《医学免疫学教学课件》03antibody.ppt
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1、医学免疫学,第四章 免疫球蛋白,Lecture 3 Antibody,1.Concepts2.Structure of immunoglobulins3.Immunogenicity of immunoglobulins(Isotypes,Allotypes,&Idiotypes)4.The function of antibodies 5.Antibody classes 6.Artificial Antibody,Outline of the lecture,Emil von Behring(1845-1917),antibody,-In 1890 by von Behring and K
2、itasato described an activity in serum of toxin-immunized animals that neutralized toxin.Transfer of immune serum could protect nave animals from diphtheria or tetanus.,History,抗体(antibody,Ab):是B细胞接受抗原刺激后增殖分化为浆细胞所产生的糖蛋白。主要存在于血清等体液中,能与相应抗原特异性结合显示免疫功能。是介导体液免疫的重要效应分子。免疫球蛋白(Immunoglobulin,Ig):具有抗体活性或化学结
3、构与抗体类似的球蛋白。-分泌型(secreted Ig,sIg):Ab-膜 型(membrane Ig,mIg):BCR,Day 02468,Resting B cell,Antibodyforming cell,AFC(plasma cell),Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,Y,1.Concepts2.Structure of Antibody3.Immunogenicity of Antibody(Isotypes,Allotypes,&Idiotypes)4.The function of
4、antibodies 5.Antibody classes 6.Artificial Antibody,Outline of the lecture,Structure of antibody,Basic structureHeavy chain and Light chain(重链和轻链)Variable region and Constant region(可变区和恒定区)Other structuresHinge region(铰链)Joining chain(J链)Secretory component(SC,分泌片)Domains(功能区)Fragmentation of Ig by
5、 proteolytic cleavage,1.Basic structure,Heavy chain and Light chainVariable region and Constant regionOther structuresHinge region(铰链)Joining chain(J链)Secretory component(SC,分泌片),The basic structure,Four-polypeptides structureTwo identical heavy chain and two identical light chain(2H+2L)Light chain
6、combine with heavy chain through interchain disulfide bonds;and two heavy chains combine with each other also through interchain disulfide bonds.,重链(heavy chain,H)约440-550个氨基酸,根据重链恒定区结构和免疫原性的差异而分为五类:、,相应Ig:IgG、IgA、IgM、IgD、IgE轻链(light chain,L)约220个氨基酸,根据轻链恒定区免疫原性不同,分为和两型。一个天然Ig分子两条轻链的型别是相同的。在不同种属的动物与
7、链的比例不同:人:2:1,小鼠:20:1,1)Heavy chain(H)&Light chain(L),Ig根据重链恒定区结构的差异分为五类,According the degree of variability in amino acid sequence.V region are the N-terminal quarter of the H-chain and the N-terminal half of the L-chain.C region are the C-terminal three-quarters of the H-chain and the C-terminal ha
8、lf of the L-chain.,2)Variable region(V region)and constant region(C region),V regions(VL+VH)are the site where antigens bind specifically to antibodies.Fab(antigen binding fragment)are the N-terminal half of the H-chain and all of the L-chain.Fc(crystallized fragment)are the C-terminal half of the H
9、-chain fragment that crystallized).,Fab,Fc,Hypervariable regions(高变区,HV):Sequence variability in V regions is concentrated in several regions,called Hypervariable regions。They are also called complementary-determining regions(互补决定区,CDRs)。It is comlementary to the structure of epitope.Framework regio
10、ns(骨架区,FR):the remain regions in V regions.,Hypervariable regions(HV,CDR)and framework regions(FR),Domains of Ig,Hinge region(铰链区)Joining chain and secretory component(SC)(J链和分泌片),3)Other structures,IgG,IgD and IgA contain an extended peptide sequence between CH1 and CH2 domains.This region,called h
11、inge region.Be rich in prolines and is flexible,giving IgG,IgD and IgA segmental flexibility.IgM,IgE lack hinge region,but they have CH2 in this region and have extra CH4.,(1)Hinge region(except for IgE,IgM),Flexibility of immunoglobulins,Joining chain aid to combine monomers into polymers.Five mole
12、cules of IgM usually polymerize into a larger pentamer.Secretory IgA is a dimmer.Secretory component(SC)can prevent the secretory IgA dimmers from degradation of other proteases.Secretory IgA always distribute on lumenal surface.,(2)Joining chain and secretory component(SC),Secretory IgA is a dimmer
13、,IgM polymerize into a pentamer,2.The domains of Ig,Both H-and L-chains have intrachain disulfide bridges every 90 amino acid residues,which create polypeptide loops,domains,of 110 amino acids.,免疫球蛋白的功能区,-H chain Variable region is one domain,referred to as VH;constant region has three or four domai
14、ns,referred to as CH1,CH2,CH3,CH4.(IgG,IgA,IgD has three domains-CH1,CH2,CH3 in C region;while IgM,IgE has four domains-CH1,CH2,CH3,CH4 in C region).-L-chain Variable region is one domain,referred to as VL;constant region also has only one domain,referred to as CL.,Domains of IgG,IgA,IgD,1)H chain:V
15、 region:VH;C region:CH1,CH2,CH3.(IgE,IgM has another CH4)2)L chain:V region:VL;C region:CL;,3.Immunoglobulin fragments,Papain(木瓜蛋白酶)digestion:Fab fragment antigen binding Fc fragment.crystallizablePepsin(胃蛋白酶)digestion:F(ab)2(composed of two Fab-like fragments);The Fc fragment is degraded into many
16、small fragment.,1.Concepts2.Structure of immunoglobulins3.Immunogenicity of immunoglobulins(Isotypes,Allotypes,&Idiotypes)4.The function of antibodies 5.Antibody classes6.Artificial Antibody,Outline of the lecture,抗体的异质性,抗体的异质性指抗体的结构和功能上的不均一性或差异性。多种机制导致抗体的异质性:抗原的多样性:不同抗原含有不同的抗原表位,刺激产生特异性不同的抗体(V区不同)。
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