CnA1Lk 21 - IMMUNL SS1LM 1

Chapter 21 - Immune System: Innate & Adapt|ve 8ody Defenses

Immun|ty: 1wo Intr|ns|c Defense Systems
lnnaLe (nonspeclflc) sysLem responds qulckly and conslsLs of:
llrsL llne of defense - lnLacL skln and mucosae prevenL enLry of mlcroorganlsms
Second llne of defense - anLlmlcroblal proLelns, phagocyLes, and oLher cells
lnhlblL lnvaders spread LhroughouL Lhe body
lnflammaLlon ls lLs hallmark and mosL lmporLanL mechanlsm
AdapLlve (speclflc) defense sysLem
1hlrd llne of defense - mounLs aLLack agalnsL parLlcular forelgn subsLances
1akes longer Lo reacL Lhan Lhe lnnaLe sysLem
Works ln con[uncLlon wlLh Lhe lnnaLe sysLem
Innate Defenses
Surface 8arr|ers: Sk|n and Mucosae
Skln, mucous membranes, and Lhelr secreLlons make up Lhe flrsL llne of defense
keraLln ln Lhe skln:
resenLs a formldable physlcal barrler Lo mosL mlcroorganlsms
ls reslsLanL Lo weak aclds and bases, bacLerlal enzymes, and Loxlns
Mucosae provlde slmllar mechanlcal barrlers
Lp|the||a| Chem|ca| 8arr|ers
LplLhellal membranes produce proLecLlve chemlcals LhaL desLroy mlcroorganlsms
Skln acldlLy (pP of 3 Lo 3) lnhlblLs bacLerlal growLh
Sebum conLalns chemlcals Loxlc Lo bacLerla
SLomach mucosae secreLe concenLraLed PCl and proLeln-dlgesLlng enzymes
Sallva and lacrlmal fluld conLaln lysozyme
Mucus Lraps mlcroorganlsms LhaL enLer Lhe dlgesLlve and resplraLory sysLems
kesp|ratory 1ract Mucosae
Mucus-coaLed halrs ln Lhe nose Lrap lnhaled parLlcles
Mucosa of Lhe upper resplraLory LracL ls clllaLed
Cllla sweep dusL- and bacLerla-laden mucus away from lower resplraLory passages
Interna| Defenses: Ce||s and Chem|ca|s
1he body uses nonspeclflc cellular and chemlcal devlces Lo proLecL lLself
hagocyLes and naLural klller (nk) cells
AnLlmlcroblal proLelns ln blood and Llssue fluld
lnflammaLory response enllsLs macrophages, masL cells, W8Cs, and chemlcals
Parmful subsLances are ldenLlfled by surface carbohydraLes unlque Lo lnfecLlous organlsms
hagocytes
Macrophages are Lhe chlef phagocyLlc cells
lree macrophages wander LhroughouL a reglon, ln search of cellular debrls
kupffer cells (llver) and mlcroglla (braln) are flxed macrophages
neuLrophlls become phagocyLlc when encounLerlng lnfecLlous maLerlal
Loslnophlls are weakly phagocyLlc agalnsL paraslLlc worms
MasL cells blnd and lngesL a wlde range of bacLerla


