Pathway, Mannose-Binding Lectin
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.
Complement C1 Inhibitor Protein
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.
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.
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.
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.
Complement C3-C5 Convertases, Classical Pathway
Blood Bactericidal Activity
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.
Protein Structure, Tertiary
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.
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.
Protein Processing, Post-Translational
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Mannose-Binding Protein-Associated Serine Proteases
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.
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).
Lupus Erythematosus, Systemic
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 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.
Sequence Homology, Amino Acid
Electrophoresis, Polyacrylamide Gel
Enzyme-Linked Immunosorbent Assay
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
A 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.
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.
Aspartic Acid Endopeptidases
Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe. Structurally, they include small peptides, proteins, and glycoproteins. They are under the regulation of neural signals (NEUROTRANSMITTERS) or neuroendocrine signals (HYPOTHALAMIC HORMONES) from the hypothalamus as well as feedback from their targets such as ADRENAL CORTEX HORMONES; ANDROGENS; ESTROGENS.
A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.
The common precursor polypeptide of pancreatic GLUCAGON and intestinal GLUCAGON-LIKE PEPTIDES. Proglucagon is the 158-amino acid segment of preproglucagon without the N-terminal signal sequence. Proglucagon is expressed in the PANCREAS; INTESTINES; and the CENTRAL NERVOUS SYSTEM. Posttranslational processing of proglucagon is tissue-specific yielding numerous bioactive peptides.
Surface Plasmon Resonance
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.
Disease Models, Animal
Gene Expression Regulation
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP).
Dose-Response Relationship, Immunologic
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.)
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).
Genetic Complementation Test
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.
Complement C5a, des-Arginine
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 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.
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)
Reverse Transcriptase Polymerase Chain Reaction
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
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.
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)
A 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.
NF-kappa B p52 Subunit
Recombinant Fusion Proteins
A 69-amino acid peptide derived from the N-terminal of PROGLUCAGON. It is mainly produced by the INTESTINAL L CELLS. Further processing of glicentin yield a 30-amino acid N-terminal peptide (glicentin-related polypeptide) and a 37-amino acid peptide OXYNTOMODULIN. Both glicentin and oxyntomodulin can reduce digestive secretions and delay gastric emptying.
Animal Testing Alternatives
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).
Dose-Response Relationship, Drug
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
Major Histocompatibility Complex
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.
Complement activation in patients with systemic lupus erythematosus without nephritis. (1/30)OBJECTIVE: To study the association between disease activity and complement activation prospectively in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Twenty-one SLE patients were examined monthly for 1 yr. Disease activity, autoantibodies, conventional complement tests and the following complement activation products were investigated: C1rs-C1inh complexes, C4bc, Bb, C3a, C3bc, C5a and the terminal SC5b-9 complement complex (TCC). RESULTS: Modest variation in disease activity was noted. None of the patients had nephritis. Flare was observed at 27 visits. Four patients had anti-C1q antibodies in conjunction with modestly low C1q concentrations. The complement parameters were rather constant during the observation period. Slightly to moderately decreased C4 (0.05-0.10 g/l) was found in 10 patients and severely decreased C4 (<0.05 g/l) in seven patients. Decreased C4 was not associated with increased complement activation. Complement activation products were either normal or slightly elevated. TCC was the only activation product correlating significantly with score for disease activity at flare. None of the variables tested predicted flares. CONCLUSION: Complement tests are of limited importance in routine examination of SLE without nephritis, although TCC is suggested to be one of the most sensitive markers for disease activity. (+info)
Cooperation between decay-accelerating factor and membrane cofactor protein in protecting cells from autologous complement attack. (2/30)Decay-accelerating factor (DAF or CD55) and membrane cofactor protein (MCP or CD46) function intrinsically in the membranes of self cells to prevent activation of autologous complement on their surfaces. How these two regulatory proteins cooperate on self-cell surfaces to inhibit autologous complement attack is unknown. In this study, a GPI-anchored form of MCP was generated. The ability of this recombinant protein and that of naturally GPI-anchored DAF to incorporate into cell membranes then was exploited to examine the combined functions of DAF and MCP in regulating complement intermediates assembled from purified alternative pathway components on rabbit erythrocytes. Quantitative studies with complement-coated rabbit erythrocyte intermediates constituted with each protein individually or the two proteins together demonstrated that DAF and MCP synergize the actions of each other in preventing C3b deposition on the cell surface. Further analyses showed that MCP's ability to catalyze the factor I-mediated cleavage of cell-bound C3b is inhibited in the presence of factors B and D and is restored when DAF is incorporated into the cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two proteins individually, and DAF is required for MCP to catalyze the cleavage of cell-bound C3b in the presence of excess factors B and D. These data are relevant to xenotransplantation, pharmacological inhibition of complement in inflammatory diseases, and evasion of tumor cells from humoral immune responses. (+info)
Rejection of pig liver xenografts in patients with liver failure: implications for xenotransplantation. (3/30)The pathophysiological state of rejection in liver xenotransplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig-to-human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xenoreactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b-9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure. (+info)
Complement 1 inhibitor is a regulator of the alternative complement pathway. (4/30)We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. C1-INH prevented lysis, induced by the alternative complement pathway, of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes in human serum. It inhibited the binding of both factors B and C3 to PNH and rabbit erythrocytes and blocked the ability of factor B to restore alternative-pathway function in factor B-depleted serum. C1-INH did not bind to factors B or D but did bind to immobilized C3b and cobra venom factor (CVF), a C3b analogue. C1-INH prevented factor B from binding to CVF-coated beads and dissociated bound factor B from such beads. Factor B and C1-INH showed cross competition in binding to CVF-coated beads. Factor D cleaved factor B into Bb and Ba in the presence of C3b. Cleavage was markedly inhibited when C3b was preincubated with C1-INH. C1-INH inhibited the formation of CVFBb and decreased the C3 cleavage. Removal of C1-INH from serum, in the presence of Mg-EGTA with an anti-C1-INH immunoabsorbant, markedly increased alternative-pathway lysis. C1-INH interacts with C3b to inhibit binding of factor B to C3b. At physiologic concentrations, it is a downregulator of the alternative pathway convertase. (+info)
Complement activation in chromosome 13 dementias. Similarities with Alzheimer's disease. (5/30)Chromosome 13 dementias, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with neurodegeneration and cerebrovascular amyloidosis, with striking neuropathological similarities to Alzheimer's disease (AD). Despite the structural differences among the amyloid subunits (ABri in FBD, ADan in FDD, and Abeta in AD), these disorders are all characterized by the presence of neurofibrillary tangles and parenchymal and vascular amyloid deposits co-localizing with markers of glial activation, suggestive of local inflammation. Proteins of the complement system and their pro-inflammatory activation products are among the inflammation markers associated with AD lesions. Immunohistochemistry of FBD and FDD brain sections demonstrated the presence of complement activation components of the classical and alternative pathways as well as the neo-epitope of the membrane attack complex. Hemolytic experiments and enzyme-linked immunosorbent assays specific for the activation products iC3b, C4d, Bb, and C5b-9 indicated that ABri and ADan are able to fully activate the complement cascade at levels comparable to those generated by Abeta1-42. ABri and ADan specifically bound C1q with high affinity and formed stable complexes in physiological conditions. Activation proceeds approximately 70-75% through the classical pathway while only approximately 25-30% seems to occur through the alternative pathway. The data suggest that the chronic inflammatory response generated by the amyloid peptides in vivo might be a contributing factor for the pathogenesis of FBD and FDD and, in more general terms, to other neurodegenerative conditions. (+info)
Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase. (6/30)The C-terminal fragment, Bb, of factor B combines with C3b to form the pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb consists of a von Willebrand factor type A (vWFA) domain that is structurally similar to the I domains of integrins and a serine protease (SP) domain that is in inactive conformation. The structure of the C3bBb complex would be important in deciphering the activation mechanism of the SP domain. However, C3bBb is labile and not amenable to X-ray diffraction studies. We engineered a disulfide bond in the vWFA domain of Bb homologous to that shown to lock I domains in active conformation. The crystal structures of Bb(C428-C435) and its inhibitor complexes reveal that the adoption of the "active" conformation by the vWFA domain is not sufficient to activate the C3-convertase catalytic apparatus and also provide insights into the possible mode of C3-convertase activation. (+info)
Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay. (7/30)Decay-accelerating factor (DAF; CD55) inhibits the complement (C) cascade by dissociating the multimolecular C3 convertase enzymes central to amplification. We have previously demonstrated using surface plasmon resonance (Biacore International) that DAF mediates decay of the alternative pathway C3 convertase, C3bBb, but not of the inactive proenzyme, C3bB, and have shown that the major site of interaction is with the larger cleavage subunit factor B (Bb) subunit. In this study, we dissect these interactions and demonstrate that the second short consensus repeat (SCR) domain of DAF (SCR2) interacts only with Bb, whereas SCR4 interacts with C3b. Despite earlier studies that found SCR3 to be critical to DAF activity, we find that SCR3 does not directly interact with either subunit. Furthermore, we demonstrate that properdin, a positive regulator of the alternative pathway, does not directly interact with DAF. Extending from studies of binding to decay-accelerating activity, we show that truncated forms of DAF consisting of SCRs 2 and 3 bind the convertase stably via SCR2-Bb interactions but have little functional activity. In contrast, an SCR34 construct mediates decay acceleration, presumably due to SCR4-C3b interactions demonstrated above, because SCR3 alone has no binding or functional effect. We propose that DAF interacts with C3bBb through major sites in SCR2 and SCR4. Binding to Bb via SCR2 increases avidity of binding, concentrating DAF on the active convertase, whereas more transient interactions through SCR4 with C3b directly mediate decay acceleration. These data provide new insights into the mechanisms involved in C3 convertase decay by DAF. (+info)
Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. (8/30)Complement promotes the rapid recognition and elimination of pathogens, infected cells, and immune complexes. The biochemical basis for its target specificity is incompletely understood. In this report, we demonstrate that properdin can directly bind to microbial targets and provide a platform for the in situ assembly and function of the alternative pathway C3 convertases. This mechanism differs from the standard model wherein nascent C3b generated in the fluid phase attaches nonspecifically to its targets. Properdin-directed complement activation occurred on yeast cell walls (zymosan) and Neisseria gonorrhoeae. Properdin did not bind wild-type Escherichia coli, but it readily bound E. coli LPS mutants, and the properdin-binding capacity of each strain correlated with its respective serum-dependent AP activation rate. Moreover, properdin:single-chain Ab constructs were used to direct serum-dependent complement activation to novel targets. We conclude properdin participates in two distinct complement activation pathways: one that occurs by the standard model and one that proceeds by the properdin-directed model. The properdin-directed model is consistent with a proposal made by Pillemer and his colleagues >50 years ago. (+info)
Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Ctr Biomat Chem, Kalmar, Sweden.. ...
