Complement c5b. Medical search

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Antibodies produced by a single clone of cells.

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

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

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

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

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

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

Established cell cultures that have the potential to propagate indefinitely.

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

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

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

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

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

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

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

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

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

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

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

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

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

Proteins prepared by recombinant DNA technology.

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

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

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

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

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

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

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

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

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

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

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

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

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

Proteins found in any species of bacterium.

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

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

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

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

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

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

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

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

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

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

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

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

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

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

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

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

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

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

Glycoproteins found on the membrane or surface of cells.

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

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

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

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

The rate dynamics in chemical or physical systems.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Immunoglobulins produced in a response to BACTERIAL ANTIGENS.

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

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

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

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

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

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

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

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

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

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

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

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

Mechanism of complement-dependent haemolysis via the lectin pathway: role of the complement regulatory proteins. (1/26)

Mannan-binding lectin (MBL) is an acute phase protein which activates the classical complement pathway at the level of C4 and C2 via two novel serine proteases homologous to C1r and C1s. We recently reported that haemolysis via this lectin pathway requires alternative pathway amplification. The present experiments sought to establish the basis for this requirement, and hence focused on the activity and regulation of the C3 convertases. Complement activation was normalized between the lectin and classical pathways such that identical amounts of bound C4 and of haemolytically active C4,2 sites were present on the indicator cells. Under these conditions, there was markedly less haemolysis, associated with markedly less C3 and C5 deposited, via the lectin pathway than via the classical pathway, particularly when alternative pathway recruitment was blocked by depletion of factor D. Lectin pathway activation was associated with enhanced binding in the presence of MBL of complement control proteins C4bp and factor H to C4b and C3b, respectively, with decreased stability of the C3-converting enzyme C4b,2a attributable to C4bp. Immunodepletion of C4bp and/or factor H increased lectin pathway haemolysis and allowed lysis to occur in absence of the alternative pathway. Thus, the lectin pathway of humans is particularly susceptible to the regulatory effects of C4bp and factor H, due at least in part to MBL enhancement of C4bp binding to C4b and factor H binding to C3b. (+info)

Glomerular complement regulation is overwhelmed in passive Heymann nephritis. (2/26)

BACKGROUND: An injection of anti-Fx1A antibodies in rats leads to passive Heymann nephritis (PHN), a model of membranous nephropathy. Fx1A is a crude extract of renal cortex that contains megalin as a principal component. However, when rats are given anti-megalin antibodies, abnormal proteinuria does not occur. Because of the established complement dependence of PHN, we hypothesized that antibodies neutralizing complement regulatory proteins in the rat glomerulus also were required to induce PHN. Two likely targets are Crry and CD59, proteins abundant on the rat podocyte and contained within Fx1A that inhibit the C3 convertase and C5b-9 assembly, respectively. METHODS: Rats were injected with anti-megalin monoclonal antibodies, followed by anti-Crry and/or anti-CD59 F(ab')(2) antibodies five days later. In a second group of experiments, rats were injected with anti-Fx1A or anti-Fx1A immunodepleted of reactivity against Crry and/or CD59. RESULTS: In the setting of podocyte-associated anti-megalin monoclonal antibodies, simultaneous neutralization of Crry and CD59 function led to the development of significant proteinuria (11.0 +/- 2.1 mg/day, P < 0.001 vs. all other groups). In contrast, animals that had neither or only one of these complement regulators inhibited had normal urinary protein excretion (< or =6 mg/day). In animals given anti-Fx1A depleted of anti-Crry and/or anti-CD59, all groups developed typical PHN, characterized by heavy proteinuria and extensive glomerular deposition of C3 and C5b-9. CONCLUSION: Crry and CD59 play an important role in restraining complement-mediated injury following subepithelial immune complex deposition; however, in PHN, their regulatory capacity is overwhelmed. (+info)

Role of membrane cofactor protein (CD46) in regulation of C4b and C3b deposited on cells. (3/26)

C4b and C3b deposited on host cells undergo limited proteolytic cleavage by regulatory proteins. Membrane cofactor protein (MCP; CD46), factor H, and C4b binding protein mediate this reaction, known as cofactor activity, that also requires the plasma serine protease factor I. To explore the roles of the fluid phase regulators vs those expressed on host cells, a model system was used examining complement fragments deposited on cells transfected with human MCP as assessed by FACS and Western blotting. Following incubation with Ab and complement on MCP(+) cells, C4b was progressively cleaved over the first hour to C4d and C4c. There was no detectable cleavage of C4b on MCP(-) cells, indicating that MCP (and not C4BP in the serum) primarily mediates this cofactor activity. C3b deposition was not blocked on MCP(+) cells because classical pathway activation occurred before substantial C4b cleavage. Cleavage, though, of deposited C3b was rapid (<5 min) and iC3b was the dominant fragment on MCP(-) and MCP(+) cells. Studies using a function-blocking mAb further established factor H as the responsible cofactor. If the level of Ab sensitization was reduced 8-fold or if Mg(2+)-EGTA was used to block the classical pathway, MCP efficiently inhibited C3b deposition mediated by the alternative pathway. Thus, for the classical pathway, MCP is the cofactor for C4b cleavage and factor H for C3b cleavage. However, if the alternative pathway mediates C3b deposition, then MCP's cofactor activity is sufficient to restrict complement activation. (+info)

Regulation of glycoprotein IIb-IIIa receptor function studied with platelets permeabilized by the pore-forming complement proteins C5b-9. (4/26)

Recent evidence suggests that the cytoplasmic domains of platelet glycoprotein (GP) IIb-IIIa are involved in the agonist-initiated transformation of this integrin into a receptor for fibrinogen. To identify intracellular reactions that regulate the receptor function of GP IIb-IIIa, membrane-impermeable agonists and antagonists were introduced into the platelet by permeabilizing the plasma membrane with the pore-forming complement proteins C5b-9. Platelet responses were then analyzed by flow cytometry. Non-lytic concentrations of C5b-9 caused permeabilization of the platelet plasma membrane, as determined by uptake of a water-soluble fluorescent tracer dye. The complement pores were large enough to permit the entry of fluorescein isothiocyanate (FITC)-labeled oligopeptides in a size-dependent manner. Under conditions of low external Ca2+, C5b-9 treatment per se did not activate GP IIb-IIIa, as measured by binding of the activation-dependent antibody FITC-PAC1. However, FITC-PAC1 binding to C5b-9-permeabilized platelets was stimulated by a thrombin receptor agonist acting at the cell surface and by guanosine 5'-O-(thiotriphosphate), a membrane-impermeable activator of G proteins. Permeabilization also permitted the entry of cyclic AMP and the peptide, RFARKGALRQKNV, a pseudo-substrate inhibitor of protein kinase C. Each of these inhibited agonist-induced FITC-PAC1 binding to permeabilized platelets but not to intact platelets. Agonist-induced GP IIb-IIIa activation in permeabilized platelets was also inhibited by tyrphostin-23, a protein tyrosine kinase inhibitor. Thus, C5b-9 can be used to permeabilize the plasma membrane to permit the selective entry of small peptides and other bioactive compounds into permeabilized platelets. Results obtained with these platelets indicate that GP IIb-IIIa receptor function is regulated by a network of signaling reactions involving G proteins, serine/threonine kinases, and tyrosine kinases. (+info)

Persistent complement activation on tumor cells in breast cancer. (5/26)

The neoantigens of the C5b-9 complement complex, IgG, C3, C4, S-protein/vitronectin, fibronectin, and macrophages were localized on 17 samples of breast cancer and on 6 samples of benign breast tumors using polyclonal or monoclonal antibodies and the streptavidin-biotin-peroxidase technique. All the tissue samples with carcinoma in each the TNM stages presented C5b-9 deposits on the membranes of tumor cells, thin granules on cell remnants, and diffuse deposits in the necrotic areas. When chemotherapy and radiation therapy preceded surgery, C5b-9 deposits were more intense and extended. The C5b-9 deposits were absent in all the samples with benign lesions. S-protein/vitronectin was present as fibrillar deposits in the connective tissue matrix and as diffuse deposits around the tumor cells, less intense and extended than fibronectin. IgG, C3, and C4 deposits were present only in carcinoma samples. The presence of C5b-9 deposits is indicative of complement activation and its subsequent pathogenetic effects in breast cancer. (+info)

The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation. (6/26)

Complement activation with formation of biologically potent mediators like C5a and the terminal C5b-9 complex (TCC) contributes essentially to development of inflammation and tissue damage in a number of autoimmune and inflammatory conditions. A particular role for complement in the ischaemia/reperfusion injury of the heart, skeletal muscle, central nervous system, intestine and kidney has been suggested from animal studies. Previous experiments in C3 and C4 knockout mice suggested an important role of the classical or lectin pathway in initiation of complement activation during intestinal ischaemia/reperfusion injury while later use of factor D knockout mice showed the alternative pathway to be critically involved. We hypothesized that alternative pathway amplification might play a more critical role in classical pathway-induced C5 activation than previously recognized and used pathway-selective inhibitory mAbs to further elucidate the role of the alternative pathway. Here we demonstrate that selective blockade of the alternative pathway by neutralizing factor D in human serum diluted 1 : 2 with mAb 166-32 inhibited more than 80% of C5a and TCC formation induced by solid phase IgM and solid- and fluid-phase human aggregated IgG via the classical pathway. The findings emphasize the influence of alternative pathway amplification on the effect of initial classical pathway activation and the therapeutic potential of inhibiting the alternative pathway in clinical conditions with excessive and uncontrolled complement activation. (+info)

