humoralimmunity-120122202508-phpapp01

8/18/2019 humoralimmunity-120122202508-phpapp01

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Humoral ImmunityAntibody Mediated

Dr.T.V.Rao MD

Dr.T.V.Rao MD 1


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Humoral Immunity• Results in

production ofproteins called“immunoglobulin's

” or “antibodies”.• Body exposed to

“foreign” materialtermed “antigen”

!ic! may be!armful to body"#irus$ bacteria$ etc.

• %ntigen !as bypassed

ot!er protecti#emec!anisms$ ie$ &rst Dr.T.V.Rao MD


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WHAT ARE ANTIBODIES? • %ntigen speci&c proteins produced

by plasma cells• Belong to immunoglobulin

superfamily• (ocated in blood and extra#ascular

tissues$ secretions and excretions

• Bind pat!ogenic microorganismand t!eir toxins in extracellularcompartments

• )ecreted form of immunoglobulin'sDr.T.V.Rao MD *


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C ASSES !ISOT"#ES$ O%IMM&NO' OB& INS

• +lasses based on constant region of!ea#y c!ains – ,mmunoglobulin % -,g% – ,mmunoglobulin D -,gD – ,mmunoglobulin / -,g/ – ,mmunoglobulin 0 -,g0 – ,mmunoglobulin M -,gM

• Di erentiation of !ea#y c!ains – (engt! of + region$ location of disul&de

bonds$ !inge region$ distribution ofcarbo!ydrate

• Cla((e( )a*e di+erent e+e,torDr.T.V.Rao MD 2


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Di+erent ,la((e( o- Antibodie(

Dr.T.V.Rao MD 3


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Stru,tural ,on /uration o-Antibody

Dr.T.V.Rao MD 4


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THREE DIMENSIONASTR&CT&RE O% ANTIBODIES

• Antibodie( -un,tion in (ettin/ o- in-e,tiou(0ro,e(( – #roteolyti, en1yme(2 (alt and 0H di+eren,e(

• Antibodie( remain (table ba(ed on – Se3uen,e o- domain(

• Sin/le domain ,on(i(t( o- – 455 6 445 amino a,id( -olded into ,om0a,t and

(table ,on-ormation

• Domain( – Variable !V$• Sin/le V domain in H and ,)ain(

– Con(tant !C$• Sin/le C domain in ,)ain(

• T)ree to -our !C$ domain( in H ,)ain(Dr.T.V.Rao MD 5


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Antibodie( are #rodu,ed by Bym0)o,yte(

Dr.T.V.Rao MD 6


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Immuno/lobulin Cla((e(I. IgGStructure: Monomer

Percentage serum antibodies: 80%

Location: Blood, lymph, intestineal!"li!e in serum: #$ daysomplement &i'ation: (es

Placental )rans!er: (es*no+n &unctions: nhances phagocytosis,neutrali-es to'ins and .iruses, protects !etus andne+born/

Dr.T.V.Rao MD 7


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Immuno/lobulin Cla((e(II. I/M

Structure: Pentamer Percentage serum antibodies: "10%Location: Blood, lymph, B cell sur!ace 2monomer3

al!"li!e in serum: daysomplement &i'ation: (es

Placental )rans!er: 4o

*no+n &unctions: &irst antibodies producedduring an in!ection/ !!ecti.e against microbesand agglutinating antigens/

Dr.T.V.Rao MD 18


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Immuno/lobulin Cla((e(

III. I/AStructure: 5imer Percentage serum antibodies: 10"1 %Location: Secretions 2tears, sali.a, intestine,mil63, blood and lymph/

al!"li!e in serum: 7 daysomplement &i'ation: 4o

Placental )rans!er: 4o*no+n &unctions: Locali-ed protection o!mucosal sur!aces/ Pro.ides immunity to in!antdigesti.e tract/

Dr.T.V.Rao MD 11


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Immuno/lobulin Cla((e(

IV. I/DStructure: Monomer Percentage serum antibodies: 0/#%

Location: B"cell sur!ace, blood, and lymphal!"li!e in serum: $ daysomplement &i'ation: 4o

Placental )rans!er: 4o*no+n &unctions: In serum !unction is un6no+n/

n B cell sur!ace, initiate immune response/

Dr.T.V.Rao MD 1


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Immuno/lobulin Cla((e(V. I/E

