Adaptive Immunology

8/17/2019 Adaptive Immunology

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Immunology Part 2

CAPE Biology

R.Wint


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Objectives1. Defne “antigen” and “epitope”

2. Defne “immune response”

3. Desri!e t"e origin and di#erentiation o$ %&ells' CD( and A)D*

+. Desri!e t"e origin and di#erentiation o$ B&ells

,. E-plain t"e proess o$ antigen presentation initiating an immune response

. *tate t"e types o$ anti!odies /.A.0.E.D

. a!el and annotate t"e struture o$ anti!ody(. utline t"e me"anism o$ "umoral mediated response

4. utline t"e me"anism o$ ell&mediated response

15.E-plain t"e role o$ memory ells in on$erring long&term immunity

11.E-plain t"e types o$ ati6e and passi6e immunity

12.Defne 6aine

13.E-plain "o7 6aine on$er immunity

1+.Defne monolonal anti!ody

1,.Desri!e t"e appliations o$ monolonal anti!odies in aner drug0a!%"era' pregnany testing' A)D* %est


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Immune System

• %"e immune system o$ animals ser6es toprotet t"e organism $rom in6ading ells8$oreign su!stanes.

•

)t is an ela!orate and oordinated system t"atto generate an enormous 6ariety o$ ells andmoleules apa!le o$ speifally reogni9ingand eliminating an apparently limitless 6arietyo$ $oreign in6aders.

• Animal )mmune system is defned $or its a!ilityo$ recognition ' efector response andmemory


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Lymphatic System


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Immunity

•

Immunity is our a!ility to 7ard o#diseases aused !y pat"ogens or t"eirproduts and to protet againsten6ironmental agents.

• %"ere are t7o general types o$ immunity:• Innate Immunity: re$ers to de$enes t"at

are present at !irt"' does not eliit a

speif reognition o$ pat"ogen' nor doesit "a6e a memory response

• Adaptive Immunity: a speif responseto a speif miro!e ;slo7er< and it "as a

memory omponent


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Immunity Map !y"#$I%&'Immunity

Adaptive Innate

(ellMediate

d

)umoralAntibody

'

Anatomic

Phagocytosis

(omplem

ent

In*ammati

on+

ActivePassive

%atural Arti,cial Arti,cial%atural


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A-AP&I./ IMM0%I&1

Cell&0ediated and =umoral 0ediated )mmunity


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Adaptive Immunity• Adapti6e immunity e#ets a "ig"ly speif

response against an antigen' and it is"araterised !y its memory omponent.

• Antigen: a moleule t"at eliits anti!ody$ormation and an immune response. >ound on

miro!es8 $oreign agents

• Antigen specifcity is possi!le !eause t"eadapti6e immune system an generatetremendous diversity o$ ells to reognise t"e!illions o$ uni?ue antigens

• Immunolgic Memory: t"e seond enounter7it" t"e same antigen indues a $aster and more

intense immune response


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!ranches o AdaptiveImmunity

3# )umoral Immunity: e#ets an immuneresponse !y inati6ating antigen usingantibodies produed !y !4lymphocytes

2# (ell4mediated is oordinated !y &4lymphocytes t"at proli$erate and e#etan immune response among t"emsel6esand stimulate ot"er immune ells

B&ells and %&ells !eome ati6ated upone-posure o$ an antigen


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Overvie5


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!4(ell Maturation6-iferentiation

• Reall t"at all !lood ells originate $rom stem ells in t"ered !one marro7 in a proess @no7n as haemopoeisis#

• utline

1. B&lymp"oytes mature in t"e !one marro7 into a na7ve!4cell e-pressing a uni?ue antigen !inding reeptor;antibody) on its mem!rane.

2# Activation: W"en t"e na7ve !4cell enounters and !indsa omplementary antigen $or t"e frst time' t"is induest"e B&ell to rapidly di6ide.

8# (lonal /9pansion: %"e B&ell progeny proli$erates anddi#erentiates into memory !4cell' and t"e e#etors

plasma cells# ;ate:

– memory !4cell e-press t"e same uni?ue anti!ody as parent B&ell on t"eir sur$ae

– Plasma cells instead serete anti!ody t"at are maor e#etors

in "umoral immunity


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!4cell -iferentiation


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&4lymphocyte-iferentiation

• %&lymp"oytes di#erentiate in t"e red !onemarro7' !ut it matures in t"e thymus gland

• Outline

1. %&ell matures in t"ymus' e-pressing &4cellreceptors &(" on ell mem!rane.

