醫(yī)學免疫學英文版課件：Chapter 3 Immunoglobulin

1、Chapter 3 ImmunoglobulinDefinitionAntibody (Ab) : Ab is one kind of globulin that can combine with a corresponding Ag specifically. It is produced by B cells in the response to a stimulation of Ag.Immunoglobulin( Ig): All glubulins that posses the activation of Ab or show a similar structure to Ab T

2、herefore, All Abs are Igs, but not all Igs possess the functions of Abs.Part I. Molecular Structure of Ig I. Basic structureH and L chain:Ig is composed of four polypeptide chains joined by inter-chain disulfide bonds( S-S). It show “T” or “Y” shape. Four peptide chains Two heavy chains (H): 450 550

3、aa, 5075KD Two light chains (L): 214 aa, 25KDFour peptide chainsDisulfide bonds(s-s) Inter-chain s-s bond Intra-chain s-s bond Two terminal end s of each peptide “N” terminal end “C” terminal end L chains attach to H chains from “N” end 2.classes and types of Ig According to the differences of heavy

4、 chains ( amino acid composition ,sequence), Igs can be divided into 5 classes(isotypes): Five classes of H Chain: , , , , Five classes of Ig : IgG, IgA, IgM, IgD, IgEAccording to differences of thestructure in light chains, Ig s can be divided into two types:Two types of L chain : , Two types of Ig

5、: type and type ( the ratio of : is 20:1 in mice , but, 2:1 in human,)3. Two regions of each peptide: V and C region Constant region(C): CH, CLVariable region (V): VH, VL Hypervariable region(HVR) Framework region (FR) 1)Variable region ( V ) : VH,VLHypervariable region ( HVR): There are three highl

6、y divergent stretches within the V region ,they are called HVR.Complementarity-determining region (CDR): Because the three HVR of L chain and H chain can be brought together to form antigen-binding surface, so HVR is also called CDR.Framework region (FR)CDRs institues Ag-binding sitesL: CDR1, CDR2,

7、CDR3 H: CDR1, CDR2,CDR3 Idiotype of IgIgs produced by different B cells possess unique structure in hypervariable region . The unique strcture of Ig is called Idiotype of IgInfact: idiotype HVR CDR are the same sites of Ig 2) Constant region (C region)CH: 3/4 or 4/5 of Heavy chain near carboxy termi

8、nus CL:1/2 of Light chain near carboxy terminus4. hinge region: hinge region:between CH1 and CH2 (rich in proline ,easy flex ) flexible and suitable for CDR of Ig combing with antigenic determinants. II. Other parts of Ig 1. Joining chain(J chain) : glycoprotein produced by plasma cellsFunctions: co

9、mpose dimer 、pentamer and polymer( Ig A, IgM)2.Secretary piece( SP): glycoprotein produced by mucosa epithelial cells - exist in secretary IgA (SIg A)Functions: protect SIgA,resist proteolysis in extra secretory liquid.III. Domains of Ig 1. Domain : Polypeptide chains of Ig are folded by intra chain

10、 s-s bind into globular shape in each 110aa regions which is called a domain 2. Domains of IgL chain: VL, CLH chain(45 ): VH, CH1, CH2, CH3/CH4( IgM,IgE)3.function of each domain VH , VL: antigen-binding siteCH1, CL: allogeneic markerCH2: complement-fixing site CH3/CH4: cell-binding site CH(IgG):pla

11、centa-crossing siteIV. Hydrolysis fragments of Ig and their functions1) Digested with papain:2) Digested with pepsin Papain 2Fab (fragment of Ag binding) Ig- Fc ( fragment crystallized ) 1)fixing complement , 2)crossing the placenta, 3) fixing different cell Position of papain: near the hinge region

12、 before H inter-chain S-S bonds pepsin F(ab)2 : bind antigen ( 2 value) Ig- pFc: no function Position of Pepsin : In the hinge region after H-H inter-chain disufide bondsSignificance Be useful in elucidating structure and function relationships of Igs.Decrease the immunogenicity of Ig for clinical t

13、reatmentPart II. Biological efforts of Ab 1.bind specifically to antigen2.fix complement3.bind to Fc receptor on some cells hypersensitivity type I- mast cell and basophils opsonization-macrophageantibody dependent cell mediated cytoxicity, ADCC 4. transfer selectively :planceta transfer or mucus tr

14、ansfer 5. bear antigenicity go1)opsonization-Ig interact with macrophage back2)ADCC( antibody dependent cell mediated cytoxicity) -macrophage, NK and Killer cellsback3)hypersensitivity type I- mast cell and basophils backPart III Five clasess of Ig and their functions I.IgGFour subclasses : IgG1, Ig

15、G2, IgG3, IgG4IgG 1.Highest concentration in serum(75% of totle Ig)2.Four subclasses : IgG1, IgG2, IgG3, IgG4.3.Unique Ig that can pass through placenta.4.half-life is longer( 20-23 days)5.The individual starts to produce Ig G at 2-3 month after birth and reach the level of adult at 5 years old 5.Fu

16、nctions:against bacteria and virus,neutralize toxinsome belong to the auto-antibodies: eg.long actin thyriod stimulator(LATS) in thyrotoxemiacombine with the Fc receptor(FcR)II. IgA1.Two types serum type ：monomer secretary type（SIgA）：dimer，trimer or polymer2.two subclasses：IgA1，IgA23.to be produced

17、at 4 month after birth4.exist in almost all humoral5.activate the complement by alternative pathway 6.local immunity of mucosa Immune barrier rich in colostrum neutralize virus/toxinIII. IgM1.highest MW：pentamer（90KD）Valences：10 valences in theory2.half-life is shorter(45 days)3.the first Ig to be s

18、ynthesized be produced during fetus appear in the early stage after infection the first mIg of the B cells,act as the antigen receptors(BCR)4.Function:IgM is more effect anti-infection,anti-bacteriumnatural Ab to blood-type antigen auto-antibody :reumatiod factor(RF)IV. IgD1.concerntration in serum

19、is low and sensitive to proteinase2.act as the antigen receptor on B cells: regulate differentiation of B cellsV. IgE1.concerntration in serum is lowest in normal individual, but is very high in some patients2.related to type hypersensitivitySection IV. Preparation of Ab Polyclonal AbMonoclonal AbGene engineering Ab1.Polyclonal Ab heterogeneous population of antibody molecules :a mixture of Ab molecules of different specificities and affinities against different epitopesgenerated in a natural response or afte