Structure: Monomer Percentage serum antibodies: 0/00#%Location: Bound to mast cells and basophilsthroughout body/ Blood/

al!"li!e in serum: # daysomplement &i'ation: 4o

Placental )rans!er: 4o*no+n &unctions: 9llergic reactions/ Possiblylysis o! +orms/

Dr.T.V.Rao MD 1*


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C ASSES !ISOT"#ES$ O%IMM&NO' OB& INS• %dditional

classi&cation based onlig!t c!ains – 7a00a – ambda

• /ac! ,0 !as eit!er9appa or lambda$ notbot! – I/' 8a00a – I/' lambda

• :o functionaldi erences bet eenlig!t c!ains Dr.T.V.Rao MD 12


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B Cell Re,e0tor( -orAnti/en(• B cell receptors

– Bind to speci&c$ intact antigens – %re often called membrane antibodies or

membrane immunoglobulin's Antigen-

bindingsite

Antigen-

binding siteDisulfidebridge

Lightchain

Heavy chains

Cytoplasm of B cell

A B cell receptor consists of two identical heavychains and two identical light chains lin ed byseveral disulfide bridges!

2a3

"ariableregions

Constantregions

#ransmembraneregion

$lasmamembrane

B cell

Dr.T.V.Rao MD 13


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Antibodies bond to antigenic determinantsAntigenic determinants are portions of the antigen

Dr.T.V.Rao MD 14


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Antibodie( are #rotein( t)atRe,o/ni1e S0e,i , Anti/en(

Dr.T.V.Rao MD 15


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E0ito0e(9 Anti/en Re/ion(t)at Intera,t :it) Antibodie(

Dr.T.V.Rao MD 16


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Dynami,( o- Antibody#rodu,tion

• #rimaryimmunere(0on(e – (atent period – 0radual rise in

antibody

productionta9ing days toee9s

– ;lateau reac!ed – %ntibody le#el Dr.T.V.Rao MD 17


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Se,ondary Re(0on(e

• )econd exposure to)%M/ antigen.

• Memory cells are abeautiful t!ing.

• Recognition ofantigen is immediate.

• Results in immediate

production ofprotecti#e antibody$mainly ,g0 but maysee some ,gM

Dr.T.V.Rao MD 8


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Dynami,( o- Antibody#rodu,tion

• Antibody 0rodu,tion – ,nitial antibody produced in ,gM

– (asts 18


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• In t)e (e,ondaryimmune re(0on(e

– Memory ,ell( -a,ilitate a -a(ter2 moree;,ient re(0on(e

A n

t i b o

d y c o n c e n

t r a

t i o n

% a r b

i t r a r y u n

i t s

&

'( )

'( *

'( +

'( '

'( (

( , ') +' + *. )+ )/ .0

#ime %days&

9ntibodiesto 9 9ntibodiesto B

Primaryresponse toantigen A

produces anti-bodies to A


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THE #RIMAR" H&MORAIMM&NE RES#ONSE

• ,mmune response initially produces ,gMantibodies t!en s itc!es to ,g0antibodies

• ?uestion – >!y s itc! from ,gM to ,g0@

• %ns er –

(imited e ector mec!anisms for ,gM – Range of e ector mec!anisms for ,g0• Mec!anism

– ,sotope or class s itc!ingDr.T.V.Rao MD *


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IL 1

Autocrinestimulation

IL 2

Humoral (antibody-mediated) Immunity

Dr.T.V.Rao MD 2


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ISOT"#E OR C ASS SWITCHIN'

• ;rocess by !ic! B cell c!anges class of,0 produced !ile preser#ing antigenicspeci&city

• ,n#ol#es somatic recombination !ic!attac!es di erent !ea#y c!ain constantregion to #ariable region

• Accurs only during acti#e immune

response• Mec!anisms in#ol#es recombination

bet een – ) itc! se uences -regions

Dr.T.V.Rao MD 3


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• Clonal (ele,tion o- B ,ell( – 0enerates a clone of s!ort


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MemoryCells

Humoral (antibody-mediated) Immunity

Dr.T.V.Rao MD 5


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enefits of Immunological Memory

Dr.T.V.Rao MD 6


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Clonal Selection

!nly one type ofantibody"and one

type of cell" responds to the

antigenic determinant

#hat cell typethen produces alarge number of

clonesDr.T.V.Rao MD 7


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=C:+T,A:) %:D ;RA;/RT,/) A=%:T,BAD

• Neutrali1ation – Direct inacti#ation of pat!ogen or toxin

t!ereby pre#enting its interaction it!

