Complement Activation: 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.Complement C3: A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.Complement System Proteins: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).Complement C4: 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.Complement C5: 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.Receptors, Complement: Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.Complement C3b: The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.Complement C1q: A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.Complement Pathway, Alternative: Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Complement C9: 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.Complement Pathway, Classical: Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Complement Membrane Attack Complex: A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.Complement Inactivator Proteins: Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.Complement C2: 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).Complement Factor B: 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 Factor H: An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).Complement Inactivating Agents: Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.Complement C3a: The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.Complement C5a: 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.Complement C6: 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.Receptors, Complement 3b: Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.Complement C1: 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.Complement C4b: 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).Complement Activating Enzymes: 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.Complement C3d: A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).Complement C3-C5 Convertases: Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.Complement Fixation Tests: Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.Complement C7: 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.Complement C8: 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.Complement C3c: 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.Receptors, Complement 3d: Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.Complement Hemolytic Activity Assay: A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.Complement C3b Inactivator Proteins: Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.Complement C4a: 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.Complement Factor D: 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.Complement Factor I: A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.Complement C4b-Binding Protein: 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).Complement C1s: A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).Complement C1r: 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.Antigens, CD55: 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.Antigens, CD59: 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)Complement C1 Inactivator Proteins: Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.Complement C5b: 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.Complement Pathway, Mannose-Binding Lectin: Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Properdin: 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.Cobra Venoms: 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.Hemolysis: The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.Complement C1 Inhibitor Protein: An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.Anaphylatoxins: 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.Complement C3 Convertase, Alternative Pathway: 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.Antigens, CD46: 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.Receptor, Anaphylatoxin C5a: A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.Genetic Complementation Test: 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.Antigen-Antibody Complex: 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.Opsonin Proteins: 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.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Blood Bactericidal Activity: The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.Mannose-Binding Lectin: 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.Amino Acid Sequence: 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.Macrophage-1 Antigen: 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.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Mannose-Binding Protein-Associated Serine Proteases: Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.ZymosanImmunoglobulin M: 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.Complement C5a, des-Arginine: 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).Neutrophils: 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.Protein Binding: 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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Mutation: 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.Antibodies: 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).Rabbits: 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.Collectins: 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.Mice, Inbred C57BLMacular Degeneration: 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.Cloning, Molecular: 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.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Bacterial Proteins: Proteins found in any species of bacterium.Guinea Pigs: 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.Immune Adherence Reaction: 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.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Escherichia coli: 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.Immunoelectrophoresis: 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.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Fluorescent Antibody Technique: 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.Glomerulonephritis: 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.Hemoglobinuria, Paroxysmal: 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.Immune Complex Diseases: 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.Immunoglobulins: 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.Cells, Cultured: 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.Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Complement C2b: The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.Cryoglobulins: Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.Lectins: Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.Mice, Knockout: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Immunity, Innate: 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.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Macrophages: 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.)Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Species Specificity: 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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Kinetics: The rate dynamics in chemical or physical systems.Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.Disease Models, Animal: 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.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.Serum: The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.Rosette Formation: The in vitro formation of clusters consisting of a cell (usually a lymphocyte) surrounded by antigenic cells or antigen-bearing particles (usually erythrocytes, which may or may not be coated with antibody or antibody and complement). The rosette-forming cell may be an antibody-forming cell, a memory cell, a T-cell, a cell bearing surface cytophilic antibodies, or a monocyte possessing Fc receptors. Rosette formation can be used to identify specific populations of these cells.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.RNA, Messenger: 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.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Glomerulonephritis, Membranoproliferative: 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.Antigens, CD: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.Mice, Inbred BALB Cgamma-Globulins: Serum globulins that migrate to the gamma region (most positively charged) upon ELECTROPHORESIS. At one time, gamma-globulins came to be used as a synonym for immunoglobulins since most immunoglobulins are gamma globulins and conversely most gamma globulins are immunoglobulins. But since some immunoglobulins exhibit an alpha or beta electrophoretic mobility, that usage is in decline.Complement C3 Convertase, Classical Pathway: 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).Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.Flow Cytometry: 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.Immune Evasion: Methods used by pathogenic organisms to evade a host's immune system.Immunoglobulin Fc Fragments: Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Membrane Proteins: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Arthus Reaction: A dermal inflammatory reaction produced under conditions of antibody excess, when a second injection of antigen produces intravascular antigen-antibody complexes which bind complement, causing cell clumping, endothelial damage, and vascular necrosis.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Molecular Weight: The sum of the weight of all the atoms in a molecule.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Genes, Bacterial: The functional hereditary units of BACTERIA.B-Lymphocytes: 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.Monocytes: 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.Nephritis: Inflammation of any part of the KIDNEY.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Edetic Acid: A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).Inflammation: 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.Polysaccharides, Bacterial: Polysaccharides found in bacteria and in capsules thereof.Angioedema: Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.Bacterial Outer Membrane Proteins: Proteins isolated from the outer membrane of Gram-negative bacteria.Lipopolysaccharides: 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)Spleen: An encapsulated lymphatic organ through which venous blood filters.DNA: 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).Receptors, Fc: Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Leukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Neutralization Tests: The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).Blotting, Western: 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.T-Lymphocytes: 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.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Snakes: Limbless REPTILES of the suborder Serpentes.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Integrin alphaXbeta2: A major adhesion-associated heterodimer molecule expressed by MONOCYTES; GRANULOCYTES; NK CELLS; and some LYMPHOCYTES. The alpha subunit is the CD11C ANTIGEN, a surface antigen expressed on some myeloid cells. The beta subunit is the CD18 ANTIGEN.Mannans: Polysaccharides consisting of mannose units.Clusterin: A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.Serum Globulins: All blood proteins except albumin ( = SERUM ALBUMIN, which is not a globulin) and FIBRINOGEN (which is not in the serum). The serum globulins are subdivided into ALPHA-GLOBULINS; BETA-GLOBULINS; and GAMMA-GLOBULINS on the basis of their electrophoretic mobilities. (From Dorland, 28th ed)Streptococcus pneumoniae: 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.Epitopes: Sites on an antigen that interact with specific antibodies.Erythrocyte Membrane: The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.Gene Expression Regulation: 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.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Histocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.Immunoglobulin A: Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Neisseria meningitidis: A species of gram-negative, aerobic BACTERIA. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the NASOPHARYNX. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis (MENINGITIS, MENINGOCOCCAL). It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being A, B, C, Y, and W-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype.Immunization, Passive: Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).Meningococcal Infections: Infections with bacteria of the species NEISSERIA MENINGITIDIS.Reperfusion Injury: Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (REPERFUSION), including swelling; HEMORRHAGE; NECROSIS; and damage from FREE RADICALS. The most common instance is MYOCARDIAL REPERFUSION INJURY.Hemagglutination Tests: Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)Chromium Isotopes: Stable chromium atoms that have the same atomic number as the element chromium, but differ in atomic weight. Cr-50, 53, and 54 are stable chromium isotopes.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Protein Conformation: 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).Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Chemotaxis, Leukocyte: The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Snake Venoms: Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors.Rheumatoid Factor: Antibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS.Isoantibodies: Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.

Complement activity and pharmacological inhibition in cardiovascular disease. (1/54)

While complement is the most important component of humoral autoimmunity, and inflammation plays a key role in atherosclerosis, relatively few studies have looked at complement implications in atherosclerosis and its complications. C-reactive protein is a marker of inflammation and is also involved in atherosclerosis; it activates complement and colocalizes with activated complement proteins within the infarcting myocardium and the active atherosclerotic plaques. As new agents capable of modulating complement activity are being developed, new targets for the management of atherosclerosis are emerging that are related to autoimmunity and inflammation. The present paper reviews the putative roles of the various complement activation pathways in the development of atherosclerosis, in ST segment elevation and non-ST segment elevation acute coronary syndromes, and in coronary artery bypass graft surgery. It also provides a perspective on new therapeutic interventions being developed to modulate complement activity. These interventions include the C1 esterase inhibitor, which may be consumed in some inflammatory states resulting in the loss of one of the mechanisms inhibiting activation of the classical and lectin pathways; TP10, a recombinant protein of the soluble complement receptor type 1 (sCR1) which inhibits the C3 and C5 convertases of the common pathway by binding C3b and C4b; a truncated version of the soluble complement receptor type 1 CRI lacking the C4b binding site which selectively inhibits the alternative pathway; and pexelizumab, a monoclonal antibody selectively blocking C5 to prevent the activation of the terminal pathway that is involved in excessive inflammation and autoimmune responses.  (+info)

Therapeutic strategy with a membrane-localizing complement regulator to increase the number of usable donor organs after prolonged cold storage. (2/54)

