An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
A 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.
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.
Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.
A 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.
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.
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.
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.
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.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.
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.
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
A 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.
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.
Optic disk bodies composed primarily of acid mucopolysaccharides that may produce pseudopapilledema (elevation of the optic disk without associated INTRACRANIAL HYPERTENSION) and visual field deficits. Drusen may also occur in the retina (see RETINAL DRUSEN). (Miller et al., Clinical Neuro-Ophthalmology, 4th ed, p355)
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
The 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.
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.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
A 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.
A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
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.
Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium.
The thin, highly vascular membrane covering most of the posterior of the eye between the RETINA and SCLERA.
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
A 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.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.
A pathological process consisting of the formation of new blood vessels in the CHOROID.
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.
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.
The single layer of pigment-containing epithelial cells in the RETINA, situated closely to the tips (outer segments) of the RETINAL PHOTORECEPTOR CELLS. These epithelial cells are macroglia that perform essential functions for the photoreceptor cells, such as in nutrient transport, phagocytosis of the shed photoreceptor membranes, and ensuring retinal attachment.
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.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
A form of MACULAR DEGENERATION also known as dry macular degeneration marked by occurrence of a well-defined progressive lesion or atrophy in the central part of the RETINA called the MACULA LUTEA. It is distinguishable from WET MACULAR DEGENERATION in that the latter involves neovascular exudates.
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.
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).
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.
Immune complex disease caused by the administration of foreign serum or serum proteins and characterized by fever, lymphadenopathy, arthralgia, and urticaria. When they are complexed to protein carriers, some drugs can also cause serum sickness when they act as haptens inducing antibody responses.
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.
An individual in which both alleles at a given locus are identical.
A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.
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).
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.
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.
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.
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.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
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.
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.
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.
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.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
A 206-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
The layer of pigment-containing epithelial cells in the RETINA; the CILIARY BODY; and the IRIS in the eye.
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.
An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
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.
An essential amino acid that is required for the production of HISTAMINE.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
Proteins found in any species of bacterium.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
A 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.
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.
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.
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.
Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.
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.
An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
A plasma protein that circulates in increased amounts during inflammation and after tissue damage.
Genotypic differences observed among individuals in a population.
Proteins prepared by recombinant DNA technology.

Protein H, an antiphagocytic surface protein in Streptococcus pyogenes. (1/741)

Surface-associated M protein is a major virulence factor in Streptococcus pyogenes which confers bacterial resistance to phagocytosis. However, many S. pyogenes strains also express additional structurally related so-called M-like proteins. The strain studied here is of the clinically important M1 serotype and expresses two structurally related surface proteins, the M1 protein and protein H. Mutants were generated that expressed only one or none of these proteins at the bacterial surface. For survival in human blood either protein H or M1 protein was sufficient, whereas the double mutant was rapidly killed. The protein-binding properties of protein H, M1 protein, and the mutants suggest that bacterial binding of immunoglobulin G and factor H or factor H-like protein 1, which are regulatory proteins in the complement system, contribute to the antiphagocytic property.  (+info)

Multicenter trial of the quantitative BTA TRAK assay in the detection of bladder cancer. (2/741)

BACKGROUND: Human complement factor H-related protein (hCFHrp) is produced by several bladder cancer cell lines and may be useful as a cancer marker. The aim of this study was to compare urinary hCFHrp and cytology for the detection of bladder cancer found by cystoscopy in patients with suggestive signs, symptoms, or preliminary test results. METHODS: The BTA TRAK assay, a quantitative enzyme immunoassay for the bladder tumor-associated antigen in urine, was compared with exfoliative cytology in 220 patients (155 men, 65 women; mean age, 64.2 years) presenting with signs, symptoms, or preliminary diagnostic results suggestive of this disease. Cystoscopy was the standard of detection. RESULTS: In the 100 patients found to have bladder cancer, the overall sensitivities of the BTA TRAK assay (at a previously determined decision threshold of 14 kilounits/L) and cytology were 66% (66 of 100) and 33% (33 of 100), respectively (P <0.001). The BTA TRAK assay proved to be statistically more sensitive than cytology for tumor grades I and II and for stage Ta and T1 tumors. In contrast, the overall specificity of the BTA TRAK assay in the 120 patients without cystoscopically confirmed bladder cancer was 69% (83 of 120) and that of cytology was 99% (119 of 120; P <0.001). The specificity of the BTA TRAK assay was higher in patients without benign or malignant genitourinary disease other than bladder cancer (76%; n = 89) than in patients with these conditions. When the BTA TRAK assay and cytology were used together such that a positive result in either test was scored as positive and the results compared with those of the BTA TRAK assay alone, increases in overall sensitivity and equivalent specificity were observed. CONCLUSION: Because of its relatively high sensitivity, the BTA TRAK assay could complement cytology as an adjunct to cystoscopy in the diagnosis and follow-up of most patients with bladder cancer.  (+info)

In vitro analysis of complement-dependent HIV-1 cell infection using a model system. (3/741)

Previous studies based on the use of human serum as a source of C have provided evidence for the C-dependent enhancement of cell infection by HIV-1. The present study was undertaken to distinguish C from other serum factors and to identify the proteins and the mechanisms involved in C-dependent cell infection by HIV-1. The classical C activation pathway was reconstituted from the proteins C1q, C1r, C1s, C4, C2, C3, factor H, and factor I; each were purified to homogeneity. A mixture of these proteins at physiological concentrations was shown to reproduce the ability of normal human serum to enhance the infection of MT2 cells by HIV-1 at low doses of virus. This enhancing effect was abolished when heat-inactivated serum and C2- or C3-depleted serum were used, and was restored upon addition of the corresponding purified proteins. A mixture of two synthetic peptides corresponding to positions 10-15 and 90-97 of human C receptor type 2 (CD21) as well as soluble CD4 both inhibited the C-dependent infection process. These data provide unambiguous evidence that HIV-1 triggers a direct activation of the classical C pathway in vitro and thereby facilitates the infection of MT2 cells at low doses of virus. These findings are consistent with a mechanism involving increased interaction between the virus opsonized by C3b-derived fragment(s) and the CD21 cell receptors and subsequent virus entry through CD4 receptors.  (+info)

Disruption of disulfide bonds is responsible for impaired secretion in human complement factor H deficiency. (4/741)

Factor H, a secretory glycoprotein composed of 20 short consensus repeat modules, is an inhibitor of the complement system. Previous studies of inherited factor H deficiency revealed single amino acid substitutions at conserved cysteine residues, on one allele arginine for cysteine 518 (C518R) and on the other tyrosine for cysteine 941 (C941Y) (Ault, B. H., Schmidt, B. Z., Fowler, N. L., Kashtan, C. E., Ahmed, A. E., Vogt, B. A., and Colten, H. R. (1997) J. Biol. Chem. 272, 25168-25175). To ascertain if the phenotype, impaired secretion of factor H, is due to the C518R substitution or the C941Y substitution and to ascertain the mechanism by which secretion is impaired, we studied COS-1 and HepG2 cells transfected with wild type and several mutant factor H molecules. The results showed markedly impaired secretion of both C518R and C941Y factor H as well as that of factor H molecules bearing alanine or arginine substitutions at the Cys518-Cys546 disulfide bond (C518A, C546A, C546R, C518A-C546A). In each case, mutant factor H was retained in the endoplasmic reticulum and degraded relatively slowly as compared with most other mutant secretory and membrane proteins that are retained in the endoplasmic reticulum. These data indicate that impaired secretion of the naturally occurring C518R and C941Y mutant factor H proteins is due to disruption of framework-specific disulfide bonds in factor H short consensus repeat modules.  (+info)

Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura. (5/741)

Familial hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) carry a very poor outcome and have been reported in association with decreased serum levels of the third complement component (C3). Uncontrolled consumption in the microcirculation, possibly related to genetically determined deficiency in factor H--a modulator of the alternative pathway of complement activation--may account for decreased C3 serum levels even during disease remission and may predispose to intravascular thrombosis. In a case-control study by multivariate analysis, we correlated putative predisposing conditions, including low C3 serum levels, with history of disease in 15 cases reporting one or more episodes of familial HUS and TTP, in 25 age- and gender-matched healthy controls and in 63 case-relatives and 56 control-relatives, respectively. The relationship between history of disease, low C3, and factor H abnormalities was investigated in all affected families and in 17 controls. Seventy-three percent of cases compared with 16% of controls (P < 0.001), and 24% of case-relatives compared with 5% of control-relatives (P = 0.005) had decreased C3 serum levels. At multivariate analysis, C3 serum level was the only parameter associated with the disease within affected families (P = 0.02) and in the overall study population (P = 0.01). Thus, subjects with decreased C3 serum levels had a relative risk of HUS or TTP of 16.56 (95% confidence interval [CI], 1.66 to 162.39) within families and of 27.77 (95% CI, 2.44 to 314.19) in the overall population, compared to subjects with normal serum levels. Factor H abnormalities were found in four of the cases, compared with three of the healthy family members (P = 0.02) and none of the controls (P = 0.04) and, within families, factor H abnormalities were correlated with C3 reduction (P < 0.05). Reduced C3 clusters in familial HUS and TTP is likely related to a genetically determined deficiency in factor H and may predispose to the disease. Its demonstration may help identify subjects at risk in affected families.  (+info)

Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency. (6/741)

BACKGROUND: In a recent study of three families we have found that inherited haemolytic uraemic syndrome (HUS) maps to a region of chromosome 1q containing the gene for complement factor H. In one of these families and also in a case of sporadic D-HUS, we have identified mutations in the factor H gene. A further family with inherited HUS has therefore been investigated. METHODS: DNA extracted from the family members and DNA extracted from archival post-mortem material from a deceased family member, was studied. Review of renal biopsies and study of complement components was also undertaken. RESULTS: This family demonstrates an inherited deficiency of complement factor H. Non-diarrhoeal HUS has affected at least two family members with half normal levels of factor H. CONCLUSION: These findings represent further evidence of the association between factor H dysfunction and HUS.  (+info)

Identification of human complement Factor H as a ligand for L-selectin. (7/741)

The selectin family of adhesion molecules (E-, P- and L-selectins) is involved in leukocyte recruitment to sites of inflammation and tissue damage. Recently it has been shown that L-selectin is involved not only in leukocyte tethering and rolling, but also plays an important role in leukocyte activation. For example, glycosylation-dependent cell-adhesion molecule 1 (GlyCAM-1), a known ligand for L-selectin, has been shown to enhance beta2-integrin function. GlyCAM-1 is a secreted protein and is present in mouse serum at a concentration of approx. 1.5 microg/ml. There is no obvious GlyCAM-1 homologue in man and, to date, L-selectin ligand(s) from human serum have not been characterized. Therefore we have used L-selectin affinity chromatography, followed by ion-exchange chromatography, to isolate specific ligand(s) for L-selectin. Using this procedure, we have isolated three major glycoproteins of apparent molecular masses 170 kDa, 70kDa and 50 kDa. The 170 kDa protein band was digested with trypsin and peptides were analysed by delayed extraction matrix-assisted laser desorption ionization MS and protein database searching. The 170 kDa protein was identified as the human complement protein Factor H. Human Factor H, isolated by a different method, was shown to bind specifically to L-selectin in the presence of CaCl2, and binding was inhibited by anti-L-selectin antibodies, fucoidan and lipopolysaccharide. Only a part of the purified Factor H preparation bound to immobilized L-selectin. The interaction of Factor H with leukocyte L-selectin was shown to induce the secretion of tumour necrosis factor-alpha (TNF-alpha). Pretreatment of Factor H with sialidase reduced both the binding of L-selectin to Factor H and the Factor H-induced L-selectin-mediated TNF-alpha secretion by leukocytes. Taken together, these results demonstrate that a post-translationally modified form of human plasma Factor H is a potential physiological ligand for L-selectin.  (+info)

Resistance to both complement activation and phagocytosis in type 3 pneumococci is mediated by the binding of complement regulatory protein factor H. (8/741)

To study the role of surface-associated proteins in the virulence of Streptococcus pneumoniae, we used two serotype 3 strains, ATCC 6303 and WU2, and two PspA-negative mutants of WU2, an encapsulated one, JY1123 (Caps(+)/PspA(-)), and an unencapsulated one, DW3.8 (Caps(-)/PspA(-)). ATCC 6303 and WU2 were highly virulent in mice, while the virulence of JY1123 was slightly decreased (50% lethal doses [LD(50)s], 24, 6, and 147 CFU/mouse, respectively); DW3.8 was avirulent (LD(50), 2 x 10(8) CFU). In vitro, ATCC 6303, WU2, and JY1123 (Caps(+)/PspA(-)) strongly resisted complement activation and complement-dependent opsonophagocytosis, whereas DW3.8 (Caps(-)/PspA(-)) was easily phagocytized in fresh serum. Trypsin treatment of ATCC 6303, WU2, and JY1123 (Caps(+)/PspA(-)) resulted in enhanced complement activation and complement-dependent opsonophagocytosis. Trypsin had no deleterious effect on the polysaccharide capsule. In addition, trypsin pretreatment of ATCC 6303 strongly reduced virulence upon intraperitoneal challenge in mice. This indicated that surface proteins play a role in the resistance to complement activation and opsonophagocytosis and contribute to the virulence of type 3 pneumococci. In subsequent experiments, we could show that the modulation of complement activation was associated with surface components that bind complement regulator factor H; binding is trypsin sensitive and independent of prior complement activation. Immunoblotting of cell wall proteins of the virulent strain ATCC 6303 with anti-human factor H antibody revealed three factor H-binding proteins of 88, 150, and 196 kDa. Immunogold electron microscopy showed a close association of factor H-binding components with the outer surface of the cell wall. The role of these factor H-binding surface proteins in the virulence of pneumococci is interesting and warrants further investigation.  (+info)

Complement Factor H is a protein involved in the regulation of the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Specifically, Complement Factor H helps to regulate the activation and deactivation of the complement component C3b, preventing excessive or unwanted activation of the complement system and protecting host tissues from damage.

Complement Factor H is a crucial protein in maintaining the balance between the protective effects of the complement system and the potential for harm to the body's own cells and tissues. Deficiencies or mutations in Complement Factor H have been associated with several diseases, including age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and C3 glomerulopathy.

Complement Factor B is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. Specifically, Factor B is a component of the alternative pathway of the complement system, which provides a rapid and amplified response to microbial surfaces.

Factor B is cleaved by another protease called Factor D into two fragments, Ba and Bb. The formation of the C3 convertase (C3bBb) is essential for the activation of the alternative pathway. This complex can cleave and activate more C3 molecules, leading to a cascade of reactions that result in the formation of the membrane attack complex (MAC), which forms pores in the membranes of target cells, causing their lysis and elimination.

Deficiencies or mutations in Complement Factor B can lead to various complement-mediated diseases, such as atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD).

Complement C3b inactivator proteins, also known as complement regulators or decay-accelerating factor (DAF), are a group of proteins that play a crucial role in regulating the complement system. The complement system is a part of the immune system that helps to eliminate pathogens and damaged cells from the body.

The complement C3b inactivator proteins include two main types: complement receptor 1 (CR1) and decay-accelerating factor (DAF). These proteins work by regulating the formation of the membrane attack complex (MAC), a protein structure that forms pores in the cell membrane, leading to cell lysis.

Complement C3b inactivator proteins bind to C3b and C4b components of the complement system, preventing them from forming the MAC. By doing so, they help to prevent excessive activation of the complement system, which can damage healthy cells and tissues.

Deficiencies or dysfunction of complement C3b inactivator proteins have been associated with several diseases, including autoimmune disorders, inflammatory diseases, and infectious diseases. Therefore, understanding the role of these proteins in regulating the complement system is essential for developing new therapies to treat these conditions.

Macular degeneration, also known as age-related macular degeneration (AMD), is a medical condition that affects the central part of the retina, called the macula. The macula is responsible for sharp, detailed vision, which is necessary for activities such as reading, driving, and recognizing faces.

In AMD, there is a breakdown or deterioration of the macula, leading to gradual loss of central vision. There are two main types of AMD: dry (atrophic) and wet (exudative). Dry AMD is more common and progresses more slowly, while wet AMD is less common but can cause rapid and severe vision loss if left untreated.

