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Complement ActivationAntigens, Differentiation, T-LymphocyteAntigens, CDLectins, C-TypeComplement C3Complement System ProteinsComplement C4Complement Pathway, AlternativeComplement Membrane Attack ComplexComplement Pathway, ClassicalComplement C3bComplement C1qComplement C5Receptors, ComplementComplement Inactivator ProteinsComplement C3aAntigens, SurfaceComplement Factor BComplement C9Complement C5aComplement C3dComplement Factor HComplement C2Complement C4bComplement Inactivating AgentsAntigensComplement C1Receptors, Complement 3bAntibodies, MonoclonalAntigens, CD55Complement C3-C5 ConvertasesComplement C3cLymphocyte ActivationComplement C6Antigens, CD3T-LymphocytesReceptors, Very Late AntigenAntigens, NeoplasmComplement Hemolytic Activity AssayAntigens, CD59Complement Activating EnzymesAnaphylatoxinsComplement C4b-Binding ProteinProperdinComplement Factor DB-LymphocytesFlow CytometryAntigens, Differentiation, B-LymphocyteAntigens, BacterialAntigens, CD8Antigens, CD46Complement Fixation TestsComplement C3b Inactivator ProteinsCobra VenomsReceptors, Complement 3dAntigens, DifferentiationComplement Pathway, Mannose-Binding LectinMolecular Sequence DataComplement C4aMannose-Binding LectinComplement C8Complement C7Antigens, CD28Receptors, Interleukin-2Complement Factor IAntigens, CD27Antigens, CD34Antigens, CD38Complement C3 Convertase, Alternative PathwayAmino Acid SequenceCD4-Positive T-LymphocytesComplement C1 Inactivator ProteinsMembrane GlycoproteinsHLA-DR AntigensReceptor, Anaphylatoxin C5aAntigens, CD20Antigens, CD19Immunoglobulin GAntigen-Antibody ComplexComplement C1sAntigens, CD40Cell LineAntigens, ViralHemolysisComplement C5bCells, CulturedCD40 LigandComplement C1rComplement C1 Inhibitor ProteinAntigens, CD44Antigens, CD14EpitopesMannose-Binding Protein-Associated Serine ProteasesAntigens, CD7Opsonin ProteinsAntigens, CD2Fluorescent Antibody TechniqueImmunophenotypingDipeptidyl Peptidase 4Receptors, Antigen, T-Cell
DysregulationProteinsMembraneInhibitorApoptotic cellsSubsequent complement activationImmunoglobulinCleavage of complementImmune complexesPathwaysGenesReceptorAtypicalRetrievalComplexesStimulationAHUSSubsetPhagocytosisProteinSystemNeutrophilsLysisPathophysiologyTherapiesFragmentCellsClinicalDiseasesFactorSecondaryBindsExpressionCell
Dysregulation3
  • The role of complement dysregulation on vascular endothelial cells has been well established in atypical hemolytic uremic syndrome (aHUS), a thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and target organ injury. (jrheum.org)
  • Accumulating evidence suggests that a large percentage of the patients diagnosed with secondary TMA exhibit genetic abnormalities associated with complement dysregulation. (ekjt.org)
  • The dysregulation of complement system activation usually results in acute or chronic inflammation and can contribute to the development of various diseases. (bvsalud.org)
Proteins6
  • Furthermore, if C3b does bind to a host-cell surface, regulators of complement activity (RCAs), a group of genetically-, structurally-, and functionally-related proteins, inactivate the complement component. (wikipedia.org)
  • Effector proteins interacting with the Fc portion of immunoglobulin M (IgM) include complement and complement receptors. (medscape.com)
  • Partial or complete deficiencies of the components of the complement system, including its receptors and regulatory proteins, are now described in humans and may be of a genetic or familial origin or acquired. (medscape.com)
  • Defects in the expression of complement or complement receptors may result in loss of tolerance to self-proteins and the development of immune complex-mediated autoimmune diseases such as systemic lupus erythematosus (SLE). (medscape.com)
  • 10 This distinction is not absolute because genetic defects in complement proteins have been identified in secondary TMA. (jrheum.org)
  • The affected patients' genetic backgrounds revealed significant genetic heterogeneity in several genes involved in complement regulation, including the complement factor H, complement factor H-related proteins, complement factor I, complement factor B, complement component 3, and CD46 genes in the alternative complement pathway. (ekjt.org)
Membrane3
  • C3 cleavage may result in formation of the membrane attack complex (MAC), the cytotoxic component of the complement system. (msdmanuals.com)
  • Factor I, with cofactors including membrane cofactor protein (CD46), inactivates C3b and C4b. (msdmanuals.com)
  • Defective gene expression of the membrane complement inhibitor CD46 in patients with progressive immunoglobulin A nephropathy. (edu.pl)
Inhibitor1
  • The aim of the present study was to use in silico computational modeling to investigate the hypothesis that these complement system inhibitor peptides interact with their target molecules in zebrafish, for subsequent in vivo validation. (bvsalud.org)
Apoptotic cells1
  • C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. (wikipedia.org)
Subsequent complement activation1
Immunoglobulin1
  • Alternate pathway activation occurs when components of microbial cell surfaces (eg, yeast walls, bacterial cell wall lipopolysaccharide [endotoxin]) or immunoglobulin (eg, nephritic factor, aggregated IgA) cleave small amounts of C3. (msdmanuals.com)
