An#body structure & funcon - KSUfac.ksu.edu.sa/.../antibody_structure_and_function_0.pdf ·...
Transcript of An#body structure & funcon - KSUfac.ksu.edu.sa/.../antibody_structure_and_function_0.pdf ·...
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An#bodystructure&func#on
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Objec&ves
Youshouldbeableto:ü Definean&bodyü Describean&bodystructureü Comparebetweendifferenttypesorclassesofan&bodyandtheirfunc&on
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An#bodies=Immunoglobulin
• Glycoproteinsfoundinserumand&ssuefluidswhichareproducedinresponsetocontactwithimmunogenicforeignmolecules.Theybindspecificallytothean&genthatinducedthereforma&on.
• Amajorcomponentofhumoralimmunity.
• FiveClassesIgM,IgG,IgA,IgDandIgE.
• Allhavethesamebasican#bodystructure.
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BASICANTIBODYSTRUCTUREo Twoiden&callightchainsλorΚ,
220AA(25KDa).
o Twoiden&calHeavychains,450AA(50KDa).
o Covalentandnon-covalentforces.o Twoiden&calan&genbindingsites.
o Carbohydrate(CHO).o Eachlightchainboundtoheavychainby
disulfidebond(L-H)andalso(H-H)
o Hingeregion
C
C
Ag
Ag
N
N
N
N
CHO
CHO
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Variable&ConstantRegions
Constant
regions
Variable
regions
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ImmunoglobulinDomainStructure
Agbinding
Effectorfunc#on
1. Domainsa) VL&CLb) VH&CH1-CH3(orCH4)
2. Oligosaccharides3. Complementarity
DeterminingRegions(CDR) املناطق احملددة التكميلية
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CDR1
CDR2
CDR1
CDR2
CDR3 CDR3
AG
LightchainHeavychain
ABasican#bodybindingsite
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ImmunoglobulinFragments
1-Fab– Agbinding– Valence=1– SpecificitydeterminedbyVHandVL
Papain
Fc
Fab
2-Fc– Effectorfunc&ons
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3-F(ab’)2Pepsin
Fc Peptides
F(ab’)2
ImmunoglobulinFragments
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Ag Binding
ComplementBindingSiteBinding to Fc
Receptors
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An#bodyFunc#ons
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Classesofimmunoglobulin
Differences:
• NumberofbasicsubunitswhichformtheAb• Thepolypep&desequenceintheheavychainconstantregionsaredifferent,givingdifferentfunc&onalcharacteris&cs
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Classesofimmunoglobulin.
1. IgM - Mu (µ) heavy chains
2. IgG - Gamma (γ) heavy chains
3. IgA - Alpha (α) heavy chains
4. IgD - Delta (δ) heavy chains
5. IgE - Epsilon (ε) heavy chains
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Subclassesofimmunoglobulin.
• IgG Subclasses: IgG1, IgG2, IgG3 and IgG4
• IgA subclasses: IgA1 and IgA2
• No subclasses of IgM, IgD, and IgE
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ImmunoglobulinLightChainTypes
1. Kappa (κ) 60% Human 2. Lambda (λ) 40% • Kappa 95% Mouse • Lambda 5%
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IgM
• 10%ofnormalserumIg(1.8mg/ml)
• Pentamercomposedof5basicIgmonomers
• 10an&genbindingsites
• Heavychainhasfivedomains
C�4
J Chain
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PentamericIgM
• 10lightchains• 10heavychains• 10iden&calan&genbindingsites
• 1Jchain
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IgM
• PredominantAbofprimaryimmuneresponse
• Mostefficientcomplementfixingan&body
• Halflife10days
• Notfoundextravascularly• GoodatOpsonisa&on
• FoundatBlymphocytecellsurfaceasamembraneboundmonomer.Hereitactsasacellsurfacereceptorinan&genrecogni&on.
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IgG
• IgG:4subclassesγ1-γ4heavychains• 75%ofnormalserumIg(12mg/ml)
• Basicmonomerstructure
• 4subclassesIgG1,IgG2,IgG3,IgG4,whichare70%,20%,8%and2%ofthenormalserumIgGinhumans
• InmousetheseareIgG1,IgG2a,IgG2b,IgG3
• Lifespan:21days
IgG1, IgG2 and IgG4 IgG3
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• Predominant Ab of a secondary immune response
• Extravascular
• Fixes complement IgG3 > IgG1 > IgG2 > IgG4
• Opsonisation
• Placental transfer IgG1, 3 and 4
IgG
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Lymphocyteormonocyte
IgGBindstocellsurfaceFcreceptorsonlymphocytesandmonocytes
An#gen
IgG
Fcreceptor
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IgA
• IgA 2 subclasses α1, α2 heavy chains
• 10-15% of normal serum Ig
• In human serum mainly monomeric (above 80%)
• Subclasses IgA1 and IgA2
• Predominant Ig in secretions eg. saliva and colostrum and in the gut where it is present as a dimer of two Ig monomers one J chain and one secretory component polypeptide.
• Life span: 6 days
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SecretoryIgA
Secretorycomponentproducedbyepithelialcells.Protec#onfromcleavage.
JChain
SpecialisedfortransporttoareasinwhichAbproducingBcellsareabsenteg.gutandviacolostrumtothenewborn
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OriginofSecretoryComponentofsIgA
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IgD
• Verylowlevelsinserumatleast1000foldlowerthanIgG(<1%)
• Basicmonomerstructure.
• Foundonthesurfaceofcircula&ngBlymphocytesohenco-expressedwithIgM.
• Lifespan:3days
Tail Piece
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Bcell
An#gen
IgDatcellsurface
Igatthecellsurfaceallowsan#genbindingandtriggersBcellac#va#on
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IgE
• Lowestserumconcentra&ons0.0003mg/ml
• Basicmonomerstructure
• Heavychainconsistsof5domains
• BindstotheFcreceptorsofmastcellsandbasophils.Contactwithan&genssubsequentlyleadstothereleaseofpro-inflammatoryagents
• Halflife:2days
C�4
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IgE and mast cell - activation
Y Y
Ag IgE FcεRI
Histamine PGD2 proteases heparin Cytokines
TNF-α, IL-4 etc
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Summary:
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By the end you will be able to answer these questions
• What is antibody? • Draw and describe the structure of Ab? • Compare between Ab classes?
• What are the function of Ab?