The exact causes of AMD are not fully understood, but risk factors include age, smoking, family history, high blood pressure, obesity, and exposure to sunlight. While there is no cure for AMD, treatments such as vitamin supplements, laser therapy, and medication injections can help slow its progression and reduce the risk of vision loss.

Complement Factor I is a protein involved in the regulation of the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Specifically, Complement Factor I is a serine protease that regulates the complement component C3b by cleaving it into inactive fragments, thereby preventing the excessive activation of the complement system and protecting host tissues from damage.

Complement Factor I functions in conjunction with other regulatory proteins, such as complement receptor 1 (CR1) and membrane cofactor protein (MCP), to control the activity of the complement system at various stages. Deficiencies or mutations in Complement Factor I have been associated with several diseases, including atypical hemolytic uremic syndrome (aHUS), age-related macular degeneration (AMD), and systemic lupus erythematosus (SLE).

Complement C3b is a protein fragment that plays a crucial role in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. C3b is generated during the activation of the complement system, particularly via the classical, lectin, and alternative pathways.

Once formed, C3b can bind covalently to the surface of microbes or other target particles, marking them for destruction by other components of the immune system. Additionally, C3b can interact with other proteins in the complement system to generate the membrane attack complex (MAC), which forms pores in the membranes of targeted cells, leading to their lysis and removal.

In summary, Complement C3b is a vital protein fragment involved in the recognition, tagging, and elimination of pathogens and damaged cells during the immune response.

Complement C3 is a protein that plays a central role in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Complement C3 can be activated through three different pathways: the classical pathway, the lectin pathway, and the alternative pathway. Once activated, it breaks down into two fragments, C3a and C3b.

C3a is an anaphylatoxin that helps to recruit immune cells to the site of infection or injury, while C3b plays a role in opsonization, which is the process of coating pathogens or damaged cells with proteins to make them more recognizable to the immune system. Additionally, C3b can also activate the membrane attack complex (MAC), which forms a pore in the membrane of target cells leading to their lysis or destruction.

In summary, Complement C3 is an important protein in the complement system that helps to identify and eliminate pathogens and damaged cells from the body through various mechanisms.

Complement activation is the process by which the complement system, a part of the immune system, is activated to help eliminate pathogens and damaged cells from the body. The complement system consists of a group of proteins that work together to recognize and destroy foreign substances.

Activation of the complement system can occur through three different pathways: the classical pathway, the lectin pathway, and the alternative pathway. Each pathway involves a series of proteolytic reactions that ultimately result in the formation of the membrane attack complex (MAC), which creates a pore in the membrane of the target cell, leading to its lysis and removal.

The classical pathway is typically activated by the binding of antibodies to antigens on the surface of a pathogen or damaged cell. The lectin pathway is activated by the recognition of specific carbohydrate structures on the surface of microorganisms. The alternative pathway can be spontaneously activated and serves as an amplification loop for both the classical and lectin pathways.

Complement activation plays a crucial role in the immune response, but uncontrolled or excessive activation can also lead to tissue damage and inflammation. Dysregulation of complement activation has been implicated in various diseases, including autoimmune disorders, inflammatory conditions, and neurodegenerative diseases.

Complement Factor D is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Specifically, Factor D is a serine protease that is involved in the alternative pathway of the complement system.

In this pathway, Factor D helps to cleave another protein called Factor B, which then activates a complex called the C3 convertase. The C3 convertase cleaves complement component 3 (C3) into C3a and C3b, leading to the formation of the membrane attack complex (MAC), which creates a pore in the membrane of the target cell, causing its lysis and removal from the body.

Deficiencies or mutations in Complement Factor D can lead to an impaired alternative pathway and increased susceptibility to certain infections, particularly those caused by Neisseria bacteria. Additionally, abnormal regulation of the complement system has been implicated in a variety of diseases, including autoimmune disorders, inflammatory conditions, and neurodegenerative diseases.

The complement system is a group of proteins found in the blood and on the surface of cells that when activated, work together to help eliminate pathogens such as bacteria, viruses, and fungi from the body. The proteins are normally inactive in the bloodstream. When they encounter an invading microorganism or foreign substance, a series of reactions take place leading to the activation of the complement system. Activation results in the production of effector molecules that can punch holes in the cell membranes of pathogens, recruit and activate immune cells, and help remove debris and dead cells from the body.

There are three main pathways that can lead to complement activation: the classical pathway, the lectin pathway, and the alternative pathway. Each pathway involves a series of proteins that work together in a cascade-like manner to amplify the response and generate effector molecules. The three main effector molecules produced by the complement system are C3b, C4b, and C5b. These molecules can bind to the surface of pathogens, marking them for destruction by other immune cells.

Complement proteins also play a role in the regulation of the immune response. They help to prevent excessive activation of the complement system, which could damage host tissues. Dysregulation of the complement system has been implicated in a number of diseases, including autoimmune disorders and inflammatory conditions.

In summary, Complement System Proteins are a group of proteins that play a crucial role in the immune response by helping to eliminate pathogens and regulate the immune response. They can be activated through three different pathways, leading to the production of effector molecules that mark pathogens for destruction. Dysregulation of the complement system has been linked to various diseases.

Hemolytic-Uremic Syndrome (HUS) is a serious condition that affects the blood and kidneys. It is characterized by three major features: the breakdown of red blood cells (hemolysis), the abnormal clotting of small blood vessels (microthrombosis), and acute kidney failure.

The breakdown of red blood cells leads to the release of hemoglobin into the bloodstream, which can cause anemia. The microthrombi can obstruct the flow of blood in the kidneys' filtering system (glomeruli), leading to damaged kidney function and potentially acute kidney failure.

HUS is often caused by a bacterial infection, most commonly Escherichia coli (E. coli) that produces Shiga toxins. This form of HUS is known as STEC-HUS or Stx-HUS. Other causes include infections with other bacteria, viruses, medications, pregnancy complications, and certain medical conditions such as autoimmune diseases.

Symptoms of HUS may include fever, fatigue, decreased urine output, blood in the stool, swelling in the face, hands, or feet, and irritability or confusion. Treatment typically involves supportive care, including dialysis for kidney failure, transfusions to replace lost red blood cells, and managing high blood pressure. In severe cases, a kidney transplant may be necessary.

The alternative complement pathway is one of the three initiating pathways of the complement system, which is a part of the innate immune system that helps to clear pathogens and damaged cells from the body. The other two pathways are the classical and lectin pathways.

The alternative pathway is continuously activated at a low level, even in the absence of infection or injury, through the spontaneous cleavage of complement component C3 into C3a and C3b by the protease factor D in the presence of magnesium ions. The generated C3b can then bind covalently to nearby surfaces, including pathogens and host cells.

On self-surfaces, regulatory proteins like decay-accelerating factor (DAF) or complement receptor 1 (CR1) help to prevent the formation of the alternative pathway convertase and thus further activation of the complement system. However, on foreign surfaces, the C3b can recruit more complement components, forming a complex called the alternative pathway convertase (C3bBb), which cleaves additional C3 molecules into C3a and C3b.

The generated C3b can then bind to the surface and participate in the formation of the membrane attack complex (MAC), leading to the lysis of the target cell. The alternative pathway plays a crucial role in the defense against gram-negative bacteria, fungi, and parasites, as well as in the clearance of immune complexes and apoptotic cells. Dysregulation of the alternative complement pathway has been implicated in several diseases, including autoimmune disorders and atypical hemolytic uremic syndrome (aHUS).

Complement C2 is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. Specifically, C2 is a component of the classical complement pathway, which is activated by the binding of antibodies to antigens on the surface of foreign particles or cells.

When the classical pathway is activated, C2 is cleaved into two fragments: C2a and C2b. C2a then binds to C4b to form the C3 convertase (C4b2a), which cleaves C3 into C3a and C3b. C3b can then go on to form the membrane attack complex, which creates a pore in the membrane of the target cell, leading to its lysis.

In summary, Complement C2 is a protein that helps to activate the complement system and destroy foreign particles or cells through the formation of the C3 convertase and the membrane attack complex.

Complement C3d is a protein fragment that is formed during the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens such as bacteria and viruses from the body by tagging them for destruction and attracting immune cells to the site of infection.

C3d is a cleavage product of complement component C3, which is one of the central proteins in the complement system. When C3 is activated, it is cleaved into two fragments: C3a and C3b. C3b can then be further cleaved into C3d and C3c.

C3d plays a role in the activation of the immune system by helping to link the complement system with the adaptive immune response. It does this by binding to receptors on B cells, which are a type of white blood cell that produces antibodies. This interaction can help to stimulate the production of antibodies and enhance the immune response to pathogens.

C3d has also been implicated in the development of certain autoimmune diseases, as it can contribute to the formation of immune complexes that can cause tissue damage.

Complement C4 is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Complement C4 is involved in the early stages of the complement activation cascade, where it helps to identify and tag foreign or abnormal cells for destruction by other components of the immune system.

Specifically, Complement C4 can be cleaved into two smaller proteins, C4a and C4b, during the complement activation process. C4b then binds to the surface of the target cell and helps to initiate the formation of the membrane attack complex (MAC), which creates a pore in the cell membrane and leads to lysis or destruction of the target cell.

Deficiencies or mutations in the Complement C4 gene can lead to various immune disorders, including certain forms of autoimmune diseases and susceptibility to certain infections.

Membranoproliferative Glomerulonephritis (MPGN) is a type of glomerulonephritis, which is a group of kidney disorders characterized by inflammation and damage to the glomeruli, the tiny blood vessels in the kidneys responsible for filtering waste and excess fluids from the blood.

MPGN is specifically characterized by thickening of the glomerular basement membrane and proliferation (increased number) of cells in the mesangium, a region within the glomerulus. This condition can be primary or secondary to other diseases such as infections, autoimmune disorders, or monoclonal gammopathies.

MPGN is typically classified into three types based on the pattern of injury seen on electron microscopy: Type I, Type II (Dense Deposit Disease), and Type III. Each type has distinct clinical features, laboratory findings, and treatment approaches. Symptoms of MPGN may include hematuria (blood in urine), proteinuria (protein in urine), hypertension (high blood pressure), edema (swelling), and eventually progress to chronic kidney disease or end-stage renal disease if left untreated.

Optic disk drusen are small, calcified deposits that form within the optic nerve head, also known as the optic disc. They are made up of protein and calcium salts and can vary in size and number. These deposits can be seen on ophthalmic examination using an instrument called an ophthalmoscope.

Optic disk drusen are typically asymptomatic and are often discovered during routine eye examinations. However, in some cases, they may cause visual disturbances or even vision loss if they compress the optic nerve fibers. They can also increase the risk of developing other eye conditions such as glaucoma.

Optic disk drusen are more commonly found in individuals with a family history of the condition and tend to occur in younger people, typically before the age of 40. While there is no cure for optic disk drusen, regular eye examinations can help monitor any changes in the condition and manage any associated visual symptoms or complications.

Complement C5 is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. The complement system is a complex series of biochemical reactions that help to identify and destroy foreign substances, such as bacteria and viruses.

Complement C5 is one of several proteins in the complement system that are activated in a cascading manner in response to an activating event, such as the binding of an antibody to a pathogen. Once activated, Complement C5 can be cleaved into two smaller proteins, C5a and C5b.

C5a is a powerful anaphylatoxin, which means it can cause the release of histamine from mast cells and basophils, leading to inflammation and increased vascular permeability. It also acts as a chemoattractant, drawing immune cells to the site of infection or injury.

C5b, on the other hand, plays a role in the formation of the membrane attack complex (MAC), which is a protein structure that can punch holes in the membranes of pathogens, leading to their lysis and destruction.

Overall, Complement C5 is an important component of the immune system's response to infection and injury, helping to eliminate pathogens and damaged cells from the body.

Complement C5a is a protein fragment that is generated during the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens and damaged cells from the body by tagging them for destruction and attracting immune cells to the site of infection or injury.

C5a is formed when the fifth component of the complement system (C5) is cleaved into two smaller fragments, C5a and C5b, during the complement activation cascade. C5a is a potent pro-inflammatory mediator that can attract and activate various immune cells, such as neutrophils, monocytes, and eosinophils, to the site of infection or injury. It can also increase vascular permeability, promote the release of histamine, and induce the production of reactive oxygen species, all of which contribute to the inflammatory response.

However, excessive or uncontrolled activation of the complement system and generation of C5a can lead to tissue damage and inflammation, contributing to the pathogenesis of various diseases, such as sepsis, acute respiratory distress syndrome (ARDS), and autoimmune disorders. Therefore, targeting C5a or its receptors has been explored as a potential therapeutic strategy for these conditions.

Complement C3-C5 convertases are proteins that play a crucial role in the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens and damaged cells from the body by marking them for destruction and attracting immune cells to the site of infection or injury.

The C3-C5 convertases are formed during the activation of the complement component 3 (C3) protein, which is a central player in the complement system. The formation of the C3-C5 convertase involves two main steps:

1. C3 convertase formation: In this step, a complex of proteins called the C3 convertase is formed by the cleavage of C3 into C3a and C3b fragments. This complex can then cleave additional C3 molecules into C3a and C3b fragments, amplifying the complement response.
2. C5 convertase formation: In this step, the C3b fragment from the C3 convertase binds to another protein called C4b2a, forming a new complex called the C5 convertase. The C5 convertase can then cleave the C5 protein into C5a and C5b fragments.

The C5b fragment goes on to form the membrane attack complex (MAC), which creates a pore in the membrane of the target cell, leading to its lysis or destruction. The C3a and C5a fragments are small proteins called anaphylatoxins that can cause inflammation and attract immune cells to the site of infection or injury.

Overall, the formation of Complement C3-C5 convertases is a critical step in the activation of the complement system and plays a key role in the body's defense against pathogens and damaged cells.

Complement receptors are proteins found on the surface of various cells in the human body, including immune cells and some non-immune cells. They play a crucial role in the complement system, which is a part of the innate immune response that helps to eliminate pathogens and damaged cells from the body. Complement receptors bind to complement proteins or fragments that are generated during the activation of the complement system. This binding triggers various intracellular signaling events that can lead to diverse cellular responses, such as phagocytosis, inflammation, and immune regulation.

There are several types of complement receptors, including:

1. CR1 (CD35): A receptor found on erythrocytes, B cells, neutrophils, monocytes, macrophages, and glomerular podocytes. It functions in the clearance of immune complexes and regulates complement activation.
2. CR2 (CD21): Expressed mainly on B cells and follicular dendritic cells. It facilitates antigen presentation, B-cell activation, and immune regulation.
3. CR3 (CD11b/CD18, Mac-1): Present on neutrophils, monocytes, macrophages, and some T cells. It mediates cell adhesion, phagocytosis, and intracellular signaling.
4. CR4 (CD11c/CD18, p150,95): Expressed on neutrophils, monocytes, macrophages, and dendritic cells. It is involved in cell adhesion, phagocytosis, and intracellular signaling.
5. C5aR (CD88): Found on various immune cells, including neutrophils, monocytes, macrophages, mast cells, eosinophils, and dendritic cells. It binds to the complement protein C5a and mediates chemotaxis, degranulation, and inflammation.
6. C5L2 (GPR77): Present on various cell types, including immune cells. Its function is not well understood but may involve regulating C5a-mediated responses or acting as a receptor for other ligands.

These receptors play crucial roles in the immune response and inflammation by mediating various functions such as chemotaxis, phagocytosis, cell adhesion, and intracellular signaling. Dysregulation of these receptors has been implicated in several diseases, including autoimmune disorders, infections, and cancer.

Complement C1q is a protein that is part of the complement system, which is a group of proteins in the blood that help to eliminate pathogens and damaged cells from the body. C1q is the first component of the classical complement pathway, which is activated by the binding of C1q to antibodies that are attached to the surface of a pathogen or damaged cell.

C1q is composed of six identical polypeptide chains, each containing a collagen-like region and a globular head region. The globular heads can bind to various structures, including the Fc regions of certain antibodies, immune complexes, and some types of cells. When C1q binds to an activating surface, it triggers a series of proteolytic reactions that lead to the activation of other complement components and the formation of the membrane attack complex (MAC), which can punch holes in the membranes of pathogens or damaged cells, leading to their destruction.