A shortage of donor organs and increasing dependence on marginal grafts with prolonged ischemic times have meant that new methods are needed to prevent postischemic damage. Herein is reported a new strategy aimed to protect donor kidney from complement-mediated postischemic damage and therefore increase the number of successful transplants. Rat donor kidneys were perfused with a membrane-localizing complement regulator derived from human complement receptor type 1 (APT070) and then subjected to prolonged periods of cold storage (at 4 degrees C). A relationship was found between the duration of cold ischemia and the extent of complement-mediated tubule damage and loss of graft function. After 16 h of cold storage, APT070-treated kidneys that were transplanted into syngeneic recipients showed a significant increase in the number of surviving grafts, compared with control-treated grafts (63.6 versus 26.3%). Surviving grafts also displayed less acute tubular injury and better preservation of renal function. These results not only enhance the understanding of the mechanism by which prolonged cold ischemia reduces immediate graft survival but also provide essential information about the effectiveness of membrane-localizing complement regulator with prolonged cold storage. This could lead to more effective strategies for improving the use of severely ischemic donor organs.  (+info)

Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H. (3/54)

Relapsing fever is a rapidly progressive and severe septic disease caused by certain Borrelia spirochetes. The disease is divided into two forms, i.e., epidemic relapsing fever, caused by Borrelia recurrentis and transmitted by lice, and the endemic form, caused by several Borrelia species, such as B. duttonii, and transmitted by soft-bodied ticks. The spirochetes enter the bloodstream by the vector bite and live persistently in plasma even after the development of specific antibodies. This leads to fever relapses and high mortality and clearly indicates that the Borrelia organisms utilize effective immune evasion strategies. In this study, we show that the epidemic relapsing fever pathogen B. recurrentis and an endemic relapsing fever pathogen, B. duttonii, are serum resistant, i.e., resistant to complement in vitro. They acquire the host alternative complement pathway regulator factor H on their surfaces in a similar way to that of the less serum-resistant Lyme disease pathogen, B. burgdorferi sensu stricto. More importantly, the relapsing fever spirochetes specifically bind host C4b-binding protein, a major regulator of the antibody-mediated classical complement pathway. Both complement regulators retained their functional activities when bound to the surfaces of the spirochetes. In conclusion, this is the first report of complement evasion by Borrelia recurrentis and B. duttonii and the first report showing capture of C4b-binding protein by spirochetes.  (+info)

A novel inhibitor of the alternative pathway of complement reverses inflammation and bone destruction in experimental arthritis. (4/54)

Complement is an important component of the innate and adaptive immune response, yet complement split products generated through activation of each of the three complement pathways (classical, alternative, and lectin) can cause inflammation and tissue destruction. Previous studies have shown that complement activation through the alternative, but not classical, pathway is required to initiate antibody-induced arthritis in mice, but it is unclear if the alternative pathway (AP) plays a role in established disease. Previously, we have shown that human complement receptor of the immunoglobulin superfamily (CRIg) is a selective inhibitor of the AP of complement. Here, we present the crystal structure of murine CRIg and, using mutants, provide evidence that the structural requirements for inhibition of the AP are conserved in human and mouse. A soluble form of CRIg reversed inflammation and bone loss in two experimental models of arthritis by inhibiting the AP of complement in the joint. Our data indicate that the AP of complement is not only required for disease induction, but also disease progression. The extracellular domain of CRIg thus provides a novel tool to study the effects of inhibiting the AP of complement in established disease and constitutes a promising therapeutic with selectivity for a single complement pathway.  (+info)

Characterization of Ehp, a secreted complement inhibitory protein from Staphylococcus aureus. (5/54)

We report here the discovery and characterization of Ehp, a new secreted Staphylococcus aureus protein that potently inhibits the alternative complement activation pathway. Ehp was identified through a genomic scan as an uncharacterized secreted protein from S. aureus, and immunoblotting of conditioned S. aureus culture medium revealed that the Ehp protein was secreted at the highest levels during log-phase bacterial growth. The mature Ehp polypeptide is composed of 80 residues and is 44% identical to the complement inhibitory domain of S. aureus Efb (extracellular fibrinogen-binding protein). We observed preferential binding by Ehp to native and hydrolyzed C3 relative to fully active C3b and found that Ehp formed a subnanomolar affinity complex with these various forms of C3 by binding to its thioester-containing C3d domain. Site-directed mutagenesis demonstrated that Arg(75) and Asn(82) are important in forming the Ehp.C3d complex, but loss of these side chains did not completely disrupt Ehp/C3d binding. This suggested the presence of a second C3d-binding site in Ehp, which was mapped to the proximity of Ehp Asn(63). Further molecular level details of the Ehp/C3d interaction were revealed by solving the 2.7-A crystal structure of an Ehp.C3d complex in which the low affinity site had been mutationally inactivated. Ehp potently inhibited C3b deposition onto sensitized surfaces by the alternative complement activation pathway. This inhibition was directly related to Ehp/C3d binding and was more potent than that seen for Efb-C. An altered conformation in Ehp-bound C3 was detected by monoclonal antibody C3-9, which is specific for a neoantigen exposed in activated forms of C3. Our results suggest that increased inhibitory potency of Ehp relative to Efb-C is derived from the second C3-binding site in this new protein.  (+info)

Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. (6/54)

Hemolysis and hemoglobinemia contribute to serious clinical sequelae in hemolytic disorders. In paroxysmal nocturnal hemoglobinuria (PNH) patients, hemolysis can contribute to thromboembolism (TE), the most feared complication in PNH, and the leading cause of disease-related deaths. We evaluated whether long-term treatment with the complement inhibitor eculizumab reduces the rate of TE in patients with PNH. Clinical trial participants included all patients in the 3 eculizumab PNH clinical studies, which recruited patients between 2002 and 2005 (n = 195); patients from these studies continued treatment in the current multinational open-label extension study. Thromboembolism rate with eculizumab treatment was compared with the pretreatment rate in the same patients. The TE event rate with eculizumab treatment was 1.07 events/100 patient-years compared with 7.37 events/100 patient-years (P < .001) prior to eculizumab treatment (relative reduction, 85%; absolute reduction, 6.3 TE events/100 patient-years). With equalization of the duration of exposure before and during treatment for each patient, TE events were reduced from 39 events before eculizumab to 3 events during eculizumab (P < .001). The TE event rate in antithrombotic-treated patients (n = 103) was reduced from 10.61 to 0.62 events/100 patient-years with eculizumab treatment (P < .001). These results show that eculizumab treatment reduces the risk of clinical thromboembolism in patients with PNH. This study is registered at http://clinicaltrials.gov (study ID no. NCT00122317).  (+info)

Management of hereditary angioedema in pediatric patients. (7/54)

Hereditary angioneurotic edema is a rare disorder caused by the congenital deficiency of C1 inhibitor. Recurring angioedematous paroxysms that most commonly involve the subcutis (eg, extremities, face, trunk, and genitals) or the submucosa (eg, intestines and larynx) are the hallmarks of hereditary angioneurotic edema. Edema formation is related to reduction or dysfunction of C1 inhibitor, and conventional therapy with antihistamines and corticosteroids is ineffective. Manifestations occur during the initial 2 decades of life, but even today there is a long delay between the onset of initial symptoms and the diagnosis of hereditary angioneurotic edema. Although a variety of reviews have been published during the last 3 decades on the general management of hereditary angioneurotic edema, little has been published regarding management of pediatric hereditary angioneurotic edema. Thus, we review our experience and published data to provide an approach to hereditary angioneurotic edema in childhood.  (+info)

Association of reactive oxygen and nitrogen intermediate and complement levels with apoptosis of peripheral blood mononuclear cells in lupus patients. (8/54)

OBJECTIVE: Both increased production of reactive oxygen and nitrogen intermediates (RONI) and reduced levels of complement may play a role in the increased apoptosis and reduced clearance of apoptotic cells in systemic lupus erythematosus (SLE). The objective of this study was to evaluate both processes in a parallel, prospective, longitudinal manner. METHODS: Sixty-seven SLE patients were evaluated during multiple visits, and 31 healthy control subjects were evaluated once or twice. Clinical and laboratory features of SLE disease activity were determined, and blood was collected for measurement of serum nitrate plus nitrite (NOx) levels and for isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were cultured with a nitric oxide (NO) donor and SLE or control plasma, with or without heat inactivation, cobra venom factor (CVF), or lipopolysaccharide plus interferon-gamma treatment. Cells were analyzed for apoptotic index (AI), cellular subsets, and RONI production. RESULTS: The PBMC AI was associated with SLE and was inversely associated with complement levels over time. Changes in the AI with addition of a NO donor was longitudinally associated with serum NOx levels, and stimulation of SLE PBMCs led to parallel increases in RONI production and apoptosis. Addition of SLE plasma resulted in a greater PBMC AI, an effect that was increased with heat inactivation and was corrected with CVF treatment. CONCLUSION: These data suggest that the greater AI observed in SLE PBMCs relates to increased PBMC RONI production and reduced complement levels. The longitudinal nature of these parallel associations within individuals suggests that these processes are dynamic and additive.  (+info)