Recombinant C345C and factor I modules of complement components C5 and C7 inhibit C7 incorporation into the complement membrane attack complex. (7/26)

Complement component C5 binds to components C6 and C7 in reversible reactions that are distinct from the essentially nonreversible associations that form during assembly of the complement membrane attack complex (MAC). We previously reported that the approximately 150-aa residue C345C domain (also known as NTR) of C5 mediates these reversible reactions, and that the corresponding recombinant module (rC5-C345C) binds directly to the tandem pair of approximately 75-residue factor I modules from C7 (C7-FIMs). We suggested from these and other observations that binding of the C345C module of C5 to the FIMs of C7, but not C6, is also essential for MAC assembly itself. The present report describes a novel method for assembling a complex that appears to closely resemble the MAC on the sensor chip of a surface plasmon resonance instrument using the complement-reactive lysis mechanism. This method provides the ability to monitor individually the incorporation of C7, C8, and C9 into the complex. Using this method, we found that C7 binds to surface-bound C5b,6 with a K(d) of approximately 3 pM, and that micromolar concentrations of either rC5-C345C or rC7-FIMs inhibit this early step in MAC formation. We also found that similar concentrations of either module inhibited complement-mediated erythrocyte lysis by both the reactive lysis and classical pathway mechanisms. These results demonstrate that the interaction between the C345C domain of C5 and the FIMs of C7, which mediates reversible binding of C5 to C7 in solution, also plays an essential role in MAC formation and complement lytic activity. (+info)

Regulatory control of the terminal complement proteins at the surface of human endothelial cells: neutralization of a C5b-9 inhibitor by antibody to CD59. (8/26)

Functionally inhibitory antibody to the plasma membrane complement inhibitor CD59 has been used to investigate control of the terminal complement proteins at the endothelial cell surface. Antibodies against purified human erythrocyte CD59 (polyclonal anti-CD59 and monoclonal antibodies [MoAbs] 1F1 and 1F5) were found to bind specifically to monolayers of cultured human umbilical vein endothelial cells, and by Western blotting to recognize an 18- to 21-Kd endothelial protein. When bound to the endothelial monolayer, anti-CD59 (immunoglobulin G or Fab fragment) potentiated membrane pore formation induced upon C9 binding to C5b-8, and augmented the C5b-9-induced cellular responses, including stimulated secretion of von Willebrand factor and expression of catalytic surface for the prothrombinase enzyme complex. Although potentiating endothelial responses to the terminal complement proteins, anti-CD59 had no effect on the response of these cells to stimulation by histamine. Taken together, these data suggest that human endothelial cells express the CD59 cell surface inhibitor of the terminal complement proteins, which serves to protect these cells from pore-forming and cell-stimulatory effects of the C5b-9 complex. These data also suggest that the inactivation or deletion of this cell surface regulatory molecule would increase the likelihood for procoagulant changes in endothelium exposed to complement activation in plasma. (+info)

There are two main types of hemolysis:

1. Intravascular hemolysis: This type occurs within the blood vessels and is caused by factors such as mechanical injury, oxidative stress, and certain infections.
2. Extravascular hemolysis: This type occurs outside the blood vessels and is caused by factors such as bone marrow disorders, splenic rupture, and certain medications.

Hemolytic anemia is a condition that occurs when there is excessive hemolysis of RBCs, leading to a decrease in the number of healthy red blood cells in the body. This can cause symptoms such as fatigue, weakness, pale skin, and shortness of breath.

Some common causes of hemolysis include:

1. Genetic disorders such as sickle cell anemia and thalassemia.
2. Autoimmune disorders such as autoimmune hemolytic anemia (AIHA).
3. Infections such as malaria, babesiosis, and toxoplasmosis.
4. Medications such as antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and blood thinners.
5. Bone marrow disorders such as aplastic anemia and myelofibrosis.
6. Splenic rupture or surgical removal of the spleen.
7. Mechanical injury to the blood vessels.

Diagnosis of hemolysis is based on a combination of physical examination, medical history, and laboratory tests such as complete blood count (CBC), blood smear examination, and direct Coombs test. Treatment depends on the underlying cause and may include supportive care, blood transfusions, and medications to suppress the immune system or prevent infection.

The term "systemic" refers to the fact that the disease affects multiple organ systems, including the skin, joints, kidneys, lungs, and nervous system. LES is a complex condition, and its symptoms can vary widely depending on which organs are affected. Common symptoms include fatigue, fever, joint pain, rashes, and swelling in the extremities.

There are several subtypes of LES, including:

1. Systemic lupus erythematosus (SLE): This is the most common form of the disease, and it can affect anyone, regardless of age or gender.
2. Discoid lupus erythematosus (DLE): This subtype typically affects the skin, causing a red, scaly rash that does not go away.
3. Drug-induced lupus erythematosus: This form of the disease is caused by certain medications, and it usually resolves once the medication is stopped.
4. Neonatal lupus erythematosus: This rare condition affects newborn babies of mothers with SLE, and it can cause liver and heart problems.

There is no cure for LES, but treatment options are available to manage the symptoms and prevent flares. Treatment may include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, immunosuppressive medications, and antimalarial drugs. In severe cases, hospitalization may be necessary to monitor and treat the disease.

It is important for people with LES to work closely with their healthcare providers to manage their condition and prevent complications. With proper treatment and self-care, many people with LES can lead active and fulfilling lives.

Idiopathic membranous nephropathy (IMN) is an autoimmune disorder that causes GNM without any identifiable cause. Secondary membranous nephropathy, on the other hand, is caused by systemic diseases such as lupus or cancer.

The symptoms of GNM can vary depending on the severity of the disease and may include blood in the urine, proteinuria, edema, high blood pressure, and decreased kidney function. The diagnosis of GNM is based on a combination of clinical findings, laboratory tests, and renal biopsy.

Treatment for GNM is aimed at slowing the progression of the disease and managing symptoms. Medications such as corticosteroids, immunosuppressive drugs, and blood pressure-lowering drugs may be used to treat GNM. In some cases, kidney transplantation may be necessary.

The prognosis for GNM varies depending on the severity of the disease and the underlying cause. In general, the prognosis for IMN is better than for secondary membranous nephropathy. With proper treatment, some patients with GNM can experience a slowing or stabilization of the disease, while others may progress to end-stage renal disease (ESRD).

The cause of GNM is not fully understood, but it is believed to be an autoimmune disorder that leads to inflammation and damage to the glomerular membrane. Genetic factors and environmental triggers may also play a role in the development of GNM.

There are several risk factors for developing GNM, including family history, age (GMN is more common in adults), and certain medical conditions such as hypertension and diabetes.

The main complications of GNM include:

1. ESRD: Progression to ESRD is a common outcome of untreated GNM.
2. High blood pressure: GNM can lead to high blood pressure, which can further damage the kidneys.
3. Infections: GNM increases the risk of infections due to impaired immune function.
4. Kidney failure: GNM can cause chronic kidney failure, leading to the need for dialysis or a kidney transplant.
5. Cardiovascular disease: GNM is associated with an increased risk of cardiovascular disease, including heart attack and stroke.
6. Malnutrition: GNM can lead to malnutrition due to decreased appetite, nausea, and vomiting.
7. Bone disease: GNM can cause bone disease, including osteoporosis and bone pain.
8. Anemia: GNM can cause anemia, which can lead to fatigue, weakness, and shortness of breath.
9. Increased risk of infections: GNM increases the risk of infections due to impaired immune function.
10. Decreased quality of life: GNM can significantly decrease a person's quality of life, leading to decreased mobility, pain, and discomfort.

It is important for individuals with GNM to receive early diagnosis and appropriate treatment to prevent or delay the progression of these complications.

The symptoms of glomerulonephritis can vary depending on the underlying cause of the disease, but may include:

* Blood in the urine (hematuria)
* Proteinuria (excess protein in the urine)
* Reduced kidney function
* Swelling in the legs and ankles (edema)
* High blood pressure

Glomerulonephritis can be caused by a variety of factors, including:

* Infections such as staphylococcal or streptococcal infections
* Autoimmune disorders such as lupus or rheumatoid arthritis
* Allergic reactions to certain medications
* Genetic defects
* Certain diseases such as diabetes, high blood pressure, and sickle cell anemia

The diagnosis of glomerulonephritis typically involves a physical examination, medical history, and laboratory tests such as urinalysis, blood tests, and kidney biopsy.

Treatment for glomerulonephritis depends on the underlying cause of the disease and may include:

* Antibiotics to treat infections
* Medications to reduce inflammation and swelling
* Diuretics to reduce fluid buildup in the body
* Immunosuppressive medications to suppress the immune system in cases of autoimmune disorders
* Dialysis in severe cases

The prognosis for glomerulonephritis depends on the underlying cause of the disease and the severity of the inflammation. In some cases, the disease may progress to end-stage renal disease, which requires dialysis or a kidney transplant. With proper treatment, however, many people with glomerulonephritis can experience a good outcome and maintain their kidney function over time.

