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Nonspecifc Body Deensesand Immunity
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Deense Systems1.Innate
(nonspecifc)
deenses– External body
membranes
– Inammation
• Antimicrobialproteins,pa!ocytes andoter cells
2.Adaptive(specifc)deenses
– " cells and B cells
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Innate Deense System
• Surace Barriers
– #irst line o deense$ mecanical and cemicalprotection
%& S'in
(& )ucosal )embranes
• Internal Nonspecifc Deenses
– Second line o deenses
%& *a!ocytes
(& Natural +iller cells N+ lympocytes-
.& Inammation
/& Antimicrobial proteins
0& #e1er
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S'in and )ucosal )embranes
Mechanical Protection• Epidermis
– nose airs, nails
• )ucous membranes 2 line certain or!an systems– mucus pre1ents dryin!, traps orei!n tin!s
– respiratory tract cilia s3eep mucus out
• 4acrimal apparatus 22 tear !lands and ducts– 3as te eye to dilute microbial !ro3t
• Sali1a 2 dilute microbes on te oral ca1ity
• 5rine 2 o3 dilutes, and acid p6 elps 'ill,microor!anisms
• Deecation and 1omitin! 2 expel toxins andmicrobes
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S'in and )ucosal )embranes
he!ical Protection$ reduce bacterial !ro3t
•S'in– sebum unsaturated #A7s- orms oily layer
– perspiration as atty acids, salts Na8l-, and mildly acid p6
•4yso9yme
– in perspiration, tears, sali1a, nasal secretions, oter tissueuids
– en9yme brea's do3n bacterial cell 3alls
•6yaluronic acid– !el2li'e matrix in most connecti1e tissues
– slo3s te spread o many inectious a!ents
•:astric ;uice 2 stomac nearly sterile due to acid p6,
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Innate Deense$ *a!ocytes
• )acropa!es deri1ed rom monocytes-
are te cie tissue pa!ocytic cells– #ree macropa!es 3ander trou! tissues in
searc o microbes and cellular debris
– #ixed macropa!es$ +up>er cells li1er-,micro!lia brain-, dust cells lun!s-
• Neutropils become pa!ocytic 3en
encounterin! inectious material• Eosinopils are 3ea'ly pa!ocytic, deploy
destructi1e !ranules a!ainst parasitic
3orms
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)ecanism o *a!ocytosis• 8emotaxis
• Aderence – reco!nitiono externalcarboydrates andproteins
– Aided by opsonins• In!estion
• +illin! and di!estion
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8ells
– Distinct !roup o lar!e !ranular lympocytes
N+ lympocytes ? Null +iller lympocytes-
– Nonspecifc 'illers respond to te lac' osel2anti!ens and to te presence o certain
surace oli!osaccarides– +ill 1irus2inected body cells and some
tumor cells by releasin! 1arious deensi1emolecules – not by pa!ocytosis
– Act beore te anti!en2specifc immunesystem is acti1ated
– Secrete potent cemical si!nals tat
enance te inammatory response
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Innate Deense$ Inammation
1. In"a!!ation
• Si!ns$%& @edness
(& 6eat
.& S3ellin!
/& *ain0& 4oss o #unction
• #unction$%& *re1ent spread o
dama!e(& Dispose o
pato!ens anddebris
.& Set sta!e or tissuerepair
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Inammation$ Sta!e %
• Edema – increased plasma fltrate seepsinto tissue spaces brin!in! some immuneproteins
– 6elps to dilute armul substances
– Increases supply o oxy!en and nutrientsneeded or metabolism, inammation andrepair
– Allo3s entry o clottin! proteins, 3ic
reduces te spread o mibrobes
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Inammation
Sta#e 2. Pha#oc$te
!o%li&ation%&4eu'ocytosis2inducin!