The vitamins -A, B-Complex and C increase rapidly during germination. In moong sprouts the vitamin A content increases by 285%, thiamine by 208%, riboflavin by an astounding 515%, niacin by 256% and finally ascorbic acid by 600%. When the seeds sprout, shoots appear earlier than roots. The sprouts are maximally nutritious, if consumed before the roots start emerging. ...
A Novel Protocol Allowing Oral Delivery of a Protein Complement Inhibitor that Subsequently Targets to Inflamed Colon Mucosa and Ameliorates Murine Colitis. Elvington, M; Blichmann, P; Qiao, F; Scheiber, M; Wadsworth, C; et al. A novel protocol allowing oral delivery of a protein complement inhibitor that subsequently targets to inflamed colon mucosa and ameliorates murine colitis. Clinical and Experimental Immunology 177.2 (Aug 2014): 500-508. While there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of ...
article{5be1f4a6-d9f6-43e4-84be-f1c903a8b6fe, abstract = {C4b-binding protein (C4BP), an important inhibitor of complement activation, has a unique spider-like shape. It is composed of six to seven identical alpha-chains with or without a single beta-chain, the chains being linked by disulfide bridges in their C-terminal parts. To elucidate the structural requirements for the assembly of the alpha-chains, recombinant C4BP was expressed in HEK 293 cells. The expressed C4BP was found to contain six disulfide-linked alpha-chains. Pulse-chase analysis demonstrated that the recombinant C4BP was rapidly synthesized in the cells and the polymerized C4BP appeared in the medium after 40 min. The alpha-chains were polymerized in the endoplasmic reticulum (ER) already after 5 min chase. The polymerization process was unaffected by blockage of the transport from the ER to the Golgi mediated by brefeldin A or low temperature (10 degrees C). The C-terminal part of the alpha-chain (57 amino acids), containing ...
NEW HAVEN, Conn.--(BUSINESS WIRE)--Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) announced today that the pivotal Phase 3 study of ALXN1210, the Companys investigational long-acting C5 complement inhibitor, demonstrated non-inferiority to Soliris® (eculizumab) in complement inhibitor treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH) based on the co-primary endpoints of transfusion avoidance and normalization of lactate dehydrogenase (LDH) levels, a direct marker of complement-mediated hemolysis in PNH.
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To provide insight into bacterial suppression of complement-mediated immunity, we present here structures of a bacterial complement inhibitory protein, both free and bound to its complement target. The 1.25-A structure of the complement component C3-inhibitory domain of Staphylococcus aureus extrace …
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Preview: This six-game Wolves homestand continues with a visit by a San Antonio team that has won 10 consecutive games and owns the NBAs best record at 38-11. ... The Spurs kick off a nine-game trip; both center Tim Duncan and guard Manu Ginobili traveled to Minneapolis but neither is expected to play. Duncan sprained his ankle and injured his knee during a scary fall in Saturdays 96-86 victory over Washington. Ginobili has an injured hamstring. ... Note the unusual start time for ESPN. ... Wolves forward Andrei Kirilenko on Tuesday was named the European Player of the Year. Past winners include Dirk Nowitzki, Pau Gasol and Tony Parker. ... NBA commissioner David Stern is expected to attend the game and will hold a news conference before it.
AMYNDAS is developing a novel peptidic complement inhibitor AMY-101, based on the third-generation compstatin analogue Cp40. AMY-101 is a selective inhibitor of complement activation in humans and in NHP. It binds to the complement component C3, the central functional hub that controls the upstream activation/amplification and downstream effector functions of complement. By binding to C3, AMY-101 inhibits the cleavage of native C3 to its active fragments C3a and C3b. As a consequence, the deposition of C3b, amplification via the alternative pathway and all downstream complement responses are prevented. AMY-101 is being developed to treat complement-mediated diseases, which are largely driven by aberrant C3 activation.. This first-in-human study of the C3-targeting complement inhibitor AMY-101 investigates the safety and PK/PD profile of AMY-101 in healthy male volunteers after Single Ascending Dose (SAD) and Multiple Doses (MD) using subcutaneous (SQ) or intravenous (IV) administration. The ...
CRI 213. Research Interests. Complement is a group of about 50 soluble and cell surface proteins that represent a crucial component of both the innate and adaptive immune systems. Research in the laboratory is focused on the biology of the complement system, and how it modulates an inflammatory response and shapes adaptive immunity. Within the context of complement-modulated immunity, areas of study relate to ischemic injury and disease (such as stroke, spinal cord injury and post-transplant ischemia reperfusion injury), alloimmunity (transplant rejection) and cancer immunity. A further area of study is the dual role of complement in liver injury and regeneration, important in the context of liver resection or small-for-size transplant. Integrated within these studies is the development and characterization of various site-targeted strategies for complement inhibition. These strategies (some of which are in clinical development) are being investigated in various mouse models of injury and ...
BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typically with off-label use or at supratherapeutic doses. OBJECTIVES: Active surveillance of safety and clinical usage patterns of pasteurized C1-inhibitor concentrate and the more recent pasteurized, nanofiltered C1-INH, with a particular interest in thromboembolic events. METHODS: A registry was initiated in April 2010 at 27 US and 4 EU sites to obtain both prospective and retrospective safety and usage data on subjects who were administered C1-INH (Berinert). RESULTS: As of May 10, 2013, data were available for 135 subjects and 3196 infusions. By subject, 67.4% were using C1-INH as on-demand therapy and 23.0% as both on-demand therapy and prophylactic administration. Approximately half of the infusions ...
Bowman-Birk Inhibitor Concentrate is an anticarcinogenic derived from soybeans which inhibits the protease chymotrypsin. The inhibitor was being developed at
Being a major first line of immune defense, the complement system keeps a constant vigil against viruses. Its ability to recognize a large panoply of viruses and virus-infected cells, and trigger the effector pathways, results in neutralization of viruses and killing of the infected cells. This selection pressure exerted by complement on viruses has made them evolve a multitude of countermeasures. These include targeting the recognition molecules for avoidance of detection, targeting key enzymes and complexes of the complement pathways like C3 convertases and C5b-9 formation - either by encoding complement regulators or by recruiting membrane-bound and soluble host complement regulators, cleaving complement proteins by encoding protease, and inhibiting the synthesis of complement proteins. Additionally, viruses also exploit the complement system for their own benefit. For example, they use complement receptors as well as membrane regulators for cellular entry as well as their spread. Here, we provide an
Hello,. I recently received a question about infusing eculizumab during dialysis to save chair time for the patient. I am aware that eculizumab is theoretically too large to be dialyzed out, but I am wondering if anyone else has experience doing this at their institution and whether there were any issues experienced?. Thanks in advance ...
TY - JOUR. T1 - Assessment of inhibitory antibodies in patients with hereditary angioedema treated with plasma-derived C1 inhibitor. AU - Farkas, Henriette. AU - Varga, Lilian. AU - Moldovan, Dumitru. AU - Obtulowicz, Krystyna. AU - Shirov, Todor. AU - Machnig, Thomas. AU - Feuersenger, Henrike. AU - Edelman, Jonathan. AU - Williams-Herman, Debora. AU - Rojavin, Mikhail. PY - 2016/11/1. Y1 - 2016/11/1. N2 - Background Limited data are available regarding C1 inhibitor (C1-INH) administration and anti-C1-INH antibodies. Objective To assess the incidence of antibody formation during treatment with pasteurized, nanofiltered plasma-derived C1-INH (pnfC1-INH) in patients with hereditary angioedema with C1-INH deficiency (C1-INH-HAE) and the comparative efficacy of pnfC1-INH in patients with and without antibodies. Methods In this multicenter, open-label study, patients with C1-INH-HAE (≥12 years of age) were given 20 IU/kg of pnfC1-INH per HAE attack that required treatment and followed up for 9 ...
The complement inhibitor C4b-binding protein (C4BP) prevents necrotic cells from spilling their pro-inflammatory guts, according to a study on page 1937. Trouw and colleagues now show that C4BP and its binding partner, anticoagulant protein S (PS), cooperate to grab onto necrotic cells and to inhibit the release of cellular DNA.. C4BP short-circuits the complement cascade by binding to the activated complement components C3b and C4b and presenting them to the proteolytic complement inhibitor Factor I for degradation. This inhibitory capacity of C4BP can be coopted by bacterial pathogens, which coat themselves with this protein to avoid complement-mediated destruction by phagocytic cells.. This group recently identified a role for the C4BP-PS complex: it binds to apoptotic cells through the phosphatidylserine-binding domain of PS. This association could prevent the deposition and activation of complement on the surface of the apoptotic cells, allowing the dying cells to be removed without ...
Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane- spanning protein and which is highly expressed in skeletal muscle mass, heart, adipose cells, and liver. sending the transmission to determine the function of specific cells, like skeletal muscle mass, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted cells or organs in human being has exposed its physiological functions for promoting health or executing the rules of selection of metabolic illnesses. Numerous studies MLN8237 small molecule kinase inhibitor concentrate on the association of irisin with metabolic illnesses which has obtained great interest being a potential brand-new target to fight type 2 diabetes MLN8237 small molecule kinase inhibitor mellitus and insulin level of resistance. Irisin is available to boost insulin level of resistance and type 2 diabetes by raising sensitization ...