Arteriolosclerosis is often associated with conditions such as hypertension, diabetes, and atherosclerosis, which is the buildup of plaque in the arteries. It can also be caused by other factors such as smoking, high cholesterol levels, and inflammation.

The symptoms of arteriolosclerosis can vary depending on the location and severity of the condition, but may include:

* Decreased blood flow to organs or tissues
* Fatigue
* Weakness
* Shortness of breath
* Dizziness or lightheadedness
* Pain in the affected limbs or organs

Arteriolosclerosis is typically diagnosed through a combination of physical examination, medical history, and diagnostic tests such as ultrasound, angiography, or blood tests. Treatment for the condition may include lifestyle changes such as exercise and dietary modifications, medications to control risk factors such as hypertension and high cholesterol, and in some cases, surgical intervention to open or bypass blocked arterioles.

In summary, arteriolosclerosis is a condition where the arterioles become narrowed or obstructed, leading to decreased blood flow to organs and tissues and potentially causing a range of health problems. It is often associated with other conditions such as hypertension and atherosclerosis, and can be diagnosed through a combination of physical examination, medical history, and diagnostic tests. Treatment may include lifestyle changes and medications to control risk factors, as well as surgical intervention in some cases.

1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

There are several types of lupus nephritis, each with its own unique characteristics and symptoms. The most common forms include:

* Class I (mesangial proliferative glomerulonephritis): This type is characterized by the growth of abnormal cells in the glomeruli (blood-filtering units of the kidneys).
* Class II (active lupus nephritis): This type is characterized by widespread inflammation and damage to the kidneys, with or without the presence of antibodies.
* Class III (focal lupus nephritis): This type is characterized by localized inflammation in certain areas of the kidneys.
* Class IV (lupus nephritis with crescentic glomerulonephritis): This type is characterized by widespread inflammation and damage to the kidneys, with crescent-shaped tissue growth in the glomeruli.
* Class V (lupus nephritis with sclerotic changes): This type is characterized by hardening and shrinkage of the glomeruli due to scarring.

Lupus Nephritis can cause a range of symptoms, including:

* Proteinuria (excess protein in the urine)
* Hematuria (blood in the urine)
* Reduced kidney function
* Swelling (edema)
* Fatigue
* Fever
* Joint pain

Lupus Nephritis can be diagnosed through a combination of physical examination, medical history, laboratory tests, and kidney biopsy. Treatment options for lupus nephritis include medications to suppress the immune system, control inflammation, and prevent further damage to the kidneys. In severe cases, dialysis or a kidney transplant may be necessary.

There are several key features of inflammation:

1. Increased blood flow: Blood vessels in the affected area dilate, allowing more blood to flow into the tissue and bringing with it immune cells, nutrients, and other signaling molecules.
2. Leukocyte migration: White blood cells, such as neutrophils and monocytes, migrate towards the site of inflammation in response to chemical signals.
3. Release of mediators: Inflammatory mediators, such as cytokines and chemokines, are released by immune cells and other cells in the affected tissue. These molecules help to coordinate the immune response and attract more immune cells to the site of inflammation.
4. Activation of immune cells: Immune cells, such as macrophages and T cells, become activated and start to phagocytose (engulf) pathogens or damaged tissue.
5. Increased heat production: Inflammation can cause an increase in metabolic activity in the affected tissue, leading to increased heat production.
6. Redness and swelling: Increased blood flow and leakiness of blood vessels can cause redness and swelling in the affected area.
7. Pain: Inflammation can cause pain through the activation of nociceptors (pain-sensing neurons) and the release of pro-inflammatory mediators.

Inflammation can be acute or chronic. Acute inflammation is a short-term response to injury or infection, which helps to resolve the issue quickly. Chronic inflammation is a long-term response that can cause ongoing damage and diseases such as arthritis, asthma, and cancer.

There are several types of inflammation, including:

1. Acute inflammation: A short-term response to injury or infection.
2. Chronic inflammation: A long-term response that can cause ongoing damage and diseases.
3. Autoimmune inflammation: An inappropriate immune response against the body's own tissues.
4. Allergic inflammation: An immune response to a harmless substance, such as pollen or dust mites.
5. Parasitic inflammation: An immune response to parasites, such as worms or fungi.
6. Bacterial inflammation: An immune response to bacteria.
7. Viral inflammation: An immune response to viruses.
8. Fungal inflammation: An immune response to fungi.

There are several ways to reduce inflammation, including:

1. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying anti-rheumatic drugs (DMARDs).
2. Lifestyle changes, such as a healthy diet, regular exercise, stress management, and getting enough sleep.
3. Alternative therapies, such as acupuncture, herbal supplements, and mind-body practices.
4. Addressing underlying conditions, such as hormonal imbalances, gut health issues, and chronic infections.
5. Using anti-inflammatory compounds found in certain foods, such as omega-3 fatty acids, turmeric, and ginger.

It's important to note that chronic inflammation can lead to a range of health problems, including:

1. Arthritis
2. Diabetes
3. Heart disease
4. Cancer
5. Alzheimer's disease
6. Parkinson's disease
7. Autoimmune disorders, such as lupus and rheumatoid arthritis.

Therefore, it's important to manage inflammation effectively to prevent these complications and improve overall health and well-being.

There are three main forms of ACH:

1. Classic congenital adrenal hyperplasia (CAH): This is the most common form of ACH, accounting for about 90% of cases. It is caused by mutations in the CYP21 gene, which codes for an enzyme that converts cholesterol into cortisol and aldosterone.
2. Non-classic CAH (NCAH): This form of ACH is less common than classic CAH and is caused by mutations in other genes involved in cortisol and aldosterone production.
3. Mineralocorticoid excess (MOE) or glucocorticoid deficiency (GD): These are rare forms of ACH that are characterized by excessive production of mineralocorticoids (such as aldosterone) or a deficiency of glucocorticoids (such as cortisol).

The symptoms of ACH can vary depending on the specific form of the disorder and the age at which it is diagnosed. In classic CAH, symptoms typically appear in infancy and may include:

* Premature puberty (in girls) or delayed puberty (in boys)
* Abnormal growth patterns
* Distended abdomen
* Fatigue
* Weight gain or obesity
* Easy bruising or bleeding

In NCAH and MOE/GD, symptoms may be less severe or may not appear until later in childhood or adulthood. They may include:

* High blood pressure
* Low blood sugar (hypoglycemia)
* Weight gain or obesity
* Fatigue
* Mood changes

If left untreated, ACH can lead to serious complications, including:

* Adrenal gland insufficiency
* Heart problems
* Bone health problems
* Increased risk of infections
* Mental health issues (such as depression or anxiety)

Treatment for ACH typically involves hormone replacement therapy to restore the balance of hormones in the body. This may involve taking medications such as cortisol, aldosterone, or other hormones to replace those that are deficient or imbalanced. In some cases, surgery may be necessary to remove an adrenal tumor or to correct physical abnormalities.

With proper treatment, many individuals with ACH can lead healthy, active lives. However, it is important for individuals with ACH to work closely with their healthcare providers to manage their condition and prevent complications. This may involve regular check-ups, hormone level monitoring, and lifestyle changes such as a healthy diet and regular exercise.

Proteinuria is usually diagnosed by a urine protein-to-creatinine ratio (P/C ratio) or a 24-hour urine protein collection. The amount and duration of proteinuria can help distinguish between different underlying causes and predict prognosis.

Proteinuria can have significant clinical implications, as it is associated with increased risk of cardiovascular disease, kidney damage, and malnutrition. Treatment of the underlying cause can help reduce or eliminate proteinuria.

There are two main types of MD:

1. Dry Macular Degeneration (DMD): This is the most common form of MD, accounting for about 90% of cases. It is caused by the gradual accumulation of waste material in the macula, which can lead to cell death and vision loss over time.
2. Wet Macular Degeneration (WMD): This type of MD is less common but more aggressive, accounting for about 10% of cases. It occurs when new blood vessels grow underneath the retina, leaking fluid and causing damage to the macula. This can lead to rapid vision loss if left untreated.

The symptoms of MD can vary depending on the severity and type of the condition. Common symptoms include:

* Blurred vision
* Distorted vision (e.g., straight lines appearing wavy)
* Difficulty reading or recognizing faces
* Difficulty adjusting to bright light
* Blind spots in central vision

MD can have a significant impact on daily life, making it difficult to perform everyday tasks such as driving, reading, and recognizing faces.

There is currently no cure for MD, but there are several treatment options available to slow down the progression of the disease and manage its symptoms. These include:

* Anti-vascular endothelial growth factor (VEGF) injections: These medications can help prevent the growth of new blood vessels and reduce inflammation in the macula.
* Photodynamic therapy: This involves the use of a light-sensitive drug and low-intensity laser to damage and shrink the abnormal blood vessels in the macula.
* Vitamin supplements: Certain vitamins, such as vitamin C, E, and beta-carotene, have been shown to slow down the progression of MD.
* Laser surgery: This can be used to reduce the number of abnormal blood vessels in the macula and improve vision.