2 CnA1Lk 21 - IMMUNL SS1LM

Mechan|sm of hagocytos|s
Mlcrobes adhere Lo Lhe phagocyLe
seudopods engulf Lhe parLlcle (anLlgen) lnLo a phagosome
hagosomes fuse wlLh a lysosome Lo form a phagolysosome
Mlcrobes ln Lhe phagolysosome are enzymaLlcally dlgesLed
lndlgesLlble and resldual maLerlal ls removed by exocyLosls
Natura| k|||er (Nk) Ce||s
Cells LhaL can lyse and klll cancer cells and vlrus-lnfecLed cells
naLural klller cells:
Are a small, dlsLlncL group of large granular lymphocyLes
8eacL nonspeclflcally and ellmlnaLe cancerous and vlrus-lnfecLed cells
klll Lhelr LargeL cells by releaslng cyLolyLlc chemlcals
SecreLe poLenL chemlcals LhaL enhance Lhe lnflammaLory response
Inf|ammat|on: 1|ssue kesponse to In[ury
1he lnflammaLory response ls Lrlggered whenever body Llssues are ln[ured
revenLs Lhe spread of damaglng agenLs Lo nearby Llssues
ulsposes of cell debrls and paLhogens
SeLs Lhe sLage for repalr processes
1he four cardlnal slgns of acuLe lnflammaLlon are redness, heaL, swelllng, and paln
Inf|ammatory kesponse
8eglns wlLh a flood of lnflammaLory chemlcals released lnLo Lhe exLracellular fluld
lnflammaLory medlaLors:
lnclude klnlns, prosLaglandlns (Cs), complemenL, and cyLoklnes
Are released by ln[ured Llssue, phagocyLes, lymphocyLes, and masL cells
Cause local small blood vessels Lo dllaLe, resulLlng ln hyperemla
Inf|ammatory kesponse: Vascu|ar ermeab|||ty
Chemlcals llberaLed by Lhe lnflammaLory response
lncrease Lhe permeablllLy of local caplllarles
LxudaLe (fluld conLalnlng proLelns, cloLLlng facLors, and anLlbodles):
Seeps lnLo Llssue spaces causlng local edema (swelllng)
1he edema conLrlbuLes Lo Lhe sensaLlon of paln
Inf|ammatory kesponse: Ldema
1he surge of proLeln-rlch flulds lnLo Llssue spaces (edema):
Pelps Lo dlluLe harmful subsLances
8rlngs ln large quanLlLles of oxygen and nuLrlenLs needed for repalr
Allows enLry of cloLLlng proLelns, whlch prevenL Lhe spread of bacLerla
Inf|ammatory kesponse: hagocyt|c Mob|||zat|on
Cccurs ln four maln phases:
LeukocyLosls - neuLrophlls are released from Lhe bone marrow ln response Lo leukocyLosls-
lnduclng facLors released by ln[ured cells
MarglnaLlon - neuLrophlls cllng Lo Lhe walls of caplllarles ln Lhe ln[ured area
ulapedesls - neuLrophlls squeeze Lhrough caplllary walls and begln phagocyLosls
ChemoLaxls - lnflammaLory chemlcals aLLracL neuLrophlls Lo Lhe ln[ury slLe
CnA1Lk 21 - IMMUNL SS1LM 3

Ant|m|crob|a| rote|ns
Lnhance Lhe lnnaLe defenses by:
ALLacklng mlcroorganlsms dlrecLly
Plnderlng mlcroorganlsms' ablllLy Lo reproduce
1he mosL lmporLanL anLlmlcroblal proLelns are:
lnLerferon
ComplemenL proLelns
Interferon (IIN)
Cenes LhaL synLheslze lln are acLlvaLed when a hosL cell ls lnvaded by a vlrus
lnLerferon molecules leave Lhe lnfecLed cell and enLer nelghborlng cells
lnLerferon sLlmulaLes Lhe nelghborlng cells Lo acLlvaLe genes for k8 (an anLlvlral proLeln)
k8 nonspeclflcally blocks vlral reproducLlon ln Lhe nelghborlng cell
Interferon Iam||y
lnLerferons are a famlly of relaLed proLelns each wlLh sllghLly dlfferenL physlologlcal effecLs
LymphocyLes secreLe gamma () lnLerferon, buL mosL oLher W8Cs secreLe alpha () lnLerferon
llbroblasLs secreLe beLa () lnLerferon
lnLerferons also acLlvaLe macrophages and moblllze nks
luA-approve ls used:
As an anLlvlral drug agalnsL hepaLlLls C vlrus
1o LreaL genlLal warLs caused by a herpes vlrus
Comp|ement
20 or so proLelns LhaL clrculaLe ln Lhe blood ln an lnacLlve form
roLelns lnclude C1 Lhrough C9, facLors 8, u, and , and regulaLory proLelns
rovldes a ma[or mechanlsm for desLroylng forelgn subsLances ln Lhe body
Ampllfles all aspecLs of Lhe lnflammaLory response
kllls bacLerla and cerLaln oLher cell Lypes (our cells are lmmune Lo complemenL)
Lnhances Lhe effecLlveness of boLh nonspeclflc and speclflc defenses
Comp|ement athways
ComplemenL can be acLlvaLed by Lwo paLhways: classlcal and alLernaLlve
Classlcal paLhway ls llnked Lo Lhe lmmune sysLem
uepends upon Lhe blndlng of anLlbodles Lo lnvadlng organlsms
SubsequenL blndlng of C1 Lo Lhe anLlgen-anLlbody complexes (complemenL flxaLlon)
AlLernaLlve paLhway ls Lrlggered by lnLeracLlon among facLors 8, u, and , and polysaccharlde
molecules presenL on mlcroorganlsms
Lach paLhway lnvolves a cascade ln whlch complemenL proLelns are acLlvaLed ln an orderly
sequence and where each sLep caLalyzes Lhe nexL
8oLh paLhways converge on C3, whlch cleaves lnLo C3a and C3b
C3b lnlLlaLes formaLlon of a membrane aLLack complex (MAC)
MAC causes cell lysls by lnLerferlng wlLh a cell's ablllLy Lo e[ecL Ca
2+