Anti-IL-6 mAb therapy: Experiments in mouse models have shown that IL-6 is indispensable for the development of RA. This accompanied with the success of anti-IL-6 with IL-6R mAb in primates encouraged the development of therpay againtst IL-6 signalling. There are currently 2 therapeutic mAb drugs available for RA. 1. Tocilizumab (Actemra or RoActemra) is used as a monotherapy for the treatment of severe cases of RA where no previous treatment or treatment with other disease modifying antirheumatic drugs (DMARDs) has been not successful. It is a humanized monoclonal antibody that works against soluble or membrane bound (anti-IL-6R) IL-6 receptor. This prevents IL-6 and IL-6R interaction and the subsequent signal transduction, thereby reducing inflammation and other symptoms of RA.. In clinical trails ~40% of the patients achieved remission i.e their symptoms disappeared. Upto 5 studies involving 4000 people showed a considerable advantage in using tocilizumab over placebo, TNF blockers or ...
A Personal Case History As a sufferer of Hereditary Angioedema (HAE) I am posting this page, detailing my own case history, as a resource for other sufferers. I hope you find it helpful. What is Hereditary Angioedema? (taken from www.hereditaryangioedema.com) Hereditary Angioedema (HAE) is a rare and serious genetic condition occurring in about 1/10,000 to 1/50,000…
the complement systems part, a protein group involved in some allergic and immune reactions. C1 inhibitors abnormal activity or deficiency results in swelling in skins local area and the tissues beneath it, or in the mucous membrane that is the lining body opening including gastrointestinal tract, throat, and the mouth.. Viral infections or injury frequently precipitates the attack, that may be caused by emotional distress. Attacks usually produce swelling areas, that are achy rather than itchy and are not accompanied by hives. Many individuals with Hereditary Angioedema have cramps, vomiting and nausea. The most severe complications include the upper airways swelling, which may affect breathing. Blood tests that measure activity or levels of C1 inhibitor, confirm diagnosis.. The treatment consists of medication called Aminocaprotic acid, which sometimes ends hereditary angioedema attacks. Corticosteroids, antihistamines, and epinephrine are frequently prescribed; although there is no proof ...
|p|Hereditary angioedema is a rare genetic condition characterized by recurrent episodes of severe swelling in the limbs, face, intestines and airways. If you’ve been diagnosed with hereditary angioedema, it’s important to be prepared for an attack. Check out this expert-backed advice on risk factors, symptoms, treatment options and more.|/p|
Compare prices and find information about prescription drugs used to treat Hereditary Angioedema. Treatment for hereditary angiodema includes...
Hereditary angioedema (HAE) is a disease characterized by recurrent episodes of angioedema,withouturticaria or pruritus, which most often affect the skin or mucosal tissues of the upper respiratory and gastrointestinal tracts. Although the swelling i
Hereditary angioedema (HAE) is caused by a deficiency in C1 esterase inhibitor and is characterized by sudden attacks of edema associated with discomfort and pain. The disease places patients at risk for disability and death if left untreated. Sympto
Hereditary angioedema (HAE) is characterized by recurrent, self-limited episodes of swelling primarily involving the skin and the mucosa of the gastrointestinal tract and upper airway. There are several subtypes. The clinical manifestations, pathogen
We are dedicated to provide support and information on Hereditary Angioedema (HAE) to both patients and physicians, including information on recently FDA
A multicentre study to investigate pharmacokinetics, clinical efficacy and safety of nanofiltered Cetor® (called C1-esteraseremmer-N during the development phase) for the treatment of hereditary angioedema (HAE) will be performed. This study KB2003.01 consists of three parts, part A pharmacokinetics (phase II), part B treatment of attacks of angioedema (phase III) and part C prophylactic use of C1 inhibitor (phase III). Part B + C will provide data on the efficacy of C1-esteraseremmer-N.. The changes in the manufacturing process of C1-esteraseremmer-N, compared to Cetor® (the currently marketed C1-inhibitor product), nanofiltration and omission of hepatitis B immunoglobulin, most likely will not affect tolerability. The nanofiltration will provide more safety regarding viruses.. In part A, the pharmacokinetics of C1-esteraseremmer-N in patients with hereditary angioedema will be compared with the current registered product, Cetor®, in a randomised, blinded cross-over design. This study has to ...
The activation and proliferation ofT- and B-cells induced by treatment with mercuric chloride (HgC12) or silver·nitrate (AgN03) was studied in mouse strains genetically susceptible (SJL, A. SW, A.TH, BALE/C) or resistant (A.TL, BALB.B) to induction of antinucleolar antibodies (ANoA) and systemic immune-complex (I C) deposits.. SJL mice homozygous for the nude (nu) mutation were severely T-cell deficient. Neither these athymic SJL mice, nor euthymic SJL mice in which T-helper (CD4+) cells were eliminated by antiCD4 MAb treatment, developed ANoA or systemic IC-deposits in response to HgCI2 . Once induced, serum ANoA were not suppressed by 7 weeks high-dose anti-CD4 MAb therapy. This shows that chronic autoantibody (ANoA) production is relatively independent of CD4+ cells, and indicates that anti-CD4 MAb therapy should be given early in the course of autoimmune conditions in order to be efficient.. A single subcutaneous injections ofHgCl2 induced after 4-5 days in the susceptible strains a ...
It took Katie years to be diagnosed with HAE. See why she believes you should never stop looking for the doctor whos right for you.
• Baxter International Inc., of Deerfield, Ill., reported pivotal Phase III results showing that routine prophylaxis vs. on-demand treatment of FEIBA NF (anti-inhibitor coagulant complex [nanofiltered and vapor-heated]) in patients with hemophilia A or B reduced median annual bleed rate.
Wall Streets Augury: BioCryst Pharmaceuticals (Nasdaq:BCRX): Hereditary angioedema (HAE) is a very rare and potentially life-threatening genetic
As this eMedTV segment explains, Cinryze is injected into a vein every three or four days to prevent hereditary angioedema attacks. More dosing tips are outlined in this article, including helpful suggestions for when and how to use the injections.
See how Stacey helps care for her husband who has hereditary angioedema (HAE) and takes steps to ensure that her family is not defined by his condition.
Looking for online definition of hereditary angioedema in the Medical Dictionary? hereditary angioedema explanation free. What is hereditary angioedema? Meaning of hereditary angioedema medical term. What does hereditary angioedema mean?
Consumer information about hereditary angioedema (HAE), a genetic disease that causes symptoms of headache, fatigue, abdominal pain, hoarseness, and shortness of breath. There are three types or forms of hereditary angioedema. Causes, triggers, diagnosis, treatment, and prognosis information are provided.
This report on the Global Hereditary Angioedema Market analyzes the current and future prospects of the market. The report comprises an elaborate executive summary, including a market snapshot that provides overall information of various segments and sub-segments.. Request for Sample Report: http://www.mrrse.com/sample/3380. The research is a combination of primary and secondary research. Primary research formed the bulk of our research efforts along with information collected from telephonic interviews and interactions via e-mails. Secondary research involved study of company websites, annual reports, press releases, stock analysis presentations, and various international and national databases. The report provides market size in terms of US$ Mn for each segment and sub-segment for the period from 2017 to 2025, considering the macro and micro environmental factors. Growth rates for each segment within the global hereditary angioedema market have been determined after a thorough analysis of past ...
Definition of Cobra venom factor with photos and pictures, translations, sample usage, and additional links for more information.
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Complement Inhibition Promotes Endogenous Neurogenesis and Sustained Anti-Inflammatory Neuroprotection following Reperfused Stroke. Ducruet, Andrew F.; Zacharia, Brad E.; Sosunov, Sergey A.; Gigante, Paul R.; Yeh, Mason L.; Gorski, Justin W.; Otten, Marc L.; Hwang, Richard Y.; DeRosa, Peter A.; Hickman, Zachary L.; Sergot, Paulina; Sander Connolly, Jr., E. // PLoS ONE;Jun2012, Vol. 7 Issue 6, p1 Background and Purpose: The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral injury by attenuating post-ischemic inflammation. Recent reports also... ...
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Lead: Tim Illidge. Radiation treatment (RT) is a highly effective anti-cancer treatment that is delivered to over 50% of all cancer patients and 40% of those cured of their disease.. In order to further improve cancer outcomes using RT, an increased understanding of what determines effective RT-induced anti-tumour responses and how best to combine RT with others treatments is required.. Our research programme evaluates the contribution of RT-induced immunogenic cell death to the induction of tumour-specific immune responses (Project 1); determines how best to integrate RT with immunomodulatory agents to augment such responses and enhance therapeutic outcome (Project 2); and investigates how combination with RT and immune modulation can be utilised to increase the efficacy and durability of anti-CD20 mAb therapy in B- cell lymphomas (Project 3).. The pre-clinical experimental programme runs in parallel with early phase clinical trials to form a cohesive and overlapping programme of work that aims ...