It is important for individuals with MD to receive regular monitoring and treatment from an eye care professional to manage their condition and prevent complications.

There are several types of disease susceptibility, including:

1. Genetic predisposition: This refers to the inherent tendency of an individual to develop a particular disease due to their genetic makeup. For example, some families may have a higher risk of developing certain diseases such as cancer or heart disease due to inherited genetic mutations.
2. Environmental susceptibility: This refers to the increased risk of developing a disease due to exposure to environmental factors such as pollutants, toxins, or infectious agents. For example, someone who lives in an area with high levels of air pollution may be more susceptible to developing respiratory problems.
3. Lifestyle susceptibility: This refers to the increased risk of developing a disease due to unhealthy lifestyle choices such as smoking, lack of exercise, or poor diet. For example, someone who smokes and is overweight may be more susceptible to developing heart disease or lung cancer.
4. Immune system susceptibility: This refers to the increased risk of developing a disease due to an impaired immune system. For example, people with autoimmune disorders such as HIV/AIDS or rheumatoid arthritis may be more susceptible to opportunistic infections.

Understanding disease susceptibility can help healthcare providers identify individuals who are at risk of developing certain diseases and provide preventive measures or early intervention to reduce the risk of disease progression. Additionally, genetic testing can help identify individuals with a high risk of developing certain diseases, allowing for earlier diagnosis and treatment.

In summary, disease susceptibility refers to the predisposition of an individual to develop a particular disease or condition due to various factors such as genetics, environment, lifestyle choices, and immune system function. Understanding disease susceptibility can help healthcare providers identify individuals at risk and provide appropriate preventive measures or early intervention to reduce the risk of disease progression.

There are several symptoms of RA, including:

1. Joint pain and stiffness, especially in the hands and feet
2. Swollen and warm joints
3. Redness and tenderness in the affected areas
4. Fatigue, fever, and loss of appetite
5. Loss of range of motion in the affected joints
6. Firm bumps of tissue under the skin (rheumatoid nodules)

RA can be diagnosed through a combination of physical examination, medical history, blood tests, and imaging studies such as X-rays or ultrasound. Treatment typically involves a combination of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and biologic agents. Lifestyle modifications such as exercise and physical therapy can also be helpful in managing symptoms and improving quality of life.

There is no cure for RA, but early diagnosis and aggressive treatment can help to slow the progression of the disease and reduce symptoms. With proper management, many people with RA are able to lead active and fulfilling lives.

Explanation: Genetic predisposition to disease is influenced by multiple factors, including the presence of inherited genetic mutations or variations, environmental factors, and lifestyle choices. The likelihood of developing a particular disease can be increased by inherited genetic mutations that affect the functioning of specific genes or biological pathways. For example, inherited mutations in the BRCA1 and BRCA2 genes increase the risk of developing breast and ovarian cancer.

The expression of genetic predisposition to disease can vary widely, and not all individuals with a genetic predisposition will develop the disease. Additionally, many factors can influence the likelihood of developing a particular disease, such as environmental exposures, lifestyle choices, and other health conditions.

Inheritance patterns: Genetic predisposition to disease can be inherited in an autosomal dominant, autosomal recessive, or multifactorial pattern, depending on the specific disease and the genetic mutations involved. Autosomal dominant inheritance means that a single copy of the mutated gene is enough to cause the disease, while autosomal recessive inheritance requires two copies of the mutated gene. Multifactorial inheritance involves multiple genes and environmental factors contributing to the development of the disease.

Examples of diseases with a known genetic predisposition:

1. Huntington's disease: An autosomal dominant disorder caused by an expansion of a CAG repeat in the Huntingtin gene, leading to progressive neurodegeneration and cognitive decline.
2. Cystic fibrosis: An autosomal recessive disorder caused by mutations in the CFTR gene, leading to respiratory and digestive problems.
3. BRCA1/2-related breast and ovarian cancer: An inherited increased risk of developing breast and ovarian cancer due to mutations in the BRCA1 or BRCA2 genes.
4. Sickle cell anemia: An autosomal recessive disorder caused by a point mutation in the HBB gene, leading to defective hemoglobin production and red blood cell sickling.
5. Type 1 diabetes: An autoimmune disease caused by a combination of genetic and environmental factors, including multiple genes in the HLA complex.

Understanding the genetic basis of disease can help with early detection, prevention, and treatment. For example, genetic testing can identify individuals who are at risk for certain diseases, allowing for earlier intervention and preventive measures. Additionally, understanding the genetic basis of a disease can inform the development of targeted therapies and personalized medicine."

The disorder is caused by mutations in the HBB gene that codes for the beta-globin subunit of hemoglobin. These mutations result in the production of abnormal hemoglobins that are unstable and prone to breakdown, leading to the release of free hemoglobin into the urine.

HP is classified into two types based on the severity of symptoms:

1. Type 1 HP: This is the most common form of the disorder and is characterized by mild to moderate anemia, occasional hemoglobinuria, and a normal life expectancy.
2. Type 2 HP: This is a more severe form of the disorder and is characterized by severe anemia, recurrent hemoglobinuria, and a shorter life expectancy.

There is no cure for HP, but treatment options are available to manage symptoms and prevent complications. These may include blood transfusions, folic acid supplements, and medications to reduce the frequency and severity of hemoglobinuria episodes.

The term "immune complex disease" was first used in the 1960s to describe a group of conditions that were thought to be caused by the formation of immune complexes. These diseases include:

1. Systemic lupus erythematosus (SLE): an autoimmune disorder that can affect multiple organ systems and is characterized by the presence of anti-nuclear antibodies.
2. Rheumatoid arthritis (RA): an autoimmune disease that causes inflammation in the joints and can lead to joint damage.
3. Type III hypersensitivity reaction: a condition in which immune complexes are deposited in tissues, leading to inflammation and tissue damage.
4. Pemphigus: a group of autoimmune diseases that affect the skin and mucous membranes, characterized by the presence of autoantibodies against desmosomal antigens.
5. Bullous pemphigoid: an autoimmune disease that affects the skin and is characterized by the formation of large blisters.
6. Myasthenia gravis: an autoimmune disorder that affects the nervous system, causing muscle weakness and fatigue.
7. Goodpasture's syndrome: a rare autoimmune disease that affects the kidneys and lungs, characterized by the presence of immune complexes in the glomeruli of the kidneys.
8. Hemolytic uremic syndrome (HUS): a condition in which red blood cells are destroyed and waste products accumulate in the kidneys, leading to kidney failure.

Immune complex diseases can be caused by various factors, including genetic predisposition, environmental triggers, and exposure to certain drugs or toxins. Treatment options for these diseases include medications that suppress the immune system, such as corticosteroids and immunosuppressive drugs, and plasmapheresis, which is a process that removes harmful antibodies from the blood. In some cases, organ transplantation may be necessary.

In conclusion, immune complex diseases are a group of disorders that occur when the body's immune system mistakenly attacks its own tissues and organs, leading to inflammation and damage. These diseases can affect various parts of the body, including the skin, kidneys, lungs, and nervous system. Treatment options vary depending on the specific disease and its severity, but may include medications that suppress the immune system and plasmapheresis.

C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to multiple molecules of C9 to form ... cells from complement-mediated damage. CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for ... there are several different kinds of regulatory proteins that disrupt the complement activation process: Complement Receptor 1 ... The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, ...

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

... is involved in the complement system. It is cleaved into C5a and C5b: C5a plays an important role in ... C5b forms the first part of the complement membrane attack complex. Deficiency is thought to cause Leiner's disease. Complement ... The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for ... Identification of the C5b-binding domain in complement C6". J. Biol. Chem. 264 (30): 18041-51. doi:10.1016/S0021-9258(19)84676- ...

https://en.wikipedia.org/wiki/Complement_component_5

Subsequent interactions between C5b and other terminal components C6, C7, C8, and C9 form the membrane attack complex or the ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ... The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune ... Activation of the complement pathway through the classical, lectin or alternative complement pathway is followed by a cascade ...

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

C5b initiates the membrane attack pathway, which results in the membrane attack complex (MAC), consisting of C5b, C6, C7, C8, ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...

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

"Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood". Journal of Neuroimmunology. 276 ( ... Expression of several complement components are reported to be upregulated in the samples isolated from ALS patients and ... Apart from the three phenotypes discussed, peripheral macrophages/ monocytes and the complement system are also suggested to be ... "Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial ...

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

Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-6-7 complex. The C5b-6-7 complex binds to ... If the pre-MAC complexes of C5b-7, C5b-8 or C5b-9 do not insert into a membrane, they can form inactive complexes with Protein ... Another complement protein, C6, binds to C5b. The C5bC6 complex is bound by C7. This junction alters the configuration of the ... MAC is composed of a complex of four complement proteins (C5b, C6, C7, and C8) that bind to the outer surface of the plasma ...

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

"Entrez Gene: RGC32 response gene to complement 32". Fosbrink M, Niculescu F, Rus H (2005). "The role of c5b-9 terminal ... Regulator of cell cycle RGCC (RGCC) also known as response gene to complement 32 protein (RGC-32) is a protein that in humans ... It is induced by p53 in response to DNA damage, or by sublytic levels of complement system proteins that result in activation ... 1998). "Molecular cloning and characterization of RGC-32, a novel gene induced by complement activation in oligodendrocytes". J ...