actors$ increaseneutropil production
(&)ar!inationpa1ementin!-
.&Diapedesis amoeboidmo1ement-
/&8emotaxis o B8s• neutropils – rapid arri1al
• monocytes – slo3erarri1al
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Inammation
Sta#e '. issue
repair– "issue re!ro3t and
repair o dama!e orscar ormation
– *us• dead pa!ocytes and
oter B8s,dama!ed tissue, andperaps microbes
• i too numerous ore>ecti1e remo1al bypa!ocytes, anabscess may de1elop
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E>ects o Inammation
• Increased blood
o3 results inincreased localtemperature andlocal cellularmetabolism
• Increasedcapillarypermeability andpa!ocyticmi!ration to tein;ured tissue
I D A i i bi l
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Innate Deense$ Antimicrobial*roteins
%& Attac' microor!anisms directly
(& Interere 3it microbial reproduction
• "e most important are$
%& Intererons
(& "e 8omplement System.& "ranserrins 3ic bind #e(B in plasma,
inibitin! bacterial !ro3t
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I#Ns-
• *roduced by most tissue cells3en inected by a 1irus
• Di>uses to uninected cellsand binds to suracereceptors
– stimulates macropa!es andnatural 'iller lympocytes
– stimulates production oantiviral proteins 3ic bloc'1iral replication
– inibits !ro3t o 1irallyinected cells
– suppresses !ro3t o tumorcells
• Alpha IFN is used a!ainst$– epatitis 8 1irus
– erpes 1irus !enital 3arts-
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"e 8omplement System
• (C plasma and cell membrane proteins tatexist as inacti1e precursors
• en acti1ated, te complement systemunctions to complement or enance
certain immune, inammatory, and aller!icresponses
• +ills bacteria and certain oter microbial celltypes our cells normally are protected romcomplement attac'-
• Stimulates cemotaxis in leuc'ocytes
• Enances te e>ecti1eness o bot
nonspecifc and specifc deenses
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lassical Patha$ is tri!!ered by te
specifc immune system– @eFuires bindin! o antibodies to anti!ens oin1adin! or!anisms
– 8omplement 8% ten binds to te anti!en2
antibody complexes complement fxation-
Alternative Patha$ is tri!!ered by non2
specifc interaction amon! actors B, D,and *, and microbial cell 3allpolysaccarides complement fxation-
Bot pat3ays in1ol1e an en9yme cascade
8omplement *at3ays
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8omplement*at3ays
• Bot pat3ayscon1er!e on 8., 3icclea1es into 8.a and8.b
• 8.b initiates ormationo a membrane attac'complex )A8-
• )A8 causes cell lysis bycreatin! many undredso microscopic oles inte cell7s plasmalemma
• 8.b is also an opsonin
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Innate Deense$ #e1er
• P$ro#ens reset te temperature set2point in
te ypotalamus
• Inibits some microbes rom !ro3in!
• Increases body7s metabolic rate, 3ic speeds
up immune deenses and tissue repair
• Increases e>ects o antimicrobial substancesproduced by te immune system
• Stimulates li1er and spleen to seFuester ironand 9inc needed by microor!anisms-
• High fevers are dangerous
i
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Innate Deense System$ @e1ie3
• Surace Barriers
%& S'in
(& )ucosal membranes
• Internal Nonspecifc Deenses%& *a!ocytes
(& Natural +iller cells N+ lympocytes-
.& Inammation/& Antimicrobial proteins
0& #e1er
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Adapti1e Deense
• "e adapti1e immune system$
– Acts to immobili9e, neutrali9e, or destroyorei!n substances and cells
– Amplifes te inammatory response andacti1ates complement
– Is anti!en2specifcG, systemic, and as memory•G@eco!ni9es specifc orei!n molecules
– 6as t3o interdependent arms
•6umoral, or antibody2mediated immunity A)I-
•8ellular, or cell2mediated immunity 8)I-
Ad i D
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Adapti1e Deense
• Defnitions$
– Immunity$ te ability o te body to deenditsel a!ainst specifc orei!n in1aders
molecules or cells-
– Immuno!enicity$ te ability to stimulateprolieration o specifc lympocytes and
specifc antibody production
– @eacti1ity$ te ability o acti1atedlympocytes and teir products, antibodies,
etc&, to interact 3it specifc anti!ens
Ad ti D
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Adapti1e Deense
• Defnitions$
– Specifcity$ te anti!en tri!!ers ocusedimmune deenses rom particularlympocytes linea!es- tat respond only tote anti!ens o tis orei!n substanceHcell