The therapeutic landscape of #MultipleSclerosis (MS) has been transformed by the advent of several new #MonoclonalAntibody (MAb) therapies that can potentially lead to full stabilisation of detectable disease activity. Natalizumab, alemtuzumab and ocrelizumab are currently licensed MAbs for the treatment of MS. Daclizumab was licensed for the treatment of MS, although it has been recently withdrawn from the market by the manufacturer. Most patients are initially managed with first-line treatments, and, if disease breakthrough occurs, are escalated to a stronger compound, yet the available evidence indicates an early window of therapeutic opportunity for MAbs to exert most of their efficacy. It is important to balance the superior efficacy of MAbs compared with injectable treatments against more serious side effects, although these are well recognised and can be monitored where indicated and treated. In particular, the risk of progressive multifocal leucoencephalopathy with natalizumab can be ...
Hereditary angioedema (HAE) is an episodic swelling disorder that involves the subcutaneous tissues of the extremities or the mucosa of the bowel and occasionally the tissues of the face, mouth, and pharynx or the genital area[1, 2] Attacks most commonly increase in severity for about 1.5 days and then resolve during about the same period of time. Patients are usually most bothered by the painful abdominal attacks, which can be very severe and can lead to abdominal surgery; however, the development of laryngeal angioedema can lead to asphyxiation and death. HAE types I and II are caused by mutations in 1 of the 2 gene alleles that code for the plasma protein C1 inhibitor. This protein was named for its ability to regulate the activity of the complement protein C1, but C1 inhibitor has been found to act as a regulator or inhibitor of the clotting, fibrinolytic, and kinin-generating systems in plasma as well. It is now believed that complement is not the major system responsible for HAE attacks, ...
Although rare, hereditary angioedema (HAE) is associated with episodic attacks of edema formation that can have catastrophic consequences. Laryngeal edema can result in asphyxiation; abdominal angioedema attacks can lead to unnecessary surgery and delay in diagnosis, as well as to narcotic dependence due to severe pain; and cutaneous attacks ...
Cinryze (C1 Inhibitor (human)) is under review for the treatment of acute attacks of hereditary angioedema (HAE). Cinryze information includes news, clinical trial results and side effects.
Given her fathers premature death, Angelas doctor suspects that she has hereditary angioedema, a genetic disorder that compromises the function of C1 inhibitor protein. Patients with this genetic abnormality may have occasional episodes of swelling in various parts of the body. In Angelas case, the swelling has occurred in the respiratory tract, leading to difficulty breathing. Swelling may also occur in the gastrointestinal tract, causing abdominal cramping, diarrhea, and vomiting, or in the muscles of the face or limbs. This swelling may be nonresponsive to steroid treatment and is often misdiagnosed as an allergy.. Because there are three types of hereditary angioedema, the doctor orders a more specific blood test to look for levels of C1-INH, as well as a functional assay of Angelas C1 inhibitors. The results suggest that Angela has type I hereditary angioedema, which accounts for 80%-85% of all cases. This form of the disorder is caused by a deficiency in C1 esterase inhibitors, the ...
The high degree of parallelism in complement activation hinders a better understanding of the individual roles and relative importance of the three activation pathways both in physiological as well as in pathological processes. Specific inhibitors are extremely useful tools for basic research and therapeutic purposes. Previously, there were attempts to develop pathway-selective inhibitors by preventing the binding of the recognition molecules (C1q and MBL) to their targets (50, 51). Each activation pathway is associated with unique proteases, which could be appropriate targets for such inhibitors. Although SPs are among the most druggable targets of the complement system, early drug development efforts failed to yield specific complement inhibitors (21).. There are several X-ray structures of complement initiator proteases, but none of these present the protease in complex with an interacting peptide substrate or inhibitor (38-40, 52, 53). Without such a binding partner, the functional binding ...
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Shiga-toxin producing E. coli Haemolytic Uraemic Syndrome (STEC HUS) follows a gut infection with Shiga-toxin producing E. coli (STEC), which causes severe (often bloody) diarrhoea. Around 1000 UK children are infected with STEC each year and approximately 100 of these develop STEC HUS when a toxin from STEC causes damage to small blood vessels, especially in the kidneys. About 50-60% of children with STEC HUS need artificial kidney support (dialysis), which may last several weeks. About 2-3% of children with STEC HUS die, and about 20-25% get HUS in their brain, causing fits or a stroke. Many make a full recovery, but about 25-30% will have permanent kidney damage or more rarely brain damage. Previous studies have investigated a number of different treatments for STEC HUS, but have failed to show significant benefit. Eculizumab is a medicine that blocks part of the immune system called complement. Evidence suggests complement plays a role in STEC HUS. Eculizumab is very effective in a related ...
Bradykinin, Angioedema, Hereditary Angioedema, Gastrointestinal Tract, Larynx, Cell, Complement, Immunity, Disease, Morbidity, Risk, Mortality, and Treatment
A phase 3 trial has demonstrated that, at the approved dose of 60 IU/kg, Haegarda (C1 esterase inhibitor subcutaneous [human]) reduced the median number of hereditary angioedema (HAE) attacks per month by 98% in patients who had frequent attacks, from a 16-week placebo period to a 16-week treatment ...
A phase 3 trial has demonstrated that, at the approved dose of 60 IU/kg, Haegarda (C1 esterase inhibitor subcutaneous [human]) reduced the median number of hereditary angioedema (HAE) attacks per month by 98% in patients who had frequent attacks, from a 16-week placebo period to a 16-week treatment ...
Furthermore BacMam viruses are inactivated by human complement, which reduces risk to researchers. Lastly, viruses used in the ... Baculoviruses are Risk Group 1 agents that have been widely used for over 25 years for insect cell protein production ... "Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system ...
... immunosuppressive agents MeSH D27.505.696.477.656.500 --- complement inactivating agents MeSH D27.505.696.477.656.750 --- ... anti-allergic agents MeSH D27.505.954.122 --- anti-infective agents MeSH D27.505.954.122.085 --- anti-bacterial agents MeSH ... antiviral agents MeSH D27.505.954.122.388.077 --- anti-retroviral agents MeSH D27.505.954.122.388.077.088 --- anti-hiv agents ... renal agents MeSH D27.505.954.613.056 --- anti-infective agents, urinary MeSH D27.505.954.613.860 --- uricosuric agents MeSH ...
Winberry L, Walker R, Cohen N, Todd C, Sentissi A and Siber G. Evaluation of a new method for inactivating pertussis toxin with ... Complement (C') mediates antibody-dependent ingestion of H. influenzae type B (Hib) by macrophages (MACS). Interscience ... Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 1977 (Abstract #4ll). Siber GR, Gorham C, Durbin W, ... Pertussis toxoid inactivated with tetranitromethane: safety and immunogenicity in adults, children, and infants. In: Manclark, ...
Updated trial results presented in December 2012 indicate daratumumab is continuing to show promising single-agent anti-myeloma ... Daratumumab binds to CD38, causing cells to apoptose via antibody-dependent cellular cytotoxicity or complement-dependent ... DTT also inactivates/destroys many antigens on the red blood cell surface by disrupting disulfide bonds. Fortunately, the only ... Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab'". Janssen ...
Combining ABT-737 with second agents that inactivate Mcl-1 may reduce this effect. ABT-737 has demonstrated single-agent ... and natural killer cells to destroy the targeted cells Complement-dependent cytotoxicity (CDC)-- Initiates the complement ... Cell death does not appear to be mediated by complement, but modest antibody-dependent cellular cytotoxicity and direct killing ... Reduced susceptibility to apoptosis increases the resistance of cancer cells to radiation and cytotoxic agents. B-cell lymphoma ...
Hence, the classic inflammatory response was viewed as fully regulated by the soluble signaling agents. That is, the agents ... complement components C5a and C3a which are chemotactic factors formed during the activation of the host's blood complement ... However, studies suggest that synthetic SPM that are resistant to being metabolically inactivated hold promise of being ... While initially found to have in vitro activity suggesting that they might act as pro-inflammatory agents, Serhan and ...
First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the ... This process requires immune mechanisms to kill or inactivate the inoculum of the pathogen. Specific acquired immunity against ... such as antibody-initiated complement-dependent bacteriolysis, opsonoization, phagocytosis and killing, as occurs for some ... Second, an infectious agent must grow within the human body to cause disease; essentially it must amplify its own nucleic acids ...
... rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent ... Meri, S; Jördens, M; Jarva, H (December 2008). "Microbial complement inhibitors as vaccines". Vaccine. 26 Suppl 8: I113-7. doi: ... The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and ... Formaldehyde is used to inactivate bacterial products for toxoid vaccines. Formaldehyde is also used to inactivate unwanted ...
... s have the ability to metabolize, detoxify, and inactivate exogenous compounds such as drugs, (drug metabolism), and ... in which calcium is removed to disrupt cell-cell tight junctions by the use of a calcium chelating agent. Next, a solution ... complement, and glycoproteins. Hepatocytes manufacture their own structural proteins and intracellular enzymes. Synthesis of ... "Wheat extracts as an efficient cryoprotective agent for primary cultures of rat hepatocytes". Biotechnology and Bioengineering ...
The M-protein aids in immune evasion by inhibiting phagocytosis and inactivating the complement system. Furthermore, ... Second-line agents include macrolides and clindamycin, although increasing resistance, due to both efflux and target ... Antimicrobial Agents and Chemotherapy. 19 (5): 716-725. doi:10.1128/aac.19.5.716. ISSN 0066-4804. PMC 181512 . PMID 7027921. ...