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

Terminal C5b-9 complement deposition coincides with cholesterol accumulation in the aortic intima of hypercholesterolemic ... Investigation of the complement system led Bhakdi to the area of atherosclerosis. In 1989 he discovered through animal ... He contributed to a better understanding of the mechanisms with which the large molecules of the complement system in the blood ... "S. Bhakdi, J. Tranum-Jensen: Molecular nature of the complement lesion. In: Proceedings of the National Academy of Sciences of ...

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

Hydrophobic sites are probably exposed upon C5 activation because C5b undergoes aggregation when C5 is converted to C5b in the ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... complement component C6 and the C5b6 complex is formed. However, when C6 is added after C5 has been converted to C5b, the C5b6 ... The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ...

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

... and C5b, which then forms the terminal complement complex C5b-9 which also has prothrombotic and proinflammatory effects. Both ... By inhibiting the complement cascade at this point, the normal, disease-preventing functions of proximal complement system are ... Eculizumab specifically binds to the terminal complement component 5, or C5, which acts at a late stage in the complement ... C5a and C5b-9 cause the complement-mediated events that are characteristic of PNH and aHUS. The metabolism of eculizumab is ...

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

2009). "Response gene to complement 32 is required for C5b-9 induced cell cycle activation in endothelial cells". Exp. Mol. ... Complement component 6 is a protein that in humans is encoded by the C6 gene. Complement component 6 is a protein involved in ... "Entrez Gene: complement component 6 C6 complement C6 (Homo sapiens (human)) Gene ID: 729". www.ncbi.nlm.nih.gov. 24 November ... Complement+C6 at the US National Library of Medicine Medical Subject Headings (MeSH) v t e (Articles with short description, ...

https://en.wikipedia.org/wiki/Complement_component_6

C9 is one member of the complement membrane attack complex (MAC), which also includes complement components C5b, C6, C7 and C8 ... MAC formation starts with the assembly of a tetrameric complex with the complement components C6, C7, C8, and C5b. The final ... Complement component 9 (C9) is a MACPF protein involved in the complement system, which is part of the innate immune system. ... Complement+9 at the US National Library of Medicine Medical Subject Headings (MeSH) PDBe-KB provides an overview of all the ...

https://en.wikipedia.org/wiki/Complement_component_9

Deposition of the C5b-9 complement attack complex, subsarcolemmal deposition of calcium and expression of MHC1 complex also ...

https://en.wikipedia.org/wiki/Myopathy,_X-linked,_with_excessive_autophagy

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

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

... is a macrocyclic peptide that binds to the protein complement component 5 (C5) and inhibits its cleavage into C5a ... and C5b. Howard JF, Kaminski HJ, Nowak RJ, Wolfe GI, Benatar MG, Ricardo A, Hoarty MD, DeMarco SJ, Farzaneh-Far R, Duda PW ( ... 2018). "RA101495, a subcutaneously administered peptide inhibitor of complement component 5 (C5) for the treatment of ...

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

The formation of complement proteins (C3a, C3b, C5a, C5b, etc.) ultimately congregates into a membrane-attack complex to lyse ... pathogens and bind to C3 convertase to catalyze the formation of C5 convertase to produce C5a and C5b for terminal complement ... Antibodies can also trigger the classical pathway - one of the three pathways of the complement cascade. Briefly, the C1 ... In addition to the generation of complement proteins, C1 complex also induces the activation of B cells, monocytes, macrophages ...

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

Staphopain A was shown to inhibit activation of the complement system activation by cleaving components that are part of all ... although inactivating C5b). However, it has yet to prove any significant impact on the outcome of infection. Inhibition of ... Staphopain A can cleave and lower the activity α1-antitrypsin, and inactivate several complement system components. ... "Staphylococcal proteases aid in evasion of the human complement system". Journal of Innate Immunity. 6 (1): 31-46. doi:10.1159/ ...

https://en.wikipedia.org/wiki/Staphopain_A_(Staphylococcus_aureus)

... deposition of C4d and C5b-9 in human subjects of trauma and patients with severe trauma maintain high deposition of complement ... Tsokos established the role of complement activation in tissue injury and regeneration. His findings demonstrated for the first ... His work also confirmed that an anaphylatoxin molecule of complement activation "C3a" enhances intestinal stem cell expansion, ... "Complement deposition on the surface of RBC after trauma serves a biomarker of moderate trauma severity: A prospective study". ...

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

... a protein of the complement system C5-convertase, an enzyme which splits C5 into C5b Complement component 5a, an inflammatory ... one of the cervical vertebrae of the vertebral column Cervical spinal nerve 5 Complement component 5, ...

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

The immune complex serves as an activator that triggers a response from the C5b - C9 complements, which form a membrane attack ... Immunofluorescence microscopy will reveal typical granular deposition of immunoglobulins and complement along the basement ...

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

... which cleaves C5 into C5a and C5b. C5b associates with C6, C7, C8, and C9, all of which form a complex that results in a pore ... The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. This activated C1 ... C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the ... The key to the success of the complement system in clearing antigens is regulating the effects of C3b to pathogens alone and ...

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

Similarly again, C5b is bound and C5a is released. C5b recruits C6, C7, C8 and multiple C9s. C5, C6, C7, C8 and C9 form the ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ... "/"self turned nonself" type pathogen pattern are also identified and destroyed (e.g. by complement fixation or other cytotoxic ...

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

... complement c5b MeSH D12.776.124.486.274.550 - complement c6 MeSH D12.776.124.486.274.650 - complement c7 MeSH D12.776.124.486. ... complement c1 MeSH D12.776.124.486.274.050.270 - complement c1q MeSH D12.776.124.486.274.050.280 - complement c1r MeSH D12.776. ... complement c2 MeSH D12.776.124.486.274.150.500 - complement c2a MeSH D12.776.124.486.274.150.750 - complement c2b MeSH D12.776. ... complement c3c MeSH D12.776.124.486.274.250.260.750 - complement c3d MeSH D12.776.124.486.274.350 - complement c4 MeSH D12.776. ...

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

The first C-5B was delivered to Altus Air Force Base in January 1986. In April 1989, the last of 50 C-5B aircraft was added to ... aircraft companies began studying heavy jet transport designs that would replace the Douglas C-133 Cargomaster and complement ... The C-5B is an improved version of the C-5A. It incorporated all modifications and improvements made to the C-5A with improved ... The C-5B assigned to the 436th Airlift Wing and flown by a reserve crew from the 709th Airlift Squadron, 512th Airlift Wing ...

https://en.wikipedia.org/wiki/Lockheed_C-5_Galaxy

C5B minus the field jacket Winter Accoutrements (for wear with any order of dress in cold weather): Cadet Parka with outer ... provide additional training intended to support or complement that offered at the home unit from September to June. Across the ... Sports shorts T-shirt Running shoes Tilley hat Order of Dress C5B (Field Training Dress or Combats) Black beret with RCSC cap ...

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

Soluble C5b-9 levels may be used to identify complement-mediated end-organ injury in preeclampsia. ... We sought to determine if soluble levels of C5b-9, the terminal complement complex, correlate with end-organ injury in ... Plasma and urine C5b-9 levels were measured in all participants and stratified by quartile (Q1-4), from lowest to highest C5b-9 ... Soluble concentrations of the terminal complement complex C5b-9 correlate with end-organ injury in preeclampsia. ...

https://pesquisa.bvsalud.org/portal/resource/pt/mdl-35820290

The mutant did not bind to C5b-7 that was immobilized onto a BIAcore chip, whereas wild-type clusterin did, indicating that the ... Shiga toxin-induced complement-mediated hemolysis and release of complement-coated red blood cell-derived microvesicles in ... A novel mutation in the complement regulator clusterin in recurrent hemolytic uremic syndrome Anne-lie Ståhl 1 , AnnCharlotte ... Complement dysfunction in hemolytic uremic syndrome. Zipfel PF, Skerka C. Zipfel PF, et al. Curr Opin Rheumatol. 2006 Sep;18(5 ...

https://pubmed.ncbi.nlm.nih.gov/19446882

Eculizumab decreases complement-induced hemolysis by preventing cleavage of C5 into C5a and C5b; however, this activity also ... which could be from complement alone or complement activated by naturally acquired IgM. However, 50 µg/mL of eculizumab (a ... A) Complement-mediated bactericidal activity of an IgG-depleted human serum pool from 3 unvaccinated adult donors... ... A) Complement-mediated bactericidal activity of an IgG-depleted human serum pool from 3 unvaccinated... ...

https://wwwnc.cdc.gov/eid/article/24/8/18-0228_article

Early deposition of complement components C3 and C5 in the retina, suggest a contributing role of complement in AMD. It is ... Inhibiting C5 may prevent its cleavage to C5a and C5b thus decreasing membrane attack complex (MAC) formation. ... Complement factor H variant increases the risk of age-related macular degeneration. Science. 2005 Apr 15. 308(5720):419-21. [ ... Complement factor H polymorphism and age-related macular degeneration. Science. 2005 Apr 15. 308(5720):421-4. [QxMD MEDLINE ...