In addition to its role in the immune system, C1q has also been found to have roles in various physiological processes, including tissue remodeling, angiogenesis, and the clearance of apoptotic cells. Dysregulation of the complement system, including abnormalities in C1q function, has been implicated in a variety of diseases, including autoimmune disorders, inflammatory diseases, and neurodegenerative conditions.

The Complement Membrane Attack Complex (MAC), also known as the Terminal Complement Complex (TCC), is a protein structure that forms in the final stages of the complement system's immune response. The complement system is a part of the innate immune system that helps to eliminate pathogens and damaged cells from the body.

The MAC is composed of several proteins, including C5b, C6, C7, C8, and multiple subunits of C9, which assemble on the surface of target cells. The formation of the MAC creates a pore-like structure in the cell membrane, leading to disruption of the membrane's integrity and ultimately causing cell lysis or damage.

The MAC plays an important role in the immune response by helping to eliminate pathogens that have evaded other immune defenses. However, uncontrolled activation of the complement system and formation of the MAC can also contribute to tissue damage and inflammation in various diseases, such as autoimmune disorders, age-related macular degeneration, and ischemia-reperfusion injury.

Single Nucleotide Polymorphism (SNP) is a type of genetic variation that occurs when a single nucleotide (A, T, C, or G) in the DNA sequence is altered. This alteration must occur in at least 1% of the population to be considered a SNP. These variations can help explain why some people are more susceptible to certain diseases than others and can also influence how an individual responds to certain medications. SNPs can serve as biological markers, helping scientists locate genes that are associated with disease. They can also provide information about an individual's ancestry and ethnic background.

Blood proteins, also known as serum proteins, are a group of complex molecules present in the blood that are essential for various physiological functions. These proteins include albumin, globulins (alpha, beta, and gamma), and fibrinogen. They play crucial roles in maintaining oncotic pressure, transporting hormones, enzymes, vitamins, and minerals, providing immune defense, and contributing to blood clotting.

Albumin is the most abundant protein in the blood, accounting for about 60% of the total protein mass. It functions as a transporter of various substances, such as hormones, fatty acids, and drugs, and helps maintain oncotic pressure, which is essential for fluid balance between the blood vessels and surrounding tissues.

Globulins are divided into three main categories: alpha, beta, and gamma globulins. Alpha and beta globulins consist of transport proteins like lipoproteins, hormone-binding proteins, and enzymes. Gamma globulins, also known as immunoglobulins or antibodies, are essential for the immune system's defense against pathogens.

Fibrinogen is a protein involved in blood clotting. When an injury occurs, fibrinogen is converted into fibrin, which forms a mesh to trap platelets and form a clot, preventing excessive bleeding.

Abnormal levels of these proteins can indicate various medical conditions, such as liver or kidney disease, malnutrition, infections, inflammation, or autoimmune disorders. Blood protein levels are typically measured through laboratory tests like serum protein electrophoresis (SPE) and immunoelectrophoresis (IEP).

Genotype, in genetics, refers to the complete heritable genetic makeup of an individual organism, including all of its genes. It is the set of instructions contained in an organism's DNA for the development and function of that organism. The genotype is the basis for an individual's inherited traits, and it can be contrasted with an individual's phenotype, which refers to the observable physical or biochemical characteristics of an organism that result from the expression of its genes in combination with environmental influences.

It is important to note that an individual's genotype is not necessarily identical to their genetic sequence. Some genes have multiple forms called alleles, and an individual may inherit different alleles for a given gene from each parent. The combination of alleles that an individual inherits for a particular gene is known as their genotype for that gene.

Understanding an individual's genotype can provide important information about their susceptibility to certain diseases, their response to drugs and other treatments, and their risk of passing on inherited genetic disorders to their offspring.

The "Classical Complement Pathway" is one of the three pathways that make up the complement system, which is a part of the immune system in humans and other animals. The complement system helps to enhance the ability of antibodies and phagocytic cells to clear pathogens from the body.

The Classical Complement Pathway is initiated by the binding of the first component of the complement system, C1, to an activator surface, such as an antigen-antibody complex. Activation of C1 results in the sequential activation of other components of the complement system, including C4 and C2, which form the C3 convertase (C4b2a). The C3 convertase cleaves the third component of the complement system, C3, into C3a and C3b. C3b then binds to the activator surface and forms a complex with other components of the complement system, leading to the formation of the membrane attack complex (MAC), which creates a pore in the membrane of the target cell, causing its lysis.

The Classical Complement Pathway plays an important role in the immune response to pathogens and can also contribute to inflammation and tissue damage in certain diseases, such as autoimmune disorders and allergies.

Retinal drusen are yellow-white, deposits of extracellular material that accumulate beneath the retina, most commonly in the macula. They are a common age-related finding and can also be seen in various other conditions such as inherited retinal diseases. Drusen can vary in size and number, and their presence is often associated with an increased risk of developing age-related macular degeneration (AMD), a leading cause of vision loss in older adults. However, not all individuals with drusen will develop AMD, and the significance of drusen depends on factors such as size, number, and location. It's important to monitor drusen and have regular eye examinations to assess any changes or progression that may indicate a higher risk for developing AMD.

The choroid is a layer of the eye that contains blood vessels that supply oxygen and nutrients to the outer layers of the retina. It lies between the sclera (the white, protective coat of the eye) and the retina (the light-sensitive tissue at the back of the eye). The choroid is essential for maintaining the health and function of the retina, particularly the photoreceptor cells that detect light and transmit visual signals to the brain. Damage to the choroid can lead to vision loss or impairment.

Complement inactivator proteins are a group of regulatory proteins that help to control and limit the activation of the complement system, which is a part of the immune system. The complement system is a complex series of biochemical reactions that help to eliminate pathogens and damaged cells from the body. However, if not properly regulated, the complement system can also cause damage to healthy tissues and contribute to the development of various diseases.

Complement inactivator proteins work by inhibiting specific components of the complement system, preventing them from activating and causing an immune response. Some examples of complement inactivator proteins include:

1. C1 inhibitor (C1INH): This protein regulates the activation of the classical pathway of the complement system by inhibiting the C1 complex, which is a group of proteins that initiate this pathway.
2. Decay-accelerating factor (DAF or CD55): This protein regulates the activation of both the classical and alternative pathways of the complement system by accelerating the decay of the C3/C5 convertases, which are enzymes that activate the complement components C3 and C5.
3. Membrane cofactor protein (MCP or CD46): This protein regulates the activation of the alternative pathway of the complement system by serving as a cofactor for the cleavage and inactivation of C3b, a component of the C3 convertase.
4. Factor H: This protein also regulates the activation of the alternative pathway of the complement system by acting as a cofactor for the cleavage and inactivation of C3b, and by preventing the formation of the C3 convertase.

Deficiencies or dysfunction of complement inactivator proteins can lead to various diseases, including hereditary angioedema (C1INH deficiency), atypical hemolytic uremic syndrome (factor H deficiency or dysfunction), and age-related macular degeneration (complement component overactivation).

CD46, also known as membrane cofactor protein (MCP), is a regulatory protein that plays a role in the immune system and helps to protect cells from complement activation. It is found on the surface of many different types of cells in the body, including cells of the immune system such as T cells and B cells, as well as cells of various other tissues such as epithelial cells and endothelial cells.

As an antigen, CD46 is a molecule that can be recognized by the immune system and stimulate an immune response. It is a type I transmembrane protein that consists of four distinct domains: two short cytoplasmic domains, a transmembrane domain, and a large extracellular domain. The extracellular domain contains several binding sites for complement proteins, which helps to regulate the activation of the complement system and prevent it from damaging host cells.

CD46 has been shown to play a role in protecting cells from complement-mediated damage, modulating immune responses, and promoting the survival and proliferation of certain types of immune cells. It is also thought to be involved in the development of some autoimmune diseases and may be a target for immunotherapy in the treatment of cancer.

Complement inactivating agents are substances or drugs that inhibit the complement system, which is a part of the immune system responsible for the recognition and elimination of foreign substances and microorganisms. The complement system consists of a group of proteins that work together to help eliminate pathogens from the body.

Complement inactivating agents are used in medical settings to prevent or treat various conditions associated with excessive or unwanted activation of the complement system, such as inflammation, autoimmune diseases, and transplant rejection. These agents can inhibit different components of the complement pathway, including C1 esterase inhibitors, C3 convertase inhibitors, and C5a receptor antagonists.

Examples of complement inactivating agents include eculizumab, ravulizumab, and Alexion's Ultomiris, which are monoclonal antibodies that target C5, a protein involved in the final steps of the complement pathway. These drugs have been approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and other complement-mediated diseases.

Other complement inactivating agents include C1 esterase inhibitors, such as Berinert and Ruconest, which are used to treat hereditary angioedema (HAE). These drugs work by inhibiting the activation of the classical pathway of the complement system, thereby preventing the release of inflammatory mediators that can cause swelling and pain.

Overall, complement inactivating agents play an important role in the treatment of various complement-mediated diseases, helping to reduce inflammation, prevent tissue damage, and improve patient outcomes.

Gene frequency, also known as allele frequency, is a measure in population genetics that reflects the proportion of a particular gene or allele (variant of a gene) in a given population. It is calculated as the number of copies of a specific allele divided by the total number of all alleles at that genetic locus in the population.

For example, if we consider a gene with two possible alleles, A and a, the gene frequency of allele A (denoted as p) can be calculated as follows:

p = (number of copies of allele A) / (total number of all alleles at that locus)

Similarly, the gene frequency of allele a (denoted as q) would be:

q = (number of copies of allele a) / (total number of all alleles at that locus)

Since there are only two possible alleles for this gene in this example, p + q = 1. These frequencies can help researchers understand genetic diversity and evolutionary processes within populations.

Choroidal neovascularization (CNV) is a medical term that refers to the growth of new, abnormal blood vessels in the choroid layer of the eye, which is located between the retina and the sclera. This condition typically occurs as a complication of age-related macular degeneration (AMD), although it can also be caused by other eye diseases or injuries.

In CNV, the new blood vessels that grow into the choroid layer are fragile and can leak fluid or blood, which can cause distortion or damage to the retina, leading to vision loss. Symptoms of CNV may include blurred or distorted vision, a blind spot in the center of the visual field, or changes in color perception.

Treatment for CNV typically involves medications that are designed to stop the growth of new blood vessels, such as anti-VEGF drugs, which target a protein called vascular endothelial growth factor (VEGF) that is involved in the development of new blood vessels. Laser surgery or photodynamic therapy may also be used in some cases to destroy the abnormal blood vessels and prevent further vision loss.

Complement C9 is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. Specifically, C9 is one of the components of the membrane attack complex (MAC), which is a protein structure that forms pores in the membranes of target cells, leading to their lysis or destruction.

When activated, C9 polymerizes and inserts itself into the cell membrane, forming a transmembrane pore that disrupts the membrane's integrity and causes the cell to lyse. This process is an essential part of the complement system's ability to destroy pathogens and clear damaged cells from the body.

Defects in the C9 gene can lead to a rare genetic disorder called complement component 9 deficiency, which is characterized by recurrent bacterial infections and immune complex-mediated diseases. Additionally, mutations in the C9 gene have been associated with an increased risk of age-related macular degeneration (AMD), a leading cause of blindness in older adults.

Complement C3a is a protein fragment that is generated during the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens and damaged cells from the body by marking them for destruction and attracting immune cells to the site of infection or injury.

C3a is produced when the third component of the complement system (C3) is cleaved into two smaller fragments, C3a and C3b, during the complement activation cascade. C3a is a potent anaphylatoxin, which means it can cause the release of histamine and other mediators from mast cells and basophils, leading to inflammation, increased vascular permeability, and smooth muscle contraction.

C3a also has chemotactic properties, meaning it can attract immune cells such as neutrophils and monocytes to the site of complement activation. Additionally, C3a can modulate the activity of various immune cells, including dendritic cells, T cells, and B cells, and play a role in the regulation of the adaptive immune response.

It's important to note that while C3a has important functions in the immune response, uncontrolled or excessive activation of the complement system can lead to tissue damage and inflammation, contributing to the pathogenesis of various diseases such as autoimmune disorders, inflammatory diseases, and allergies.

The retinal pigment epithelium (RPE) is a single layer of cells located between the photoreceptor cells of the retina and the choroid, which is a part of the eye containing blood vessels. The RPE plays a crucial role in maintaining the health and function of the photoreceptors by providing them with nutrients, removing waste products, and helping to regulate the light-sensitive visual pigments within the photoreceptors.

The RPE cells contain pigment granules that absorb excess light to prevent scattering within the eye and improve visual acuity. They also help to form the blood-retina barrier, which restricts the movement of certain molecules between the retina and the choroid, providing an important protective function for the retina.

Damage to the RPE can lead to a variety of eye conditions, including age-related macular degeneration (AMD), which is a leading cause of vision loss in older adults.

A Complement Hemolytic Activity Assay is a laboratory test used to measure the functionality and activity level of the complement system, which is a part of the immune system. The complement system is a group of proteins that work together to help eliminate pathogens from the body.

The assay measures the ability of the complement system to lyse (break open) red blood cells. This is done by mixing the patient's serum (the liquid portion of the blood) with antibody-coated red blood cells and incubating them together. The complement proteins in the serum will then bind to the antibodies on the red blood cells and cause them to lyse.

The degree of hemolysis (red blood cell lysis) is directly proportional to the activity level of the complement system. By measuring the amount of hemolysis, the assay can determine whether the complement system is functioning properly and at what level of activity.

This test is often used to diagnose or monitor complement-mediated diseases such as autoimmune disorders, infections, and some types of cancer. It may also be used to evaluate the effectiveness of treatments that target the complement system.

Genetic predisposition to disease refers to an increased susceptibility or vulnerability to develop a particular illness or condition due to inheriting specific genetic variations or mutations from one's parents. These genetic factors can make it more likely for an individual to develop a certain disease, but it does not guarantee that the person will definitely get the disease. Environmental factors, lifestyle choices, and interactions between genes also play crucial roles in determining if a genetically predisposed person will actually develop the disease. It is essential to understand that having a genetic predisposition only implies a higher risk, not an inevitable outcome.

Geographic atrophy is a medical term used to describe a specific pattern of degeneration of the retinal pigment epithelium (RPE) and the underlying choroidal tissue in the eye. This condition is often associated with age-related macular degeneration (AMD), which is a leading cause of vision loss in older adults.

In geographic atrophy, there are well-defined areas of RPE and choroidal atrophy that appear as pale, irregularly shaped patches in the central part of the retina known as the macula. These patches can grow larger over time and may lead to progressive vision loss. The exact cause of geographic atrophy is not fully understood, but it is thought to be related to oxidative stress, inflammation, and other age-related changes in the eye.

Currently, there are no effective treatments for geographic atrophy, although research is ongoing to find new ways to slow or halt its progression. Regular eye exams and monitoring by an ophthalmologist are important for people with AMD or geographic atrophy to help detect any changes in their vision and manage their condition effectively.

Complement activating enzymes are proteins that play a crucial role in the activation of the complement system, which is a part of the immune system. The complement system is a complex series of biochemical reactions that help to eliminate pathogens and damaged cells from the body.

There are several types of complement activating enzymes, including:

1. Classical pathway activators: These include the C1, C4, and C2 components of the complement system. When activated, they trigger a series of reactions that lead to the formation of the membrane attack complex (MAC), which creates a pore in the membrane of the target cell, leading to its lysis.
2. Alternative pathway activators: These include factors B, D, and P. They are constantly active at low levels and can be activated by surfaces that are not normally found in the body, such as bacterial cell walls. Once activated, they also trigger the formation of the MAC.
3. Lectin pathway activators: These include mannose-binding lectin (MBL) and ficolins. They bind to carbohydrates on the surface of microbes and activate the complement system through the MBL-associated serine proteases (MASPs).

Overall, complement activating enzymes play a critical role in the immune response by helping to identify and eliminate pathogens and damaged cells from the body.

Complement C4b is a protein fragment that is formed during the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens and damaged cells from the body by tagging them for destruction and attracting immune cells to the site of infection or injury.