!uman cells• O0(oni1ation

– +oating of pat!ogens for more eEcientp!agocytosis

• A,ti*ation o- ,om0lement – More eEcient p!agocytosis – Direct 9illing

Dr.T.V.Rao MD *8


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DIVERSI%ICATION O% ANTIBODIESA%TER B CE S ENCO&NTER ANTI'EN

• Mature$ naF#e B cell !as membrane bound ,gMand ,gD antigen receptors

• Binding of antigen initiates proliferation and

di erentiation of B


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DIVERSI%ICATION O% ANTIBODIESA%TER B CE S ENCO&NTER ANTI'EN

• =ollo ing antigen acti#ation of B


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O&TCOME O% SOMATICH"#ERM&TATION

• 0i#es rise to some antibodiesit! !ig!er

– %Enity for antigen• %Enity – )trengt! of binding of one molecule

to anot!er by a single binding site• Gig!er aEnity antibodies are

produced as immune response

proceeds Dr.T.V.Rao MD **


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I/M ANTIBOD" O% THEIMM&NE RES#ONSE

• =irst isotype produced in primary response – May or may not be produced in secondary response – ;roduced before B cells undergo somatic

!ypermutation• Accurs as pentamer it! H c!ain

– =ound primarily in blood and lymp!• Multiple binding sites confers !ig! a#idity and

compensates for lo aEnity of monomers• Gig!ly e ecti#e in complement acti#ation• =unctions as r!eumatoid factor

Dr.T.V.Rao MD *2


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I/' ANTIBOD" O% THEIMM&NE RES#ONSE

• )econd isotype produced in primary response• ;rimary isotype of

– )econdary immune response – Memory immune response

• Represents approximately 53I of total serum,0

• =our subclasses -1


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I/A ANTIBOD" O% THEIMM&NE RES#ONSE

• T o subclasses -,g%1 and ,g% andt o forms -monomeric and dimeric

• Monomeri, – (ocated in blood and extracellular spaces – ;redominately ,g%1

• Ratio of ,g%1 to ,g% is 18"1 – =unctions as r!eumatoid factor

• Dimeri, – (ocated in mucous membranes and secretions – ;redominately ,g% – Ratio of ,g% to ,g%1 is *" – H c!ain li9e ,gM

Dr.T.V.Rao MD *4

/ /


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/ /O% THE IMM&NE

RES#ONSE• I/E – Binds it! !ig! aEnity to receptors on mast

cells$ basop!ils and acti#ated /osinop!ils

– (onger !alf


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Immunolo/i,al

MemoryAntibody Titer 9 )he amount o! antibodyin the serum/

Pattern o! 9ntibody Le.els 5uring In!ectionPrimary esponse:

– 9!ter initial e'posure to antigen, no antibodiesare !ound in serum !or se.eral days/

– 9 gradual increase in titer, !irst o! IgM and theno! IgG is obser.ed/

– Most B cells become plasma cells, but some B

cells become long li.ing memory cells /Dr.T.V.Rao MD *6


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Immunolo/i,al Memory!Continued$

Se,ondaryRe(0on(e9

– Sub(e3uent e@0o(ure tot)e (ame anti/en di(0lay(a -a(ter and more inten(eantibody re(0on(e.

– In,rea(ed antibodyre(0on(e i( due to t)e

e@i(ten,e o- memory,ell(2 :)i,) ra0idly0rodu,e 0la(ma ,ell(u0on anti/en (timulation.

Dr.T.V.Rao MD *7


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ANTIBODIES AS DIA'NOSTICAND THERA#E&TICS A'ENTS

• Based on speci&city and aEnity ofantibodies

• Bot! applications re uire large uantities

of identical antibodies – Monoclonal antibodies• Monoclonal antibodies are produced using

!ybridoma cell line

• Gybridoma cell line – Deri#ed from single antibody producing cell

fused it! myeloma cell -neoplastic plasmacell

Dr.T.V.Rao MD 28


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• #ro/ramme Created ByDr.T.V.Rao MD -or ba(i, learnin/

-or Medi,al and #aramedi,alStudent( in t)e De*elo0in/

World• /mail

• doctort#raoKgmail.com

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humoralimmunity-120122202508-phpapp01