https://www.medscape.com/answers/1226030-3410/is-verteporfin-visudyne-fda-approved-for-use-in-the-treatment-of-exudative-wet-age-related-macular-degeneration-amd

The complement system plays an important part in defense against pyogenic organisms. ... The complement system is part of the innate immune system. ... components C5b-9. The MAC exerts powerful killing activity by ... Cases of complement deficiency have helped defined the role of complement in host defense. [4] A registry of complement ... The complement system is part of the innate immune system. The complement system plays an important part in defense against ...

http://emedicine.medscape.com/article/886128-overview

4. The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b-9. ... A synthetic peptide from complement protein C9 binds to CD59 and enhances lysis of human erythrocytes by C5b-9.. Tomlinson S; ... Comparison of channels formed by poly C9, C5b-8 and the membrane attack complex of complement.. Zalman LS; Müller-Eberhard HJ. ... 6. Live cell imaging of outward and inward vesiculation induced by the complement c5b-9 complex.. Moskovich O; Fishelson Z. J ...

https://pubmedhh.nlm.nih.gov/biomarkers/search.php?id=11882685&mod=related&page=1&outid=&proj=

There is enhanced staining for (A) complement C5B-9 and (B) cleaved caspase-3 in capillaries, particularly at the 24 h time ... Immunohistochemistry for complement C5B-9 and activated caspase-3. Immunofluorescence staining of the contralateral and… ... Immunohistochemistry for complement C5B-9 and activated caspase-3. Immunofluorescence staining of the contralateral and ...

https://www.ncbi.nlm.nih.gov/pubmed/33906946

Human Complement C5a produced in Human plasma having a molecular mass of 10.4 kDa. ... Complement C5 is cleaved into C5a and C5b. C5a has an imperative role in chemotaxis and C5b forms the 1st part of the ... The C5b macromolecular cleavage product forms a complex with the C6 complement component, and this complex is the basis for ... Complement Component C5a (C5a) is involved in the complement system and it is encoded by the C5 gene in human. ...

https://www.prospecbio.com/complement-c5a

Deposition of terminal complement components (C5b-9 and C4d) by IHC has been demonstrated in samples taken from cutaneous ... Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five ...

https://www.nature.com/articles/s41379-021-00814-w?error=cookies_not_supported&code=f8cf3a7b-d5c9-44a0-b2e8-ffc6b2badcd2

From NCBI Gene: This gene encodes a component of the complement system, a part of the innate immune system that plays an ... C5a anaphylatoxin and C5b. The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge ... and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). Mutations in this gene cause ... complement component 5 deficiency, a disease characterized by recurrent bacterial infections. Alternative splicing results in ...

https://edrn.nci.nih.gov/data-and-resources/biomarkers/c5/

Complement C5 [D12.776.124.486.274.450] * Complement C5a [D12.776.124.486.274.450.250] * Complement C5b [D12.776.124.486. ... C5b Complement Complement 5b Complement Component 5b Pharm Action. Immunologic Factors. Registry Number. 80295-55-2. CAS Type 1 ... Complement C 5b. Public MeSH Note. 2006; COMPLEMENT C5B was indexed under COMPLEMENT 5 1982-2005. History Note. 2006 (1982). ... Complement 5b Term UI T135349. LexicalTag NON. ThesaurusID NLM (2006). Complement Component 5b Term UI T623854. Date12/14/2004 ...

https://meshb.nlm.nih.gov/record/ui?ui=D050776

Complement Complex C5b-9 Levels Are Associated with the Clinical Outcomes of Acute Ischemic Stroke and Carotid Plaque Stability ...

https://pubmedhh.nlm.nih.gov/biomarkers/search.php?id=34103026&mod=related&page=2&proj=

Complement activation products (C3d, C3a, C4a, C5a, iC3, C4d, Bb, C5b-9, and erythrocyte CR1) are raised in active disease,140- ... The terminal complement complex, C5b-9, a marker of disease activity in patients with systemic lupus erythematosus. Arthritis ... Comparison of the use of complement split products and conventional measurements of complement. Arthritis Rheum 1992;35:1028-37 ... Complement assays are occasionally useful.18,28,131-136 A single C4 is not informative and serial monitoring is necessary ...

https://jcp.bmj.com/content/53/6/424?ijkey=831023503eb5bd069afd74aae28a3924e8a12039&keytype2=tf_ipsecsha

Properdin binds independent of complement activation in an in vivo model of anti-glomerular basement membrane disease ... Properdin is the only known positive regulator of complement activation by stabilizing the alternative pathway convertase ...

https://helda.helsinki.fi/browse?value=C5b-9&type=subject

This antibody recognizes C5b-9, the terminal complement complex (TCC). TCC consist of C5b, C6, C7, C8 and C9 and contains […] ... the Terminal Complement Complex (TCC). The antibody is produced in vitro by the aE11 hybridoma and purified with protein A to a ... Diatec Monoclonals offers an excellent monoclonal antibody against human C5b-9, ... Anti-human C5b-9 Diatec Monoclonals offers an excellent monoclonal antibody against human C5b-9, the Terminal Complement ...

https://diatec.com/product/anti-human-c5b-9/

Complement profiling of the patient showed decreased C3 and FB levels, with elevated levels of the terminal membrane attack ... Complement profiling of the patient showed decreased C3 and FB levels, with elevated levels of the terminal membrane attack ... Complement components analysis using specific immunoassays was performed on frozen plasma samples from the patient and mother. ... Complement components analysis using specific immunoassays and Western blotting was performed on frozen plasma samples from the ...

https://www.frontiersin.org/articles/10.3389/fimmu.2021.608604/full?utm_source=S-TWT&utm_medium=SNET&utm_campaign=ECO_FIMMU_XXXXXXXX_auto-dlvrit

R. Vlaicu, F. Niculescu, H. G. Rus, and A. Cristea, "Immunohistochemical localization of the terminal C5b-9 complement complex ... Complementing data in vitro, serum of Apoe−/− mice containing high levels of anti-dsDNA antibody titers but not serum ...

https://www.hindawi.com/journals/scientifica/2014/952625/

The complement system, especially C5b-9, is a critical component of this inflammatory cascade. C5b-9 inserted in sublytic ... Excessive activation of the complement system is normally prevented by a series of circulating and cell-bound complement ... Complement is a series of proteins that produce inflammation-causing substances when activated by antigen-antibody complexes. ... Understanding the role of complement in human lupus pregnancy is being followed in a multi-center study called Predictors of ...

https://www.niams.nih.gov/about/future-directions-lupus-research

... thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. ... Soliris inhibits terminal complement-mediated intravascular hemolysis in PNH patients and complement-mediated thrombotic ... but is presumed to involve reduction of terminal complement complex C5b-9 deposition at the neuromuscular junction. ... but is presumed to involve inhibition of aquaporin-4-antibody induced terminal complement C5b-9 deposition. ...

https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ebcd67fa-b4d1-4a22-b33d-ee8bf6b9c722

Complement C5a and its receptor C5aR are powerful inflammatory mediators involved in the progression of a wide variety of ... Thus, vilobelimab leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism of the ... Vilobelimab is a first-in-class monoclonal anti-human complement factor C5a antibody, which highly and effectively blocks the ... In the future, InflaRx plans to develop INF904 for complement-mediated, chronic autoimmune and inflammatory diseases where oral ...

https://au.finance.yahoo.com/news/inflarx-reports-full-2022-financial-113000870.html

https://meshb-prev.nlm.nih.gov/record/ui?ui=D050776

Human Complement C5b,6, purified. C57A15N-10 10 ug. EUR 489.6 Human Complement C5a desArg, purified. ... Human C3d Complement Purified Protein. Human C3d Complement Purified Protein To Order Contact us: [email protected]. Anti- ... Description: The complement component proteins, C2, C3, C4 and C5, are potent anaphylatoxins that are released during ... Description: The complement component proteins, C2, C3, C4 and C5, are potent anaphylatoxins that are released during ...

https://www.wlsolutions.be/human-c3d-complement-purified-protein/

The complement system is an evolutionarily ancient key component of innate immunity required for the detection and removal of ... C5b and C5a are produced, with surface-bound C5b initiating the formation and insertion of the MAC on pathogens (or other ... In particular, work on the impact of complement on T cell responses led to the surprising discoveries that the complement ... Complement and the Regulation of T Cell Responses Erin E West 1 , Martin Kolev 2 , Claudia Kemper 1 2 3 ...

https://www.ncbi.nlm.nih.gov/pubmed/29677470

C5 inhibits terminal complement activation by blocking cleavage of C5 into C5a (anaphylatoxin) and C5b, thereby blocking ... Pozelimab blocks terminal complement activation. *May increase susceptibility to encapsulated bacterial infections, especially ... Efficacy, duration, and drug regimens for antibacterial drug prophylaxis not studied in patients receiving complement ... Efficacy, duration, and drug regimens for antibacterial drug prophylaxis not studied in patients receiving complement ...

http://reference.medscape.com/drug/veopoz-pozelimab-4000370

Complement C5b Entry term(s). C5b Complement C5b, Complement Complement 5b Complement Component 5b Complement, C5b Component 5b ... Complément C5b Entry term(s):. C5b Complement. C5b, Complement. Complement 5b. Complement Component 5b. Complement, C5b. ... Complement C5b - Preferred Concept UI. M0105345. Scope note. The larger fragment generated from the cleavage of C5 by C5 ... C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly- ...