2# %a7ve &4cell 6ia its %CR !ind to antigen-MHCcomplex e-pressed on antigen presenting ell

8# Activation6(lonal e9pansion: %&ellproli$erates and di#erentiates into memory Tcells and eector T cells


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(lasses o /fector & cell

• %7o main lasses o$ e#etor %&ells t"at an!e distinguis"ed !y t"e presene o$ speialsur$ae mem!rane moleules (- and (-<

3# &4helper cells: !inds 0=C&)) serete"emials t"at stimulate ati6ation o$ Bells' % ells' ot"er immune ells. E-press

CD+

2# &4cytoto9ic cells= &c: !inds 0=C&)'seretes "emials t"at are to-i topat"ogens. E-presses CD(


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M)(4 Major )istocompatibility(omple9

• M)( are glycoproteins that areresponsible or antigen presentation#

• >or %&ells to !e ati6ated' t"e antigen

must !e !ound to an 0=C repetor • 2 lasses o$ 0=C

1. 0=C&1 : $ound on all ells in organism

!ind and present endogenous antigens2# M)(4II: $ound on ell sur$ae o$ antigen

presenting ells.


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(ell4Mediated in Action

• iruses in$et ells !yinserting t"eir o7n RAor DA into t"e "ost ell.

1. )n$eted "ost ells 7ill

e-press a 0=C&)8antigen omple- t"atis reognised !y % ells

•. %C Cells 7ill !ind' 6ia %&

ell reeptors to t"e

0=C&)8antigen omple-and in$eted ell anddestroy t"e in$eted ell


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=) and %&ells

• ne =) "as entered t"e !ody' t"eimmune system initiates anti&=)anti!ody and ytoto-i % ell

prodution.

• =o7e6er' it an ta@e one to si-mont"s $or an indi6idual e-posed to

=) to produe measura!le?uantities o$ anti!ody.

• &he immune response is

5ea>ened as memory & cells


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4Inection

• =) auses illness !yin$eting and depletingCD+ % ell population.By doing t"at t"eimmune system

!eomes se6erely7ea@ened.

• =) in$ets andprograms CD+ % ells

to produe a largenum!er o$ more =)6irus' and in doing sot"e CD+ % ells isdestroyed.

• AI-S de6elops 7"enCD+ % ell ount $alls!elo7 3,5 ells8u &255ells8u

• Beause )I. destroysCD+ % ells' AI-S is"araterised !y

opportunisti in$etionsli@e tu!erulosis'pneumonia et


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=) and %&Cell


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Antigen Presentation

• Antigen presentation lin@s innate immunity to adapti6eimmunity.

• Antigen presenting ells' eg. Dendriti ells' e-press

0=C&)) on t"eir mem!rane.

1. APC p"agoytose su!stane !earing antigen

2. Antigen is proessed inside APC and t"en !ind to 0=C&))

3. 0=C&Antigen omple- is trans$erred $rom 7it"in ell tot"e ell sur$ae

+. %&ell 7it" %CR omplementary to antigen&0=C&))

omple- 7ill !ind to it and !eome ati6ated


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Antibody B /fectors o)umoral

• Antibody or immunoglobin are glo!ulinproteins t"at !ind speif antigens

• Anti!odies released !y plasma irulate inserum

• Anti!ody !ind antigen to $orm an antigen4antibody comple9

• Anti!ody !ind speif regions on t"e antigen

alled t"e epitope• %"e !inding o$ an anti!ody to an antigen

protets t"e "ost !y tagging $oreign ells andmoleules $or destrution !y p"agoytes and

omplement.


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Antibody Structure

• All anti!odies are

heterodimers –

onsists o$ +peptide "ains.

• 2 identical light

chains and 2

identical heavy

chains onneted


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Antibody Structure

3# .ariable region: t"esite t"at !ind antigenuni?ue $or only oneanti!ody

2# (onstant region:same amino aidse?uene $or a lass o$anti!odies

8# ;c region: &s"apedportion !ind to aomplement oranot"er ell


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(lasses o Antibody

• , lasses o$ anti!odies: IgC= IgA= IgM Ig/Ig-

3# IgC: most a!undant anti!ody in serum

– Can ross !lood 6essels an enter tissue – atural passi6e immunity: ross

plaenta to protet de6eloping $oetus

–

(omplement activation – En"anes p"agoytosis !y opsonisation

– eutralise 6irus and miro!ial to-ins


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(lasses o Antibodies

2# IgM : 15F o$ serum

– >irst anti!ody to appear primaryresponse to an antigen

– E#eti6e at agglutination o$antigen ;AB !lood trans$usion<

– Complement ati6ation


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(lasses o Antibody

• Immunoglobulin A 44 Ig A

–0ost a!undant in muusmem!ranes and !ody seretions

–=elps pre6ent atta"ment o$miro!ial pat"ogens to muosalmem!ranes e..g respiratory trat

