免疫学课件wxf.Antibody

Immunoglobulin And AntibodyXiaojian wang,Ph.D.Institute of ImmunologyZJU School of MedicineTel:IMMUNOLOGYimmunoglobulin1.Introduction2.The structure of immunoglobulins3.Heterogeneity of immunoglobulins4.Functions of immunoglobulins5.The structures and properties of immunoglobulin classes6.Production of antibodiesimmunoglobulinAntibody(Ab)Globulin produced by plasma cells in response to antigen and binds specifically to particular Ag.Ab is generally defined in terms of their specific binding to the immunizing Ag Immunoglobulins(Ig)The Igs are globulin which function as Abs or similar to Abs in chemical structure.Not all of Ig have the functions of Ab,e.g.Patients with multiple myeloma have very high levels of Ig,but not Ab(to irrelevant things)Secreted Ig(sIg)-mediated humoral immunity Membrane Ig(mIg):BCR B cell receptorimmunoglobulinimmunoglobulinElectrophoretic mobility of serum proteins1.Heavy Chain and Light Chain heavy chain(H chain)50-75Kd 450-550aa H chains:,Isotypes:IgM,IgG,IgA,IgE,IgD Light chain(L chain)25Kd 214aa Types of L chains:,immunoglobulinI.Basic structure of the immunoglobulinIn any given Ig,all the H chains are identical.An antibody molecule has either two light chains or two light chains,but never one of each.In humans,about 60%of Ab molecules have light chains,and 40%have light chains.Market changes in this ratio can occur in patients with monoclonal B cell tumors.immunoglobulin 2.Variable region and constant region 1)Variable region(V region)Light Chain-VL(110 aa)Heavy Chain-VH(110 aa)immunoglobulinimmunoglobulin HVR(hypervariable region):9-12aa,3 HVRs CDR(complementarity-determining region):CDR1,CDR2,CDR3 FR(framework region):15-30aaimmunoglobulinCDR binds with epitope of antigenAntigen peptideAntigen peptide 2)Constant region(C region)Light chain-CL(110 aa)Heavy chain-CH(330-440 aa)CH1,CH2,CH3,(CH4)immunoglobulinimmunoglobulin3.Hinge Region-between the CH1 and CH2 region-rich in proline residues flexibility:allow the two Fab arms to bind epitope;be cleaved by proteases.-IgM and IgE have no hinge regionStructure of the immunoglobulinsimmunoglobulin3D images of the Ig molecule show that it is not straight as depicted in Figure.It is folded into globular regions,each of which contains an intra-chain disulfide bond.These regions are called domains.Light Chain Domains-VL and CLHeavy Chain Domains-VH,CH1,CH2,CH3 IgA,IgD,IgG (CH4 in IgE and IgM)4.Domains of immunoglobulinimmunoglobulinDownloaded from:StudentConsult(on 1 June 2006 01:58 PM)2005 Elsevier Binding of an antigen by an antibody.immunoglobulinFunctions of the domains on IgVH和和VL:抗原结合部位抗原结合部位CH1-3和和CL:Ig 遗传标志遗传标志CH2(IgG)、CH3(IgM):补体结合部补体结合部位位CH2-CH3(IgG):结合并通过胎盘结合并通过胎盘CH3(IgG)CH4(IgE)：FcR结合部结合部位位FabFcII.Other components in the Ig1.Joining chainJ chain is a small acidic protein that is synthesized by all plasma cells that secrete polymeric Igs(i.e.IgM and sIgA).Join the momomer to polymerimmunoglobulin2.Secretory piece(SP)Secretory component(SC)is a single glycopeptide with MW of 70KD.Produced by mucosa epithelial cells Functions:protect sIgA,resist proteolysis in extra secretory liquid.immunoglobulinlumenIII.Immunoglobulin fragmentsFab(fragment of antigen binding)Fc (fragment crystalizable)immunoglobulinHeterogenecity of IgCharacterist of Ig1.Binding to antigen2.ImmunogenicityIsotype Isotypes are the antigenic features of a class of Ig H(e.g.chain is different from ).Isotypes of one species can induce immune response in another species.immunoglobulinHeterogenecity of IgClasses and subclasses of Ig IgG-(gamma)IgA-(alpha)IgM-(Mu)IgD-(delta)IgE-(epsilon)subclass IgG1IgG4,IgA1IgA2,IgM1Igm2 Type and subtype Type:(Kappa)(lambda)subtype:14immunoglobulinAllotypeimmunoglobulinThis refers to genetic variation between individuals within a species.CH和和CL上的一个或数个氨基酸残基的差异上的一个或数个氨基酸残基的差异-遗传标志遗传标志Gm1-30Idiotype(Id)immunoglobulinVariation in the V domain,particularly in CDR,produces idiotype.Functions of immunoglobulinsFunctions of V regions Recognition and binding to antigen -HVR(CDR)-neutralization of toxins(e.g.diphtheria,tetanus);-immobilization of microorganisms;-neutralization of viral activityAntibody:monomer(IgG,IgE)-2价价 dimer(sIgA)-4价价 Petamer(IgM)-5价价immunoglobulinNeutralizationBacterial toxinsHost cellToxin receptorsNeutralization by antibodyPhagocytosis of antibody-antigen complex by macrophageFc receptorForming phagosomeneutralization of viral activityFunction of C regions(Fc portion)1.Activation of complement:IgM,IgG Ab(IgM、IgG)+Ag-C1q-补体经典途径补体经典途径 IgG4、IgA和和IgE的凝聚物的凝聚物-补体旁路途径补体旁路途径2.Binding to Fc receptor of cells Opsonization:enhancement of Ag uptake by macrophages(M)Antibody-dependent cell-mediated cytotoxicity(ADCC):NK cells.Participation in type I hypersensitivity:IgE3.Passage through the placenta(IgG,CH2)and mucosa(sIgA)immunoglobulinimmunoglobulinOpsonization of antibodyimmunoglobulinAntibody-dependent cell-mediated cytotoxicity(ADCC)passage through the placenta(IgG)and mucosal(SIgA)Passage through mucosal(SIgA)Function of imm