C4b is generated when the C4 protein is cleaved into two smaller fragments, C4a and C4b, during the activation of the classical or lectin pathways of the complement system. C4b then binds covalently to the surface of the target cell or pathogen, forming a complex with other complement proteins that can create a membrane attack complex (MAC) and cause cell lysis.

C4b can also act as an opsonin, coating the surface of the target cell or pathogen and making it easier for immune cells to recognize and phagocytose them. Additionally, C4b can activate the alternative pathway of the complement system, leading to further amplification of the complement response.

Complement receptor 3b (CR3b or CD11b/CD18) is not a medical definition itself, but I can provide you with the relevant information regarding this term.

Complement receptor 3 (CR3) is a heterodimeric receptor consisting of two subunits, CD11b (also known as Mac-1 or CR3 alpha) and CD18 (also known as beta2 integrin). There are two forms of the CD11b/CD18 heterodimer: CR3a (CD11b/CD18) and CR3b (CD11b/CD18'). The difference between these two forms lies in the conformation of the CD11b subunit.

Complement receptor 3b (CR3b or CD11b/CD18') is a less common form of the CR3 receptor, which is primarily expressed on myeloid cells such as monocytes, macrophages, and neutrophils. CR3b has a higher affinity for complement component C3b and its fragments iC3b and C3dg compared to CR3a.

CR3b plays a role in various immune functions, including:

1. Phagocytosis: Binding of C3b or its fragments to CR3b facilitates the recognition and uptake of opsonized pathogens by phagocytes.
2. Adhesion: The integrin component of CR3b mediates cell-cell and cell-matrix interactions, contributing to leukocyte migration and recruitment to sites of inflammation or infection.
3. Intracellular signaling: Activation of CR3b can lead to intracellular signaling events that modulate immune responses, such as the release of pro-inflammatory cytokines and reactive oxygen species.

In summary, Complement receptor 3b (CR3b or CD11b/CD18') is a less common form of CR3 primarily expressed on myeloid cells that binds complement component C3b and its fragments with high affinity, mediating phagocytosis, adhesion, and intracellular signaling.

Serum sickness is an immune-mediated hypersensitivity reaction that typically occurs within 1 to 3 weeks after the administration of foreign proteins or drugs, such as certain types of antibiotics, antiserums, or monoclonal antibodies. It is characterized by symptoms such as fever, rash, joint pain, and lymphadenopathy (swollen lymph nodes). These symptoms are caused by the formation of immune complexes, which deposit in various tissues and activate the complement system, leading to inflammation. Serum sickness can be treated with antihistamines, corticosteroids, and other immunomodulatory agents. It is important to note that serum sickness is different from anaphylaxis, which is a more severe, life-threatening allergic reaction that occurs immediately after exposure to an allergen.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

A homozygote is an individual who has inherited the same allele (version of a gene) from both parents and therefore possesses two identical copies of that allele at a specific genetic locus. This can result in either having two dominant alleles (homozygous dominant) or two recessive alleles (homozygous recessive). In contrast, a heterozygote has inherited different alleles from each parent for a particular gene.

The term "homozygote" is used in genetics to describe the genetic makeup of an individual at a specific locus on their chromosomes. Homozygosity can play a significant role in determining an individual's phenotype (observable traits), as having two identical alleles can strengthen the expression of certain characteristics compared to having just one dominant and one recessive allele.

Human chromosome pair 1 refers to the first pair of chromosomes in a set of 23 pairs found in the cells of the human body, excluding sex cells (sperm and eggs). Each cell in the human body, except for the gametes, contains 46 chromosomes arranged in 23 pairs. These chromosomes are rod-shaped structures that contain genetic information in the form of DNA.

Chromosome pair 1 is the largest pair, making up about 8% of the total DNA in a cell. Each chromosome in the pair consists of two arms - a shorter p arm and a longer q arm - connected at a centromere. Chromosome 1 carries an estimated 2,000-2,500 genes, which are segments of DNA that contain instructions for making proteins or regulating gene expression.

Defects or mutations in the genes located on chromosome 1 can lead to various genetic disorders and diseases, such as Charcot-Marie-Tooth disease type 1A, Huntington's disease, and certain types of cancer.

Complement C4b-binding protein (C4bp) is a regulatory protein in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. C4bp regulates the complement system by binding to and inhibiting the activity of C4b, an activated component of the classical and lectin pathways of the complement system. By doing so, C4bp helps to prevent excessive or inappropriate activation of the complement system, which could otherwise lead to tissue damage and inflammation.

C4bp is a complex protein that consists of several subunits, including a central α-chain and multiple β-chains. It is produced by liver cells and can also be found on the surface of some cells in the body. Mutations in the genes encoding C4bp have been associated with certain immune disorders, such as systemic lupus erythematosus (SLE) and atypical hemolytic uremic syndrome (aHUS).

Complement C3 Convertase, Alternative Pathway is a complex enzyme composed of the proteins C3b and Bb. It plays a crucial role in the alternative pathway of the complement system, which is a part of the innate immune system that helps to defend the body against invading pathogens.

The alternative pathway is continuously activated at a low level, and C3 Convertase is responsible for amplifying this activation. It does so by cleaving the complement component C3 into C3a and C3b. The C3b then binds to the surface of the pathogen and can form additional C3 Convertases, leading to a positive feedback loop that results in the rapid accumulation of complement components on the surface of the pathogen.

This accumulation of complement components helps to mark the pathogen for destruction by other immune cells, such as neutrophils and macrophages. Additionally, the cleavage products C3a and C5a generated during this process can act as anaphylatoxins, inducing inflammation and attracting more immune cells to the site of infection.

Regulation of Complement C3 Convertase is critical to prevent damage to host tissues. Several regulatory proteins, such as factor H and decay-accelerating factor (DAF), help to limit the formation and activity of C3 Convertase on host cells and tissues. Dysregulation of the complement system, including the alternative pathway and Complement C3 Convertase, has been implicated in a variety of diseases, including autoimmune disorders, inflammatory diseases, and infectious diseases.

A case-control study is an observational research design used to identify risk factors or causes of a disease or health outcome. In this type of study, individuals with the disease or condition (cases) are compared with similar individuals who do not have the disease or condition (controls). The exposure history or other characteristics of interest are then compared between the two groups to determine if there is an association between the exposure and the disease.

Case-control studies are often used when it is not feasible or ethical to conduct a randomized controlled trial, as they can provide valuable insights into potential causes of diseases or health outcomes in a relatively short period of time and at a lower cost than other study designs. However, because case-control studies rely on retrospective data collection, they are subject to biases such as recall bias and selection bias, which can affect the validity of the results. Therefore, it is important to carefully design and conduct case-control studies to minimize these potential sources of bias.

A haplotype is a group of genes or DNA sequences that are inherited together from a single parent. It refers to a combination of alleles (variant forms of a gene) that are located on the same chromosome and are usually transmitted as a unit. Haplotypes can be useful in tracing genetic ancestry, understanding the genetic basis of diseases, and developing personalized medical treatments.

In population genetics, haplotypes are often used to study patterns of genetic variation within and between populations. By comparing haplotype frequencies across populations, researchers can infer historical events such as migrations, population expansions, and bottlenecks. Additionally, haplotypes can provide information about the evolutionary history of genes and genomic regions.

In clinical genetics, haplotypes can be used to identify genetic risk factors for diseases or to predict an individual's response to certain medications. For example, specific haplotypes in the HLA gene region have been associated with increased susceptibility to certain autoimmune diseases, while other haplotypes in the CYP450 gene family can affect how individuals metabolize drugs.

Overall, haplotypes provide a powerful tool for understanding the genetic basis of complex traits and diseases, as well as for developing personalized medical treatments based on an individual's genetic makeup.

CD55, also known as Decay-accelerating factor (DAF), is a protein that acts as an inhibitor of the complement system, which is a part of the immune system. It prevents the formation of the membrane attack complex (MAC) on host cells and tissues, thereby protecting them from damage caused by the complement activation. CD55 is found on the surface of many types of cells in the body, including red blood cells, white blood cells, and cells lining the blood vessels.

As an antigen, CD55 is a molecule that can be recognized by the immune system and stimulate an immune response. However, unlike some other antigens, CD55 does not typically elicit a strong immune response because it is a self-antigen, meaning it is normally present in the body and should not be targeted by the immune system.

In certain medical conditions, such as autoimmune disorders or transplant rejection, the immune system may mistakenly attack cells expressing CD55. In these cases, measuring the levels of CD55 antigens can provide valuable diagnostic information and help guide treatment decisions.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Genetic polymorphism refers to the occurrence of multiple forms (called alleles) of a particular gene within a population. These variations in the DNA sequence do not generally affect the function or survival of the organism, but they can contribute to differences in traits among individuals. Genetic polymorphisms can be caused by single nucleotide changes (SNPs), insertions or deletions of DNA segments, or other types of genetic rearrangements. They are important for understanding genetic diversity and evolution, as well as for identifying genetic factors that may contribute to disease susceptibility in humans.

The term "Receptor, Anaphylatoxin C5a" refers to a specific type of receptor found on the surface of various cells in the human body, including immune cells and endothelial cells. This receptor binds to a molecule called C5a, which is a cleavage product of the complement component C5 and is one of the most potent anaphylatoxins.

Anaphylatoxins are inflammatory mediators that play a crucial role in the immune response, particularly in the activation of the complement system and the recruitment of immune cells to sites of infection or injury. C5a is generated during the activation of the complement system and has a wide range of biological activities, including chemotaxis (attracting immune cells to the site of inflammation), increased vascular permeability, and the activation of immune cells such as neutrophils, monocytes, and mast cells.

The C5a receptor, also known as CD88, is a G protein-coupled receptor that belongs to the superfamily of seven transmembrane domain receptors. When C5a binds to the receptor, it triggers a series of intracellular signaling events that lead to the activation of various cellular responses, such as the release of inflammatory mediators and the recruitment of immune cells to the site of inflammation.

Abnormal activation of the C5a/C5a receptor pathway has been implicated in a variety of inflammatory diseases, including sepsis, acute respiratory distress syndrome (ARDS), and autoimmune disorders. Therefore, targeting this pathway with therapeutic agents has emerged as a promising strategy for the treatment of these conditions.

Linkage disequilibrium (LD) is a term used in genetics that refers to the non-random association of alleles at different loci (genetic locations) on a chromosome. This means that certain combinations of genetic variants, or alleles, at different loci occur more frequently together in a population than would be expected by chance.

Linkage disequilibrium can arise due to various factors such as genetic drift, selection, mutation, and population structure. It is often used in the context of genetic mapping studies to identify regions of the genome that are associated with particular traits or diseases. High levels of LD in a region of the genome suggest that the loci within that region are in linkage, meaning they tend to be inherited together.

The degree of LD between two loci can be measured using various statistical methods, such as D' and r-squared. These measures provide information about the strength and direction of the association between alleles at different loci, which can help researchers identify causal genetic variants underlying complex traits or diseases.

An allele is a variant form of a gene that is located at a specific position on a specific chromosome. Alleles are alternative forms of the same gene that arise by mutation and are found at the same locus or position on homologous chromosomes.

Each person typically inherits two copies of each gene, one from each parent. If the two alleles are identical, a person is said to be homozygous for that trait. If the alleles are different, the person is heterozygous.

For example, the ABO blood group system has three alleles, A, B, and O, which determine a person's blood type. If a person inherits two A alleles, they will have type A blood; if they inherit one A and one B allele, they will have type AB blood; if they inherit two B alleles, they will have type B blood; and if they inherit two O alleles, they will have type O blood.

Alleles can also influence traits such as eye color, hair color, height, and other physical characteristics. Some alleles are dominant, meaning that only one copy of the allele is needed to express the trait, while others are recessive, meaning that two copies of the allele are needed to express the trait.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Complement C6 is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. Specifically, C6 is a component of the membrane attack complex (MAC), which is a group of proteins that work together to form a pore in the membrane of target cells, leading to their lysis or destruction.

The complement system is activated through several different pathways, including the classical pathway, the lectin pathway, and the alternative pathway. Once activated, these pathways converge at the level of C3, which is cleaved into C3a and C3b fragments. C3b can then bind to the surface of target cells and initiate the formation of the MAC.

C6 is one of several proteins that are required for the formation of the MAC. When C6 binds to C7, it undergoes a conformational change that allows it to interact with C8 and form a stable complex. This complex then recruits additional C9 molecules, which polymerize to form the pore in the target cell membrane.

Deficiencies in complement components, including C6, can lead to increased susceptibility to certain types of infections, as well as autoimmune disorders and other medical conditions.

Complement C1 is a protein complex that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. The complement system consists of a group of proteins that work together to destroy microbes and remove debris.

Complement C1 is composed of three subunits: C1q, C1r, and C1s. When activated, C1q binds to the surface of a pathogen or damaged cell, leading to the activation of C1r and C1s. Activated C1r then cleaves and activates C1s, which in turn cleaves and activates other complement components, ultimately resulting in the formation of the membrane attack complex (MAC), a protein structure that forms a pore in the membrane of the target cell, leading to its lysis and destruction.

Defects in the complement component C1 can lead to immune disorders, such as hereditary angioedema, which is characterized by recurrent episodes of swelling in various parts of the body.

Surface Plasmon Resonance (SPR) is a physical phenomenon that occurs at the interface between a metal and a dielectric material, when electromagnetic radiation (usually light) is shone on it. It involves the collective oscillation of free electrons in the metal, known as surface plasmons, which are excited by the incident light. The resonance condition is met when the momentum and energy of the photons match those of the surface plasmons, leading to a strong absorption of light and an evanescent wave that extends into the dielectric material.

In the context of medical diagnostics and research, SPR is often used as a sensitive and label-free detection technique for biomolecular interactions. By immobilizing one binding partner (e.g., a receptor or antibody) onto the metal surface and flowing the other partner (e.g., a ligand or antigen) over it, changes in the refractive index at the interface can be measured in real-time as the plasmons are disturbed by the presence of bound molecules. This allows for the quantification of binding affinities, kinetics, and specificity with high sensitivity and selectivity.

Serine endopeptidases are a type of enzymes that cleave peptide bonds within proteins (endopeptidases) and utilize serine as the nucleophilic amino acid in their active site for catalysis. These enzymes play crucial roles in various biological processes, including digestion, blood coagulation, and programmed cell death (apoptosis). Examples of serine endopeptidases include trypsin, chymotrypsin, thrombin, and elastase.

Properdin is defined as a positive regulatory protein in the complement system, which is a part of the immune system. It plays a crucial role in the alternative pathway of complement activation. Properdin stabilizes the C3 convertase (C3bBb), preventing its decay and increasing the efficiency of the alternative pathway. This results in the production of the membrane attack complex, which leads to the lysis of foreign cells or pathogens. Deficiencies in properdin can lead to an increased susceptibility to bacterial infections.

Heparin is defined as a highly sulfated glycosaminoglycan (a type of polysaccharide) that is widely present in many tissues, but is most commonly derived from the mucosal tissues of mammalian lungs or intestinal mucosa. It is an anticoagulant that acts as an inhibitor of several enzymes involved in the blood coagulation cascade, primarily by activating antithrombin III which then neutralizes thrombin and other clotting factors.

Heparin is used medically to prevent and treat thromboembolic disorders such as deep vein thrombosis, pulmonary embolism, and certain types of heart attacks. It can also be used during hemodialysis, cardiac bypass surgery, and other medical procedures to prevent the formation of blood clots.

It's important to note that while heparin is a powerful anticoagulant, it does not have any fibrinolytic activity, meaning it cannot dissolve existing blood clots. Instead, it prevents new clots from forming and stops existing clots from growing larger.

Complement C3c is a protein component of the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Complement C3c is formed when the third component of the complement system (C3) is cleaved into two smaller proteins, C3a and C3b, during the complement activation process.

C3b can then be further cleaved into C3c and C3dg. C3c is a stable fragment that remains in the circulation and can be measured in blood tests as a marker of complement activation. It plays a role in the opsonization of pathogens, which means it coats them to make them more recognizable to immune cells, and helps to initiate the membrane attack complex (MAC), which forms a pore in the cell membrane of pathogens leading to their lysis or destruction.

