1、Immunoglobulin研究生免疫學英文課件抗體AbThe structure and Function of Immunoglobulin (antibody)Ig genes and synthesis of proteinDiversity of Ig and its mechanism Application of antibodyThe structure and Function of Introduction Antibody (Ab) - protein produced by plasma cells in response to immunization and bin

2、ds specifically to particular Ag. -Ab is generally defined in terms of their specific binding to the immunizing Ag Introduction Antibody (Ab)IntroductionImmunoglobulins (Ig) - The Igs are globulin which function as Abs or similar to Abs in chemical structure. - Igs derive their name from the finding

3、 that when Ab-containing serum is place in an electrical field, they migrate with the globular proteins- secreted Ig(sIg) ; membrane Ig(mIg)IntroductionImmunoglobulins (IStructure and function of the IgStructure and function of theRodney Porter 1917-1985Nobel Prize in 1972Gerald Edelman 1929 -Nobel

4、Prize in 1972for their discoveries concerning the chemical structure of antibodiesRodney Porter 1917-1985Gerald 1)Heavy Chain and Light Chain heavy chain (H chain) 5075Kd 450550aa H chain: isotype:IgM, IgG,IgA,IgE, IgD IgG:IgG14 IgA:IgA1 ,IgA2 1, structure1)Heavy Chain and Light Chain1研究生免疫學英文課件抗體Ab

5、1)Heavy Chain and Light Chain light chain (L chain) 25Kd 214aa classes of L chain: : 1 4structure of the Ig1)Heavy Chain and Light Chains2.variable region and constant region variable region(V region) Light Chain - VL (110 aa) Heavy Chain - VH (110 aa) HVR or CDR FR 2.variable region and constantHVR

6、 or CDRHVR: hypervariable regions CDR: the complementarity determining regions. CDR are found in both the H and the L chains.HVR or CDR研究生免疫學英文課件抗體AbFramework regionsFR (framework region) regions between the CDR in the V region are called the FR. VL and VH: Ag binding siteFramework regions constant

7、region(C region) Light Chain - CL (110 aa) Heavy Chain - CH (330-440 aa) : CH1, CH2, CH3,( CH4)研究生免疫學英文課件抗體Ab3. 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 region研究生免

8、疫學英文課件抗體Ab研究生免疫學英文課件抗體Ab研究生免疫學英文課件抗體AbDomains - globular regions of 3D images of the Ig are called domains.Light Chain Domains VL , CL2. Heavy Chain Domains VH, CH1,CH2, CH3 (or CH4)Domains of IgDomains Domains of Ig研究生免疫學英文課件抗體AbDomains of IgDomains of IgJ chain and SP J chain (Joining chain) a pol

9、ypeptide chainJoin the monomer to polymerJ chain and SP J chain (Join研究生免疫學英文課件抗體AbJ chain and SP Secretory piece(SP) J chain and SP Secretory piecIg fragmentsIg fragmentsHeterogeneity of Ig1. Classification of Ig class subclass IgG1IgG4 type subtype 1 2 3 42. Diversity of Ig induced by exogenous fa

10、ctors3. Serotypes of Ig induced by endogenous factorsHeterogeneity of Ig1. ClassifiIsotype The genes for isotype variants are present in all healthy member of a species.Isotype(2) Allotype This refers to genetic variation between individuals within a species.(2) Allotype(3) Idiotype Variation in the

11、 V domain ,particularly in CDR, produces idiotype.(3) IdiotypeFunction of antibodyFunction of antibodyNeutralization of microbes and microbial ToxinsNeutralization of microbes andNeutralization of microbes and microbial ToxinsNeutralization of microbes andNeutralization of microbes and microbial Tox

12、insNeutralization of microbes andOpsonization and phagocytosis of microbesopsonization :a process by which phagocytosis is facilitated by the deposition of opsonins(Ab or C3b) on the antigen.Opsonization and phagocytosis Ab-dependent cell-mediated cytotoxicity,ADCCAb-dependent cell-mediated cytCompl

13、ement activationComplement activationMucosal immunityMucosal immunity研究生免疫學英文課件抗體Ab Rearrangement of Ig genes and synthesis of IgOrganization of Ig gene lociThree separate loci encode, respectively, all the Ig heavy chains, the Ig light chain, and the Ig light chain. Each locus is on a different chr

14、omosome. Rearrangement of Ig genes an研究生免疫學英文課件抗體Ab研究生免疫學英文課件抗體Ab研究生免疫學英文課件抗體AbRearrangement of V region of Ig moleculeRearrangement of V region of IMechanisms of V(D)J RecombinationV(D)J Recombinase:Rag-1/Rag-2Recombination signal sequences(RSS) RSS=heptamer+spacer+nonamer12/23 ruleLooping out and

15、inversionMechanisms of V(D)J RecombinatConserved heptamer (7 bp) and nonamer (9 bp) sequences, separated by 12- or 23-bp spacers, are located adjacent to V and J exons (for and loci) or to V, D, and J exons (in the H chain locus). The V(D)J recombinase recognizes these recombination signal sequences

16、 and brings the exons together Conserved heptamer (7 bp) and Recombination of V and J exons may occur by deletion of intervening DNA and ligation of the V and J segments Recombination of V and J exonsif the V gene is in the opposite orientation, by inversion of the DNA followed by ligation of adjace

17、nt gene segments. if the V gene is in the opposiSynapsis: Portions of the antigen receptor chromosome are made accessible to the recombination machinery, and two selected coding segments and their adjacent RSSs are brought together by a chromosomal looping event and held in position for subsequent c

18、leavage, processing, and joining. Cleavage: Double-strand breaks are enzymatically generated at RSS-coding sequence junctions using machinery that is lymphoid specific. process of V(D)J recombinationSynapsis: Portions of the antiCoding end processing: The broken coding ends (but not the signal/RSS e

19、nds) are modified by the addition or removal of bases, and thus greater diversity is generated. Joining: The broken coding ends as well as the signal ends are brought together and ligated by a double-strand break repair process found in all cells that is called non-homolgous end joining. process of

20、V(D)J recombinationCoding end processing: The broConsequences of VDJ recombinationConsequences of VDJ recombinatIg gene recombination and expressionAllelic exclusion and Isotype exclusionIg gene recombination and exprIg gene recombination and expressionIg gene recombination and expr Generation of Di

21、versity of Ig Diversity ( repertoire) is the total of all the Ab specificities that an organism is capable of expressing.History -Germ line theory -Somatic mutation Generation of Diversity of I Generation of Diversity of IgCurrent conceptsCombinatorial diversity V-D-J-C or V-J-C H-LJunctional diversity P-nucleotide N-region insertionSomatic hypermutation antigen stimulation Generation of Diversity of ICombinatorial diversityCombinatorial diversity Junctional diversity Junctional diversity Junctional diversity Junctional diversitySomatic hypermutationSomatic hypermu