Complement regulation of T cell immunity | SpringerLink
Results of studies published since 2002 reveal that T cells and antigen-presenting cells (APCs) produce complement proteins. The immune cell-derived, alternative pathway complement components activate
Persistent decrease in multiple components of the perineuronal net following status epilepticus - McRae - 2012 - European...
In the rodent model of temporal lobe epilepsy, there is extensive synaptic reorganization within the hippocampus following a single prolonged seizure event, after which animals eventually develop epilepsy. The perineuronal net (PN), a component of the neural extracellular matrix (ECM), primarily surrounds inhibitory interneurons and, under normal conditions, restricts synaptic reorganization. The objective of the current study was to explore the effects of status epilepticus (SE) on PNs in the adult hippocampus. The aggrecan component of the PN was studied, acutely (48 h post-SE), sub-acutely (1 week post-SE) and during the chronic period (2 months post-SE). Aggrecan expressing PNs decreased by 1 week, likely contributing to a permissive environment for neuronal reorganization, and remained attenuated at 2 months. The SE-exposed hippocampus showed many PNs with poor structural integrity, a condition rarely seen in controls. Additionally, the decrease in the aggrecan component of the PN was ...
Complement C3 assay - Randox Online Store
Complement is a complex biological system which works in conjunction with antibody and other factors to protect the body from invasion by pathogens. When activated by either the classical or alternative pathway Complement acts on biological membranes and may cause cell death. The human complement cascade consists of several distinct plasma proteins. Complement C3 and Complement C4 levels are important in determining inherited or acquired deficiencies. Conversely, levels may rise in a variety of inflammatory and necrotic disorders as part of the acute-phase plasma protein response.. Available Applications. ...
Frontiers | The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct...
Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b and C9b on agarose-coated plates in a dose dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B
does MHC class III genes encode Interleukin Beta microglobulinc Tumor necro
does MHC class III genes encode Interleukin Beta microglobulinc Tumor necro MHC class III genes encodes proteins of classic and alternate complement pathways (C2 and C4, properdin factor B), soluble proteins, tumor necrosis factors (TNF alpha, beta), HSP 70 and the 21 hydroxy
RCSB PDB - Launch Viewer for 2WY7
2WY7: A Structural Basis for Staphylococcal Complement Subversion: X-Ray Structure of the Complement- Binding Domain of Staphylococcus Aureus Protein Sbi in Complex with Ligand C3D.
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Properdin | Definition of Properdin by Merriam-Webster
Properdin definition is - a blood serum protein that participates in the activation of complement in a pathway which does not involve the presence of antibodies.
Interferon gamma induces synthesis of complement alternative pathway proteins by human endothelial cells in culture. | Journal...
Human umbilical vein endothelial cells grown in vitro under standard conditions contain a high level of mRNA specific for the complement regulatory factors H and I. An additional 1.8-kb mRNA encoding a truncated form of factor H is also present. IFN-gamma stimulation of the cells causes a 6-7 fold increase in both factor H mRNA species, and a greater than 10-fold increase in factor I mRNA. IL-1 and LPS slightly suppressed factor H mRNA, while TNF had no effect. mRNA for factor B is also detectable in IFN-gamma-stimulated cells, but messengers for C1q, C4bp, and CR3 beta chain were not found. Secretion of factor H protein was also stimulated by IFN-gamma. The presence of mRNA for factors H, B, and I, together with C3 secretion, demonstrated by others, suggests that endothelial cells can assemble the complete alternative complement pathway. Endothelial cell complement may be involved in leukocyte-endothelium interactions mediated by leukocyte C3 receptors. ...
Anti- Factor B (FB, Complement Factor B, CFB, AHUS4, BF, BFD, C3/C5 Convertase, CFAB, FBI12, Glyc... by USBiological, Cat. No....
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Anti- Factor B (FB, Complement Factor B, CFB, AHUS4, BF, BFD, C3/C5 Convertase, CFAB, FBI12, Glyc... by USBiological, Cat. No....
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RCSB PDB - 6RUV: Structure of the SCIN stabilized C3bBb convertase bound to Properdin and a the non-inhibitory nanobody hFPNb1
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Tissue expression of SCIN - Summary - The Human Protein Atlas
Summary of SCIN (KIAA1905) expression in human tissue. Distinct cytoplasmic expression in distal renal tubules, gastrointestinal tract, placental trophoblasts and chondrocytes.
Complement factor b | definition of Complement factor b by Medical dictionary
Looking for online definition of Complement factor b in the Medical Dictionary? Complement factor b explanation free. What is Complement factor b? Meaning of Complement factor b medical term. What does Complement factor b mean?
complement factor B | S1: Chymotrypsin | IUPHAR Guide to IMMUNOPHARMACOLOGY
The IUPHAR/BPS Guide to Pharmacology. complement factor B - S1: Chymotrypsin. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Prognostic Value of Complement Properdin in Cancer
The complement system is readily triggered by the presence of damage-associated molecular patterns on the surface of tumor cells. The complement alternative pathway provides rapid amplification of the molecular stress signal, leading to complement cascade activation to deal with pathogens or maligna …
Activator, C3 Convertase - Medical Dictionary online-medical-dictionary.org
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 ...
Publication | Luxembourg Institute of Health
Directing selective complement activation towards tumour cells is an attractive strategy to promote their elimination. In the present work, we have generated heteromultimeric immunoconjugates that selectively activate the complement alternative pathway (AP) on tumour cells. We used the C4b-binding protein C-terminal-alpha-/beta-chain scaffold for multimerisation to generate heteromultimeric immunoconjugates displaying (a) a multivalent-positive regulator of the AP, the human factor H-related protein 4 (FHR4) with; (b) a multivalent targeting function directed against erbB2 (HER2); and (c) a monovalent enhanced GFP tracking function. Two distinct VH H targeting two different epitopes against HER2 and competing either with trastuzumab or with pertuzumab-recognising epitopes [VH H(T) or VH H(P)], respectively, were used as HER2 anchoring moieties. Optimised high-FHR4 valence heteromultimeric immunoconjugates [FHR4/VH H(T) or FHR4/VH H(P)] were selected by sequential cell cloning and a selective ...
SCIN | Oceanit
For several decades, techniques for modifying the surface of steel pipes were practiced with varying results. In addition, these methods did not address either the hydrophobicity of the carbon steel or steel/cement interfacial bond, other than the use of surfactants in spacers and cement slurry. SCIN offers an economical solution to this issue by achieving a superhydrophilic pipe surface that is chemically reactive to Portland cement, allowing an effective bond to cement.
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Barraquer-Simons syndrome - Wikipedia
Barraquer-Simons syndrome (or acquired partial lipodystrophy, cephalothoracic lipodystrophy, and progressive lipodystrophy)) is a rare form of lipodystrophy, which usually first affects the head, and then spreads to the thorax. It is named for Luis Barraquer Roviralta (1855-1928), a Spanish physician, and Arthur Simons (1879-1942), a German physician. Some evidence links it to LMNB2. The etiology of this condition has not been fully elucidated. Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. C3 nephritic factor induces the lysis of adipocytes that secrete adipsin, a product identical to complement factor D. The distribution of the lipoatrophy is postulated to be dictated by the variable amounts of adipsin secreted by the adipocytes at different locations. Human PTRF mutations may cause ...
Alternative pathway | Definition of Alternative pathway at Dictionary.com
Alternative pathway definition, the activation of complement by contact with polysaccharides on bacteria, protozoa, or yeast cells: a nonspecific immune response. See more.
AccessGUDID - DEVICE: Anti Human Properdin FITC (B1761082)
AccessGUDID - Anti Human Properdin FITC (B1761082)- Fluorescein conjugated polyclonal goat antiserum to Human Complement Properdin
Download PDF Early embryonic somatic movements in birds and in mammals other than man by George Ellett Coghill Ebook
View Test Prep - SCIN Week 8 Quiz Bank from SCIN at American Public University. art 1 of 1 Question 1 of 10 / Points / Points Metatherian mammals have a .