Cleavage of complement2
  • C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. (wikipedia.org)
  • Activation of the complement cascade always leads to the enzymatic cleavage of complement fraction C3, which is important in host defense to bacterial infections and phagocytosis. (medscape.com)
Immune complexes2
  • Complement and complement receptors play a critical role in immune defense by initiating the rapid destruction of invading microorganisms, amplifying the innate and adaptive immune responses, and mediating solubilization and clearance of immune complexes. (medscape.com)
  • They tend to enhance the effects of complement and are highly important in the binding of opsonized immune complexes on B cells. (medscape.com)
Pathways4
  • A further complicating factor is the cross-talk between complement, neutrophils, and coagulation pathways in the pathophysiology of TMA. (jrheum.org)
  • Activation of the complement system occurs through the classical (CP), lectin (LP), or alternative (AP) pathways. (jrheum.org)
  • All three major pathways of complement activation, including the classical, lectin, and alternative pathways, are involved in human anti-GBM disease. (bvsalud.org)
  • Although the activation of complement pathways is essential for innate defense, exacerbated activity of this system may be harmful to the host. (bvsalud.org)
Genes2
  • They are encoded by separate but linked genes termed regulation of complement activation (RCA) genes, located on the q32 region of chromosome 1. (medscape.com)
  • Once bound, JUN can either activate or repress the transcription of these genes, depending on the context and the presence of other cofactors. (cusabio.com)
Receptor5
  • In both cases C3b interacts with the C3b receptor, complement receptor 1 on phagocytic cells, such as macrophages and neutrophils, allowing for engulfment of the pathogen. (wikipedia.org)
  • Furthermore, host cells express p33 (globular C1q receptor) on the surface, which binds C1q, and prevents it from initiating complement activation. (wikipedia.org)
  • Note the image below, as well as the article Pediatric Complement Receptor Deficiency may be helpful. (medscape.com)
  • Our findings identify an endogenous receptor-mediated event that drives Tr1 differentiation and suggest that the complement system has a previously unappreciated role in T-cell-mediated immunity and tolerance. (nature.com)
  • CR2/CD21 interacts with C3b degradation products C3dg and C3d and can act synergistically with the B-cell antigen receptor (BCR) in B-cell activation. (medscape.com)
Atypical3
  • 7 - 9 A TMA is called "primary" when a genetic or acquired defect in a complement protein is identified (as in atypical hemolytic uremic syndrome [aHUS]) or "secondary" when occurring in the context of another disease process or factor such as infection, autoimmune disease, malignancy, or drugs. (jrheum.org)
  • Many recent studies on atypical hemolytic uremic syndrome have described genetic abnormalities related to excessive activation of the alternative complement pathway. (ekjt.org)
  • Background: Complement activation in atypical hemolytic uremic syndrome (aHUS), C3 glomerulonephropathy (C3G) and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) may be associated with rare genetic variants. (bvsalud.org)
Retrieval1
  • After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). (cusabio.com)
Complexes1
  • 8 , 11 - 14 Numerous stimuli can drive the activation of the complement system, including apoptotic debris, pathogens, and antibody-antigen complexes, in addition to ischemia-reperfusion injuries associated with organ transplantation. (jrheum.org)
Stimulation1
  • Figure 1: CD3/CD46 stimulation induces IL-10 production in human peripheral blood CD4 + T lymphocytes. (nature.com)
AHUS1
  • Advancements in the understanding of the etiopathogenesis of aHUS paved the way for the successful development of anticomplement therapies (complement C5 inhibitors), which have revolutionized the treatment of aHUS. (jrheum.org)
Subset2
  • A CD4 + T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. (nature.com)
  • Each distinct CD4 + T-cell subset has a specific function and can mainly be distinguished by its cytokine profile, the expression pattern of cell surface molecules, and the activation of specific transcription factors 8 . (nature.com)
Phagocytosis1
  • Additionally, C3b molecules can attach to the Fc regions of antigen-bound antibodies leading to phagocytosis or movement to the liver, where the C3b-tagged immune complex is then destroyed. (wikipedia.org)
Protein3
  • They are single-chain molecules present on host cellular membranes and belong to the complement control protein family. (medscape.com)
  • The complement system is a tightly regulated, cascading protein network representing a key component linking the innate and humoral immune systems. (jrheum.org)
  • The complement system is a tightly regulated, cascading protein network that performs multiple roles in homeostasis and disease prevention and is a key component of both the innate and the humoral immune systems. (jrheum.org)
System9
  • The key to the success of the complement system in clearing antigens is regulating the effects of C3b to pathogens alone and not healthy, host cells. (wikipedia.org)
  • The fetal tissues including the placenta must be protected from activation of the maternal immune system. (frontiersin.org)
