Presentation on theme: "The Complement System Concepts Complement Activation"— Presentation transcript:
1 The Complement System Concepts Complement Activation Regulation of the Complement SystemBiological Function of Complement
2 1. Simple history of complement research Concepts1. Simple history of complement researchBehring antitoxinPfeiffer temperature sensitive component in serumnecessary for bacteriolysisBordet alexin (1920 Nobel prize)Ehrlich complement Ab to cause bacterolysisFerrata C1, C2Ritz C3Gorder C4Muller-Eberhard Classical pathway
3 antiserum to the bacterium normal human/Guinea pig serum 1895 Bordet: the experiment of the lysis ofVibrio choleraeantigen (bacteria)antiserum to the bacteriumnormal human/Guinea pig serumresultsfresholdagglutinationlysisVibrio cholerae+-
4 Presumption:There is a component in the fresh serum that helps the antibody to lyse the bacteria.The chemical property of this component is not stable.This component is not antigen specific.
5 The complement is a group of temperature sensitive protein existing in the serum and tissue fluid of human and vertebrate.After activated, they have enzymatic activity.They are the major molecules of the innate immune system.
7 Complement Components involved in the classical pathway (the components were named in order of their discovery)
8 3. Denomination of the components of the complement system With enzymatic activity after activation: C1, C4b2bPeptide fragments formed by activation of a component: C3a, C3b (the smaller fragment is designated “a” and the larger fragment designated “b”)Inactivated components: iC2aFactors: B, P (capitalization)
9 4. Basic Characteristics of Complement The complement components interact in a highly regulated cascade.Complement serves by amplifying the response: C1q, C3 convertaseUnstability: 56°C, 30minDualism of the functions: physiological functions, pathological functionsRestriction of reaction: easy to be inactivated, antibody, suppression component
10 Complement Activation 1. classical pathway2. alternative pathway3. lectin pathway
12 b. activation condition 1. classical pathwayb. activation conditionThe formation of an antigen-antibody complex inducesconformational changes in the Fc portion of the Ab moleculethat expose a binding site for the complement.C1 binds to exposed C1q-binding sites in the CH2 domain of IgG1-3 or the CH3 domain of IgM.C1 binds to at least two Fc portions of Ab.
15 C1q(1) the biggest molecular weight, composed of 18 polypeptide chains that associate to form six collagen-like triple helical arm(2) the only component of complement that circulate in the serum in functionally active forms(3) For activation, it need to bind to at least two IgG or one IgM and need the presence of Ca2+.(4) Free or soluble Ab can not bind to the complement; the formation of an antigen-antibody complex inducesconformational changes in the Fc portion of the Ab molecule.
29 Overview of the complement activation pathways.
30 membrane attack complex, MAC Composition: C5b678 (9)n , C9Size: nm inner diameterEffects: This complex forms a large channelthrough the membrane of the target cell, enabling ions and small molecules to diffuse freely across the membrane.
39 Complement and Clinic 1. Complement deficiencies 2. Serum complement level and disease3. Pathological damage by complement4. Clinical application of complement
40 Diseases about Complement deficiencies Proteins in defect Functions influenced DiseasesC1, C2 , C deficiency in cleanup of IC SLE, pyogenic infectiondeficiency in the activation ofclassical pathwayC inability of cleanup of IC SLE, pyogenic infectioncomplement activation glomerular nephritisC1INH loss of control in the production hereditary angiodysplasiaof inflammatory mediatorsfactor H loss of control in the activation SLE, pyogenic infectionof alternative pathway glomerular nephritislow concentration of C3 in the serumDAF, CD cytotoxic function of complement paroxysmal nocturnalto host cell hemoglobinuriaCR deficiency in adhesion of PBMC infection (aeruginosus Bacillus,pseudomonad etc.)
41 *** Definition, basic characteristics and components of complement *** Characteristics of complement activation and the sameness and differentia of three complement activation pathways** Biological Function of Complement** Regulation of the Complement System and its significance* Key biological significance of complement receptor and membrane-binding protein* Relation between complement system and diseases