Villa La Sila in Palmi - Italian Breaks
Villa La Sila in Palmi - VILLA LA SILA - PALMI AREA Located 150m from the beaches of Scinà and walking distance from the nearest restaurant, Villa La Sila offers a g...
Iris View Profile
I conduct research into genetic kidney disease and perform a weekly nephrology clinic specializing in the care of patients and families with hereditary kidney problems, including polycystic kidney disease, unexplained familial kidney failure, inherited microscopic haematuria syndromes and renal cancer syndromes.. Using linkage mapping, next generation sequencing and other techniques I have described and identified the molecular defects responsible for the genetic diseases HIF2α erythrocytosis, which results from a defect in cellular oxygen sensing, and CFHR5 nephropathy, which results from a defect of complement alternative pathway regulation and which is endemic in people of Cypriot ancestry.. Ongoing projects aim firstly to improve understanding of the pathophysiology of these diseases; secondly to develop rational approaches to their treatment; and thirdly to investigate other families with inherited kidney disease in order to uncover the genetic change responsible in each one. ...
Braingenie | Alternative Pathways for Photosynthesis
Engaging math & science practice! Improve your skills with free problems in Alternative Pathways for Photosynthesis and thousands of other practice lessons.
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... C3 convertase formation can occur in three different pathways: the classical, lectin, and alternative pathways. Cleavage of ...
Complement factor B
... components of the alternative-pathway C3 convertase of complement". The Biochemical Journal. 253 (3): 667-75. doi:10.1042/ ... The active subunit Bb is a serine protease that associates with C3b to form the alternative pathway C3 convertase. Bb is ... This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in ... Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the ...
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... It binds to preformed alternative pathway C3-convertases. Properdin also inhibits the Factor H - mediated cleavage of C3b by ... The alternative pathway is not dependent on antibodies. This branch of the complement system is activated by IgA immune ... a Positive Regulator of the Alternative Pathway of Complement". J Biol Chem. 259 (7): R4582-4588. doi:10.1016/S0021-9258(17) ...
C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. C3 ... due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial ... Around 83% of APL patients had low complement 3 (C3) levels and the presence of polyclonal immunoglobulin C3 nephritic factor. ... Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic ...
Complement component 3
In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 ... The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase. C3bBb is deactivated in steps. First, the ... Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are ... "Entrez Gene: C3 complement component 3". Sahu A, Lambris JD (Apr 2001). "Structure and biology of complement protein C3, a ...
... the alternative complement pathway is one element of innate immunity. Once the alternative C3 convertase ... the classical complement pathway, the alternative complement pathway, and the lectin pathway. The alternative pathway accounts ... July 2009). "Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ...
The MASPs cleave C4 and C2, resulting in C3 convertase formation. The alternative pathway of complement activation is typically ... Levels of complement are regulated by moderating convertase formation and enzymatic activity. C3 convertase formation is ... C3 convertase activity is also regulated without C3b inactivation, through complement control proteins, including decay- ... C3a formation occurs through activation and cleavage of complement component 3 in a reaction catalyzed by C3-convertase. There ...
The term C3 convertase may refer to: C3-convertase, an enzyme Alternative-complement-pathway C3/C5 convertase, an enzyme This ...
M. Amin Arnaout
C3 nephritic factor is an autoantibody to the complement C3bBb convertase that activates the alternative complement pathway, a ... finding that suggested the potential of B cell or complement C5 depletion as adjunct therapies in certain forms of kidney ...
... alternative pathway and the classical pathway. All pathways culminate in the production of a C3 convertase, which catalyses C3 ... Consequently, levels of all complement proteins become low. The complement pathway is composed of several subset pathways: the ... classical complement pathway). In brief, the crucial role of C1q in the pathway is its importance as the first protein to start ... in the complement pathway) named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement ...
"Alternative pathway of complement: Recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of ... and C3b produced by cleavage mediated by the classical pathway C3 convertase (C4bC2a). The formation of the alternative pathway ... DiScipio RG (1982). "The activation of the alternative pathway C3 convertase by human plasma kallikrein". Immunology. 45 (3): ... Cell-bound C3 and C5 convertase differ in their C3b requirement. C3-convertase (C3bBb) need only one molecule of C3b to form, ...
... the alternative pathway C3-convertase. Factor D is synthesized by the liver and adipocytes with the latter being the major ... Factor D is involved in the alternative complement pathway of the complement system where it cleaves factor B. The protein ... Factor D (EC 126.96.36.199, C3 proactivator convertase, properdin factor D esterase, factor D (complement), complement factor D, ... The encoded protein is a component of the alternative complement pathway best known for its role in humoral suppression of ...
List of EC numbers (EC 3)
... complement factor I EC 188.8.131.52: complement factor D EC 184.108.40.206: alternative-complement-pathway C3/C5 convertase EC 3.4. ... classical-complement-pathway C3/C5 convertase EC 220.127.116.11: Now EC 18.104.22.168, classical-complement-pathway C3/C5 convertase EC ... classical-complement-pathway C3/C5 convertase EC 22.214.171.124: Now EC 126.96.36.199, classical-complement-pathway C3/C5 convertase EC ... 188.8.131.52: complement factor I EC 184.108.40.206: complement factor D EC 220.127.116.11: alternative-complement-pathway C3/C5 convertase ...
Outline of immunology
C5a C3-convertase C5-convertase Late stage Membrane attack complex (MAC) C6 C7 C8 C9 Complement pathway inhibitors C1-inhibitor ... MASP2 Mannan-binding lectin Alternative complement pathway Factor B Factor D Factor P (Properdin) Middle stage C3 - C3a / C3b ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... divided by pathway) Classical complement pathway C1Q complex - C1R / C1S C4 - C4a C2 Mannan-binding lectin pathway MASP1 / ...
... thereby preventing formation of the C4b2a C3-convertase, and interaction of DAF with C3b of the alternative pathway interferes ... Thus, by limiting the amplification convertases of the complement cascade, DAF indirectly blocks the formation of the membrane ... or C3 (alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with ... thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. ...
Complement control protein
C3b.Bb is an important convertase that is part of the alternative pathway, and it is formed when factor B binds C3b and is ... Convertases, specifically the C3 convertases C3b.Bb and C4b.2a, are the enzymes that drive complement activation by activating ... 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- ...
Thioester-containing protein 1
C3 like molecules in a diverse range of species suggests that the complement pathway in particular the alternative complement ... Furthermore, both the TEP1 pathway and the alternative pathway utilise convertase mediated amplification loops to increase ... Therefore, unlike the classical complement pathway the TEP1 pathway is antibody independent and instead relies on the presence ... from a complement-like protein to a complement-like pathway". Cell Host Microbe. 3 (6): 364-74. doi:10.1016/j.chom.2008.05.007 ...
Complement factor I
"Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral ... C3), factor B, factor H and properdin in blood, due to unregulated activation of C3 convertase, and to low levels of IgG, due ... Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ (June 2010). "Mutations in alternative pathway complement proteins in ... This contribution is thought to be due to the dysregulation of the alternative pathway, leading to increased inflammation in ...
... and decay accelerating activity against the alternative pathway C3-convertase, C3bBb. Factor H exerts its protective action on ... amongst other complement proteins and factors, leading to regulation of the alternative pathway of complement in particular. ... Its principal function is to regulate the alternative pathway of the complement system, ensuring that the complement system is ... such as complement factor H-related genes, as well as in other complement proteins (e.g. factor I, C2/factor B, and C3) have ...
Alternative complement pathway
This complex is also known as a fluid-phase C3-convertase. This convertase, the alternative pathway C3-convertase, although ... The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the ... and C3 glomerulonephritis (Dense Deposit Disease or MPGN Type II). Classical complement pathway Lectin pathway Conrad DH, Carlo ... a stable compound which can bind an additional C3b to form alternative pathway C5-convertase. The C5-convertase of the ...
Complement 3 deficiency
... alternative pathway, and the lectin pathway). Each of these pathways involves the formation of a C3-convertase, which will ... Both primary and secondary C3 deficiency are characterized by low levels or absence of C3. Complement component 3 (C3) is a ... C3 is one of over 30 complement proteins circulating in the blood. C3 circulates in an inactive form but can be activated in ... C3 is the most abundant complement component and is a particularly important complement component because there are three ways ...
Complement receptor 1
... protects host cells from complement-mediated damage by regulating the activation of C3 convertases on host cell surfaces; ... mediate immune adherence and phagocytosis and inhibit both the classic and alternative pathways. The number of CR1 molecules ... 1989). "Immunoregulatory functions of complement: structural and functional studies of complement receptor type 1 (CR1; CD35) ... complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1". The Journal ...
The complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin ... and initiate the formation of a C3-convertase. The subsequent complement cascade catalyzed by C3-convertase results in creating ... Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system. Another important ... In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), ...
... alternative pathway and lectin pathway) that ultimately lead to the formation of a C3 convertase. Formation of a C3 convertase ... inactivate the complement component. Given the C3 is constantly being turned over in the alternative pathway and its ability to ... In the alternative pathway, C3, present in the blood stream, spontaneously cleaves at low rates into C3b and C3a. If a microbe ... Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound ...
Classical complement pathway
... which cleaves the C3 protein. The C3b component of the cleaved C3 binds to C3 convertase (C4b2b) to generate C5 convertase ( ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ... Activation of the complement pathway through the classical, lectin or alternative complement pathway is followed by a cascade ... The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune ...