Abnormal levels of C3c may indicate an underlying inflammatory or immune-mediated condition, such as infection, autoimmune disease, or cancer.

Human chromosome pair 10 refers to a group of genetic materials that are present in every cell of the human body. Chromosomes are thread-like structures that carry our genes and are located in the nucleus of most cells. They come in pairs, with one set inherited from each parent.

Chromosome pair 10 is one of the 22 autosomal chromosome pairs, meaning they contain genes that are not related to sex determination. Each member of chromosome pair 10 is a single, long DNA molecule that contains thousands of genes and other genetic material.

Chromosome pair 10 is responsible for carrying genetic information that influences various traits and functions in the human body. Some of the genes located on chromosome pair 10 are associated with certain medical conditions, such as hereditary breast and ovarian cancer syndrome, neurofibromatosis type 1, and Waardenburg syndrome type 2A.

It's important to note that while chromosomes carry genetic information, not all variations in the DNA sequence will result in a change in phenotype or function. Some variations may have no effect at all, while others may lead to changes in how proteins are made and function, potentially leading to disease or other health issues.

The pigment epithelium of the eye, also known as the retinal pigment epithelium (RPE), is a layer of cells located between the photoreceptor cells of the retina and the choroid, which is the vascular layer of the eye. The RPE plays a crucial role in maintaining the health and function of the photoreceptors by providing them with nutrients, removing waste products, and helping to regulate the light that enters the eye.

The RPE cells contain pigment granules that absorb excess light, preventing it from scattering within the eye and improving visual acuity. They also help to create a barrier between the retina and the choroid, which is important for maintaining the proper functioning of the photoreceptors. Additionally, the RPE plays a role in the regeneration of visual pigments in the photoreceptor cells, allowing us to see in different light conditions.

Damage to the RPE can lead to various eye diseases and conditions, including age-related macular degeneration (AMD), which is a leading cause of vision loss in older adults.

The Mannose-Binding Lectin (MBL) pathway is a part of the complement system, which is a group of proteins that play a crucial role in the body's immune defense against infectious agents. The MBL pathway is an alternative activation pathway of the complement system, which can be initiated without the need for antibodies.

MBL is a protein found in blood plasma and other bodily fluids. It recognizes and binds to specific sugars (mannose and fucose) found on the surface of many microorganisms, including bacteria, viruses, fungi, and parasites. When MBL binds to these sugars, it triggers a series of proteolytic cleavage events that activate the complement components C4 and C2, forming the C3 convertase (C4b2a).

The C3 convertase then cleaves the complement component C3 into C3a and C3b. C3b can bind to the surface of microorganisms, leading to their opsonization (coating) and subsequent phagocytosis by immune cells. Additionally, C3b can also trigger the formation of the membrane attack complex (MAC), which creates a pore in the membrane of microorganisms, leading to their lysis and death.

Overall, the MBL pathway plays an essential role in innate immunity, providing a rapid and effective defense against invading microorganisms.

The Complement C1 Inhibitor protein, also known as C1-INH, is a protein involved in the regulation of the complement system and the contact system, which are parts of the immune system. The complement system helps to eliminate pathogens (e.g., bacteria, viruses) from the body, while the contact system helps to regulate blood coagulation and inflammation.

C1-INH works by inhibiting the activation of C1, an enzyme complex that is the first component of the classical complement pathway. By inhibiting C1, C1-INH prevents the activation of downstream components of the complement system, thereby helping to regulate the immune response and prevent excessive inflammation.

Deficiencies or dysfunction in the C1-INH protein can lead to a group of genetic disorders known as C1 inhibitor deficiency disorders, which include hereditary angioedema (HAE) and acquired angioedema (AAE). These conditions are characterized by recurrent episodes of swelling in various parts of the body, such as the face, hands, feet, and airway, which can be painful and potentially life-threatening if they affect the airway.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

An amino acid substitution is a type of mutation in which one amino acid in a protein is replaced by another. This occurs when there is a change in the DNA sequence that codes for a particular amino acid in a protein. The genetic code is redundant, meaning that most amino acids are encoded by more than one codon (a sequence of three nucleotides). As a result, a single base pair change in the DNA sequence may not necessarily lead to an amino acid substitution. However, if a change does occur, it can have a variety of effects on the protein's structure and function, depending on the nature of the substituted amino acids. Some substitutions may be harmless, while others may alter the protein's activity or stability, leading to disease.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Histidine is an essential amino acid, meaning it cannot be synthesized by the human body and must be obtained through dietary sources. Its chemical formula is C6H9N3O2. Histidine plays a crucial role in several physiological processes, including:

1. Protein synthesis: As an essential amino acid, histidine is required for the production of proteins, which are vital components of various tissues and organs in the body.

2. Hemoglobin synthesis: Histidine is a key component of hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. The imidazole side chain of histidine acts as a proton acceptor/donor, facilitating the release and uptake of oxygen by hemoglobin.

3. Acid-base balance: Histidine is involved in maintaining acid-base homeostasis through its role in the biosynthesis of histamine, which is a critical mediator of inflammatory responses and allergies. The decarboxylation of histidine results in the formation of histamine, which can increase vascular permeability and modulate immune responses.

4. Metal ion binding: Histidine has a high affinity for metal ions such as zinc, copper, and iron. This property allows histidine to participate in various enzymatic reactions and maintain the structural integrity of proteins.

5. Antioxidant defense: Histidine-containing dipeptides, like carnosine and anserine, have been shown to exhibit antioxidant properties by scavenging reactive oxygen species (ROS) and chelating metal ions. These compounds may contribute to the protection of proteins and DNA from oxidative damage.

Dietary sources of histidine include meat, poultry, fish, dairy products, and wheat germ. Histidine deficiency is rare but can lead to growth retardation, anemia, and impaired immune function.

Complement fixation tests are a type of laboratory test used in immunology and serology to detect the presence of antibodies in a patient's serum. These tests are based on the principle of complement activation, which is a part of the immune response. The complement system consists of a group of proteins that work together to help eliminate pathogens from the body.

In a complement fixation test, the patient's serum is mixed with a known antigen and complement proteins. If the patient has antibodies against the antigen, they will bind to it and activate the complement system. This results in the consumption or "fixation" of the complement proteins, which are no longer available to participate in a secondary reaction.

A second step involves adding a fresh source of complement proteins and a dye-labeled antibody that recognizes a specific component of the complement system. If complement was fixed during the first step, it will not be available for this secondary reaction, and the dye-labeled antibody will remain unbound. Conversely, if no antibodies were present in the patient's serum, the complement proteins would still be available for the second reaction, leading to the binding of the dye-labeled antibody.

The mixture is then examined under a microscope or using a spectrophotometer to determine whether the dye-labeled antibody has bound. If it has not, this indicates that the patient's serum contains antibodies specific to the antigen used in the test, and a positive result is recorded.

Complement fixation tests have been widely used for the diagnosis of various infectious diseases, such as syphilis, measles, and influenza. However, they have largely been replaced by more modern serological techniques, like enzyme-linked immunosorbent assays (ELISAs) and nucleic acid amplification tests (NAATs), due to their increased sensitivity, specificity, and ease of use.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Blood bactericidal activity refers to the ability of an individual's blood to kill or inhibit the growth of bacteria. This is an important aspect of the body's immune system, as it helps to prevent infection and maintain overall health. The bactericidal activity of blood can be influenced by various factors, including the presence of antibodies, white blood cells (such as neutrophils), and complement proteins.

In medical terms, the term "bactericidal" specifically refers to an agent or substance that is capable of killing bacteria. Therefore, when we talk about blood bactericidal activity, we are referring to the collective ability of various components in the blood to kill or inhibit the growth of bacteria. This is often measured in laboratory tests as a way to assess a person's immune function and their susceptibility to infection.

It's worth noting that not all substances in the blood are bactericidal; some may simply inhibit the growth of bacteria without killing them. These substances are referred to as bacteriostatic. Both bactericidal and bacteriostatic agents play important roles in maintaining the body's defense against infection.

Tertiary protein structure refers to the three-dimensional arrangement of all the elements (polypeptide chains) of a single protein molecule. It is the highest level of structural organization and results from interactions between various side chains (R groups) of the amino acids that make up the protein. These interactions, which include hydrogen bonds, ionic bonds, van der Waals forces, and disulfide bridges, give the protein its unique shape and stability, which in turn determines its function. The tertiary structure of a protein can be stabilized by various factors such as temperature, pH, and the presence of certain ions. Any changes in these factors can lead to denaturation, where the protein loses its tertiary structure and thus its function.

Bacterial proteins are a type of protein that are produced by bacteria as part of their structural or functional components. These proteins can be involved in various cellular processes, such as metabolism, DNA replication, transcription, and translation. They can also play a role in bacterial pathogenesis, helping the bacteria to evade the host's immune system, acquire nutrients, and multiply within the host.

Bacterial proteins can be classified into different categories based on their function, such as:

1. Enzymes: Proteins that catalyze chemical reactions in the bacterial cell.
2. Structural proteins: Proteins that provide structural support and maintain the shape of the bacterial cell.
3. Signaling proteins: Proteins that help bacteria to communicate with each other and coordinate their behavior.
4. Transport proteins: Proteins that facilitate the movement of molecules across the bacterial cell membrane.
5. Toxins: Proteins that are produced by pathogenic bacteria to damage host cells and promote infection.
6. Surface proteins: Proteins that are located on the surface of the bacterial cell and interact with the environment or host cells.

Understanding the structure and function of bacterial proteins is important for developing new antibiotics, vaccines, and other therapeutic strategies to combat bacterial infections.

An Enzyme-Linked Immunosorbent Assay (ELISA) is a type of analytical biochemistry assay used to detect and quantify the presence of a substance, typically a protein or peptide, in a liquid sample. It takes its name from the enzyme-linked antibodies used in the assay.

In an ELISA, the sample is added to a well containing a surface that has been treated to capture the target substance. If the target substance is present in the sample, it will bind to the surface. Next, an enzyme-linked antibody specific to the target substance is added. This antibody will bind to the captured target substance if it is present. After washing away any unbound material, a substrate for the enzyme is added. If the enzyme is present due to its linkage to the antibody, it will catalyze a reaction that produces a detectable signal, such as a color change or fluorescence. The intensity of this signal is proportional to the amount of target substance present in the sample, allowing for quantification.

ELISAs are widely used in research and clinical settings to detect and measure various substances, including hormones, viruses, and bacteria. They offer high sensitivity, specificity, and reproducibility, making them a reliable choice for many applications.

Complement C7 is a protein that plays a role in the complement system, which is a part of the immune system that helps to clear pathogens and damaged cells from the body. Specifically, C7 is a component of the membrane attack complex (MAC), which is a group of proteins that forms a pore in the membrane of target cells, leading to their lysis or destruction.

C7 is activated when it binds to the C5b-7 complex, which is formed by the cleavage of C5 and C6 by the C5 convertase. Once bound to the C5b-7 complex, C7 undergoes a conformational change that allows it to insert into the target cell membrane. This forms the basis for the formation of the MAC and subsequent lysis of the target cell.

Deficiencies in complement components, including C7, can lead to increased susceptibility to certain infections and autoimmune disorders. Additionally, abnormal regulation of the complement system has been implicated in a variety of diseases, including inflammatory and degenerative conditions.

Complement receptor 3d (CR3d or CD11b/CD18) is not a medical definition in itself, but rather a specific type of integrin receptor that plays a crucial role in the immune system. Here's a breakdown of the components:

1. Complement Receptors: These are proteins found on the surface of various cells, including white blood cells (leukocytes), that recognize and bind to complement components, which are proteins involved in the immune response. The binding of complement components to their receptors helps facilitate communication between cells, enhances phagocytosis (the process by which certain cells engulf and destroy foreign particles or microorganisms), and contributes to the inflammatory response.
2. CR3 (Complement Receptor 3): Complement Receptor 3 is a heterodimeric receptor composed of two subunits, CD11b (also known as integrin alpha M) and CD18 (also known as integrin beta 2). Together, they form the integrin Mac-1 or αMβ2.
3. CR3d (CD11b/CD18): CR3d specifically refers to the CD11b subunit of the Complement Receptor 3 heterodimer. The CD11b subunit is responsible for recognizing and binding to complement component C3b, iC3b, and C4b fragments, as well as other ligands such as fibrinogen, ICAM-1 (Intercellular Adhesion Molecule 1), and factor X.

In summary, Complement Receptor 3d (CR3d or CD11b/CD18) is a type of integrin receptor found on the surface of various immune cells that recognizes and binds to complement components C3b, iC3b, and C4b fragments, as well as other ligands. This binding facilitates communication between cells, enhances phagocytosis, and contributes to the inflammatory response.

Cobra venoms are a type of snake venom that is produced by cobras, which are members of the genus Naja in the family Elapidae. These venoms are complex mixtures of proteins and other molecules that have evolved to help the snake immobilize and digest its prey.

Cobra venoms typically contain a variety of toxic components, including neurotoxins, hemotoxins, and cytotoxins. Neurotoxins target the nervous system and can cause paralysis and respiratory failure. Hemotoxins damage blood vessels and tissues, leading to internal bleeding and organ damage. Cytotoxins destroy cells and can cause tissue necrosis.

The specific composition of cobra venoms can vary widely between different species of cobras, as well as between individual snakes of the same species. Some cobras have venoms that are primarily neurotoxic, while others have venoms that are more hemotoxic or cytotoxic. The potency and effects of cobra venoms can also be influenced by factors such as the age and size of the snake, as well as the temperature and pH of the environment.

Cobra bites can be extremely dangerous and even fatal to humans, depending on the species of cobra, the amount of venom injected, and the location of the bite. Immediate medical attention is required in the event of a cobra bite, including the administration of antivenom therapy to neutralize the effects of the venom.

Complement C8 is a protein component of the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. Specifically, C8 is a part of the membrane attack complex (MAC), which forms a pore in the membrane of target cells, leading to their lysis or destruction.

C8 is composed of three subunits: alpha, beta, and gamma. It is activated when it binds to the complement component C5b67 complex on the surface of a target cell. Once activated, C8 undergoes a conformational change that allows it to insert into the target cell membrane and form a pore, which disrupts the cell's membrane integrity and can lead to its death.

Deficiencies in complement components, including C8, can make individuals more susceptible to certain infections and autoimmune diseases. Additionally, mutations in the genes encoding complement proteins have been associated with various inherited disorders, such as atypical hemolytic uremic syndrome (aHUS), which is characterized by thrombotic microangiopathy and kidney failure.

The term "Asian Continental Ancestry Group" is a medical/ethnic classification used to describe a person's genetic background and ancestry. According to this categorization, individuals with origins in the Asian continent are grouped together. This includes populations from regions such as East Asia (e.g., China, Japan, Korea), South Asia (e.g., India, Pakistan, Bangladesh), Southeast Asia (e.g., Philippines, Indonesia, Thailand), and Central Asia (e.g., Kazakhstan, Uzbekistan, Tajikistan). It is important to note that this broad categorization may not fully capture the genetic diversity within these regions or accurately reflect an individual's specific ancestral origins.

Anaphylatoxins are a group of small protein molecules that are released during an immune response, specifically as a result of the activation of the complement system. The term "anaphylatoxin" comes from their ability to induce anaphylaxis, a severe and rapid allergic reaction. There are three main anaphylatoxins, known as C3a, C4a, and C5a, which are derived from the cleavage of complement components C3, C4, and C5, respectively.

Anaphylatoxins play a crucial role in the immune response by attracting and activating various immune cells, such as neutrophils, eosinophils, and mast cells, to the site of infection or injury. They also increase vascular permeability, causing fluid to leak out of blood vessels and leading to tissue swelling. Additionally, anaphylatoxins can induce smooth muscle contraction, which can result in bronchoconstriction and hypotension.

While anaphylatoxins are important for the immune response, they can also contribute to the pathogenesis of various inflammatory diseases, such as asthma, arthritis, and sepsis. Therefore, therapies that target the complement system and anaphylatoxin production have been developed and are being investigated as potential treatments for these conditions.

