Antibody Structure (3)

8/6/2019 Antibody Structure (3)

http://slidepdf.com/reader/full/antibody-structure-3 1/28

ANTIBODY STRUCTURE

Pn Mahani Mahadi



Learning Outcomes

At t he end of t his lec tur e, stu den t sh oul d be able to:

Iden t ify stru ctur e for each imm unoglobul inCompa re 5 classes of an t ibo dy m olec ules.



Introduction

Humoral Immunity re f e rs to t he p ro duct ion of antibody molecules in response to an antigen .T hese an t ibo dy m olec ules circula te in the bloo d and en te r t he t issue via inflamma t ion.

Hum or a l imm uni ty is most effective againstbacteria, bacterial toxins, and viruses prior tothese agents entering cells .



A ntibodies or immunoglobulins a re speci f ic glycop rot ein con f igur a t ions p ro duced by B-lymph ocytes and p lasma ce lls in response to a

specific antigen and capable of reacting withthat antigen . The simp les t an t ibo dies, such as IgG, IgD, and IgE, a re "Y"-shaped mac ro m olec ules ca lled monomers .



A m onome r is comp osed of four glycoproteinchains : two iden t ica l heavy chains and twoiden t ica l light chains . T he two hea vy chains ha ve a high m olec ula rweigh t t ha t va ries w ith the class of an t ibo dy. T he ligh t chains come in two v a rie t ies : kappa orlamda and ha ve a low e r m olec ula r w eigh t .

T he four gly cop rot ein chains a re connec ted toone an ot he r by dis ulf ide (S-S) bo nds and non -cova len t bo nds .



T he two t ips of t he "Y" m onome r a re re f e rred to as the Fab portions of t he an t ibo dy. T he f irst 110 amin o acids or f irst domain of bot h the hea vy and ligh t chain of t he Fabre gion of t he an t ibo dy provide specificity forbinding an epitope on an antigen .The botto m pa rt of t he "Y", the C te rmina lre gion of each glycop rot ein chain, is ca lled the Fc portion .



T he Fc port ion, as we ll as one domain of bot h the hea vy and ligh t chain of t he Fab r e gion has a constant amino acid sequence tha t de f ines the class and sub class of each an t ibo dy.

The Fc port ion is resp onsi ble for t he biologicalactivity of t he an t ibo dy how e ve r, the Fc

portion only becomes biologically after theFab component has bound to itscorresponding antigen .



Dependin g o n the class and sub class of an t ibo dy, b iolog ica l ac t ivit ies of t he Fc port ion of an t ibo dies inc lude the ab ility to:

1. A ctivate the complement pathway (IgG &IgM )

2 . B ind to phagocytes (IgG)3 . B ind to mast cells, basophils, and eosinophils

(IgE)

4. B

ind to NK cells (IgG)5 . D etermine the tissue distribution of theantibodies , tha t is, to w ha t t issues types the an t ibo dy m olec ules a re able to go .



T he Fab port ion of t he an t ibo dy has the comp lemen ta rity-de te rminin g re gions (red ) p rov idin g speci f icity for b indin g an epi to pe of an an t igen. T he Fc port ion (pur p le ) direc ts the b iolog ica l ac t ivity of t he an t ibo dy. (S-S = dis ulf ide bo nd; N =amin o t e rmina l of gly cop rot ein; C = ca rboxy t e rmina l of glycop rot ein; CHO = ca rbo hyd ra te. )





IgG (Imm unoglobul in G)4 sub classes, IgG1-4

app rox ima te ly 80% of t he se ru m an t ibo dies.

ha lf-lif e of 7-23 da ys dependin g o n the sub class.

is a m onome r and has 2 epi to pe -b indin g sites

Fc port ion of IgG can activate the classicalcomplement pathway

Fc port ion of IgG can bind to macrophage andneutrophils for enhanced pha go cyto sis



Fc port ion of IgG can bind to NK cells foran t ibo dy-dependen t cytotox icity or AD CC.

Fc port ion of IgG ena bles it to cross theplacenta .

IgG is the on ly class of an t ibo dy t ha t can cro ss the p lacen ta and en te r t he f e ta l circula t ion.

Feed bac k inhi b it ion of B-lymph ocyte ac t iva t ion. High le ve ls of IgG f eed bac k to B-lymph ocytes to p re ven t t hei r ac t iva t ion in or de r to tur n off an t ibo dy p ro duct ion.



Func t ions :

1 . Ops oniza t ion

2 . Comp lemen t ac t iva t ion,3 . An t ibo dy dependen t ce ll-media ted

cytotox icity,

4 . Ne ona ta l imm uni ty and inhi b it ion inhi b it ionof B ce lls.