https://decs.bvsalud.org/en/ths/resource/?id=50827

Crystal Structure of Human Complement Component C8. 3p5c. The structure of the LDLR/PCSK9 complex reveals the receptor in an ... Solution structure of the tenth complement type repeat of human megalin. 2m7p. RXFP1 utilises hydrophobic moieties on a ... NMR SOLUTION STRUCTURE OF COMPLEMENT-LIKE REPEAT CR3 FROM THE LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN (LRP). EVIDENCE ... such as the C9 component of complement. The first repeat of the human LDL receptor has been expressed in Escherichia coli as a ...

https://smart.embl.de/smart/do_annotation.pl?DOMAIN=LDLa&START=3624&END=3661&E_VALUE=4.9e-13&TYPE=SMART&BLAST=DEMDCVIECKEDQFQCKNKAYCIPIRWLCDGIYDCVDG

Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency ( ... complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated ... IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy ... Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and ...

https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-4146-5

Complement C5 is cleaved into C5a and C5b. C5a plays an important role in chemotaxis and C5b forms the first part of the ... The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for ... Recombinant Human Complement Component C5a是ChemWhat品牌授权产品并通过沃尔森销售，下面是ChemWhat上的该产品链接 Recombinant Human Complement Component C5a ... Complement C5, also named C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4,

https://www.watson-bio.cn/recombinant-human-complement-component-c5a-rhuc5a/

16) Which of the following complement proteins may act as Opsonins:. 1. c3b. 2. C3a. 3 C5b 9 complex. 4. C3a & C5a ... 3. Complement proteins. 4. NK cells. 30) A 40 years old male suffering from cervical lymphadenopathy. Biopsy report shows ... 21) ---- is also called Cytotoxic Hypersensitivity because it utilizes antibodies that can destroy normal cells by complement ...

https://nursingipd.com/tag/mbbs/

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)
Purified antigens might have contaminants, or might not contain the full complement of native proteins. (bmj.com)
Atypical hemolytic uremic syndrome (aHUS) is mostly attributed to dysregulation of the alternative complement pathway (ACP) secondary to disease-causing variants in complement components or regulatory proteins. (frontiersin.org)
To date, about two thirds of patients with aHUS carry identifiable mutations or likely-pathogenic risk variants in genes encoding complement pathway proteins ( 2 - 5 ). (frontiersin.org)
Description: The complement component proteins, C2, C3, C4 and C5, are potent anaphylatoxins that are released during complement activation. (wlsolutions.be)
Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. (embl.de)
These proteins have natural affinity for C3b and/or C4b, which confers on them the ability to accelerate the intrinsic decay of C3/C5 convertases and/or act as co-factor for the cleavage and inactivation (i) of C3b and C4b by complement factor I (CFI). (hycultbiotech.com)
The soluble membrane attack complex (sMAC, a.k.a., sC5b-9 or TCC) is generated on activation of complement and contains the complement proteins C5b, C6, C7, C8, C9 together with the regulatory proteins clusterin and/or vitronectin. (promisekit.org)
Deficiencies in complement proteins may be inherited or acquired (secondary). (medicalnotes.info)
Acquired deficiencies in complement proteins are more common than inherited complement disorders. (medicalnotes.info)
The complement system consists of a group of circulating proteins that have immunologic effects when they are activated. (medicalnotes.info)
Other indications of C activity are the presence of the C3 breakdown fragment C3b and assembly of the membrane-inserted complex containing proteins C5b through C9. (ubc.ca)

Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). (nih.gov)
This deposition provides for the assembly of the membrane attack complex (MAC), components C5b-9. (medscape.com)
C5a has an imperative role in chemotaxis and C5b forms the 1st part of the complement membrane attack complex. (prospecbio.com)
The C5b macromolecular cleavage product forms a complex with the C6 complement component, and this complex is the basis for creation of the membrane attack complex, which includes supplementary complement components. (prospecbio.com)
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 . (nih.gov)
Complement profiling of the patient showed decreased C3 and FB levels, with elevated levels of the terminal membrane attack complex, while his healthy heterozygous mother showed intermediate levels of C3 consumption. (frontiersin.org)
While loss-of-function mutations are commonly implicated in genes encoding regulatory complement components, including complement Factor H ( CFH ), complement Factor I ( CFI ) and membrane cofactor protein (MCP, CD46 ), gain-of-function mutations are usually associated with complement Factor B ( CFB ) and C3 ( 6 - 8 ). (frontiersin.org)
The drug is not believed to impact the formation of the membrane attack complex (C5b-9). (clinicaltrialsarena.com)
Activation of complement (C5) leads to injury both through formation of the membrane attack complex (C5b-9) or by generation of the anaphylatoxin and cell activator C5a. (genome.jp)
The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX. (lookformedical.com)
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. (lookformedical.com)
C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. (lookformedical.com)
Eculizumab binds with high affinity to human complement C5 and blocks the generation of C5a and C5b-9, which prevents the formation of membrane attack complexes and activation of the pro-inflammatory pathway, thus protecting against end-organ damage [ 7 ]. (biomedcentral.com)
The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for formation of the membrane attack complex, which includes additional complement components. (watson-bio.cn)
CD35), decay-accelerating factor (CD55), and membrane co-factor protein (CD46) all are members of the regulators of complement activation family. (hycultbiotech.com)
The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. (promisekit.org)
This protein mediates the interaction of C8 with the C5b-7 membrane attack complex precursor. (nih.gov)

Properdin is the only known positive regulator of complement activation by stabilizing the alternative pathway convertase through C3 binding, thus prolonging its half-life. (helsinki.fi)
A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. (lookformedical.com)
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. (lookformedical.com)
CFH is the first regulatory protein of the alternative pathway of the complement system. (hycultbiotech.com)

Most forms of aHUS are associated with dysregulation of the alternative complement pathway (ACP), resulting in complement-mediated endothelial cell injury, with ensuing end-organ tissue damage ( 1 , 2 ). (frontiersin.org)
RATIONALE & OBJECTIVE: C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. (bvsalud.org)

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). (nih.gov)
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. (lookformedical.com)
C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. (promisekit.org)

Another complement protein, C6, binds to C5b. (promisekit.org)
When CRP aggregates or binds to macromolecule ligands, the classical pathway of complement activation can be achieved through interactions with C1q ( 11 , 12 ). (spandidos-publications.com)

The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)
Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)
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. (lookformedical.com)
In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. (biomedcentral.com)
Individuals with primary immunodeficiencies such as the autosomal recessive terminal complement pathway deficiencies have a 7000-10,000 fold higher risk of IMD compared to the general population and more than half of these patients develop recurrent episodes of IMD [ 6 ]. (biomedcentral.com)
In addition to inherited deficiencies of the terminal complement pathway, a number of medical conditions and treatments can lead to acquired or secondary complement deficiency. (biomedcentral.com)

C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. (lookformedical.com)
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. (lookformedical.com)

The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. (nih.gov)
It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A. (lookformedical.com)

Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.com)
Complement deficiencies are said to comprise between 1 and 10% of all primary immunodeficiencies. (medscape.com)
[ 4 ] A registry of complement deficiencies has been established as a means to promote joint projects on treatment and prevention of diseases associated with defective complement function. (medscape.com)
This article outlines some of the disease states associated with complement deficiencies and their clinical implications. (medscape.com)
Complement pathways and deficiencies. (medscape.com)
Deficiencies in complement predispose patients to infection via 2 mechanisms: (1) ineffective opsonization and (2) defects in lytic activity (defects in MAC). (medscape.com)
Specific complement deficiencies are also associated with an increased risk of developing autoimmune disease, such as SLE. (medscape.com)
Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies ( 5.1 ). (nih.gov)
Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. (biomedcentral.com)
Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. (biomedcentral.com)
Characterising cases of IMD in individuals with complement deficiencies is fundamental to understanding disease risk in this highly vulnerable population and developing evidence-based guidance to both prevent and rapidly treat this potentially fatal condition. (biomedcentral.com)
These acquired complement deficiencies are most commonly encountered in diseases featuring autoantibodies. (medicalnotes.info)
Which two primary complement deficiencies most commonly predispose to infection by encapsulated bacteria? (medicalnotes.info)
C3 and C5 deficiencies are the primary complement deficiencies implicated here. (medicalnotes.info)
Deficiencies of the later complement components (i.e. (medicalnotes.info)

Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome. (nih.gov)
Terminal complement complex (C5b-9) in children with recurrent hemolytic uremic syndrome. (nih.gov)
The treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy ( 1.2 ). (nih.gov)

A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. (lookformedical.com)

Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. (nih.gov)
Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)
A North African study of molecular basis of complement factor I deficiency in atypical hemolytic and uremic syndrome patients suggested that the Ile357Met mutation may be a founding effect. (medscape.com)
To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. (biomedcentral.com)
We retrospectively identified patients with complement deficiency who developed IMD in England during 2008-2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain. (biomedcentral.com)
IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains. (biomedcentral.com)
Here we describe age distribution, clinical presentation, risk of recurrence, meningococcal typing and outcome of IMD in individuals with inherited or acquired complement deficiency diagnosed in England over a ten-year period. (biomedcentral.com)
A patient with recurrent infections with encapsulated bacteria is found to have a primary complement deficiency. (medicalnotes.info)