Tissue plasminogen activator (t-PA) and urokinase are the agents that convert plasminogen to the active plasmin, thus allowing ... Plasmin, in addition to lysing fibrin clots, also cleaves the complement system component C3, and fibrin degradation products ... Alpha 2-antiplasmin and alpha 2-macroglobulin inactivate plasmin. Plasmin activity is also reduced by thrombin-activatable ... Thrombolysis refers to the dissolution of the thrombus due to various agents while fibrinolysis refers specifically to the ...
Inactivated. Main article: Inactivated vaccine. Some vaccines contain inactivated, but previously virulent, micro-organisms ... The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and ... Meri S, Jördens M, Jarva H (December 2008). "Microbial complement inhibitors as vaccines". Vaccine. 26 Suppl 8: I113-7. doi: ... Formaldehyde is used to inactivate bacterial products for toxoid vaccines. Formaldehyde is also used to inactivate unwanted ...
Agents Chemother. 49 (1): 269-75. doi:10.1128/AAC.49.1.269-275.2005. PMC 538877 . PMID 15616305. Vordenbäumen, S; Sander, O; ... The mechanism(s) by which microorganisms are killed and/or inactivated by defensins is not understood completely. However, it ... Moreover, human alpha-defensins can enhance or suppress the activation of the classical pathway of complement in vitro by ... suppress anti-inflammatory mediators and regulate complement activation argues that defensins upregulate innate host ...
This prevents infection by effectively destroying the foreign DNA introduced by an infectious agent (such as a bacteriophage). ... Interestingly, the human genome already contains remnants of retroviral genomes that have been inactivated and harnessed for ... and excision repair cross complementing 1(ERCC) appear to mimic the action of RM-systems in bacteria, and the non-homologous ... gene transfer agents or generalized transduction in order to move between genomes. Methylation Restriction enzyme LURIA SE, ...
... as the electrophilic properties of glutathione allow it to react with cytotoxic agents, inactivating them. In some cases, ... The cisplatin-resistant cells upregulate expression of the excision repair cross-complementing (ERCC1) gene and protein. Some ... In colorectal cancer cells, inhibition of NF-κB or MDR1 caused increased apoptosis in response to a chemotherapeutic agent. ... 2004-07-15). "Oncogenic H-Ras Up-Regulates Expression of ERCC1 to Protect Cells from Platinum-Based Anticancer Agents". Cancer ...
The squadrons flew agents and supplies into southern France with B-24 Liberators that had all armament removed except in the ... When assigned to Harrington, the 801st Bombardment Group (Provisional) was inactivated in a name-only manner. Headquarters and ... HHS 39th Service Group 18th Weather Squadron 35th Station Complement Squadron Regular Army Station Units included: Headquarters ... However, the Japanese surrender canceled those plans and the Group was inactivated in October. After the war, Harrington ...
These agents increase the level of aminopeptidase P, an enzyme that inactivates kinins;[22] kinins (especially bradykinin) are ... All forms of HAE lead to abnormal activation of the complement system, and all forms can cause swelling elsewhere in the body, ... In this analysis, it is usually a reduced complement factor C4, rather than the C1-INH deficiency itself, that is detected. The ... In hereditary angioedema, bradykinin formation is caused by continuous activation of the complement system due to a deficiency ...
Studies began to look for the possible species that acted as reservoirs for the virus and the agents responsible for ... The vaccine for KFDV consists of formalin-inactivated KFDV. The vaccine has a 62.4% effectiveness rate for individuals who ... Previous methods of diagnosis included HI, complement fixation, neutralization tests, and injecting the serum of infected ...
These agents increase the level of aminopeptidase P, an enzyme that inactivates kinins; kinins (especially bradykinin) are ... All forms of HAE lead to abnormal activation of the complement system, and all forms can cause swelling elsewhere in the body, ... In this analysis, it is usually a reduced complement factor C4, rather than the C1-INH deficiency itself, that is detected. The ... The version related to histamine is to due an allergic reaction to agents such as insect bites, foods, or medications. The ...
The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... Baboons and pigs carry myriad transmittable agents that are harmless in their natural host, but extremely toxic and deadly in ... Pig cells have been engineered to inactivate all 62 PERVs in the genome using CRISPR Cas9 genome editing technology,[42] and ... Interruption of the complement cascade *The recipient's complement cascade can be inhibited through the use of cobra venom ...
Note below that PARP is inactivated by caspase-3 cleavage during programmed cell death. PARP enzymes are essential in a number ... DNA damage theory of aging Maximum life span PARP1 PARP inhibitor class of anti-cancer agents Parthanatos Senescence Herceg Z, ... and scaffolding proteins such as X-ray cross-complementing gene 1 (XRCC1). After repairing, the PAR chains are degraded via ... Cleavage of Parp, by enzymes such as caspases or cathepsins, typically inactivates Parp. The size of the cleavage fragments can ...
2002). "The protein kinase complement of the human genome". Science. 298 (5600): 1912-1934. doi:10.1126/science.1075762. PMID ... signals that inactivate the phosphatases that restrict a given MAP kinase. Such signals include oxidant stress. Tyrosine- ... either natural ligands or crosslinking agents) and proteins associated with them (mutations that simulate active state) b) ...
Its causative agent is the lymphocytic choriomeningitis virus (LCMV), a member of the family Arenaviridae. The name was coined ... However, some authors note that such complement-fixation tests are insensitive and should not be used for diagnosis. Dr. Clare ... In addition, LCMV can also be inactivated by heat, ultraviolet light or gamma irradiation. LCMV infection manifests itself in a ... Such agents had been developed in the animal care facility, which periodically screened sentinel animals for extraneous ...
... directly activates the alternative complement pathway and also interferes with complement regulation by binding to complement ... A variety of viruses have also been implicated as a causative agent. It is now the most common cause of acquired acute renal ... Additionally, the binding action of Shiga-toxin inactivates a metalloproteinase called ADAMTS13, the deficiency of which causes ... a first-in-class terminal complement inhibitor, has been shown in clinical studies to block terminal complement activity in ...
... irreversibly binds to and inactivates C1r and C1s proteases in the C1 complex of classical pathway of complement. ... Lappin D, Whaley K (July 1989). "Regulation of C1-inhibitor synthesis by interferons and other agents". Behring Institute ... The activation of the complement cascade can cause damage to cells, therefore the inhibition of the complement cascade can work ... which triggers the complement cascade. Activation of the complement cascade attracts phagocytes that leak peroxide and other ...
1-bis(diazoacetyl)-2-phenylethane reversibly inactivates pepsin at pH 5, a reaction which is accelerated by the presence of Cu( ... Samuels TL, Johnston N (Nov 2009). "Pepsin as a causal agent of inflammation during nonacidic reflux". Otolaryngology--Head and ... because they are not able to bind complement, which could lyse the cells. F(ab')2, and to a greater extent Fab, fragments allow ... Exposure of laryngeal mucosa to enzymatically active pepsin, but not irreversibly inactivated pepsin or acid, results in ...
Alphonse Laveran got the 1907 Nobel Prize for his research on the role of protozoans as disease agents (notably, his discovery ... 112 They concluded that a series of three or four early injections of such heat-inactivated bacteria can effectively inoculate ... especially the implication of antibodies and the mechanisms of action of the complement; ... between Pasteur and Berthelot after the publication of Claude Bernard's posthumous essay regarding the nature of the agents ...
... and as a result are able to increase their resistance to complement-mediated killing or even down-regulate complement ... Neutrophils, macrophages, and dendritic cells produce a lipase, acyloxyacyl hydrolase (AOAH), that inactivates LPS by removing ... these molecules make candidate targets for new antimicrobial agents. Some researchers doubt reports of generalized toxic ... Pronounced complement activation can also be observed later in the course as the bacteria multiply in the blood. High bacterial ...
Complement C1 Inhibitor Protein. Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological ... The complement cascade in kidney disease: from sideline to center stage. Am J Kidney Dis. 2013 Sep;62(3):604-14. doi: 10.1053/j ... Complement fragments C3a and C5a: the salt and pepper of the immune response. Eur J Immunol. 2010 Mar;40(3):668-70. doi: ... Gasque P. Complement: a unique innate immune sensor for danger signals. Mol Immunol. 2004 Nov;41(11):1089-98. Review. ...
Complement C3. Complement Inactivating Agents. Immunologic Factors. Physiological Effects of Drugs. Immunosuppressive Agents. ... Complement protein C3 plasma levels [ Time Frame: Up to 14 days after treatment. ]. *Complement protein C4 plasma levels [ Time ... complement inhibition. C3 complement inhibitor. AMY-101. Compstatin Cp40. Paroxysmal Nocturnal Hemoglobinuria (PNH). C3 ... AMY-101 is a selective inhibitor of complement activation in humans and in NHP. It binds to the complement component C3, the ...
Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological Effects of Drugs. To Top ... Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-naïve Adult and Adolescent Patients With Atypical Hemolytic ... Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic ... ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement ...
Complement C1 Inhibitor Protein. Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological ...
Vaccines, Inactivated, Bacterial. Class Summary. These agents may be used to prevent and control outbreaks of serogroup C ... Jarva H, Ram S, Vogel U, Blom AM, Meri S. Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis. J ... Diuretics, Osmotic Agents. Class Summary. These agents are used to control ICP during elective intubation. Osmotic diuretics ... Inotropic Agents. Class Summary. These agents are used to support circulation in patients with shock. ...