  • Invading trophoblast cells will encounter maternal complement system (C) in the decidua and in the intervillous space. (frontiersin.org)
  • The complement system is an enzyme cascade that helps defend against infection. (msdmanuals.com)
  • The complement system, interacting with its regulatory molecules and cellular receptors, plays a central role in the induction and regulation of immunity. (medscape.com)
  • The immune system must distinguish not only between self and non-self, but also between innocuous and pathological foreign antigens to prevent unnecessary or self-destructive immune responses. (nature.com)
  • Therefore, a clearer understanding of the role of the complement system in TMA associated with other conditions will help to identify patients who would benefit from these therapies. (jrheum.org)
  • Thus, drugs with the potential to inhibit the activation of the complement system may be important tools in therapy for diseases associated with complement system activation. (bvsalud.org)
  • The zebrafish (Danio rerio) is a robust model for studying the complement system. (bvsalud.org)
Neutrophils1
Lysis1
  • 4 , 13 Complement plays a crucial role in host defense against foreign bodies by promoting phagocyte-mediated clearance of cell debris through activation of an inflammatory response, opsonization of pathogens, and lysis of susceptible bacteria and cells. (jrheum.org)
Pathophysiology1
  • 10 This review aims to provide an assessment of the nature and extent of complement involvement in the underlying pathophysiology of TMA associated with autoimmune diseases that will help to stratify patients for targeted therapy. (jrheum.org)
Therapies1
  • Furthermore, potential therapeutic strategies targeting complement components and associated precautions are discussed, to establish a theoretical basis for complement-targeted therapies. (bvsalud.org)
Fragment1
  • The efficacy of a therapeutic antibody depends on the Fab fragment and its binding activity to the target antigen, but also depends on the Fc fragment and its interaction with key Fc receptors.Therefore, candidates must be tested against a panel of receptors during antibody engineering. (acrobiosystems.com)
Cells10
  • CD46), which is ubiquitously expressed and plays a critical role in protecting host cells from damage by the C3b. (wikipedia.org)
  • Here we show that co-engagement of CD3 and the complement regulator CD46 in the presence of IL-2 induces a Tr1-specific cytokine phenotype in human CD4 + T cells. (nature.com)
  • These CD3/CD46-stimulated IL-10-producing CD4 + cells proliferate strongly, suppress activation of bystander T cells and acquire a memory phenotype. (nature.com)
  • Figure 2: Sorted CD3 + CD4 + CD45RA + CD45RO + T cells respond to primary and secondary activation with IL-10 production. (nature.com)
  • Figure 3: Characteristics of CD3/CD46-activated, sorted CD3 + CD4 + CD45RA + CD45RO + T cells. (nature.com)
  • Figure 4: Suppressive and proliferative properties of CD3/CD46-activated CD4 + T cells. (nature.com)
  • Shevach, E. M. S. M. R., Piccirillo, C. A. & Thornton, A. M. Control of T-cell activation by CD4 + CD25 + suppressor T cells. (nature.com)
  • This stress condition can also lead to the attraction of immune cells, notably antigen presenting cells (APCs) (i.e. immature dendritic cells), natural killer cells (NK cells), and cytotoxic T-cells to the site of infection [ 5 , 6 ]. (biomedcentral.com)
  • Virus-based immunostimulatory cytokine and chemokine expression can recruit and activate T cells, antigen-presenting cells (APCs), and natural killer (NK) cells, and subsequently, improve the therapeutic activity of OVs. (biomedcentral.com)
  • Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells. (cusabio.com)
Clinical1
  • The aim of this article is to provide a comprehensive review of the latest clinical evidence regarding the role of complement activation in anti-GBM disease. (bvsalud.org)
Diseases2
  • Yet, a great deal of complexity exists around the role of complement in TMA associated with other diseases. (jrheum.org)
  • This review aims to provide an assessment of the nature and extent of complement involvement in TMA associated with autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and scleroderma renal crisis. (jrheum.org)
Factor2
  • CR1 also regulates complement activation by acting as a cofactor for factor I in the cleavage and degradation of bound C3b and C4b to its inactive forms. (medscape.com)
  • Several complement factors, such as C3, C5b-9, and factor B, show a positive correlation with the severity of the renal injury and act as risk factors for renal outcomes. (bvsalud.org)
Secondary1
  • 10 Differentiating between a primary complement-mediated process and one triggered by secondary factors is critical since the former is nonresponsive to supportive therapy and has a high risk of recurrence. (jrheum.org)
Binds1
  • The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. (wikipedia.org)
Expression1
  • Immunogenicity of AAV vectors in humans has been linked to several limitations of the platform, including lack of efficacy due to antibody-mediated neutralization, tissue inflammation, loss of transgene expression, and in some cases, complement activation and acute toxicities. (bvsalud.org)
Cell1