Complement C5, also named C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4, is involved in the complement system and it is encoded by the C5 gene in human. (watson-bio.cn)
This gene encodes one of the three subunits of the complement component 8 (C8) protein. (nih.gov)

Diatec Monoclonals offers an excellent monoclonal antibody against human C5b-9, the Terminal Complement Complex (TCC). (diatec.com)
Monoclonal antibody 1A2 recognizes mouse complement factor H (CFH). (hycultbiotech.com)

In conjunction with genetic predisposition, acquired autoantibodies against Factor H (FH) have been implicated in the pathogenesis of aHUS in approximately 10% of cases, and are mostly attributed to genomic rearrangements or deletions in CFH / CFHR1/CFHR3/CFHR4 genes within the regulators of complement activation gene cluster ( 9 , 10 ). (frontiersin.org)

C3d is a terminal degradation product of C3 that plays an important role in modulation of the adaptive immune response through the interaction with complement receptor type 2 (CR2). (wlsolutions.be)

Soluble concentrations of the terminal complement complex C5b-9 correlate with end-organ injury in preeclampsia. (bvsalud.org)
We sought to determine if soluble levels of C5b-9 , the terminal complement complex , correlate with end-organ injury in preeclampsia . (bvsalud.org)
This antibody recognizes C5b-9, the terminal complement complex (TCC). (diatec.com)

IFX-1 is a monoclonal anti-human complement factor C5a antibody designed to inhibit the biological activity of C5a. (clinicaltrialsarena.com)
Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES. (lookformedical.com)
The complement system is a major component of innate immunity and a "complement" (from which its name is derived) to antibody-triggered responses. (medicalnotes.info)

The complement system is an evolutionarily ancient key component of innate immunity required for the detection and removal of invading pathogens. (nih.gov)

Soluble C5b-9 levels may be used to identify complement -mediated end-organ injury in preeclampsia . (bvsalud.org)

JENA, Germany, March 22, 2023 (GLOBE NEWSWIRE) -- InflaRx N.V. (Nasdaq: IFRX), a clinical-stage biopharmaceutical company developing anti-inflammatory therapeutics by targeting the complement system, today announced financial and operating results for the year ended December 31, 2022. (yahoo.com)

This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. (nih.gov)
The complement system is part of the innate immune system. (medscape.com)

in particular, interaction between the complement system and the meningococcus has proven to be important in the pathogenesis of invasive meningococcal disease (IMD). (biomedcentral.com)

Complement C5 is the 5th component of complement, which plays a central role in inflammatory and cell killing processes. (prospecbio.com)
Immune complexes comprising autoantibody and self-antigen is deposited particulary in the renal glomeruli and mediate a systemic inflammatory response by activating complement or via Fc{gamma}R-mediated neutrophil and macrophage activation. (genome.jp)
Complement C5 is the fifth component of complement, which plays an important role in inflammatory and cell killing processes. (watson-bio.cn)

C5a elevation in convalescents from severe COVID-19 is not associated with early complement activation markers C3bBbP or C4d. (nih.gov)
at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check. (medscape.com)
10. Phosphatidylcholine-directed phospholipase C: activation by complement C5b-9. (nih.gov)
The management of most disorders of the complement system featuring excessive activation focuses on the treatment of the underlying disorders. (medicalnotes.info)

Because these functions are closely tied to the actions of antibodies, defects in the complement system result in recurrent infections with extracellular bacteria, including encapsulated bacteria. (medicalnotes.info)

In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). (medscape.com)

New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. (medscape.com)
More recently, complement has also emerged as a critical player in adaptive immunity via its ability to instruct both B and T cell responses. (nih.gov)

We have previously shown that administration of complement and HMGB1 inhibitors attenuate morbidity and mortality 24 h after injury in a rat model of blast injury (BI) and HS. (bvsalud.org)

All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. (promisekit.org)

These pathways converge to form C3/C5 convertases that generate C3a, C3b,C5a, and C5b, each with substantial biologic activity. (hycultbiotech.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)
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)
An intricate system regulates complement activity. (medscape.com)
Complement Component C5a (C5a) is involved in the complement system and it is encoded by the C5 gene in human. (prospecbio.com)
In particular, work on the impact of complement on T cell responses led to the surprising discoveries that the complement system also functions within cells and is involved in regulating basic cellular processes, predominantly those of metabolic nature. (nih.gov)
IMD usually affects healthy individuals, in which a functional complement system acts as a first-line innate immune defence against invading pathogens [ 4 ]. (biomedcentral.com)
The aim of this project was to ascertain whether the complement (C) system is engaged in a PDT-treated solid tumor and if this plays a role in overall tumor response to treatment. (ubc.ca)

We identified a pattern of increased urine and low plasma C5b-9 levels in patients with preeclampsia and end-organ injury . (bvsalud.org)

Reductions in complement secondary to acquired disease processes are usually only partial and affect several complement components at once. (medicalnotes.info)
Secondary (i.e., acquired) complement defects are seldom clinically important. (medicalnotes.info)

The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. (lookformedical.com)

TCC consist of C5b, C6, C7, C8 and C9 and contains neoantigens that are absent from the individual native components. (diatec.com)
Complement components analysis using specific immunoassays was performed on frozen plasma samples from the patient and mother. (frontiersin.org)

C5b-9 concentrations in plasma and urine , using enzyme linked immunosorbent assays. (bvsalud.org)

Some new clinical entities are linked with partial complement defects. (medscape.com)

It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. (lookformedical.com)
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). (lookformedical.com)

Eculizumab decreases complement-induced he- but remained transfusion-independent. (cdc.gov)

El mayor fragmento generado por la escisión de C5 por la CONVERTASA DE C5 que produce COMPLEMENTO C5A y C5b (cadena beta + cadena alfa', la cadena alfa residual, unida por un enlace disulfuro). (bvsalud.org)

Anatomy15

Organisms10

Diseases16

Chemicals and Drugs101

Analytical, Diagnostic and Therapeutic Techniques and Equipment25

Phenomena and Processes48

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Health Care1

Mechanism of complement-dependent haemolysis via the lectin pathway: role of the complement regulatory proteins. (1/26)

Glomerular complement regulation is overwhelmed in passive Heymann nephritis. (2/26)

Role of membrane cofactor protein (CD46) in regulation of C4b and C3b deposited on cells. (3/26)

Regulation of glycoprotein IIb-IIIa receptor function studied with platelets permeabilized by the pore-forming complement proteins C5b-9. (4/26)

Persistent complement activation on tumor cells in breast cancer. (5/26)

The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation. (6/26)

Recombinant C345C and factor I modules of complement components C5 and C7 inhibit C7 incorporation into the complement membrane attack complex. (7/26)

Regulatory control of the terminal complement proteins at the surface of human endothelial cells: neutralization of a C5b-9 inhibitor by antibody to CD59. (8/26)

Complement C3

Complement C4

Complement C4a

Complement C3a

Complement C1q

Complement C5a

Complement Activation

Complement C4b

Complement C5

Complement C3b

Complement System Proteins

Complement C6

Complement C3c

Complement C3d

Complement C2

Complement C9

Receptors, Complement

Complement C1s

Complement Membrane Attack Complex

Complement C1r

Complement Inactivator Proteins

Complement C7

Complement C3-C5 Convertases

Complement Factor B

Complement Pathway, Alternative

Complement Pathway, Classical

Complement C8

Complement C1

Receptors, Complement 3b

Complement Factor H

Complement C5b

Complement C2a

Receptor, Anaphylatoxin C5a

Complement Activating Enzymes

Complement Inactivating Agents

Complement Hemolytic Activity Assay

Complement C1 Inactivator Proteins

Receptors, Complement 3d

Anaphylatoxins

Complement Fixation Tests

Complement Factor D

Complement Factor I

Complement C4b-Binding Protein

Complement C3b Inactivator Proteins

Antigens, CD55

Complement C3-C5 Convertases, Classical Pathway

Complement C2b

Antigens, CD59

Cobra Venoms

Antigen-Antibody Complex

Steroid 21-Hydroxylase

Complement C3-C5 Convertases, Alternative Pathway

Complement C1 Inhibitor Protein

Immunoglobulin G

Hemolysis

Complement C3 Convertase, Alternative Pathway

Complement C5 Convertase, Classical Pathway

Molecular Sequence Data

Complement C3 Convertase, Classical Pathway

Antigens, CD46

Opsonin Proteins

Blood Proteins

Lupus Erythematosus, Systemic

Complement C5 Convertase, Alternative Pathway

Phagocytosis

Amino Acid Sequence

Complement Pathway, Mannose-Binding Lectin

Properdin

Complement C5a, des-Arginine

Mice, Inbred C57BL

Macrophage-1 Antigen

Protein Binding

Neutrophils

Base Sequence

Kidney Glomerulus

Serum

Glomerulonephritis, Membranoproliferative

Immunoglobulin M

Schistosoma

Genetic Complementation Test