Complement Inactivating Agents / therapeutic use* Actions. * Search in PubMed * Search in MeSH ... Learnings from over 25 years of PNH experience: the era of targeted complement inhibition. Heitlinger E. Heitlinger E. Blood ... Novel insights into the treatment of complement-mediated hemolytic anemias. Berentsen S, Hill A, Hill QA, Tvedt THA, Michel M. ... Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Hillmen ...
Complement component 3 (C3) is a key component responsible for inactivating many antigens, particularly infectious agents [15 ... IgM antibodies and the C3b inactivator cleaved third component of complement in macrophage phagocytosis," Agents and Actions, ... Complement component 3 (C3) plays a central role in the activation of complement system [15]. People with C3 deficiency are ... Agents inhibiting these responses may prove to be therapeutic for radiation combined injury and improve chances for survival. ...
Inactivate.. To make biologically inactive, as viruses or bacteria, toxins, or serum complement, by any of various means, such ... 1. The agent must be shown to be present in every case of the disease by isolation in pure culture. ... Inactivated polio vaccine (IPV).. A sterile suspension of three types of inactivated polioviruses. The viruses are grown ... The infectious agent may circulate in the blood for long periods of time (months or years) and is characteristically ...
Furthermore BacMam viruses are inactivated by human complement, which reduces risk to researchers. Lastly, viruses used in the ... Baculoviruses are Risk Group 1 agents that have been widely used for over 25 years for insect cell protein production ... "Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system ...
Atopy and smoking are not risk factors for OA caused by LMW agents as they are for OA caused by HMW agents. Some of the better- ... They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in ... Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, ... Agents associated with an immunologic cause can be further divided into HMW agents, usually allergens such as proteins from ...
It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE ( ... A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. ... C4bp complement protein. physiological aspects. agonists. Carrier Proteins. chemical synthesis. Complement Inactivating Agents ... C4bp complement protein. Known as: C4bC3bINA Cofactor, Complement C3b C4b Inactivator Cofactor, Protein, Complement C4b-Binding ...
... followed by assay of components of the complement complex thereby formed; whereby the extent and nature of complement ... Also described is a method for assaying an antibody against a specific antigen or hapten for its effectiveness in complement ... immobilized antigen or hapten to form an immobilized antibody/antigen or hapten complex which is then contacted with complement ... using an inactivated sample of the serum used as source of the antibody and/or complement. Non-specific binding can be reduced ...
"Vaccination" means that an organism is challenged with an infectious agent, e.g., an attenuated or inactivated form of the ... comprising small peptides and complement factors. ... The organism, thus, is immunized against the agent/protein ... Preferably, the virus is inactivated by β-propriolacton. According to this embodiment of the invention, the inactivated virus ... Thus, a second infection with the same or a very similar infectious agent causes much milder symptoms or no symptoms at all, ...
... considered as a model for the vCJD and CJD agents.18 To complement the existing virus elimination / inactivation mechanism in ... PRV and the two model viruses for HCV, BVDV and SFV, were inactivated within 1/10, and HIV within 1/2 of the incubation time ( ... agent. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior ... Because Carimune® NF is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the ...
Use of the terminal complement inhibitor eculizumab in paediatric heart transplant recipients. Law, Y. M., Nandi, D., Molina, K ...
The preferred organic agent is diethyl ether which is used in an amount and over a period of time sufficient to kill the ... The uninfected components are returned to the patient and the infected components are treated with organic agents. ... complement, clotting factors, enzymes, and blood factors; said organic agents being otherwise proportionately too harmful to be ... To inactivate the virus a dose higher than 2.5 105 rad would be needed. It was also found that LAV reverse transcriptase ...
Complement C1 Inhibitor Protein. Phase 1. 42. Complement C1s. Phase 1. 43. Complement Inactivating Agents. Phase 1. ...
... high levels of cell killing largely required active complement, since CDC was almost absent in heat-inactivated NHS, NHS ... whereas the single agents induced only 5% and 10% lysis respectively. Despite high single agent activity of Hx-CD37 and Hx-CD20 ... Complement in therapy and disease: Regulating the complement system with antibody-based therapeutics. Mol Immunol. 2015;67(2, ... Antibodies That Efficiently Form Hexamers upon Antigen Binding Can Induce Complement-Dependent Cytotoxicity under Complement- ...
... including contacting the composition with an organic solvent and an ethyleneimine oligomer inactivating agent, are disclosed. ... Methods and compositions for selectively inactivating viruses in biological compositions, ... The solvent-detergent mixture and the selective inactivating agents complement each other and can be used simultaneously. The ... b) contacting the composition with an inactivating agent under viral inactivating conditions, wherein said inactivating agent ...
... immunosuppressive agents MeSH D27.505.696.477.656.500 --- complement inactivating agents MeSH D27.505.696.477.656.750 --- ... anti-allergic agents MeSH D27.505.954.122 --- anti-infective agents MeSH D27.505.954.122.085 --- anti-bacterial agents MeSH ... antiviral agents MeSH D27.505.954.122.388.077 --- anti-retroviral agents MeSH D27.505.954.122.388.077.088 --- anti-hiv agents ... renal agents MeSH D27.505.954.613.056 --- anti-infective agents, urinary MeSH D27.505.954.613.860 --- uricosuric agents MeSH ...
However, the parasite was not lysed if the plasma was heat-inactivate ... However, the parasite was not lysed if the plasma was heat-inactivated at 37°C for 2 h or after the addition of ... The alternative pathway of complement activation is the mechanism of innate immunity against C. salmositica. The present study ... Treatment of Cryptobia-resistant plasma with either ethylenebis(oxyethylenenitrilo)tetraacetic acid, a Ca2+-chelating agent, or ...
introduced a point mutation into the XPG gene which inactivates the nuclease (zeige DCLRE1C Antikörper) catalytic site but ... XPG mRNA expression was not predictive of trabectedin efficacy as single agent in hormone-positive, HER-2 (zeige ERBB2 ... Weitere Produktkategorien zu DNA Repair Protein Complementing XP-G Cells Antikörper * 91 anti-DNA Repair Protein Complementing ... anti-DNA Repair Protein Complementing XP-G Cells (ERCC5) Antikörper. Bezeichnung:. anti-DNA Repair Protein Complementing XP-G ...
Our functional studies complement perfectly with this structure study; critical residues of RSPO1 identified in our study ... Next we utilized R‐spondin neutralizing agents to further define critical elements of R‐spondin. SOMAmers (slow off‐rate ... LRP6 acts as the effector receptor, functioning by binding and inactivating the Axin complex. Frizzled serves as the engagement ... Furthermore, it provides us exciting opportunities of designing new therapeutic agents to block or mimic R‐spondin action to ...
Complement Activation Medicine & Life Sciences * Inflammation Medicine & Life Sciences * Complement Inactivating Agents ... Complement component 3 (C3) is the hub of all complement activation pathways, and C3 and its receptor, C3aR1 mediate synapse ... Recent studies indicate that the complement-dependent pathway and microglia that mediate synapse elimination in development are ... complement activation, synaptic loss and behavioral abnormalities. If successful, our project will create new developments in ...
The ability of the furDn gene to complement a furEc mutant suggested that the Fur protein was likely to be functional in D. ... We have identified a fur homologue in Dichelobacter nodosus, the causative agent of ovine footrot, and shown that it ... nodosus VCS1703A by double-crossover events that insertionally inactivated the fur gene (data not shown). All further studies ... The D. nodosus fur gene complements an E. coli fur mutant.The ability of H1780(pJIR2300) to form pink colonies on iron-replete ...
  • Methods and compositions for selectively inactivating viruses in biological compositions, including contacting the composition with an organic solvent and an ethyleneimine oligomer inactivating agent, are disclosed. (google.com)
  • Here we report the discovery and properties of a single chain ribosome-inactivating protein (scRIP) derived from the cytotoxic A subunit of SLT-1 (SLT-1A), harboring the 7-amino acid peptide insertion IYSNKLM (termed SLT-1A IYSNKLM ) allowing the toxin variant to selectively target and kill human melanoma cells. (biomedcentral.com)
  • Cumulatively, this growing body of work suggests a novel strategy of inhibiting the ATR pathway as a means of selectively sensitizing cancer cells to existing therapeutic agents. (aacrjournals.org)
  • In the search for safe and effective vaccines for immunizing individuals against infective pathogenic agents such as viruses, bacteria, and infective eukaryotic organisms, several strategies have been employed thus far. (justia.com)
  • In such vaccines, the pathogen is either killed or otherwise inactivated using means such as, for example, heat or chemicals. (justia.com)
  • Killed or inactivated pathogen vaccines provide protection by directly generating T-helper and humoral immune responses against the pathogenic immunogens. (justia.com)
  • Attenuated vaccines are often produced by passaging several generations of the pathogen through a permissive host until the progeny agents are no longer virulent. (justia.com)
  • Congenital immunodeficiency, leukemia, lymphoma, (ACIP) annually reviews the recommended Adult Immuniza- generalized malignancy, therapy with alkylating agents, tion Schedule to ensure that the schedule reflects current rec- antimetabolites, cerebrospinal fluid leaks, radiation, or ommendations for the use of licensed vaccines. (cdc.gov)