List of MeSH codes (D12.776.124)
... complement c3-c5 convertases MeSH D12.776.124.486.274.860.387.500 - complement c3-c5 convertases, alternative pathway MeSH ... complement c3 convertase, alternative pathway MeSH D12.776.124.486.274.860.387.500.750 - complement c5 convertase, alternative ... complement c3-c5 convertases, classical pathway MeSH D12.776.124.486.274.860.387.750.500 - complement c3 convertase, classical ... complement c3 MeSH D12.776.124.486.274.250.250 - complement c3a MeSH D12.776.124.486.274.250.260 - complement c3b MeSH D12.776. ...
Complement component 4
... participates in all three of the complement pathways (classical, alternative, and lectin); the alternative pathway is " ... the C4b-C2a complex with protease activity has been termed the C3 convertase. Protein 4b can be further cleaved into 4c and 4d ... All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar A, ...
It is also involved in the process of cleaving complement proteins, C4 and C2, into fragments to form a C3-convertase. MASP-1 ... and it can potentially activate the alternative pathway of complement in inflammatory arthritis patients. Hepatitis C (HCV), a ... C2a and C4b are used to create C3 convertase, a complex that will then be able to cleave C3 into C3a and C3b. However, MASP-1 ... is a serine protease that functions as a component of the lectin pathway of complement activation. The complement pathway plays ...
... plays an important role in the regulation of a branch of the innate immune system called the alternative complement pathway. ... 2005). "Human factor H-related protein 5 has cofactor activity, inhibits C3 convertase activity, binds heparin and C-reactive ... Like complement factor H, CFHR5 is able to bind to complement C3. A mutation in CHFR5 was found in patients with the disease ... The mutated form of the protein found in patients with this disease has impaired ability to bind to complement C3, suggesting ...
... as opposed to the alternative C3 convertase (C3bBb) involved in the alternative pathway. C4a and C2b act as potent cytokines, ... Classical complement pathway Alternative complement pathway Mannan-binding lectin Wallis R, Mitchell DA, Schmid R, Schwaeble WJ ... The lectin pathway or lectin complement pathway is a type of cascade reaction in the complement system, similar in structure to ... In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The ...
Diffuse proliferative nephritis
The classical pathway, lectin pathway, and alternative pathway of complement are all involved in glomerulonephritis, depending ... C1q, the first component of the complement system, encounters conformational change that leads to C3 convertase breaking C3 ... There are no current clinical trials for DPGN happening. Activating complement pathways plays a large role in ... There are currently drugs available that will target the complement pathway. It has been proposed that if fluorescently tagged ...
... an important complement factor responsible for the stabilization of the alternative C3 convertase, is deficient. There are ... such as the measurement of C3 and C4, do not detect low levels of the absence of properdin. These pathways are typically ... Pertaining to complement deficiencies, there is no cure and the treatments for complement deficiencies vary widely. The best ... Complement deficiencies are rare and currently not well characterized, so there has been difficulty detecting them. Currently, ...
Many of the specifics of this pathway are still being investigated. It is not yet known if Dab1 is phosphorylated as a result ... Francis PJ, Hamon SC, Ott J, Weleber RG, Klein ML (May 2009). "Polymorphisms in C2, CFB and C3 are associated with progression ... These different isoforms result from variations in alternative splicing. The transcript of type I VLDLR (VLDLR-I) is composed ... "The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family ...
In all three pathways of complement activation, there is a target for the protease to manipulate. In the classical pathway, ... the protein is cleaved two amino acid residues away from the native site that is recognized by the host C3 convertase. The ... Transcription is repressed by staphylococcal accessory regulator sarA and by alternative sigma factor σB (a stress response ... C3 is another major target of aureolysin. The active site has a high affinity for C3 and will cleave it into C3a and C3b ...
Frontiers | Soluble Mediators Regulating Immunity in Early Life
... which may be influenced by the striking neonatal deficiency of complement system proteins or enhanced neonatal production of ... The complement system, antibodies, and anti-microbial proteins and peptides can directly interact with potential pathogens, ... The complement system, antibodies, and antimicrobial proteins and peptides (APPs), can directly interact with potential ... and the alternative pathway in which spontaneous cleavage of the complement protein C3 can lead to its deposition on the ...
Estrogen suppresses cardiac IL-6 after trauma-hemorrhage via a hypoxia-inducible factor 1α-mediated pathway<...
Alternative Complement Pathway C3 C5 Convertase Medicine and Dentistry 15% View full fingerprint ... Estrogen suppresses cardiac IL-6 after trauma-hemorrhage via a hypoxia-inducible factor 1α-mediated pathway. Shock. 2009 Apr;31 ... Estrogen suppresses cardiac IL-6 after trauma-hemorrhage via a hypoxia-inducible factor 1α-mediated pathway. In: Shock. 2009 ; ... Estrogen suppresses cardiac IL-6 after trauma-hemorrhage via a hypoxia-inducible factor 1α-mediated pathway. / Nickel, Eike A ...
Complement cascade and its inhibitors | Abcam
Learn about the three pathways lead to complement activation and some of their key inhibitors. ... The alternative pathway is regulated by Factor H, CD55 and CD35, which inhibit the C3 convertase of the alternative pathway. ... The alternative pathway. The alternative pathway of complement activation is in a constant state of low-level activation (known ... C2a remains associated with C4b to form the classical pathway C3 convertase (C4b2a). C2a in the convertase complex cleaves C3 ...
S1: Chymotrypsin | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY
complement factor B Previous and unofficial names. alternative-complement pathway C3/C5 convertase , B-factor, properdin , BFD ... complement C1r Previous and unofficial names. complement C1r-A subcomponent , complement component 1, r subcomponent A , ... C1sb , complement component C1SB , r-gsp , Gm5077 , predicted gene 5077 , complement component 1 , complement component 1, s ... C2 , Factor B , H2-Bf , histocompatibility 2, complement component factor B , properdin factor B ...
Epigallocatechin-3-gallate regulates cell growth, cell cycle and phosphorylated nuclear factor-κB in human dermal fibroblasts<...
Alternative Pathway C3 Convertase C3 Convertase (C3bBb) C3 Convertase, Alternative Pathway Complement 3 Convertase, Alternative ... Alternative pathway complement C3 convertase Entry term(s):. Alternative Pathway C3 Convertase. C3 Convertase (C3bBb). C3 ... Complement C3-C5 Convertases, Alternative Pathway [D12.776.124.486.274.045.387.500] Complement C3-C5 Convertases, Alternative ... Complement C3 Convertase, Alternative Pathway [D12.776.124.486.274.045.387.500.374] Complement C3 Convertase, Alternative ...
Negative regulation of protein phosphatase 2Cβ by ISG15 conjugation<...
Alternative Complement Pathway C3 C5 Convertase Neuroscience 60% * Complement Factor B Immunology and Microbiology 60% ... In contrast to the wild type, this mutant suppressed the NF-κB pathway even in the presence of ISG15, UBE1L, and UbcH8. Thus, ... In contrast to the wild type, this mutant suppressed the NF-κB pathway even in the presence of ISG15, UBE1L, and UbcH8. Thus, ... In contrast to the wild type, this mutant suppressed the NF-κB pathway even in the presence of ISG15, UBE1L, and UbcH8. Thus, ...
Complement Factor D/Adipsin Human ELISA Kit - Invitrogen
Complement Factor D/Adipsin Human ELISA Kit from Invitrogen (96 Tests). Quantitate human Factor D in plasma, serum and ... Factor D cleaves factor B bound to C3b, generating the alternative pathway C3 convertase C3bBb and releasing the Ba fragment. ... Adipsin, C3 convertase activator, Properdin factor D, Complement factor D, complement factor D (adipsin), complement factor D ... Complement factor D is a serine protease of the alternative pathway of complement activation. The protein is a single chain ...
C3 - Overview: Complement C3, Serum
The complement system can be activated via immune complexes, and the alternative pathway (properdin pathway), which is ... C3 activation involves cleavage by C3 convertase into C3a and C3b.. When immune complexes are not involved, the alternate ... The primary complement pathway consists of recognition (Clq, Clr, Cls), activation (C4, C2, C3), and attack (C5, C6, C7, C8, C9 ... complement activation initiates the reactant sequence at C3,. bypassing C1, C4, and C2.. ...
Blockade of receptor activator of nuclear factor-κB (RANKL) signaling improves hepatic insulin resistance and prevents...
Alternative Complement Pathway C3 C5 Convertase Medicine and Dentistry 66% * Non Insulin Dependent Diabetes Mellitus ... and downstream inflammatory signaling pathways systemically and in the liver are key events in the etiology of hepatic insulin ... and downstream inflammatory signaling pathways systemically and in the liver are key events in the etiology of hepatic insulin ... and downstream inflammatory signaling pathways systemically and in the liver are key events in the etiology of hepatic insulin ...
Acute Poststreptococcal Glomerulonephritis: Practice Essentials, Background, Pathophysiology
... patterns for glomerular deposits indicates that C3 activation in APSGN is predominantly via the alternative pathway. [23, 24, ... 25] These findings suggest that the glomerular immune deposits of C3bBb convertase may be due to ongoing complement activation ... PA-Ag activates the alternative pathway.  This 43-kd protein was later identified by Yamakami et al as NAPlr.  These ... Complement fixation via the classic pathway leads to the generation of additional inflammatory mediators and recruitment of ...
Membranoproliferative glomerulonephritis type II (dense deposit disease): an update
... loss of complement regulation is caused by C3 nephritic factor, an autoantibody directed against the C3 convertase of the AP, ... The pathophysiologic basis of MPGN II is associated with the uncontrolled systemic activation of the alternative pathway (AP) ... The development of molecular diagnostic tools and new therapies directed at controlling the AP of the complement cascade either ... of the complement cascade. In most patients, ...