Medical Definition:

"Risk factors" are any attribute, characteristic or exposure of an individual that increases the likelihood of developing a disease or injury. They can be divided into modifiable and non-modifiable risk factors. Modifiable risk factors are those that can be changed through lifestyle choices or medical treatment, while non-modifiable risk factors are inherent traits such as age, gender, or genetic predisposition. Examples of modifiable risk factors include smoking, alcohol consumption, physical inactivity, and unhealthy diet, while non-modifiable risk factors include age, sex, and family history. It is important to note that having a risk factor does not guarantee that a person will develop the disease, but rather indicates an increased susceptibility.

C-reactive protein (CRP) is a protein produced by the liver in response to inflammation or infection in the body. It is named after its ability to bind to the C-polysaccharide of pneumococcus, a type of bacteria. CRP levels can be measured with a simple blood test and are often used as a marker of inflammation or infection. Elevated CRP levels may indicate a variety of conditions, including infections, tissue damage, and chronic diseases such as rheumatoid arthritis and cancer. However, it is important to note that CRP is not specific to any particular condition, so additional tests are usually needed to make a definitive diagnosis.

Genetic variation refers to the differences in DNA sequences among individuals and populations. These variations can result from mutations, genetic recombination, or gene flow between populations. Genetic variation is essential for evolution by providing the raw material upon which natural selection acts. It can occur within a single gene, between different genes, or at larger scales, such as differences in the number of chromosomes or entire sets of chromosomes. The study of genetic variation is crucial in understanding the genetic basis of diseases and traits, as well as the evolutionary history and relationships among species.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Factor I deficiency in turn leads to low levels of complement component 3 (C3), factor B, factor H and properdin in blood, due ... Complement factor I (factor I) is a protein of the complement system, first isolated in 1966 in guinea pig serum, that ... Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement ... Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. ...
... is a protein that in humans is encoded by the CFB gene. This gene encodes complement factor B, a component ... CFB complement factor B". Ambrus JL, Peters MG, Fauci AS, Brown EJ (March 1990). "The Ba fragment of complement factor B ... Christie DL, Gagnon J (January 1983). "Amino acid sequence of the Bb fragment from complement Factor B. Sequence of the major ... Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the ...
"The role of complement factor C3 in lipid metabolism". Molecular Immunology. 15th European Meeting on Complement in Human ... 12th European Meeting on Complement in Human Disease12th European Meeting on CHD12th European Meeting on Complement in Human ... that allows it to bind to a plasma protein called Factor B. This complex is then cleaved by Factor D, a serine protease, to ... Factor I, a serine protease activated by cofactors, can cleave and C3b and C4b, thus preventing convertase formation. C3 ...
Activated C3 can then interact with factor B. Factor B is then activated by factor D, to form Bb. The resultant complex, C3bBb ... "Interactions between human complement components factor H, factor I and C3b". The Biochemical Journal. 326 (2): 553-61. doi: ... Complement component 3 has been shown to interact with Factor H. Deficiencies in C3 lead to genetic infections, usually fatal ... Factor I is the protease cleaves C3b but requires a cofactor (e.g Factor H, CR1, MCP or C4BP) for activity. Several ...
This gene encodes the basic form of complement factor 4, part of the classical activation pathway. The protein is expressed as ... Complement component 4 Complement component 4A HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency ... Aoki H, Takizawa F, Tsuji S, Nagasawa S (Jul 2000). "Elongation factor-1alpha as a homologous complement activator of Jurkat ... Complement component 4B (Chido blood group) is a kind of the Complement component 4 protein that in humans is encoded by the ...
Decay Accelerating Factor, DAF (CD55) Protectin (CD59) Complement C3b/C4b Receptor 1, CR1 (CD35) Complement Regulator of the ... Complement control protein are proteins that interact with components of the complement system. The complement system is ... Complement proteins protect against malignant cells- both by direct complement attack and through initiation of Complement- ... factor H competes with factor B to bind C3b; if it manages to bind, then the convertase is not formed. Factor H can bind C3b ...
PSAP Complement component 4, partial deficiency of; 120790; C1NH Complement factor H deficiency; 609814; HF1 Complement factor ... GLA Factor V and factor VIII, combined deficiency of; 227300; MCFD2 Factor V deficiency; 227400; F5 Factor XI deficiency, ... F11 Factor XII deficiency; 234000; F12 Factor XIIIA deficiency; 613225; F13A1 Factor XIIIB deficiency; 613235; F13B Failure of ... LCAT Fletcher factor deficiency; 612423; KLKB1 Focal cortical dysplasia, Taylor balloon cell type; 607341; TSC1 Focal dermal ...
... complement subgroups factor a group into smaller pieces. As previously mentioned, complements need not exist. A p-complement is ... A Frobenius complement is a special type of complement in a Frobenius group. A complemented group is one where every subgroup ... if K is a complement of H, then H is a complement of K. Neither H nor K need be a normal subgroup of G. Complements need not ... That is, H could have two distinct complements K1 and K2 in G. If there are several complements of a normal subgroup, then they ...
"OMIM Entry - * 300383 - COMPLEMENT FACTOR PROPERDIN; CFP". www.omim.org. Retrieved 2022-03-24. editor., Leung, Donald Y. M., ... The gene responsible for the production of properdin, Complement Factor Properdin (CFP), lies on the X-chromosome at the ... Properdin deficiency is a rare X-linked disease in which properdin, an important complement factor responsible for the ... Pertaining to complement deficiencies, there is no cure and the treatments for complement deficiencies vary widely. The best ...
Like complement factor H, CFHR5 is able to bind to complement C3. A mutation in CHFR5 was found in patients with the disease ... "Entrez Gene: CFHR5 complement factor H-related 5". McRae JL, Duthy TG, Griggs KM, et al. (2005). "Human factor H-related ... 2006). "Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with ... Complement factor H-related protein 5 is a protein that in humans is encoded by the CFHR5 gene. CFHR5 is structurally related ...
Diaz-Guillen MA, Rodriguez de Cordoba S, Heine-Suner D (Jul 1999). "A radiation hybrid map of complement factor H and factor H- ... CFHR4 complement factor H-related 4". Hageman GS, Hancox LS, Taiber AJ, et al. (2007). "Extended Haplotypes in the Complement ... Complement factor H-related protein 4 is a protein that in humans is encoded by the CFHR4 gene. GRCh38: Ensembl release 89: ... 2000). "Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and ...
Complement factor H-related protein 2) at the PDBe-KB. Zipfel PF, Skerka C (1994). "Complement factor H and related proteins: ... Díaz-Guillén MA, Rodríguez de Córdoba S, Heine-Suñer D (1999). "A radiation hybrid map of complement factor H and factor H- ... "Two additional human serum proteins structurally related to complement factor H. Evidence for a family of factor H-related ... Complement factor H-related protein 2 is a protein that in humans is encoded by the CFHR2 gene. GRCh38: Ensembl release 89: ...
"Cellular adhesion mediated by factor J, a complement inhibitor. Evidence for nucleolin involvement". The Journal of Biological ... Nucleolin is also able to act as a transcriptional coactivator with Chicken Ovalbumin Upstream Promoter Transcription Factor II ...
... is produced when complement factor I cleaves C3b. Complement receptors on white blood cells are able to bind iC3b, so iC3b ... thus preventing amplification of the complement cascade through the alternative pathway. Complement factor I can further cleave ... iC3b is a protein fragment that is part of the complement system, a component of the vertebrate immune system. ... v t e (Complement system, All stub articles, Biochemistry stubs). ...
These SNPs were located in the gene encoding complement factor H, which was an unexpected finding in the research of ARMD. The ... April 2005). "Complement factor H polymorphism in age-related macular degeneration". Science. 308 (5720): 385-9. Bibcode: ... "Complement factor H variant increases the risk of age-related macular degeneration". Science. 308 (5720): 419-21. Bibcode: ... It has been identified different variants associated with transcription factor coding-genes, such as TBX3 and TBX5, NKX2-5 o ...
Wu LC, Morley BJ, Campbell RD (Jan 1987). "Cell-specific expression of the human complement protein factor B gene: evidence for ... the body signals the Complement system and the Complement component 2 protein attaches to Complement system 4 resulting in an ... It is also important to note that Complement component 2 deficiency can be caused by genetic and environmental factors. In ... Gagnon J (Sep 1984). "Structure and activation of complement components C2 and factor B". Philosophical Transactions of the ...
It can also be seen in systemic lupus erythematosus as a result of increased usage of complement factors due to the pathology ... The CH50 is testing the classical complement pathway in an individual thus requiring functioning C1-C9 factors. If an ... Total complement activity (TCA) refers to a series of tests that determine the functioning of the complement system in an ... One can interpret the CH50 value along with the individual's complement factor values to help determine the etiology. For ...
Complement factors are decreased in rheumatoid arthritis and lupus arthritis. Microscopic analysis of synovial fluid is ... Jay, GD; Britt, DE; Cha, CJ (March 2000). "Lubricin is a product of megakaryocyte stimulating factor gene expression by human ...
Markusen, James R. (May 1, 1983). "Factor movements and commodity trade as complements". Journal of International Economics. 14 ... Markusen, James R.; Venables, Anthony J. (November 1, 2007). "Interacting factor endowments and trade costs: A multi-country, ... Markusen's international trade and economics research has contributed to the identification of factors that influence trade ... Markusen's regional economics research has investigated how factors such as infrastructure and education, impact economic ...
Calippe, Bertrand; Guillonneau, Xavier; Sennlaub, Florian (March 2014). "Complement factor H and related proteins in age- ... A SNP in the F5 gene causes Factor V Leiden thrombophilia. rs3091244 is an example of a triallelic SNP in the CRP gene on human ... Other factors, like genetic recombination and mutation rate, can also determine SNP density. SNP density can be predicted by ... LD can be affected by two parameters (among other factors, such as population stratification): 1) The distance between the SNPs ...
Malhotra R, Ward M, Sim RB, Bird MI (July 1999). "Identification of human complement Factor H as a ligand for L-selectin". The ... The embryo secretes human chorionic gonadotropin (hCG), which downregulates anti-adhesion factor, MUC-1, located on the uterine ... Human sell consists of 10 exons and its transcription factor is FOXO 1, on the other hand the mouse sell gene is composed of 9 ... an adjacent epidermal growth factor-like domain, two to the consensus repeat units homologous to those found in C3/C4-binding ...
It is the first drug that selectively inhibits factor B, the active component of the complement's C3 and C5 convertases. In ... April 2019). "Small-molecule factor B inhibitor for the treatment of complement-mediated diseases". Proceedings of the National ... Iptacopan is also investigated as a drug in other complement-mediated diseases, like age-related macular degeneration and some ...
April 2005). "Complement factor H variant increases the risk of age-related macular degeneration". Science. 308 (5720): 419-21 ... Some of the factors that should be considered are the level of efficacy of various genetic tests in the general population, ... Combining molecular scale information with macro-scale clinical data, such as patients' tumor type and other risk factors, ... 2 July 2015). "Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular ...
BCX9930, an oral Factor D inhibitor for the treatment of complement-mediated diseases. FDA has granted Fast Track designation ...
In the meantime, notebooks and small form factor desktop computers complement the range. The names of the devices borrow from ... Complementing Tuxedo OS, the company is working on tools to control hardware functions and improve usability. Licensed under ...
Opsonins include Mfge8, Gas6, Protein S, antibodies and complement factors C1q and C3b. Phagoptosis has multiple functions ... Pathogenic cells such as bacteria can be opsonised by antibodies or complement factors, enabling their phagocytosis and ...
1989). "20 KDa homologous restriction factor of complement resembles T cell activating protein". Biochem. Biophys. Res. Commun ... When complement activation leads to deposition of C5b678 on host cells, CD59 can prevent C9 from polymerizing and forming the ... Ninomiya H, Sims PJ (1992). "The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the "b"domain ... 1992). "Complement regulatory proteins at the feto-maternal interface during human placental development: distribution of CD59 ...
... factor H, factor HR1 or HR3, membrane cofactor protein, factor I, factor B, complement C3, and thrombomodulin). This results in ... The complement system activation may be due to mutations in the complement regulatory proteins (factor H, factor I, or membrane ... of complement can result from production of anti-factor H autoantibodies or from genetic mutations in any of several complement ... "Platelet-associated complement factor H in healthy persons and patients with atypical HUS". Blood. 114 (20): 4538-4545. doi: ...
Lee FJ, Moss J, Vaughan M (1992). "Human and Giardia ADP-ribosylation factors (ARFs) complement ARF function in Saccharomyces ... ADP-ribosylation factor 5 is a protein that in humans is encoded by the ARF5 gene. ADP-ribosylation factor 5 (ARF5) is a member ... Shin, O H; Exton J H (August 2001). "Differential binding of arfaptin 2/POR1 to ADP-ribosylation factors and Rac1". Biochem. ... Tsuchiya M, Price SR, Tsai SC, Moss J, Vaughan M (March 1991). "Molecular identification of ADP-ribosylation factor mRNAs and ...
"Entrez Gene: CFHR3 complement factor H-related 3". Zipfel PF, Skerka C (1994). "Complement factor H and related proteins: an ... Diaz-Guillen MA, Rodriguez de Cordoba S, Heine-Suner D (Jul 1999). "A radiation hybrid map of complement factor H and factor H- ... Complement factor H-related protein 3 is a protein that in humans is encoded by the CFHR3 gene. GRCh38: Ensembl release 89: ... 2000). "Complement factor H: sequence analysis of 221 kb of human genomic DNA containing the entire fH, fHR-1 and fHR-3 genes ...
Factor I deficiency in turn leads to low levels of complement component 3 (C3), factor B, factor H and properdin in blood, due ... Complement factor I (factor I) is a protein of the complement system, first isolated in 1966 in guinea pig serum, that ... Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement ... Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. ...
Rattus norvegicus complement factor H (Cfh), mRNA Rattus norvegicus complement factor H (Cfh), mRNA. gi,77861916,ref,NM_ ... Complement factor H regulates retinal development and its absence may establish a footprint for age related macular ... Complement factor H regulates retinal development and its absence may establish a footprint for age related macular ... The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate ...
... Science. 2005 Apr 15;308(5720):419-21. doi: ... DNA resequencing of the complement factor H gene within this haplotype revealed a common coding variant, Y402H, that ...
Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A ... never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 ... Methods/Principal Findings We investigated the association between the LOC387715 A69S and complement component C3 R102G risk ... Background Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age- ...
... - Product info ... Mouse Monoclonal [clone OX-21] (IgG1) to Human CFI / Complement Factor I[CFI / Complement Factor I] ... Aplha, transcription related growth factors and stimulating factors or repressing nuclear factors are complex subunits of ... Mouse Monoclonal [clone OX-21] (IgG1) to Human CFI / Complement Factor I Antibody ...
Complement factor H. The complement system is a crucial component of the innate immunity against microbial infection. ... Complement factor H, a 155 kDaplasma glycoprotein, is an essential regulatory protein that plays a critical role in the ... Complement factor H has revealed an association with two different renal diseases, glomerulonephri-tisand atypical hemolytic ... Factor H binds to C3b, accelerates the decay of the alternative pathway C3-convertase and acts as a cofactor for the factor ...
... complement-mediated... (More). Complement factor B (FB) mutant variants are associated with excessive complement activation in ... atypical hemolytic uremic syndrome, C3 glomerulopathy, complement, danicopan, factor B, factor D. in Frontiers in Immunology. ... Factor D Inhibition Blocks Complement Activation Induced by Mutant Factor B Associated With Atypical Hemolytic Uremic Syndrome ... Complement factor B (FB) mutant variants are associated with excessive complement activation in kidney diseases such as ...
title = "Complement C4 Deficiency - A Plausible Risk Factor for Non-Tuberculous Mycobacteria (NTM) Infection in Apparently ... T1 - Complement C4 Deficiency - A Plausible Risk Factor for Non-Tuberculous Mycobacteria (NTM) Infection in Apparently ... Complement C4 Deficiency - A Plausible Risk Factor for Non-Tuberculous Mycobacteria (NTM) Infection in Apparently ... Complement C4 Deficiency - A Plausible Risk Factor for Non-Tuberculous Mycobacteria (NTM) Infection in Apparently ...