C3b also causes opsonlzaLlon, and C3a causes lnflammaLlon
Iever
Abnormally hlgh body LemperaLure ln response Lo lnvadlng mlcroorganlsms
1he body's LhermosLaL ls reseL upwards ln response Lo pyrogens, chemlcals secreLed by
leukocyLes and macrophages exposed Lo bacLerla and oLher forelgn subsLances
Plgh fevers are dangerous as Lhey can denaLure enzymes
ModeraLe fever can be beneflclal, as lL causes:
1he llver and spleen Lo sequesLer lron and zlnc (needed by mlcroorganlsms)
An lncrease ln Lhe meLabollc raLe, whlch speeds up Llssue repalr
4 CnA1Lk 21 - IMMUNL SS1LM

Adapt|ve Defenses
1he adapLlve lmmune sysLem ls a funcLlonal sysLem LhaL:
8ecognlzes speclflc forelgn subsLances
AcLs Lo lmmoblllze, neuLrallze, or desLroy Lhem
Ampllfles lnflammaLory response and acLlvaLes complemenL
1he adapLlve lmmune sysLem ls anLlgen-speclflc, sysLemlc, and has memory
lL has Lwo separaLe buL overlapplng arms
Pumoral, or anLlbody-medlaLed lmmunlLy
Cellular, or cell-medlaLed lmmunlLy
Ant|gens (Ags)
SubsLances LhaL can moblllze Lhe lmmune sysLem and provoke an lmmune response
1he ulLlmaLe LargeLs of all lmmune responses are mosLly large, complex molecules noL normally
found ln Lhe body (nonself)
Comp|ete Ant|gens
lmporLanL funcLlonal properLles:
lmmunogenlclLy - Lhe ablllLy Lo sLlmulaLe prollferaLlon of speclflc lymphocyLes and anLlbody
producLlon
8eacLlvlLy - Lhe ablllLy Lo reacL wlLh Lhe producLs of Lhe acLlvaLed lymphocyLes and Lhe
anLlbodles released ln response Lo Lhem
CompleLe anLlgens lnclude forelgn proLeln, nuclelc acld, some llplds, and large polysaccharldes
naptens (Incomp|ete Ant|gens)
Small molecules, such as pepLldes, nucleoLldes, and many hormones, LhaL are noL lmmunogenlc
buL are reacLlve when aLLached Lo proLeln carrlers
lf Lhey llnk up wlLh Lhe body's proLelns, Lhe adapLlve lmmune sysLem may recognlze Lhem as
forelgn and mounL a harmful aLLack (allergy)
PapLens are found ln polson lvy, dander, some deLergenLs, and cosmeLlcs
Ant|gen|c Determ|nants
Cnly cerLaln parLs of an enLlre anLlgen are lmmunogenlc
AnLlbodles and acLlvaLed lymphocyLes blnd Lo Lhese anLlgenlc deLermlnanLs
MosL naLurally occurrlng anLlgens have numerous anLlgenlc deLermlnanLs LhaL:
Moblllze several dlfferenL lymphocyLe populaLlons
lorm dlfferenL klnds of anLlbodles agalnsL lL
Large, chemlcally-slmple molecules (e.g., plasLlcs) have llLLle or no lmmunogenlclLy
Se|f-Ant|gens: MnC rote|ns
Cur cells are doLLed wlLh proLeln molecules (self-anLlgens) LhaL are anLlgenlc Lo us buL are
sLrongly anLlgenlc Lo oLhers
Cne Lype of Lhese, MPC proLelns, mark a cell as self
1he Lwo classes of MPC proLelns are:
Class l MPC proLelns - found on vlrLually all body cells
Class ll MPC proLelns - found on cerLaln lmmune response
MnC rote|ns
Are coded for by genes of Lhe ma[or hlsLocompaLlblllLy complex (MPC) and are unlque Lo an
lndlvldual
Lach MPC molecule has a deep groove LhaL dlsplays a pepLlde, whlch ls a normal cellular producL
of proLeln recycllng
ln lnfecLed cells, MPC proLelns blnd Lo fragmenLs of forelgn anLlgens, whlch play a cruclal role ln
moblllzlng Lhe lmmune sysLem