Acquired Partial Lipodystrophy: Background, Pathophysiology and Etiology, Epidemiology
Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ... prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. ... due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial ... in which subendothelial deposits of immunoglobulin and C3 are probably due to a deregulated alternative complement pathway. ...
Pesquisa | Portal Regional da BVS
The three complement pathways converge in the formation of C3-convertase followed by the assembly of a lethal pore-like ... It is activated via three pathways, termed Classical, Lectin and Alternative, which are mediated by antibodies, carbohydrate ... Key pathways that regulate neoblast/pluripotent cells, including the PI3K-Akt signalling pathway, are particularly dominant and ... our findings uncover new means by which a helminth parasite prevents the activation of the Lectin complement pathway to become ...
Serum proteome alterations during conventional and extracorporeal resuscitation in pigs | Journal of Translational Medicine |...
3c). Interestingly, complement 8 alpha chain, complement 9 and C3/C5 convertase from the alternative pathway showed the same ... Complement 1-4 and C3/C5 convertase of the classical pathway together with clusterin and vitronectin were associated with a ... 4c), which indicates activation of the complement system via the alternative pathway and consequently the formation of the ... Likewise, several components of the complement system (C1, C2, C3, C4 and C7) showed the same abundance behavior as described ...
Herpes simplex virus glycoproteins gC-1 and gC-2 bind to the third component of complement and provide protection against...
... activity for the alternative pathway C3 convertase of human complement. We show here that solubilized gC-1 binds to iC3- ... mAb specific for gC-1 or gC-2 and mutant viral strains were used to identify the C3-binding glycoproteins. In other experiments ... Herpes simplex virus glycoproteins gC-1 and gC-2 bind to the third component of complement and provide protection against ... Expression of gC-1 or gC-2 by isogenic insertion mutants provided protection against complement-mediated neutralization. These ...
Delves: Roitt's Essential Immunology
alternative pathway (of complement activation): Activation pathway involving complement components C3, factor B, factor D, and ... generates the alternative pathway C3 convertase C3bBb.. anaphylatoxin: A substance (e.g., C3a, C4a, or C5a) capable of directly ... classical pathway (of complement activation): Activation pathway involving complement components C1, C2, and C4 that, following ... produces the classical pathway C3 convertase C .. class switching: The process by which a B‐cell changes the class but not ...
Complement-Dependent Apoptosis and Inflammatory Gene Changes in Murine Lupus Cerebritis1 | The Journal of Immunology | American...
The role of complement activation in the brains of MRL/lpr lupus mice was determined using the potent C3 convertase inhibitor, ... Activation of C3 via the alternative pathway can induce TNF release (16), which is increased in the circulation of SLE patients ... The rodent complement protein, CR1-related y (Crry), is a potent inhibitor of the pivotal C3 convertase of the complement ... The role of complement activation in the brains of MRL/lpr lupus mice was determined using the potent C3 convertase inhibitor, ...
Genetics of Age-Related Macular Degeneration: Practice Essentials, Clinical Implications, Genetic Testing
... the alternative complement pathway by blocking formation and accelerating the decay of alternative pathway C3 convertases; it ... complement factor I (CFI), complement factor 9 (C9), and complement factor 3 (C3) genes.  ... 11] as well as other genes: factor B (BF)/complement component 2 (C2), [11, 12] complement component 3 (C3), [13, 14] and ... Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med. 2007 Aug 9. 357(6):553-61. [QxMD MEDLINE ...
Mechanism of Cold Agglutinin Disease (CAD) in the Complement Pathway
Watch a video to learn how C1 is activated initiating the classical complement pathway creating chronic hemolysis and ... The alternative pathway relies on separate factors to form C3 convertase. Once active, C3 convertase initiates the complement ... As you will recall, there are 3 distinct pathways that lead to complement activation. Normally, these pathways converge at C3 ... It also leads to activation of the classical complement pathway. Now we are going to talk about complement and complement ...
Mannose-Binding Protein-Associated Serine Proteases | Harvard Catalyst Profiles | Harvard Catalyst
Complement C3-C5 Convertases. *Complement C3-C5 Convertases, Alternative Pathway. *Complement C3-C5 Convertases, Classical ... They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE. ... Complement C3-C5 Convertases [D12.776.124.486.274.045.387]. *Mannose-Binding Protein-Associated Serine Proteases [D12.776. ... MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are ...
Kidney Biopsy of the Month: C3 Glomerulonephritis - Renal Fellow Network
Genetic testing may uncover mutations in components of the alternative pathway of complement such as CFH, CFI, MCP/CD46, and ... called C3 nephritis factor (C3NeF), which stabilize the convertase and lead to pathway overactivation. C3NeF is also commonly ... Complement C3 levels are often decreased, but a normal C3 level does not exclude C3GN. C4 levels are usually normal. C3NeF is ... characterized by dominant C3 deposition resulting from overactivation of the alternative pathway of complement (APC) from ...
Complement Deficiencies: Background, Pathophysiology, Epidemiology
The complement system plays an important part in defense against pyogenic organisms. ... The complement system is part of the innate immune system. ... of the enzyme C3 convertase of the alternative pathway. ... The pathways include the classical pathway (C1qrs, C2, C4), the alternative pathway (C3, factor B, properdin), and the lectin ... Zipfel PF, Heinen S, Jozsi M, Skerka C. Complement and diseases: defective alternative pathway control results in kidney and ...
Cluster analysis identifies distinct pathogenetic patterns in c3 glomerulopathies/immune complex-Mediated membranoproliferative...
Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) ... Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition ... Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) ... In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway ...
complement | DownHouseSoftware
... complement can be activated through three somewhat distinct pathways, each one converging at a C3 Convertase. Complement will ... Antibody Triggers the Classical Pathway; Carbohydrates Trigger the Lectin Pathway; The Alternative Pathway is triggered ... a cascade of events leads to the assembly of a C3 Convertase, which breaks C3 into the soluble anaphylatoxin C3a and the ... which precipitates onto the surface of the cell and forms a component of additional C3 convertase, thus amplifying the reaction ...
Initial findings suggest that complement-targeted treatments could help with IgA.
... and alternative (AP) pathways (AP). Each pathway converges on C3 cleavage to produce the anaphylatoxin C3a and active fragment ... C3(H2 O), resulting in the formation of fluid phase C3 convertase and therefore enhancing complement activation. This C3 ... Complement, IgA nephropathy, Alternative complement pathway, Mannan binding lectin complement pathway, IgAN pathogenesis, IgAN ... It is primarily regulated by complement Factor H (CFH), which, in cooperation with Factor I, degrades C3 to an inactive version ...
Activation of the Classical Complement Pathway - Immunology
A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions ... This C3 convertase molecule is distinct from that within the alternative pathway, but it is from this point onwards that ... ACTIVATION OF THE CLASSICAL COMPLEMENT PATHWAY. A complement cascade similar to that of the alternative pathway can be ... The functions of the classical complement pathway are similar to those described for the alternative pathway, i.e. opsonization ...
Adipsin (Complement Factor D) - Nexelis, a Q² Solutions Company
... which is the alternative pathway C3 convertase. Human complement factor D is synthesized as a 253 amino acid precursor that ... Complement factor D deficiency is associated with low activity of the alternative complement pathway and low capacity to ... Three pathways of complement activation (classical, lectin, and alternative) exist. These pathways converge in the generation ... is a serine protease that is indispensable for the initiation of complement activation via the alternative pathway. Upon ...
... alternative, and lectin . Proteolytic cleavage of C3 by C3 convertase represents the final common pathway of the three ... it is conceivable that targeting more proximate complement pathway targets in the upstream activation cascades (e.g. C3 or C4) ... The binding of C3b to C3 convertase generates C5 convertase, which in turn cleaves C5 to generate the terminal anaphylatoxins, ... Complement activation pathways: a bridge between innate and adaptive immune responses in asthma. Proc Am Thorac Soc 2007; 4: ...
Human C3c from Active Bioscience
Human C3c Complement C3c, Complement Component C3c, C3c. ... the C3b fragment which is part of the alternative C3 convertase ... hC3c plays an important role in both complement activation pathways, with different specific proteolytic systems cleaving it to ... C3 levels can be low because of decreased synthesis or due to consumption. High C3 levels are seen in highly acute or chronic ... form C3 convertase. Cleavage of C3 releases C3a and ... Unwanted complement activation is a major cause of tissue ...