and intestines


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Ig - and Ig /

• Ig -

– no defned $untion

• Ig /: –5.5552F o$ serum' !ut inreases in

allergi response

–0ediates allergi ;"ypersensiti6ity<

reations' ;eg ast"ma "ay $e6er< !ystimulating "istamine prodution

–ysis o$ parasiti 7orms


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Anti!ody *ummary

Ig C Ig -Ig AIg M Ig /

l i i


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)umoral in Action


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Antibodies


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"ole o memory cells

• 0emory ells possess t"e speifreognition apparatus t"at allo7s $ora more intense and rapid immune

response


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A?uired )mmunity

• Ati6e: diret e-posure to t"e antigent"at stimulates an immune response

• Passi6e: trans$er o$ anti!odies $romone indi6idual to anot"er – Passi6e immunity lasts only as long as

t"e anti!ody is present in serum.

– %emporary sine anti!odies "a6e a s"ortli$espan


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Active Immunity

3# %atural Active Immunity: 7"en t"eperson is e-posed to t"e antigen inen6ironment' !eomes si@ and t"en

reo6ers. )mmunologi memoryde6elops.

2# Arti,cial Active Immunity

.accination6Immunisation': t"eadministration o$ t"e 5ea>ened orm o$ t"e antigen into t"e !ody to induean immune response.


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Passive Immunity

3# %aturally passive immunity: t"etrans$er o$ anti!odies $rom mot"erto $oetus ;)g/< 8 mot"er to in$ant 6ia

!reast mil@ ;)gA<

2# Arti,cial passive immunity: t"e

trans$er o$ serum anti!odies $rom analready immune donor to a person.;normally lasts $or 3 7ee@s<


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Applications oAntibodies

• Antibodies are proteins produed !y t"e !lymphocytes o$ t"e immune system inresponse to $oreign proteins'

alled antigens#

• Ea" B ell in an organism synt"esi9es onlyone @ind o$ anti!ody speif $or one type

o$ antigen• %"ere$ore anti!odies an !e used to

identi$y t"e presene o$ speif antigens8or

su!stanes


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Monoclonal AntibodiesMA!S'

• %o use anti!odies as a tests $ordeteting antigens' anti!odies areneeded in large ?uantities.

• =o7e6er to !e use$ul as a tool'su!stantial amounts o$ a single

anti!ody ;and t"at anti!ody alone


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Monoclonal AntibodiesMA!S'

• 0onolonal anti!odiesare ultured anti!odiesprodued $rom a singletype o$ hybridoma Bcells.

• Hybridoma is a $usion o$a single type o$ B&ell7it" an immortal anerous B&ell

myeloma).• =y!ridoma B ells allo7

$or t"e unlimitedprodution o$ a single

anti!ody


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MA!S Production1. )ntrodution o$ antigen

into mouse in order toati6ate B&ells speif$or t"at antigen

2. )solate t"e ati6ated B

ells3. >use ati6ated B&ells

7it" myeloma B ells toma@e "y!ridoma

+. *reen "y!ridoma $or t"e

ones speif to t"eantigen.

,. Culture t"at single line o$"y!ridoma and isolatemonolonal anti!ody


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Appliation o$ 0AB*

0onolonal anti!odies an detet8mar@speial proteins o$ interests

1. Diagnosti pregnany %est to detet

"g "ormone in urine.

2. Diagnosti test $or A)D*& E)*A test

3. 0onolonal anti!odies an !e used to

lassi$y strains o$ a single pat"ogen.Eg !eisseria gonorrhea "as o6er (5strains


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0AB Pregany %est


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0ABt"erapy and CanerCaner ells are mutated sel$&ells t"at di6ideunontrolla!ly and in6ade ot"er tissue. Beause t"eyare still sel$&ells' it is diHult $or immune system totarget t"em.

• (ancer therapy: engineered monolonal anti!odies

!ind proteins t"at are only e-pressed !y aner ells.0ABs an 7or@ against aner in t"e $ollo7ing 7ays

1. %ag aner ells $or destrution !y t"e immunesystem

2. Deli6er anti&aner drugs speifally to aner ells3. Blo@ signals t"at allo7 aner ells to di6ide

+. Blo@ signals produed !y aner ells t"at suppressimmune system


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MA! therapy

Adaptive Immunology

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