Events / Evening Meeting / Insights from Reliability-Based Design to Complement Load and Resistance Factor Design Approach ... Insights from Reliability-Based Design to Complement Load and Resistance Factor Design Approach. ... "Insights from Reliability-Based Design to Complement Load and Resistance Factor Design Approach," by B.K. Low in the November ...
Dive into the research topics of Functional anatomy of complement Factor H. Together they form a unique fingerprint. ...
... the complement system reacts promptly to threat (AP). Protective membrane-bound and soluble r.. ... Complement Factor H: Function and Dysfunction Due to the constant monitoring of its alternate channel, the complement system ... Pathogenic microorganisms, on the other hand, frequently resist complement assault and so escape destruction. Complement factor ... Binding sites, especially for complement receptor (CR3), malondialdehyde (MDA)-modified proteins, and apolipoprotein E (apoE), ...
Background Effective regulation of complement activation may be crucial to preserving complement function during ARDS. Factor H ... Factor H preserves alternative complement function during ARDS linked to improved survival. William Bain, Mohammadreza Tabary, ... Factor H preserves alternative complement function during ARDS linked to improved survival ... Factor H preserves alternative complement function during ARDS linked to improved survival ...
... of complement factor H. The factor H deficiency was defined by undetectable complement hemolytic activity by the classic (CH50 ... 2006) noted that a defect in complement factor H results in continuous activation of the alternative complement pathway and ... Decreased levels of serum C3 and factor B but normal levels of serum C4 and factor I were found; factor H was undetectable by ... 1987) studied a family in which 3 female sibs had undetectable levels of factor H and C3 nephritic factor, low levels of factor ...
Complement receptor 1 (CR1) has factor H-like activity, permitting factor I to cleave C3b. Membrane cofactor protein also has ... Ehrlich and Morgan termed this factor complement. The complement system as understood today is a multimolecular system composed ... Factor H competes with factor B for binding to C3b and displaces Bb from C3bBb. It accelerates the inactivation of C3b by ... Here, C3b binds to factor B that is cleaved by factor D to Bb. C3bBb complex then acts as the C3 convertase and generates more ...
Variation registry for Complement factor I deficiency Select database by name. ADAbase. AICDAbase. AIREbase. AK2base. AP3B1base ...
Learn more about an association of rare mutation in the complement factor I gene and numerous episodes of recurrent aseptic ... The complement regulatory factor I (CFI) is a two-chain serine protease and an endogenous inhibitor of the classical and ... Complement Factor I Gene Variant as a Treatable Cause of Recurrent Aseptic Neutrophilic Meningitis. Neurol Neuroimmunol ... He was found to have a rare heterozygous mutation in the complement factor I gene (CFI) that was not previously associated with ...
Recombinant anti-Human Complement Factor D (Adipsin) antibody. Clone I8/1. Engineered into new species and isotypes to improve ... Complement factor D is a serine protease of the alternative pathway of complement activation.Factor D cleaves factor B bound to ... factor D Immunogen: This antibody was raised by immunizing BALB/c mice with the purified complement factor D and by the ... Immunofluorescence staining of K562 cells with anti-Complement Factor D (Ab01588) I8/1 Immunofluorescence analysis of ...
Complement C3 nephritic factor. Category. Immunology Test background. A proportion of patients with membranoproliferative ...
Recent case-control studies demonstrated an association between the complement factor H (CFH) gene, a regulator of complement, ... Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. ... Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. ... Recent case-control studies demonstrated an association between the complement factor H (CFH) gene, a regulator of complement, ...
... complement factor H [CFH], C4b binding protein, and complement factor I [CFI]) [37, 38]. Defective regulation of the complement ... 4. PE and Complement Factors. The complement system, composed of over 30 proteins that act in concert to protect the host ... 2. Angiogenic Factors and PE. Angiogenic factors and their receptors are important regulators of placental vascular development ... A. Sambola, J. Osende, J. Hathcock et al., "Role of risk factors in the modulation of tissue factor activity and blood ...
How endothelial cells protect themselves from complement by expressing decay-accelerating factor (DAF). *Frances Williams1 ... Williams, F. How endothelial cells protect themselves from complement by expressing decay-accelerating factor (DAF). Arthritis ... How endothelial cells protect themselves from complement by expressing decay-accelerating factor (DAF) ... To test the hypothesis that inflammatory cytokines and complement(C) MACs play a role in the expression of DAF, CD59 and MCP, ...
de Vries, B, Matthijsen, RA, Wolfs, TGAM, van Bijnen, AA, Heeringa, P & Buurman, WA 2003, Inhibition of complement factor C5 ... T1 - Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and ... N2 - Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and ... AB - Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and ...
Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after ... Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after ... Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after ... Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after ...
Complement factor H in AMD : Bridging genetic associations and pathobiology. In: Progress in Retinal and Eye Research. 2018 ; ... Complement factor H in AMD: Bridging genetic associations and pathobiology. Christopher B. Toomey, Lincoln V. Johnson, ... Toomey CB, Johnson LV, Bowes Rickman C. Complement factor H in AMD: Bridging genetic associations and pathobiology. Progress in ... Complement factor H in AMD: Bridging genetic associations and pathobiology. / Toomey, Christopher B.; Johnson, Lincoln V.; ...
Complement factor H,Complement factor H. C,. H [auth G]. 383. Homo sapiens. Mutation(s): 0 Gene Names: CFH, HF, HF1, HF2. ... Complement factor I. D,. I [auth H]. 321. Homo sapiens. Mutation(s): 0 Gene Names: CFI, IF. EC: 3.4.21.45. ... Complement factor I. E [auth I],. J. 244. Homo sapiens. Mutation(s): 0 Gene Names: CFI, IF. EC: 3.4.21.45. ... Complement C3. A,. F [auth E]. 645. Homo sapiens. Mutation(s): 0 Gene Names: C3, CPAMD1. ...
... recognizes human complement factor H which exists in 2 forms. The most common form, of 150 kDa, and the les… ... strong,Mouse anti Human Complement Factor H antibody, clone 028B-244.2.10X (10-10),/strong, ... Mouse anti Human Complement Factor H antibody, clone 028B-244.2.10X (10-10) recognizes human complement factor H which exists ... Complement factor H functions as a cofactor in the inactivation of C3b by factor I. It makes C3b susceptible to cleavage by ...
Adipocytes have high levels of many components of the complement system. These components are involved in antimicrobial ... Complement factor D (adipsin) levels are elevated in acquired partial lipodystrophy (Barraquer-Simons syndrome). Int. J. Mol. ... Complement-mediated adipocyte lysis by nephritic factor sera. J. Exp. Med. 177, 1827-1831 (1993). ... Kruglikov, I.L., Scherer, P.E. Control of adipose tissue cellularity by the terminal complement cascade. Nat Rev Endocrinol 19 ...
Further insights into modulation of complement activation by the factor H-related family of proteins ... Further insights into modulation of complement activation by the factor H-related family of proteins ...
We now show that complement factor H-related protein 1 (FHR-1) and factor H-like protein 1 (FHL-1), proteins of the FH protein ... Interaction of Shiga toxin 2 with complement regulators of the factor H protein family.. Poolpol K, Orth-Höller D, Speth C, ... Stx2 was shown to activate complement via the alternative pathway, to bind factor H (FH) at short consensus repeats (SCRs) 6-8 ... Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. Mol Immunol 58(1), 77-84. ...
Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury. American Journal of ... Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury. In: American Journal ... Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury. / Bhatia, Madhav; ... Bhatia, M, Saluja, AK, Singh, VP, Frossard, JL, Lee, HS, Bhagat, L, Gerard, C & Steer, ML 2001, Complement factor C5a exerts ...
  • Aplha, transcription related growth factors and stimulating factors or repressing nuclear factors are complex subunits of proteins involved in cell differentiation. (gentaur.com)
  • Binding sites, especially for complement receptor (CR3), malondialdehyde (MDA)-modified proteins, and apolipoprotein E (apoE), are dispersed throughout its 20 CCP modules (CCPs), also known as short consensus repeats, to facilitate additional 'non-canonical' FH activities. (imedpub.com)
  • The complement system as understood today is a multimolecular system composed of more than 32 proteins and consisting of serum proteins, serosal proteins, and cell membrane receptors that bind to complement fragments. (medscape.com)
  • The complement system consists of 7 serum and 9 membrane regulatory proteins, 1 serosal regulatory protein, and 8 cell membrane receptors that bind complement fragments. (medscape.com)
  • The complement regulatory factor I (CFI) is a two-chain serine protease and an endogenous inhibitor of the classical and alternative complement pathways by cleaving C3b and C4b in the presence of cofactor proteins. (discovermednews.com)
  • Cell surface proteins have evolved which prevent EC damage by the cytotoxic defence system, decay-accelerating factor (DAF), protectin (CD59) and membrane cofactor protein (MCP). (biomedcentral.com)
  • We now show that complement factor H-related protein 1 (FHR-1) and factor H-like protein 1 (FHL-1), proteins of the FH protein family that show amino acid sequence and regulatory function similarities with FH, also bind to Stx2. (leibniz-hki.de)
  • The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. (medlineplus.gov)
  • Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed. (medlineplus.gov)
  • C3 and factor B proteins were measured in culture supernatant by enzyme-linked immunosorbent assay and C3 and factor B transcripts in harvested cells by reverse transcriptase - polymerase chain reaction . (bvsalud.org)
  • Cytokine induced upregulation of C3 and factor B proteins was always associated with the upregulation of levels of C3 and factor B mRNA . (bvsalud.org)
  • This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). (ox.ac.uk)
  • thus, PIGA mutations lead to a deficiency of GPI-anchored proteins, such as complement decay-accelerating factor (also known as CD55) and CD59 glycoprotein (CD59), which are both complement inhibitors. (medscape.com)
  • Genes that encode the proteins of complement components or their isotypes are distributed throughout different chromosomes, with 19 genes comprising 3 significant complement gene clusters in the human genome. (medscape.com)
  • The important components of this system are various cell membrane-associated proteins such as complement receptor 1 (CR1), complement receptor 2 (CR2), and decay accelerating factor (DAF). (medscape.com)
  • for example, the proteins factor H and factor I inhibit the formation of the enzyme C3 convertase of the alternative pathway. (medscape.com)
  • Complement dysregulation is usually from a mutation in genes controlling complement proteins or factors but sometimes from acquired autoantibodies to certain complement factors. (msdmanuals.com)
  • Factor H binds to C3b, accelerates the decay of the alternative pathway C3-convertase and acts as a cofactor for the factor Imediated proteolyticinac-tivation of C3b. (biovendor.com)
  • Factor H (FH) is the primary negative regulator of the alternative pathway (AP) of complement. (ersjournals.com)
  • Laboratory features usually include decreased serum levels of factor H , complement component C3 (120700), and a decrease in other alternative pathway components, indicating activation of the alternative complement pathway. (findzebra.com)
  • More than 80% of patients with MPGN II are positive for serum C3 nephritic factor (C3NeF), an autoantibody directed against C3bBb, the convertase of the alternative pathway of the complement cascade. (findzebra.com)
  • 1987) studied a family in which 3 female sibs had undetectable levels of factor H and C3 nephritic factor, low levels of factor B, C3, and C5 (see 120500), and normal levels of C4-binding protein (120830), factor I (217030), and classic pathway factors. (findzebra.com)
  • Depending on the nature of complement activators, the classic pathway, the alternative pathway, or the more recently discovered lectin pathway is activated predominantly to produce C3 convertase. (medscape.com)
  • Binding of factor H to C3b increases its inactivation by factor I. Properdin stabilizes it, preventing its inactivation by factors H and I. The alternate pathway does not result in a truly nonspecific activation of complement because it requires specific types of compounds for activation. (medscape.com)
  • I8/1 antibody recognizes human complement factor D. Complement factor D is a serine protease of the alternative pathway of complement activation.Factor D cleaves factor B bound to C3b, generating the alternative pathway C3 convertase C3bBb and releasing the Ba fragment. (absoluteantibody.com)
  • Quantitation of components of the alternative pathway of complement (APC) by enzyme-linked immunosorbent assays. (absoluteantibody.com)
  • To test the hypothesis that inflammatory cytokines and complement(C) MACs play a role in the expression of DAF, CD59 and MCP, and to investigate the intracellular signalling pathway involved in DAF expression. (biomedcentral.com)
  • It is important in regulating the complement pathway, preventing unnecessary inflammation which can damage the host tissue. (bio-rad-antibodies.com)
  • Stx2 was shown to activate complement via the alternative pathway, to bind factor H (FH) at short consensus repeats (SCRs) 6-8 and 18-20 and to delay and reduce FH cofactor activity on the cell surface. (leibniz-hki.de)
  • It is widely accepted that members of the complement pathway are expressed at high levels in white adipose tissue (WAT). (nature.com)
  • Cellular lysis is counteracted by different cellular defence mechanisms that control this 'tug-of-war' behaviour of the complement system: it can be kept in check or let loose and activate a cell death pathway. (nature.com)
  • Upregulation of early and downregulation of terminal pathway complement genes in subcutaneous adipose tissue and adipocytes in acquired obesity. (nature.com)
  • Atypical hemolytic uremic syndrome (aHUS) is a disease associated with dysregulation of the immune complement system, especially of the alternative pathway (AP). (elsevierpure.com)
  • Factor H is a major plasma protein that plays a critical regulatory role in the alternative pathway of complement activation. (nih.gov)
  • and regulation of complement activation, alternative pathway. (jax.org)
  • The Response To Alcohol Pathway complements our catalog of research reagents including antibodies and ELISA kits against POMC, ALDH2, AKR1A1, AVP, ADH1B. (novusbio.com)
  • In vitro activation of the alternative pathway of complement by settled grain dust. (cdc.gov)
  • The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)
  • Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)
  • Factor I deficiency in turn leads to low levels of complement component 3 (C3), factor B, factor H and properdin in blood, due to unregulated activation of C3 convertase, and to low levels of IgG, due to loss of iC3b and C3dg production. (wikipedia.org)
  • Relative FH deficiency was associated with increased factor consumption as evidenced by lower FB and C3 levels and higher Ba:FB and C3a:C3 ratios. (ersjournals.com)
  • Conclusions Relative FH deficiency, higher Ba:FB and C3a:C3 ratios, and lower FB and C3 levels suggest a subset of ARDS with complement factor exhaustion, impaired AP function, and increased mortality that may be amenable to therapeutic targeting. (ersjournals.com)
  • Complement factor H deficiency (CFHD) can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. (findzebra.com)
  • See also complement factor I deficiency (610984), which shows phenotypic overlap with this disorder. (findzebra.com)
  • 1982) reported 2 families with partial factor H deficiency and glomerulonephritis. (findzebra.com)
  • 1986) reported a consanguineous Algerian family in which 2 brothers had early-onset glomerulonephritis with C3 deposits and low levels (less than 10% of normal) of complement factor H . The factor H deficiency was defined by undetectable complement hemolytic activity by the classic (CH50) and alternate (AP50) pathways, and low levels of C3 and factor B (138470). (findzebra.com)
  • 1993) described a consanguineous Italian family in which 3 sibs had deficiency of factor H and its spliced isoform FHL1. (findzebra.com)
  • At least 10 mutations in the CFI gene have been identified in people with complement factor I deficiency, a disorder characterized by immune system dysfunction. (medlineplus.gov)
  • The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. (medlineplus.gov)
  • This condition, which may also occur in people with complement factor I deficiency, is characterized by kidney malfunction that can be serious or life-threatening. (medlineplus.gov)
  • Baracho GV, Nudelman V, Isaac L. Molecular characterization of homozygous hereditary factor I deficiency. (medlineplus.gov)
  • In light of these findings and previous reports of HUS in patients with factor H deficiency, we postulate that abnormalities of factor H may be involved in the etiology of HUS. (nih.gov)
  • Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)
  • Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. (wikipedia.org)
  • Complement factor I (factor I) is a protein of the complement system, first isolated in 1966 in guinea pig serum, that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b. (wikipedia.org)
  • Then, factor I is cleaved by furin to yield the mature factor I protein, which is a disulfide-linked dimer of heavy chain (residues 19-335, 51 kDalton) and light chain (residues 340-583, 37 kDalton). (wikipedia.org)