ProteinsProperdinC3bBbCleavageLectin pathway of complement activationAnaphylatoxinActivatorSerumFactorSerineMoleculesInhibitorComponentCascadeC4b2aDepositionFragmentCleavesLead to complementRole of complementInflammatoryMoleculeDysregulationGenesInhibitionPatientsKnown as the complementAdaptiveProteinAntibodiesGlomerulopathyPathogensActivation of the alternative pathwayPathogenesisDownstreamBindsHemolytic activityAntibodyBiopsyActivateAntigenImmune complexesInnate immuneMembraneRegulationSystemFluid-phaseDistinctSystemicCD46ClassicalGenetic
- The complement system, antibodies, and anti-microbial proteins and peptides can directly interact with potential pathogens, protecting against systemic infection. (frontiersin.org)
- The ontogeny of plasma factors can be viewed in the context of a lower effectiveness of immune responses to infection and immunization in early life, which may be influenced by the striking neonatal deficiency of complement system proteins or enhanced neonatal production of the anti-inflammatory cytokine IL-10, among other ontogenic differences. (frontiersin.org)
- Additionally, several classes of proteins, including immunoglobulins (Igs), the complement system, and anti-microbial proteins and peptides (APPs), aid in the innate response to invading microorganisms and display age-dependent maturation (Figure 1 ). (frontiersin.org)
- Lower levels of complement proteins and anti-microbial proteins and peptides contribute to neonatal susceptibility to infection, while elevated levels of adenosine, adiponectin, and adrenomedullin in neonatal blood may influence immune cell polarization. (frontiersin.org)
- Prominent deposition of complement proteins C3 and C9 in brains of MRL/ lpr mice was indicative of complement activation and was significantly reduced by Crry. (aai.org)
- Genes that encode the proteins of complement components or their isotypes are distributed throughout different chromosomes, with 19 genes comprising 3 significant complement gene clusters in the human genome. (medscape.com)
- The important components of this system are various cell membrane-associated proteins such as complement receptor 1 (CR1), complement receptor 2 (CR2), and decay accelerating factor (DAF). (medscape.com)
- In IgA nephropathy, complement proteins in the circulation have also been studied and found to have predictive relevance. (alliedacademies.org)
- The host proteins that serve key regulatory functions within the alternative pathway (DAF, CR1 factor I, CD59) also serve similar functions within the classical pathway. (pharmacy180.com)
- The complement system comprises approximately 30 circulating plasma proteins, as well as cell-surface receptors, that function as part of the innate and adaptive immune system to eliminate pathogens. (nexelis.com)
- Complement consists of over 50 proteins that either circulate in blood, the lymph and interstitial fluids, or are expressed on cells in mostly pro-enzyme and non-activated states. (hapres.com)
- Inside our strategy, we utilized the isoprenoid biosynthesis inhibitor fosmidomycin to handle the function of proteins prenylation as an important function of isoprenoids in isoprenoid biosynthesis via the MEP pathway creates the isoprenyl precursors for proteins prenylation which nonprenylated proteins are mislocalized upon fosmidomycin treatment. (globaltechbiz.com)
- The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. (embl.de)
- These modules have been identified more than 140 times in over 20 proteins, including 12 proteins of the complement system. (embl.de)
- The complement system can be activated via immune complexes, and the alternative pathway (properdin pathway), which is activated primarily by foreign bodies such as microorganisms. (mayocliniclabs.com)
- Activation pathway involving complement components C3, factor B, factor D, and properdin that, in the presence of a stabilizing activator surface such as microbial polysaccharide, generates the alternative pathway C3 convertase C3bBb. (roitt.com)
- This C3 convertase is stabilised by Properdin. (alliedacademies.org)
- With Bb, CVF forms the CVFBb complex, a COMPLEMENT C3 convertase with a half-life of 7 h at body temperature as compared to 1.5 min for the C3bBb complex. (bvsalud.org)
- Factor D cleaves factor B bound to C3b, generating the alternative pathway C3 convertase C3bBb and releasing the Ba fragment. (thermofisher.com)
- Upon activation through reversible substrate-induced conformational change into an active enzyme, factor D functions to cleave the C3b-bound factor B, resulting in the formation of C3bBb complex, which is the alternative pathway C3 convertase. (nexelis.com)
- Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. (cusabio.com)
- Following these cleavage events, complement pathway activation continues as in the classical pathway. (abcam.com)
- C3 activation involves cleavage by C3 convertase into C3a and C3b. (mayocliniclabs.com)
- Each pathway converges on C3 cleavage to produce the anaphylatoxin C3a and active fragment C3b once activated [ 1 ][ 2 ]. (alliedacademies.org)
- Cleavage of C3 releases C3a and the C3b fragment which is part of the alternative C3 convertase. (active-bioscience.de)
- This culminates in the cleavage of the core complement effector molecules C3 and C5 into the bio-active anaphylatoxins C3a and C5a and the opsonins C3b and C5b. (hapres.com)
Lectin pathway of complement activation2
- Mannan-binding lectin (MBL) and MBL-associated serine proteases (MASPs) are involved in the initial step of the lectin pathway of complement activation. (abcam.com)
- The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. (harvard.edu)
- Once triggered, a cascade of events leads to the assembly of a C3 Convertase, which breaks C3 into the soluble anaphylatoxin C3a and the insoluble C3b, which precipitates onto the surface of the cell and forms a component of additional C3 convertase, thus amplifying the reaction, and also a C5 convertase. (downhouse.software)
- Severe recurrent bacterial infections occur in patients with homozygous C3 deficiency and in those patients with low levels of C3 secondary to the absence of C3b activator. (mayocliniclabs.com)
- MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked. (harvard.edu)
- The Human Complement Factor D (Adipsin/CFD) ELISA quantitates Hu Complement Factor D in human serum, plasma, or cell culture medium. (thermofisher.com)
- Serum serine proteases which participate in COMPLEMENT ACTIVATION. (harvard.edu)
- We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. (unimib.it)
- Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1-3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. (unimib.it)
- Likely the most exciting observation though about intracellular complement-coined the complosome to set it apart from the liver-derived and serum-circulating complement system  -is the finding that it unexpectedly serves key roles in single cell metabolism [12, 14,15] . (hapres.com)
- A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB . (bvsalud.org)
- Cobra venom factor (CVF) is a COMPLEMENT C3B analog. (bvsalud.org)
- In this study, we found that protein phosphatase 2Cβ (PP2Cβ), which functions in the nuclear factor κB (NF-κB) pathway via dephosphorylation of TGF-β-activated kinase, was ISGylated, and analysis by NF-κB luciferase reporter assay revealed that PP2Cβ activity was suppressed by co-expression of ISG15, UBE1L, and UbcH8. (elsevier.com)
- The assay will exclusively recognize both natural and recombinant Hu Complement Factor D. (thermofisher.com)
- The Human Complement Factor D solid-phase sandwich ELISA (enzyme-linked immunosorbent assay) is designed to measure the amount of the target bound between a matched antibody pair. (thermofisher.com)
- Complement factor D is a serine protease of the alternative pathway of complement activation. (thermofisher.com)
- There is compelling evidence that activation of the transcription factor nuclear factor-κB (NF-κB) and downstream inflammatory signaling pathways systemically and in the liver are key events in the etiology of hepatic insulin resistance and β-cell dysfunction, although the molecular mechanisms involved are incompletely understood. (unicatt.it)
- In most patients, loss of complement regulation is caused by C3 nephritic factor, an autoantibody directed against the C3 convertase of the AP, but in some patients, mutations in the factor H gene have been identified. (nih.gov)
- The common coding variant Y402H in the complement factor H ( CFH ) gene was the first identified. (medscape.com)
- [ 21 ] Such rare variants have been described in the complement factor H ( CFH ), complement factor I ( CFI ), complement factor 9 ( C9 ), and complement factor 3 ( C3) genes. (medscape.com)
- The most common mechanism of APC overactivation is development of autoantibodies to C3 convertase, called C3 nephritis factor (C3NeF), which stabilize the convertase and lead to pathway overactivation. (renalfellow.org)
- A North African study of molecular basis of complement factor I deficiency in atypical hemolytic and uremic syndrome patients suggested that the Ile357Met mutation may be a founding effect. (medscape.com)
- It is primarily regulated by complement Factor H (CFH), which, in cooperation with Factor I, degrades C3 to an inactive version known as iC3b (FI). (alliedacademies.org)
- Complement factor D, also known as adipsin, is a serine protease that is indispensable for the initiation of complement activation via the alternative pathway. (nexelis.com)
- Human complement factor D is synthesized as a 253 amino acid precursor that contains a signal peptide (aa 1-20), a five-residue activation/pro-peptide (aa 21-25), and the mature chain (aa 26-253). (nexelis.com)
- Complement factor D deficiency is associated with low activity of the alternative complement pathway and low capacity to opsonize bacteria. (nexelis.com)
- The Complement Factor D assay employs the quantitative sandwich enzyme immunoassay technique. (nexelis.com)
- Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. (nexelis.com)
- This process has been attributed to tissue factor (TF) mediated thrombin generation and formation of fibrin clots (extrinsic pathway) [ 3 , 4 ]. (scholars.direct)
- The solution structure of the 16th CCP module from human complement factor H has been determined by a combination of 2-dimensional nuclear magnetic resonance spectroscopy and restrained simulated annealing. (embl.de)
- The present study aimed to assess whether Bothrops jararacussu and Bothrops pirajai crude venoms and their isolated toxins, namely serine protease (BjussuSP-I) and L-amino acid oxidase (BpirLAAO-I), modulate human complement system pathways. (biomedcentral.com)
- C1 is the first molecule in the classical complement cascade and comprises C1q and two molecules of C1r and C1s respectively. (abcam.com)
- Crry prevented the increased expression of these inflammatory molecules, indicating that the changes were complement dependent. (aai.org)
- Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections. (harvard.edu)
- Note that, in the absence of antibody, many of the molecules that activate the complement system are carbohydrate or lipid in nature (e.g. lipopolysaccharides, mannose), suggesting that the system evolved mainly to recognize bacterial surfaces via their non-protein features. (pediagenosis.com)