  • Abstract Despite the best efforts of influenza scientists, companies and health officials to prepare for the next pandemic, most of the world's people will not have access to affordable supplies of vaccines and antiviral agents. (wiley.com)
  • 2-7 Vaccine companies have worked hard to develop more efficient H5N1 vaccines, 8 and the promise of using antigen sparing, adjuvanted inactivated vaccines that are cross-protective is now well established. (wiley.com)
  • 10 Nonetheless, if a pandemic virus should emerge within the next few years, the world would have to depend on a limited supply of egg-based inactivated vaccines. (wiley.com)
  • Yersinia enterocolitica YadA mediates complement evasion by recruitment and inactivation of C3 products. (semanticscholar.org)
  • 18 To complement the existing virus elimination / inactivation mechanism in the Carimune ® NF manufacturing process, nanofiltration (removing viruses via size-exclusion) was introduced as an additional virus removal step into the manufacturing process. (nih.gov)
  • Cultured cells expressing thrombomodulin variants had a diminished capacity to inactivate C3b and to promote inactivation of the anaphylatoxins, thereby diminishing protection against activated complement. (medpagetoday.com)
  • Currents were characterized on the basis of their rates of inactivation and their sensitivity to a series of calcium channel blocking agents. (nih.gov)
  • These include a low threshold (-60 mV), rapidly inactivating (tau = 42 +/- 3 ms at -10 mV) component, a high threshold (-30 mV), slowly inactivating (tau = 1790 +/- 70 ms) component and a component with an intermediate threshold (-50 mV) and rate of inactivation (tau = 187 +/- 15 ms). There is also a non-inactivating portion of evoked calcium current with a threshold of -50 mV. 3. (nih.gov)
  • The rate of inactivation, voltage dependence, and sensitivity to omega-CgTX of the slowly inactivating component suggests that it is an N-type current. (nih.gov)
  • Recent advances in complement physiology have elucidated the central role of complement dysregulation as the root cause of hematologic, glomerular and systemic diseases. (omicsonline.org)
  • Two types of OA are distinguished by whether or not they appear after a latency period: (1) immunologic, characterized by a latency period, encompassing (a) that caused by high- (HMW) and low-molecular-weight (LMW) agents for which an immunologic (IgE) mechanism has been proven, and (b) that caused by agents (e.g., western red cedar) for which a specific immune mechanism has not been identified. (clevelandclinicmeded.com)
  • To complement molecular detection systems for potential bioterror agents, as required by international biodefense regulations, sets of mAbs were generated by B cell hybridoma technology and used to develop immunological assays. (biomedcentral.com)
  • Infection, surgery, autoimmune disease and pregnancy are the major activators of the complement pathway. (omicsonline.org)
  • Brucella , a Gram-negative bacterium, is classified as a potential bioterrorism agent mainly due to the low dose needed to cause infection and the ability to transmit the bacteria via aerosols. (biomedcentral.com)
  • Because the pathogen is killed or otherwise inactivated, there is little threat of infection. (justia.com)
  • In price doxycycline pharmacy costco this infection, we used a bacteriologic lost-to-follow-up of special information of the skin-useless haversian emblem to investigate the brand of pregnant iui on drug and on the land of i' controversial complement. (txpvietnam.com)
  • Infectious diseases , also known as contagious diseases or transmissible diseases , and include communicable diseases , comprise clinically evident illness (i.e., characteristic medical signs and/or symptoms of disease) resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism. (wikibooks.org)
  • During the sepsis the coagulation cascade, the complement system and the activation system are activated, in different moments, and this contributes to the development of multiple organ failure. (unipa.it)
  • In the study we propose to compare the clinical efficacy of Linezolid in bolus vs Linezolid in continuous infusion in patients with severe sepsis and septic shock (outcome) and to analyse whether significant differences are registered in the coagulation, inflammatory and complement response between the two group of patients.METHODS: A prospective, randomized comparative trial involved not neutropenic patients admitted in ICU from January until March 2004. (unipa.it)
  • Targeted next generation sequencing for a total of 89 genes involved in complement regulation and coagulation and haemostasis was performed in all patients. (cdc.gov)
  • Since thrombomudulin simultaneously suppresses the complement and coagulation systems, its administration may have therapeutic value for some patients with the atypical hemolytic-uremic syndrome. (medpagetoday.com)
  • By the 60th cycle, the typical mutator cell carried 4-5 inactive genes among the 15% of the genome being monitored, indicating that the average cell carried at least 24-30 inactivated genes distributed throughout the genome. (genetics.org)
  • In contrast, the mean concentration of the soluble terminal complement complex (sC5b-9) was significantly elevated at the first timepoint (mean 498 ng/mL), dropping to normal values after 2 weeks. (cdc.gov)
  • O-antigen-negative strains were found to be sensitive to complement and cationic peptides, but they displayed significant resistance to bile salts and short-chain organic acids. (asm.org)
  • Until now, the accepted model of resistance implied that in the presence of β-lactam antibiotics in the surrounding medium, PBP2A must take over the biosynthesis of staphylococcal cell wall from the four native staphylococcal PBPs because the latter become rapidly acylated and inactivated at even low concentrations of the antibiotic. (pnas.org)
  • In our current model of methicillin resistance, the low-affinity PBP2A is assumed to take over the cell wall biosynthetic functions of normal PBPs in the presence of β-lactam antibiotics, which rapidly acylate (and inactivate) each of the four native staphylococcal PBPs at concentrations that are far below the minimum needed to inhibit the growth of most MRSA strains ( 6 , 7 ). (pnas.org)
  • The effects of reducing agents on the activities of the wild-type and mutant enzymes indicated the reversibility of disulfide-bond formation, which resulted in three-fold decrease in catalytic efficiency. (proteopedia.org)
  • TOF-MS analysis of the inactivated enzyme showed the Scysteinylation of Cys138 in the wild-type and Cys150 in the mutant enzymes. (proteopedia.org)
  • This metabolismcalled biotransformationoccurs in the liver where enzymes inactivate a deaden by means of changing it into more water-soluble compounds that can be excreted from the substance. (chesapeakehumane.org)
  • Complement is crucial to the immune response, but dysregulation of the system causes inflammatory disease. (edu.au)
  • Vaccination and immunization generally refer to the introduction of a non-virulent agent against which an individual's immune system can initiate an immune response which will then be available to defend against challenge by a pathogen. (justia.com)
  • The administration of killed or inactivated pathogen into an individual presents the pathogen to the individual's immune system in a noninfective form and the individual can thereby mount an immune response against it. (justia.com)
  • By using an attenuated vaccine, an agent that displays limited infectivity may be employed to elicit an immune response against the pathogen. (justia.com)
  • Dr. Conway disclosed that he holds a patent for the use of the lectinlike domain of thrombomodulin as an anti-inflammatory agent. (medpagetoday.com)
  • As an IgG 4 variant, the effector functions of IMMU-114, particularly complement-dependent cytotoxicity (CDC), are minimized ( 11 ). (aacrjournals.org)
  • By investigating several parameters in vitro, we could show that galU and R-LPS mutants were more sensitive to short-chain organic acids, cationic antimicrobial peptides, the complement system, and bile salts as well as other hydrophobic agents, indicating that their outer membrane no longer provides an effective barrier function. (asm.org)
  • activates microglia and the complement system to promote synaptic loss and behavioral changes observed in chronic stress conditions. (elsevier.com)
  • The complement system is the first line of immunological defense against foreign pathogens. (justia.com)
  • Results showed that there was no significant alterations in hemodynamic parameters or activation of the complement system. (ubc.ca)
  • The purpose of the study is to assess the safety and efficacy of ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement inhibitor. (clinicaltrials.gov)
  • XPG mRNA expression was not predictive of trabectedin efficacy as single agent in hormone-positive, HER-2 (zeige ERBB2 Antikörper )-negative advanced breast cancer. (antikoerper-online.de)
  • Associated with other systemic disorders and known etiologic agents (secundary MPGN) or may be primary, without known cause (idiopathic) in the kidney. (slideplayer.com)
  • Treatment of Cryptobia -resistant plasma with either ethylenebis(oxyethylenenitrilo)tetraacetic acid, a Ca 2+ -chelating agent, or cobra venom factor did not reduce their lytic titres. (springer.com)
  • Dichelobacter nodosus is a fastidious gram-negative anaerobe that is the causative agent of footrot in sheep, goats, and other ruminants. (asm.org)
  • Streptococcus mutans , a major pathogen of dental caries, is considered one of the causative agents of infective endocarditis (IE). (asm.org)
  • The causative agent of the intestinal disease cholera is Vibrio cholerae , a gram-negative motile bacterium. (asm.org)
  • It frequently colonizes the nasopharynx asymptomatically, but is also an important causative agent of otitis media (OM) in children, and plays a significant role in acute exacerbations of chronic obstructive pulmonary disease (COPD) in adults. (microbiologyresearch.org)
  • Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. (semanticscholar.org)
  • The strategy of β-lactam resistance in MRSA involves the addition of the new, acquired PBP2A to the complement of the four native staphylococcal PBPs. (pnas.org)