CnA1Lk 21 - IMMUNL SS1LM S

Ce||s of the Adapt|ve Immune System
1wo Lypes of lymphocyLes
8 lymphocyLes - oversee humoral lmmunlLy
1 lymphocyLes - non-anLlbody-produclng cells LhaL consLlLuLe Lhe cell-medlaLed arm of lmmunlLy
AnLlgen-presenLlng cells (ACs):
uo noL respond Lo speclflc anLlgens
lay essenLlal auxlllary roles ln lmmunlLy
Lymphocytes
lmmaLure lymphocyLes released from bone marrow are essenLlally ldenLlcal
WheLher a lymphocyLe maLures lnLo a 8 cell or a 1 cell depends on where ln Lhe body lL becomes
lmmunocompeLenL
8 cells maLure ln Lhe bone marrow
1 cells maLure ln Lhe Lhymus
1 Ce||s and 8 Ce||s
1 cells maLure ln Lhe Lhymus under negaLlve and poslLlve selecLlon pressures
negaLlve selecLlon - ellmlnaLes 1 cells LhaL are sLrongly anLl-self
oslLlve selecLlon - selecLs 1 cells wlLh a weak response Lo self-anLlgens, whlch Lhus become
boLh lmmunocompeLenL and self-LoleranL
8 cells become lmmunocompeLenL and self-LoleranL ln bone marrow
Immunocompetent 8 or 1 ce||s
ulsplay a unlque Lype of recepLor LhaL responds Lo a dlsLlncL anLlgen
8ecome lmmunocompeLenL before Lhey encounLer anLlgens Lhey may laLer aLLack
Are exporLed Lo secondary lymphold Llssue where encounLers wlLh anLlgens occur
MaLure lnLo fully funcLlonal anLlgen-acLlvaLed cells upon blndlng wlLh Lhelr recognlzed anLlgen
lL ls genes, noL anLlgen, LhaL deLermlne whlch forelgn subsLance our lmmune sysLem wlll
recognlze and reslsL
Ant|gen-resent|ng Ce||s (ACs)
Ma[or rolls ln lmmunlLy are:
1o engulf forelgn parLlcles
1o presenL fragmenL of anLlgens on Lhelr own surfaces, Lo be recognlzed by 1 cells
Ma[or ACs are dendrlLlc cells (uCs), macrophages, and acLlvaLed 8 cells
1he ma[or lnlLlaLors of adapLlve lmmunlLy are uCs, whlch acLlvely mlgraLe Lo Lhe lymph nodes
and secondary lymphold organs and presenL anLlgens Lo 1 and 8 cells
Macrophages and Dendr|t|c Ce||s
SecreLe soluble proLelns LhaL acLlve 1 cells
AcLlvaLed 1 cells ln Lurn release chemlcals LhaL:
8ev up Lhe maLuraLlon and moblllzaLlon of uCs
rod macrophages Lo become acLlvaLed macrophages, whlch are lnsaLlable phagocyLes and
release bacLerlcldal chemlcals
Adapt|ve Immun|ty: Summary
1wo-flsLed defenslve sysLem LhaL uses lymphocyLes, ACs, and speclflc molecules Lo ldenLlfy and
desLroy nonself parLlcles
lLs response depends upon Lhe ablllLy of lLs cells Lo:
8ecognlze forelgn subsLances (anLlgens) by blndlng Lo Lhem
CommunlcaLe wlLh one anoLher so LhaL Lhe whole sysLem mounLs a response speclflc Lo
Lhose anLlgens