- The role of complement activation in the brains of MRL/ lpr lupus mice was determined using the potent C3 convertase inhibitor, CR1-related y (Crry), administered both as an overexpressing Crry transgene and as Crry-Ig. (aai.org)
- Recruitment of Human C1 Esterase Inhibitor Controls Complement Activation on Blood Stage Plasmodium falciparum Merozoites. (harvard.edu)
- Endogenous and natural complement inhibitor attenuates myocardial injury and arterial thrombogenesis. (harvard.edu)
- The antimalarial agent fosmidomycin is a validated inhibitor from the nonmevalonate isoprenoid biosynthesis (methylerythritol 4-phosphate [MEP]) pathway in the malaria parasite, isoprenoid biosynthesis produces the isoprenyl substrates for protein prenylation. (globaltechbiz.com)
- The complement system is a heat-labile component of blood that confers bactericidal properties. (abcam.com)
- Herpes simplex virus glycoproteins gC-1 and gC-2 bind to the third component of complement and provide protection against complement-mediated neutralization of viral infectivity. (silverchair.com)
- These 3 pathways converge at the component C3. (medscape.com)
- Complement is an ancient component of our innate immune system that was initially discovered in the 19th century and named for its ability to complement antibody in the lysis of cells. (downhouse.software)
- Complement C3c, Complement Component C3c, C3c. (active-bioscience.de)
- Human Complement component C3c (hC3c) derived from human plasma consist of 3 peptides with a total molecular mass of 138 KDa. (active-bioscience.de)
- C3 (MW 180 000), the central component of all complement reac- tions, split by its convertase into a small (C3a) and a large (C3b) fragment. (pediagenosis.com)
- The pathophysiologic basis of MPGN II is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade. (nih.gov)
- The development of molecular diagnostic tools and new therapies directed at controlling the AP of the complement cascade either locally in the kidney or at the systemic level may lead to effective treatments for MPGN II. (nih.gov)
- Several genes not involved in the complement cascade have also been implicated. (medscape.com)
- Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.com)
- New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. (medscape.com)
- The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)
- These findings point to the complement cascade as a viable therapy target for chronic renal disease. (alliedacademies.org)
- A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions. (pharmacy180.com)
- Sensing of pathogens or danger by one or more of the three activation pathways, the classical, the lectin, or the alternative complement pathway, triggers activation of the system in a cascade-like fashion. (hapres.com)
- C2a remains associated with C4b to form the classical pathway C3 convertase (C4b2a). (abcam.com)
- C3GN is a type of glomerulonephritis characterized by dominant C3 deposition resulting from overactivation of the alternative pathway of complement (APC) from acquired or hereditary causes. (renalfellow.org)
- Overactivation of the APC leads to deposition of C3 in the glomeruli, which can lead to an inflammatory reaction and resulting glomerular injury. (renalfellow.org)
- Interestingly, it has been noted that some patients with post-infectious glomerulonephritis show persistent C3 deposition instead of fully recovering, and this so-called "resolving/atypical" post-infectious glomerulonephritis is thought to represent the development of C3GN in patients with APC abnormalities. (renalfellow.org)
- The presence of C3 distinguishes IgA nephropathy from glomerular IgA deposition in the asymptomatic stage. (alliedacademies.org)
- The classical pathway can additionally lead to complement protein deposition on insoluble antibody- antigen immune complexes circulating within blood, and in doing so promote the clearance of such potentially harmful complexes by Kupffer cells of the liver. (pharmacy180.com)
- a single activation event (whether by antibody or via innate pathways) leads to the production of many downstream events, such as deposition of C3b. (pediagenosis.com)
- The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX . (nih.gov)
- C2a in the convertase complex cleaves C3 releasing C3a and C3b. (abcam.com)
- The C1s subunit then enzymically cleaves the bound C2a to generate on the membrane a new complex termed C4b2b, which is the C3 convertase of the classical pathway. (pharmacy180.com)
Lead to complement1
- Learn about the three pathways lead to complement activation and some of their key inhibitors. (abcam.com)
Role of complement2
- Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)
- Work on better defining the instructive role of complement on adaptive immune cells led to the somewhat surprising finding that these complement effects were mostly independent of liver-derived complement but rather mediated by locally produced and activated complement-for example, C3 and C5 secreted by APCs and then activated in the extracellular space [8-10] . (hapres.com)
- The functions of complement include the attraction of inflammatory cells, opsonization to promote phagocytosis, immune complex clearance and direct microbial killing through the formation of the membrane attack complex (MAC). (abcam.com)
- Complement activation releases inflammatory mediators that can induce apoptosis. (aai.org)
- Activation of the complement system plays an important role in the regulation of immune and inflammatory reactions, and contributes to inflammatory responses triggered by envenomation provoked by Bothrops snakes. (biomedcentral.com)
- C5 (MW 180 000), split by its convertase into C5a, a small peptide that, together with C3a (anaphylatoxins), acts on mast cells, polymorphs and smooth muscle to promote the inflammatory response, and C5b, which initiates the assembly of C6, 7, 8 and 9 into the membrane damaging or 'lytic' unit. (pediagenosis.com)
- Our results indicate that TLR2 is the major pathway of pro-inflammatory signalling in ZIA and is necessary for the development of specific immune responses to zymosan. (biomedcentral.com)
- This C3 convertase molecule is distinct from that within the alternative pathway, but it is from this point onwards that parallels can be drawn between the two cascades. (pharmacy180.com)
- These mutations also cause complement dysregulation in the setting of atypical hemolytic uremic syndrome. (renalfellow.org)
- INTRODUCTION: C3 glomerulopathy (C3G) is an ultrarare, chronic and progressive nephropathy mediated by dysregulation of the alternative pathway of complement (AP), with poor prognosis and limited treatment options. (imperial.ac.uk)
- INTRODUCTION: C3 glomerulopathy (C3G) is a rare, progressive kidney disease resulting from dysregulation of the alternative pathway (AP) of complement. (imperial.ac.uk)
- Complement alternative pathway (AP) dysregulation has been implicated in geographic atrophy, an advanced form of age-related macular degeneration. (arvojournals.org)
- Genes encoding products involved in complement control and interaction with immune complexes are found within these regions. (alliedacademies.org)
- These findings present the exciting possibility that complement inhibition is a therapeutic option for lupus cerebritis. (aai.org)
- 1. Berentsen S. Complement activation and inhibition in autoimmune hemolytic anemia: focus on cold agglutinin disease. (understandingcad.com)
- For complement-driven C3GN, a variety of treatments have been attempted but inhibition of complement with anti-C5 therapy has been effective in a subset of patients, and plasmapheresis has been used for autoantibody-mediated disease. (renalfellow.org)
- The severity of inflammation, joint histology, lymphocyte proliferation and antibody production in response to zymosan were analyzed in mice deficient in TLR2 and complement C3, and the effects of Dectin-1 inhibition by laminarin were studied. (biomedcentral.com)
- In many patients, the development of C3GN is preceded by a complement-amplifying condition such as an infection. (renalfellow.org)
- Deficiencies in complement predispose patients to infection via 2 mechanisms: (1) ineffective opsonization and (2) defects in lytic activity (defects in MAC). (medscape.com)
- In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. (unimib.it)
- Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. (unimib.it)
- Both CH50 and free eculizumab level markers look promising for the monitoring of complement blockade in patients with PNH receiving eculizumab. (ashpublications.org)
Known as the complement2
- In cold agglutinin disease, certain abnormal bone marrow cells produce antibodies called cold agglutinins, which activate a part of the immune system known as the complement pathway. (understandingcad.com)
- The sushi domain is also known as the complement controle protein (CCP) module or the short consensus repeat (SCR). (embl.de)
- The complement system is a key player in innate immunity as well as a powerful link between innate and adaptive immunity. (alliedacademies.org)
- Activation of complement can be started either via adaptive or innate immune recognition. (pediagenosis.com)
- Although complement was initially considered only a key constituent of innate immunity, due to its critical role in delivering co-stimulatory signals via engagement of complement receptors on antigen presenting cells (APCs) or directly on B and T cells, it is now also widely recognized as a required functional bridge between innate and adaptive immunity [5-7] . (hapres.com)
- In the light of the above findings, we have re-investigated ZIA to elucidate the roles of the innate and adaptive immune responses in this model and to compare the effects of TLR2 deficiency and complement C3 deficiency. (biomedcentral.com)
- Furthermore, microarray analysis revealed complement-dependent up-regulation of glutamate receptor (AMPA-GluR) expression in lupus brains, which was also validated for AMPA-GluR1 mRNA and protein. (aai.org)
- The pathway starts with a protein called C1 binding to the red blood cell. (understandingcad.com)
- The classical pathway is triggered by interaction of the Fc portion of an antibody (immunoglobulin [Ig] M, IgG1, IgG2, IgG3) or C-reactive protein with C1q. (medscape.com)
- Once this occurs, a complement protein termed C1 (which comprises a single C1q subunit, two C1r subunits and two C1s subunits) binds to adjacent Fc domains in the antibody-antigen complex. (pharmacy180.com)
- A further complement protein, C2, binds to this membrane complex to give C4b2. (pharmacy180.com)
- Three-dimensional structure of a complement control protein module in solution. (embl.de)
- The complement control protein (CCP) modules (also known as short consensus repeats) are defined by a consensus sequence within a stretch of about 60 amino acid residues. (embl.de)
- the classical pathway initiated by antibodies bound to the surface of foreign bodies and the alternative and lectin pathways that provide an antibody-independent mechanism for complement activation, induced by the presence of bacteria and other micro-organisms. (abcam.com)