– )emory$ te immune system produces cloneso specifc memory lympocytes " B- 3ic
react rapidly 3en te particular orei!nsubstanceHcell is encountered a!ain
– Specicity and memory di>erentiate tis
system rom te nonspecifc innate- deenses
Ad ti D
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Adapti1e Deense
•Anti#en – any substance3ic pro1o'es specifcimmune responses
• Anti#enicdeter!inants– *arts o anti!ens tat
tri!!er te specifc immune
response– An anti!en may be an
entire microor!anism oronly small structures orsubre!ions o lar!emolecules
)ost anti!ens arecomplex and express
multiple types oanti!enic
determinants&
I l i l )
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Immunolo!ical )emory• Immuni9ation is
possible becausememory B cellsand memory "cells persist ater
te initial A!exposure
• 3it any subseFuent exposure, te immune
system responds more Fuic'ly, orceully• secondary response 2 antibodies produced
durin! subseFuent exposures are produced in!reater Fuantities and a1e a !reater attractionor anti!en
A ib di
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• Are uniFue soluble proteins secreted by
acti1ated B cells and plasma cells inresponse to an anti!en
• Are capable o bindin! specifcally 3ittat anti!en
• 8onstitute muc o te !amma !lobulinraction o plasma proteins
• Also called i!!uno#lo%ulins
Antibodies
B i A ib d S
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Basic Antibody Structure
• #our polypeptide cains
lin'ed to!eter 3itdisulfde bonds
• "e our cains boundto!eter orm an
anti%od$ !ono!er• Eac cain as a 1ariable
=- re!ion at one end anda constant 8- re!ion atte oter
• Variable regionsVariable regions o teea1y and li!t cainscombine to orm teanti#en*%indin# site
A#
A tib d St t
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• Antibodies respondin! to di>erent anti!ens
a1e di>erent = re!ions but te 8 re!ion iste same or all antibodies in a !i1enantibody class
• 8 re!ions orm te stem o te J2sapedantibody monomer and determine$
– te class o te antibody– te cells and cemicals to 3ic te antibody
can bind
– o3 an antibody class unctions in eliminatin!
anti!ens
Antibody Structure
8l A tib di
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• I#D$ monomer attaced to te surace o B cells,
important in B cell acti1ation• I#M$ pentamer released by plasma cells durin!
te primary immune response
• I#+$ monomer tat is te most abundant anddi1erse antibody in primary and secondaryresponsesK crosses te placenta and conerspassi1e immunity
• I#A$ dimer tat elps pre1ent attacment opato!ens to mucosal suraces
• I#,$ monomer tat binds to mast cells andbasopils, causin! istamine release 3enacti1ated
8lasses o Antibodies
A tib d # ti
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• All antibodies orm an anti!en2antibody immune-
complex
• Antibodies do not directly destroy anti!en, tou!tey may immobili9e or inacti1ate A!
• Antibodies act as opsonins and ta! A! or immuneattac' and destruction
• Deensi1e mecanisms tri!!ered by antibodiesinclude neutralization, agglutination, precipitation,opsonization, and complement xation
Antibody #unctions
A tib d ) i
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1. Neutrali&ation- Antibodies bind to and bloc'
specifc sites on 1iruses or exotoxins, tuspre1entin! tese anti!ens rom bindin! toreceptors on tissue cells
Antibodies bind to te same determinant on moretan one anti!en ormin! anti!en2antibodycomplexes tat are cross2lin'ed into lar!elattices
2. A##lutination- 8ellular anti!ens are cross2lin'ed, causin! cell clumpin!
'. Precipitation- Soluble molecules are cross2lin'ed into lar!e insoluble complexes
Antibody )ecanisms oAction
A tib d ) i A ti
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. /psoni&ation- Bound Abs acilitate
pa!ocyte aderence
0. o!ple!ent iation- I!) and I!:
antibodies bound to cellular A!s bindcomplement 1ia te 8lassical *at3ay• "e complement cascade causes
cemotaxis, opsoni9ation, pa!ocytosis and
cell lysis• 8omplement acti1ation enances te
inammatory response
Antibody )ecanisms o Action
Summary o Antibody Actions
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Summary o Antibody Actions
Figure 21.13
S
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Summaryo te
Immune@esponse
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Immunity
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"e End