6 CnA1Lk 21 - IMMUNL SS1LM

numora| Immun|ty kesponse
AnLlgen challenge - flrsL encounLer beLween and anLlgen and a nalve lmmunocompeLenL cell
1akes place ln Lhe spleen or oLher lymphold organ
lf Lhe lymphocyLe ls a 8 cell:
1he challenglng anLlgen provokes a humoral lmmune response
AnLlbodles are produced agalnsL Lhe challenger
C|ona| Se|ect|on
SLlmulaLed 8 cell growLh forms clones bearlng Lhe same anLlgen-speclflc recepLors
A nalve, lmmunocompeLenL 8 cell ls acLlvaLed when anLlgens blnd Lo lLs surface recepLors and
cross-llnk ad[acenL recepLors
AnLlgen blndlng ls followed by recepLor-medlaLed endocyLosls of Lhe cross-llnked anLlgen-
recepLor complexes
1hese acLlvaLlng evenLs, plus 1 cell lnLeracLlons, Lrlgger clonal selecLlon
Iate of the C|ones
MosL clone cells become anLlbody-secreLlng plasma cells
lasma cells secreLe speclflc anLlbody aL Lhe raLe of 2000 molecules per second
SecreLed anLlbodles:
8lnd Lo free anLlgens
Mark Lhe anLlgens for desLrucLlon by speclflc or nonspeclflc mechanlsms
Clones LhaL do noL become plasma cells become memory cells LhaL can mounL an lmmedlaLe
response Lo subsequenL exposures Lo an anLlgen
Immuno|og|ca| Memory
rlmary lmmune response - cellular dlfferenLlaLlon and prollferaLlon, whlch occurs on Lhe flrsL
exposure Lo a speclflc anLlgen
Lag perlod: 3 Lo 6 days afLer anLlgen challenge
eak levels of plasma anLlbody are achleved ln 10 days
AnLlbody levels Lhen decllne
Secondary lmmune response - re-exposure Lo Lhe same anLlgen
SenslLlzed memory cells respond wlLhln hours
AnLlbody levels peak ln 2 Lo 3 days aL much hlgher levels Lhan ln Lhe prlmary response
AnLlbodles blnd wlLh greaLer afflnlLy, and Lhelr levels ln Lhe blood can remaln hlgh for weeks
Lo monLhs
Act|ve numora| Immun|ty
8 cells encounLer anLlgens and produce anLlbodles agalnsL Lhem
naLurally acqulred - response Lo a bacLerlal or vlral lnfecLlon
ArLlflclally acqulred - response Lo a vacclne of dead or aLLenuaLed paLhogens
vacclnes - spare us Lhe sympLoms of dlsease, and Lhelr weakened anLlgens provlde anLlgenlc
deLermlnanLs LhaL are lmmunogenlc and reacLlve
ass|ve numora| Immun|ty
ulffers from acLlve lmmunlLy ln Lhe anLlbody source and Lhe degree of proLecLlon
8 cells are noL challenged by anLlgen
lmmunologlcal memory does noL occur
roLecLlon ends when anLlgens naLurally degrade ln Lhe body
naLurally acqulred - from Lhe moLher Lo her feLus vla Lhe placenLa
ArLlflclally acqulred - from Lhe ln[ecLlon of serum, such as gamma globulln