- In other experiments, HSV-1 mutant strains and recombinants, differing only in their expression of gC, were tested for sensitivity to neutralization by human complement in the presence or absence of antibodies specific for HSV gD. (silverchair.com)
- The antibodies that activate the classical complement pathway are IgM and IgG. (pharmacy180.com)
- Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). (unimib.it)
- The complement system is a powerful arm of innate immunity that protects tissues against invading pathogens. (aai.org)
- Although the complement system is part of the body's innate, relatively nonspecific defense against pathogens, its role is hardly primitive or easily understood. (medscape.com)
- Complement will lead to direct cell death via pore formation (MAC complex formation), it will recruit leukocytes to the area of infection via chemotaxis, and will facilitate phagocytosis of pathogens via complement receptor-mediated endocytosis. (downhouse.software)
- These pathways converge in the generation of the C3 convertase, which is responsible for the initiation of a series of events leading to the generation of bacterial opsonin (that facilitates the phagocytosis of opsonized pathogens), anaphylatoxins (that mediate inflammation), and the formation of the terminal membrane attack complex (that induces the lysis of pathogens or cells). (nexelis.com)
- The classical complement system is engrained in the mind of scientists and clinicians as a blood-operative key arm of innate immunity, critically required for the protection against invading pathogens. (hapres.com)
- Regions of the body that are not protected by skin (such as the eyes and mucus membranes) have alternative methods of defense, such as tears and mucus secretions that trap and rinse away pathogens, and cilia in the nasal passages and respiratory tract that push the mucus with the pathogens out of the body. (ubooks.pub)
Activation of the alternative pathway1
- Arthritis was induced by intra-articular injection of zymosan and was thought to be mediated by activation of the alternative pathway of complement and the release of lysosomal hydrolases from activated macrophages [ 6 ]. (biomedcentral.com)
- In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). (medscape.com)
- The cobra venom-derived enzyme causes continuous COMPLEMENT ACTIVATION and depletion of downstream complement components. (bvsalud.org)
- Metabolism plays an integral role in CD4 + T cell responses with naïve cells, the various effector cell subtypes (for example, T helper type (Th) 1, Th2, Th17 and regulatory T cells), and memory T cells each utilizing their own constellation of metabolic pathways, with differing dependences on influx/efflux of nutrients, their subsequent usage and the generation of downstream metabolic products. (hapres.com)
- The latter binds to the C3 convertase complex to form C4b2a3b, the classical pathway C5 convertase. (abcam.com)
- Lyophilized venom and toxin samples solubilized in phosphate buffered saline were diluted in appropriate buffers to evaluate their hemolytic activity on the alternative and classical pathways of the complement system. (biomedcentral.com)
- At the highest concentration tested (120 μg/mL), B. jararacussu and B. pirajai crude venoms inhibited the hemolytic activity of the classical pathway (65.3 % and 72.4 %, respectively) more strongly than they suppressed the hemolytic activity of the alternative pathway (14.2 and 13.6 %, respectively). (biomedcentral.com)
- BpirLAAO-I (50 μg/mL) inhibited 24.3 and 12.4 % of the hemolytic activity of the classical and alternative pathways, respectively. (biomedcentral.com)
- The kinetic microassay described herein is useful to assess the effect of venoms and toxins on the hemolytic activity of the complement system. (biomedcentral.com)
- The alternative pathway is activated in an antibody-independent manner. (medscape.com)
- Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)
- Recent case reports demonstrating the efficacy of the humanised anti-C5 monoclonal antibody eculizumab support this notion, but more research into the involvement of complement in IgA nephropathy is needed to guide future treatment strategies. (alliedacademies.org)
- However, in contrast to the alternative pathway the activation step in the classical pathway requires specific antibody-antigen interactions. (pharmacy180.com)
- The essential feature is the requirement for a specific antigen-antibody interaction, leading via components C1, C2 and C4 to the formation of a 'convertase' which splits C3. (pediagenosis.com)
- The diagnosis requires a kidney biopsy, with routine immunofluorescence microscopy demonstrating dominant or co-dominant IgA immunodeposits, generally with complement C3, and occasionally IgG and IgM. (alliedacademies.org)
- In renal biopsy specimens, markers indicating the activation of the alternative and mannan-binding lectin (MBL) pathways are linked to disease activity and portend a worse renal outcome. (alliedacademies.org)
- Complement and clinical biomarkers, biopsy composite score, and activity and chronicity indices were assessed at baseline and analyzed by pairwise Spearman correlation analysis. (imperial.ac.uk)
- Complement activity can activate C5, leading to intravascular hemolysis and chronic inflammation. (understandingcad.com)
- In the classical pathway the initiating step is the specific binding of IgG or IgM to antigen. (pharmacy180.com)
- Ig IgM and some subclasses of IgG (in the human, IgG1-IgG3), when bound to antigen are recognized by Clq to initiate the classic pathway. (pediagenosis.com)
- When immune complexes are not involved, the alternate method of complement activation initiates the reactant sequence at C3, bypassing C1, C4, and C2. (mayocliniclabs.com)
- The complement system is part of the innate immune system. (medscape.com)
- If not controlled, this process can rapidly amplify, leading to the activation of the terminal pathway, which is marked by the release of C5a and the creation of the membrane attack complex (MAC - C5b9). (alliedacademies.org)
- The functions of the classical complement pathway are similar to those described for the alternative pathway, i.e. opsonization, leucocyte activation and membrane lysis of target cells. (pharmacy180.com)
- The term "nocturnal" refers to the belief that hemolysis is triggered by acidosis during sleep and activates complement to hemolyze an unprotected and abnormal RBC membrane. (medscape.com)
- CD46( MCP) derived to the autophosphorylation membrane of a central vein translocates it from cytoplasmic server by planning cessation of C3b and C4b, and understood membrane of CD46 on arising receptors may include to Landmark pathway( Elward K et al. (evakoch.com)
- Noris M, Remuzzi G. Overview of complement activation and regulation. (understandingcad.com)
- Recent work, however, has defined a novel and unexpected role for an intracellular complement system-the complosome-in the regulation of key metabolic events that underlie peripheral human T cell survival as well as the induction and cessation of their effector functions. (hapres.com)
- The complement system is an integral part of the body's immune defenses. (mayocliniclabs.com)
- Rare genetic variants in the complement system have also been found to play an important role in AMD. (medscape.com)
- The complement system plays an important part in defense against pyogenic organisms. (medscape.com)
- These findings underscore the duality of the complement system. (medscape.com)
- Knowledge about the complement system is expanding. (medscape.com)
- An intricate system regulates complement activity. (medscape.com)
- In physiological situations, the AP is always active at low levels and is responsible for complement system functioning. (alliedacademies.org)
- To confirm complement system activation, complement-dependent human neutrophil migration was examined using the Boyden chamber model. (biomedcentral.com)
- Together, the results of the kinetics of hemolysis and the neutrophil chemotaxis assay suggest that pre-activation of the complement system by B. jararacussu and B. pirajai crude venoms consumes complement components and generates the chemotactic factors C3a and C5a. (biomedcentral.com)
- This review summarizes the current knowledge about the emerging vital role of the complosome in T cell metabolism and discusses how viewing the evolution of the complement system from an "unconventional" vantage point could logically account for the development of its metabolic activities. (hapres.com)
- The complement system is generally considered among the evolutionary oldest parts of our immune system. (hapres.com)
- The growing notion that compartmentalization of complement-mediated activity in immunity may exist was then supported by the discovery of an intracellularly generated and functioning complement system in human CD4 + and CD8 + T cells [11,12] . (hapres.com)
- Further, and based on those new aspects of complement activity, we move into more uncharted areas and discuss a hypothetical alternative to the currently accepted model on how the complement system may have evolved and finally outline some of the key questions and challenges in this exciting new research area. (hapres.com)
- These structural changes allow Factors B (FB) and D (FD) to bind to the bioactive form of C3, C3(H2 O), resulting in the formation of fluid phase C3 convertase and therefore enhancing complement activation. (alliedacademies.org)
- In summary, complement can be activated through three somewhat distinct pathways, each one converging at a C3 Convertase. (downhouse.software)
- Decreased C3 may be associated with acute glomerulonephritis, membranoproliferative glomerulonephritis, immune complex disease, active systemic lupus erythematosus, septic shock, and end-stage liver disease. (mayocliniclabs.com)
- A decrease in C3 levels to the abnormal range is consistent with disease activation in systemic lupus erythematosus (SLE). (mayocliniclabs.com)
- Systemic complement AP activation was evident by reduced median concentrations of C3 and C5, elevated sC5b-9, and normal C4, relative to reference ranges. (imperial.ac.uk)
- Genetic testing may uncover mutations in components of the alternative pathway of complement such as CFH, CFI, MCP/CD46, and CFHR. (renalfellow.org)
- Complement is found in the bloodstream in a physiologically inactive state and can be triggered by three mechanisms: the classical (CP), lectin (LP), and alternative (AP) pathways (AP). (alliedacademies.org)
- Key steps in the activation of the classical pathway are shown in Figure 9.7, where this pathway is also compared to the alternative pathway. (pharmacy180.com)
- The presence of two complement pathways provides for rapid (alternative) and specific (classical) activation of a key defence mechanism, and offers greater protection against the development of microbial resistance mechanisms. (pharmacy180.com)
- Three pathways of complement activation (classical, lectin, and alternative) exist. (nexelis.com)
- Its function is homologous to that of C1s in the classical pathway. (cusabio.com)
- C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. (nih.gov)
- However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. (unimib.it)
- Complement plays a key role in the aetiology of IgA nephropathy, according to mounting clinical, genetic, and biochemical evidence. (alliedacademies.org)