T he Fab port ion of t he an t ibo dy has speci f icity forb indin g an epi to pe of an an t igen. T he Fc port ion direc ts

the b iolog ica l ac t ivity of t he an t ibo dy.



O psonization (Enhanced A ttachment)T he Fab port ion of IgG b inds

to epi to pes of an an t igen.

The Fc port ion can nowa tt ach the an t igen to F crecep tor s on pha gocytes forenhanced a tt achmen t .

T his is especia lly imp ort an tagains t encaps ula ted

mic rob es.C3b and C4b fro m the

comp lemen t pa thways can a lso a tt ach an t igens

to pha gocytes.



Des tru ct ion of Viru s-In f ec ted Ce lls by NK Ce lls th roug hAn t ibo dy-Dependen t Ce llula r Cytotox icity (ADCC)



T he Fab port ion of t he an t ibo dy b inds to epi to peson the "for eign" ce ll. T

he NK ce ll then b inds to t he Fc port ion of t he an t ibo dy. T he NK ce ll is then able to con tac t t he ce lland re lease por e -for min g p rot eins ca lled pe rfor ins, p rot e olyt ic enz ymes ca lled granz ymes, and chem ok ines.

Granz ymes pass th roug h the por es and ac t iva te the enz ymes tha t lead to ap op to sis of t he inf ec ted ce llby means of des tru ct ion of its stru ctur a lcyto ske le to n p rot eins and by ch ro m osoma l

de grada t ion. As a res ult , the ce ll br ea ks in to fr agmen ts tha t a re sub seq uen tly r em oved by pha go cytes. Pe rfor ins can a lso some t imes res ult in ce ll lysis.



IgM (Imm unoglobul in M )

app rox ima te ly 13% of t he se ru m an t ibo dies and is the first antibody produced during animmune response .

has a ha lf-lif e of about 5 da ys.is a pen tame r and has 10 epi to pe -b indin g sites

Fc port ions of Ig M a re able to activate the

classical complement pathway . IgM is the m ost e ff icien t class of an t ibo dy for ac t iva t ingthe classica l comp lemen t pa thway.



Monome ric for ms of Ig M a re fou nd on the surf ace of B-lymph ocytes as B- cell receptors .

is a pen tame r and, the re for e, has 10 Fab sites.



IgA(Imm unoglobul in A)

app rox ima te ly 6% of t he se ru m an t ibo dies whe re it has a ha lf-lif e of app rox ima te ly 6 da ys.fou nd main ly in bo dy sec re t ions (sa liva, m ucou s, tea rs, colo stru m and mi lk) as sec re tory IgA ( sIgA) whe re it p rot ec ts in te rna lbo dy surf aces exposed to t he en viro nmen t byblo cking t he a tt achmen t of b ac te ria and viru ses to m ucou s mem br anes.Whi le on ly 6% of t he an t ibo dies in the se ru m a re IgA, sec re tory IgA is the m ostimm unoglobul in p ro duced.



made p rima rily in the m ucosa l-ass ocia ted lymph o id t issues (MALT ).appea rs as a dime r of 2 "Y"- shaped m olec ules and has 4 epi to pe -b indin g sites and a sec re tory comp onen t to p rot ec t it fro m

diges t ive enz ymes in the sec re t ions.Fc portion of secretory Ig A binds tocomponents of mucous and con tr ibut es tothe ab ility of m ucou s to tr ap mic rob es.can activate the lectin complement pathwayand the alternative complement pathway



Sec re tory IgA is a dime r and has 4 Fab sites. Asec re tory comp onen t he lps p rot ec t it fro m

diges t ion in bo dy sec re t ions.



IgD (Imm unoglobul in D)

app rox ima te ly 0 .2% of t he se ru m an t ibo dies.

is a m onome r and has 2 epi to pe -b indin g sites

is fou nd on the surf ace of B-lymph ocytes (a long w ith m onome ric IgM ) as a B- cellreceptor or sIg whe re it ma y con trol of B-lymph ocyte ac t iva t ion and supp ressi on.

ma y play a role in eliminating B- lymphocytesgenerating self - reactive autoantibodies .





p rot ec t exte rna l m ucosa l surf aces by promotinginflammation , ena bl ing IgG, comp lemen tp rot eins, and le ucocytes to en te r t he t issues.Fc port ion of IgE can bind to mast cells andbasophils whe re it media tes man y allergic

reactions . Cro ss linking of ce ll-bou nd IgE byan t igen tr igge rs the re lease of v as odi la tor s for an inflamma tory r esp onse.T he Fc port ion of IgE made against parasiticworms and arthropods can bind to eosinophilsenabling opsonization . T his is a maj or de f ense agains t pa rasi t ic wor ms and a rt h ro pods.



Alle rgen cro ss reac t ing w ith IgE on mas t ce ll.





Documents

Antibody Structure (3)