  • the heavy chain plays an inhibitory role in maintaining the enzyme inactive until it meets the complex formed by the substrate (either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). (wikipedia.org)
  • See the reference protein sequence for complement factor H precursor (NP_569093.2). (nih.gov)
  • Complement factor H, a 155 kDaplasma glycoprotein, is an essential regulatory protein that plays a critical role in the homeostasis of the complement system in plasma and in the protection of bystander host cells and tissues from damage by complement activation. (biovendor.com)
  • In addition, factor H has multiple physiological activities acts as an extracellularmatrix component, binds to cellular receptors of the integrintype, and interacts with a wide selection of ligands, such as the C-reactive protein, thrombospondin, bone sialoprotein, osteopontin, and heparin. (biovendor.com)
  • Complement factor H is a soluble AP suppressor that recognizes self-surfaces on autologous surfaces, either directly via particular glycosaminoglycan and sialic acid or indirectly via C-reactive protein (CRP), and operates in fluid phase. (imedpub.com)
  • Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. (leibniz-hki.de)
  • Poolpol K, Orth-Höller D, Speth C, Zipfel PF, Skerka C, de Córdoba SR, Brockmeyer J, Bielaszewska M, Würzner R (2014) Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. (leibniz-hki.de)
  • The CFI gene provides instructions for making a protein called complement factor I. This protein helps regulate a part of the body's immune response known as the complement system. (medlineplus.gov)
  • The unregulated activity of the complement system decreases blood levels of another complement protein called C3, reducing the immune system's ability to fight infections. (medlineplus.gov)
  • The CFI gene mutations identified in this disorder result in an abnormal or nonfunctional version of complement factor I. The defective protein allows uncontrolled activation of the complement system. (medlineplus.gov)
  • The overactive complement system attacks certain kidney cells, which damages the kidneys and leads to a loss of protein in the urine (proteinuria). (medlineplus.gov)
  • Complement factor H (CFH), consisting of 20 domains called complement control protein (CCP1-20), downregulates the AP as a cofactor for mediating C3 inactivation by complement factor I. However, anomalies related to CFH are known to cause excessive complement activation and cytotoxicity. (elsevierpure.com)
  • Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi. (ox.ac.uk)
  • Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. (ox.ac.uk)
  • In an individual with the sporadic/relapsing form of the disease we have found a mutation comprising a deletion, subsequent frame shift and premature stop codon leading to half normal levels of serum factor H. In one of the three families there is a point mutation in exon 20 causing an arginine to glycine change, which is likely to alter structure and hence function of the factor H protein. (nih.gov)
  • Eculizumab (Soliris) and ravulizumab-cwvz (Ultomiris) are inhibitors that work to block complement protein C5. (webmd.com)
  • There's another complement protein called C6. (webmd.com)
  • Protein expression is influenced by many factors that may vary between experiments or laboratories. (genscript.com)
  • These bacteria use the surface protein Usp2 to capture and incapacitate the major complement factor C3. (lu.se)
  • Activation of the complement pathways. (medscape.com)
  • This prevents these components of the classical and of alternative complement pathways from forming a positive feedback loop. (bio-rad-antibodies.com)
  • Complement pathways and deficiencies. (medscape.com)
  • Dive into the research topics of 'Functional anatomy of complement Factor H'. Together they form a unique fingerprint. (ed.ac.uk)
  • 2006) summarized features of MPGN relevant to the complement cascade. (findzebra.com)
  • The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
  • Mutations in the CFI gene result in an inability to control the complement cascade appropriately. (discovermednews.com)
  • How the immune response can activate the cascade process is still unknown but it is proposed to act in synergy with additional exacerbating factors such as predisposing maternal and ambient factors [ 12 ]. (hindawi.com)
  • Genetic studies have strongly supported a relationship between the alternative complement cascade, in particular the common H402 variant in Complement Factor H (CFH) and development of AMD. (johnshopkins.edu)
  • mouse homolog is a regulatory serine proteinase of the complement cascade that cleaves C3b and C4b and inactivates them [RGD, Feb 2006]. (genscript.com)
  • The effects of settled grain dust on the human serum complement cascade were investigated. (cdc.gov)
  • Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.com)
  • New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. (medscape.com)
  • Atypical hemolytic uremic syndrome is caused by complement overactivation. (wikipedia.org)
  • Complement factor B (FB) mutant variants are associated with excessive complement activation in kidney diseases such as atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy and membranoproliferative glomerulonephritis (MPGN). (lu.se)
  • Recombinant monoclonal antibody to Complement Factor D. Manufactured using AbAb's Recombinant Platform with variable regions (i.e. specificity) from the hybridoma I8/1. (absoluteantibody.com)
  • This antibody was raised by immunizing BALB/c mice with the purified complement factor D and by the subsequent generation of hybridomas. (absoluteantibody.com)
  • I8/1 antibody can be used for the identification of the complement factor D from human serum and plasma. (absoluteantibody.com)
  • For instance, this antibody was utilized in the quantitation of the factor D levels in blood of patients with renal failure via a senstive ELISA procedure (Oppermann et al. (absoluteantibody.com)
  • Immunofluorescence staining of K562 cells with anti-Complement Factor D (Ab01588) I8/1 Immunofluorescence analysis of paraformaldehyde fixed K562 cells on Shi-fix™ coverslips stained with the chimeric rabbit IgG version of I8/1 (Ab01588-23.0) at 10 µg/ml for 1h followed by Alexa Fluor® 488 secondary antibody (2 µg/ml), showing membrane staining. (absoluteantibody.com)
  • To study the effect of MAC on HMEC expression of DAF, EC monolayers were opsonised with IgG2a anti-endoglin monoclonal antibody, thus optimising complement fixation ability. (biomedcentral.com)
  • Mice were control treated or treated with BB5.1, a monoclonal antibody that prevents cleavage of complement factor C5, thereby preventing C5a generation and formation of the membrane attack complex (MAC). (maastrichtuniversity.nl)
  • Mouse anti Human Complement Factor H antibody, clone 028B-244.2.10X (10-10) recognizes human complement factor H which exists in 2 forms. (bio-rad-antibodies.com)
  • Interestingly, the most primordial defense responses employed by myeloid cells against pathogens, such as complement activation, antibody-dependent cell cytotoxicity and phagocytosis, actually seem to favor cancer progression. (frontiersin.org)
  • Cellular membrane type-1 matrix metalloproteinase (MT1-MMP) cleaves C3b, an essential component of the complement system. (nature.com)
  • Welch (2002) discussed the role of complement in renal disease. (findzebra.com)
  • In conclusion, multiple interactions of key complement inhibitors FH, FHR-1 and FHL-1 with Stx2 corroborate our hypothesis of a direct role of complement in EHEC-associated HUS. (leibniz-hki.de)
  • abstract = "Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and inflammation.De Vries B, Matthijsen RA, Wolfs TG, Van Bijnen AA, Heeringa P, Buurman WA.Department of General Surgery, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands.BACKGROUND: Complement has been implicated in the pathophysiology of renal ischemia-reperfusion (I/R) injury. (maastrichtuniversity.nl)
  • abstract = "Complement factor C5a acting via C5a receptors (C5aR) is recognized as an anaphylotoxin and chemoattractant that exerts proinflammatory effects in many pathological states. (elsevierpure.com)
  • CONCLUSIONS: Renal I/R is followed by activation of the complement system and intrarenal deposition of C3 and MAC. (maastrichtuniversity.nl)
  • Conventional protease inhibitors do not completely inactivate Factor I but they can do so if the enzyme is pre-incubated with its substrate: this supports the proposed rearrangement of the molecule upon binding to the substrate. (wikipedia.org)
  • In 1 family, of Polish origin, a teenaged male had vasculitis, thrombocytopenia, proteinuria, and depressed levels of serum factor H and complement component C3. (findzebra.com)
  • The index case had depressed serum factors H and B levels and IgA nephropathy (161950) which progressed to renal failure. (findzebra.com)
  • The most widely studied serum markers for PE, to date, are vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). (hindawi.com)
  • Factor H is secreted by the liver into the blood serum. (bio-rad-antibodies.com)
  • CspA-mediated binding of human factor H inhibits complement deposition and confers serum resistance in Borrelia burgdorferi. (ouhsc.edu)
  • Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement activity. (wikipedia.org)
  • These results suggest that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations. (lu.se)
  • The mutations result in abnormal, nonfunctional, or absent complement factor I. (medlineplus.gov)
  • Characterization of mutations in complement factor I (CFI) associated with hemolytic uremic syndrome. (medlineplus.gov)
  • Subsequent mutation analysis of the factor H gene has revealed two mutations in patients with HUS. (nih.gov)
  • Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection. (nih.gov)
  • The trouble in PNH comes from part of your immune system called the complement system. (webmd.com)
  • The complement system is part of the innate immune system. (medscape.com)
  • In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). (medscape.com)
  • The factor I light chain contains only the serine protease domain. (wikipedia.org)
  • Factor-B conversion and reductions in hemolytic complement consumption were dose related. (cdc.gov)
  • This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design. (ox.ac.uk)
  • Although the complement system is part of the body's innate, relatively nonspecific defense against pathogens, its role is hardly primitive or easily understood. (medscape.com)
  • As a first line of defense against pathogens and a mediator between innate and adaptive immunity, complement is a particular focus of evasion strategies developed by pathogens. (lu.se)
  • Background Effective regulation of complement activation may be crucial to preserving complement function during ARDS. (ersjournals.com)
  • Angiogenic factors and their receptors are important regulators of placental vascular development [ 13 ]. (hindawi.com)
  • The complement system is a crucial component of the innate immunity against microbial infection. (biovendor.com)
  • Due to the constant monitoring of its alternate channel, the complement system reacts promptly to threat (AP). (imedpub.com)
  • The complement system labels microbes and host debris for clearance. (rcsb.org)
  • The complement system has recently been found to be involved in the pathogenesis of EHEC-associated HUS. (leibniz-hki.de)
  • Adipocytes have high levels of many components of the complement system. (nature.com)
  • Up-regulation of the complement system in subcutaneous adipocytes from nonobese, hypertriglyceridemic subjects is associated with adipocyte insulin resistance. (nature.com)
  • The complement system plays an important part in host defense and inflammation . (bvsalud.org)
  • Researchers are also looking at medicines that work against other players in the complement system. (webmd.com)
  • The complement system plays an important part in defense against pyogenic organisms. (medscape.com)
  • These findings underscore the duality of the complement system. (medscape.com)
  • Knowledge about the complement system is expanding. (medscape.com)
  • An intricate system regulates complement activity. (medscape.com)
  • Complement factor D (adipsin) levels are elevated in acquired partial lipodystrophy (Barraquer-Simons syndrome). (nature.com)
  • The factor I heavy chain has four domains: an FI membrane attack complex (FIMAC) domain, CD5 domain, and low density lipoprotein receptor 1 and 2 (LDLr1 and LDLr2) domains. (wikipedia.org)
  • DAF prevents the formation and accelerates the decay of complement 3 (C3) convertases, MCP binds to C3b and C4b promoting their degradation and CD59 inhibits the membrane-attack complex (MAC). (biomedcentral.com)
  • We also review the literature on the role of other complement components in AMD pathobiologies, including C3a, C5a and the membrane attack complex (MAC), and on transgenic mouse models developed to interrogate in vivo the effects of the CFH Y402H polymorphism. (johnshopkins.edu)
  • The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy. (nih.gov)
  • Complement activation plays a crucial role in the regulation of inflammation and late apoptosis. (maastrichtuniversity.nl)
  • 4 , 6 - 9 Several factors, including inflammation, oxidative stress, and dyslipidemia, are considered decisive for the progression of atherosclerosis in ESRD. (lww.com)
  • at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check. (medscape.com)
  • Complement factor H regulates retinal development and its absence may establish a footprint for age related macular degeneration. (nih.gov)
  • Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. (ox.ac.uk)
  • This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD). (dovepress.com)
  • Association of single nucleotide polymorphism in complement factor I gene with age-related macular degeneration]. (genscript.com)
  • Genetic, behavioral, and sociodemographic risk factors for second eye progression in age-related macular degeneration. (genscript.com)
  • Enables complement component C3b binding activity and heparin binding activity. (jax.org)
  • Human keratinocytes were cultured in the presence of supernatant of activated peripheral blood mononuclear cells , interleukin-1alpha , interleukin-2 , interleukin-6 , transforming growth factor-beta1 , tumor necrosis factor-alpha , or interferon-gamma . (bvsalud.org)
  • Tumor necrosis factor-alpha induced production of C3 and interferon-gamma induced production of factor B were inhibited by cycloheximide . (bvsalud.org)
  • Similarly, sEng is a truncated form of receptor for two subtypes of transforming growth factor beta (TGF β ) specifically, TGF β 1 and TGF β 2 which are highly expressed by vascular endothelial cells and syncytiotrophoblasts. (hindawi.com)
  • BACKGROUND: Complement has been implicated in the pathophysiology of renal ischemia-reperfusion (I/R) injury. (maastrichtuniversity.nl)
  • How do endothelial cells (ECs) protect themselves against damage by complement, particularly when they are present at the interface between blood and inflamed tissue? (biomedcentral.com)
  • Mutagenesis was performed to study the effect of factor D (FD) inhibition on C3 convertase-induced FB cleavage, complement-mediated. (lu.se)
  • Complement factor H functions as a cofactor in the inactivation of C3b by factor I. It makes C3b susceptible to cleavage by factor I, resulting in iC3b. (bio-rad-antibodies.com)
  • Rattus norvegicus complement factor I (Cfi), mRNA. (genscript.com)
  • Complement factor H has revealed an association with two different renal diseases, glomerulonephri-tisand atypical hemolytic uremicsyndrome (aHUS). (biovendor.com)
  • Patients with aHUS are currently treated with eculizumab while there is no specific treatment for other complement-mediated renal diseases. (lu.se)
  • This in turn results in an exponential production of multiple factors such as cytokines and growth factors leading to the clinical manifestations of PE [ 11 ]. (hindawi.com)
  • Synthesis of complement components C3 and factor B in human keratinocytes is differentially regulated by cytokines. (bvsalud.org)
  • In skin the keratinocyte is the major cell type, it is known to produce two soluble complement components, C3 and factor B . In this study we investigated the regulation of synthesis of these components in foreskin keratinocytes by cytokines . (bvsalud.org)
  • In conclusion, synthesis of C3 and factor B in keratinocytes is regulated by some cytokines , known to be produced by inflammatory cells and keratinocytes . (bvsalud.org)
  • Crystal structure the crystal structure of human Factor I has been deposited as PDB: 2XRC. (wikipedia.org)
  • Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after xenotransplantation to nonhuman primates. (elsevierpure.com)
  • Orthologous to human CFH (complement factor H). (jax.org)
  • Another important mechanism by which bacteria resist human complement is the production of proteases that efficiently degrade complement components. (lu.se)
  • Factor H also inhibits the formation of the C3bBb complex (C3 convertase) and increases the rate of dissociation of both C3 convertase and the (C3b)NBB complex (C5 convertase). (bio-rad-antibodies.com)
  • The gene for Factor I in humans is located on chromosome 4. (wikipedia.org)
  • We showed that one common strategy is to bind complement inhibitor C4BP, which leads to decreased opsonisation of bacteria with C3b impairing phagocytosis and allowing bacterial survival. (lu.se)
  • The authors then performed a complement analysis, which revealed that component concentrations and factor levels were normal. (discovermednews.com)
  • In addition to the following diseases, low factor I is associated with recurrent bacterial infections in children. (wikipedia.org)
  • [ 3 ] A registry of complement deficiencies has been established as a means to promote joint projects on treatment and prevention of diseases associated with defective complement function. (medscape.com)
  • Furthermore, we examined the effect of inhibition of complement-factor C5 on renal I/R injury. (maastrichtuniversity.nl)
  • Here, C3b binds to factor B that is cleaved by factor D to Bb. (medscape.com)
  • Factor B (FB) and FH levels were quantified by ELISA using samples from the ARDSnet LARMA and SAILS (N=224) trials. (ersjournals.com)
  • He was found to have a rare heterozygous mutation in the complement factor I gene (CFI) that was not previously associated with neurologic manifestations. (discovermednews.com)