CnA1Lk 21 - IMMUNL SS1LM 7

Ant|bod|es (Ab)
Also called lmmunoglobullns (lgs)
ConsLlLuLe Lhe gamma globulln porLlon of blood proLelns
Are soluble proLelns secreLed by acLlvaLed 8 cells and plasma cells ln response Lo an anLlgen
Are capable of blndlng speclflcally wlLh LhaL anLlgen
1here are flve classes of anLlbodles: lgu, lgM, lgC, lgA, and lgL
C|asses of Ant|bod|es
lgu - monomer aLLached Lo Lhe surface of 8 cells, lmporLanL ln 8 cell acLlvaLlon
lgM - penLamer released by plasma cells durlng Lhe prlmary lmmune response
lgC - monomer LhaL ls Lhe mosL abundanL and dlverse anLlbody ln prlmary and secondary
response, crosses Lhe placenLa and confers passlve lmmunlLy
lgA - dlmer LhaL helps prevenL aLLachmenL of paLhogens Lo eplLhellal cell surfaces
lgL - monomer LhaL blnds Lo masL cells and basophlls, causlng hlsLamlne release when acLlvaLed
8as|c Ant|body Structure
ConslsL of four looplng polypepLlde chalns llnked LogeLher wlLh dlsulflde bonds
1wo ldenLlcal heavy (P) chalns and Lwo ldenLlcal llghL (L) chalns
1he four chalns bound LogeLher form an anLlbody monomer
Lach chaln has a varlable (v) reglon aL one end and a consLanL (C) reglon aL Lhe oLher
varlable reglons of Lhe heavy and llghL chalns comblne Lo form Lhe anLlgen-blndlng slLe
AnLlbodles respondlng Lo dlfferenL anLlgens have dlfferenL v reglons buL Lhe C reglon ls Lhe same
for all anLlbodles ln a glven class
C reglons form Lhe sLem of Lhe ?-shaped anLlbody and:
ueLermlne Lhe class of Lhe anLlbody
Serve common funcLlons ln all anLlbodles
ulcLaLe Lhe cells and chemlcals LhaL Lhe anLlbody can blnd Lo
ueLermlne how Lhe anLlbody class wlll funcLlon ln ellmlnaLlon of anLlgens
Mechan|sms of Ant|body D|vers|ty
lasma cells make over a bllllon dlfferenL Lypes of anLlbodles
Lach cell, however, only conLalns 100,000 genes LhaL code for Lhese polypepLldes
1o code for Lhls many anLlbodles, somaLlc recomblnaLlon Lakes place
Cene segmenLs are shuffled and comblned ln dlfferenL ways by each 8 cell as lL becomes
lmmunocompeLenL
lnformaLlon of Lhe newly assembled genes ls expressed as 8 cell recepLors and as anLlbodles
Ant|body D|vers|ty
8andom mlxlng of gene segmenLs makes unlque anLlbody genes LhaL:
Code for P and L chalns
AccounL for parL of Lhe varlablllLy ln anLlbodles
v gene segmenLs, called hypervarlable reglons, muLaLe and lncrease anLlbody varlaLlon
lasma cells can swlLch P chalns, maklng Lwo or more classes wlLh Lhe same v reglon
Ant|body 1argets
AnLlbodles Lhemselves do noL desLroy anLlgen, Lhey lnacLlvaLe and Lag lL for desLrucLlon
All anLlbodles form an anLlgen-anLlbody (lmmune) complex
uefenslve mechanlsms used by anLlbodles are neuLrallzaLlon, aggluLlnaLlon, preclplLaLlon, and
complemenL flxaLlon
8 CnA1Lk 21 - IMMUNL SS1LM

Comp|ement I|xat|on and Act|vat|on
ComplemenL flxaLlon ls Lhe maln mechanlsm used agalnsL cellular anLlgens
AnLlbodles bound Lo cells change shape and expose complemenL blndlng slLes
1hls Lrlggers complemenL flxaLlon and cell lysls
ComplemenL acLlvaLlon:
Lnhances Lhe lnflammaLory response
uses a poslLlve feedback cycle Lo promoLe phagocyLosls
LnllsLs more and more defenslve elemenLs
Cther Mechan|sms of Ant|body Act|on
neuLrallzaLlon - anLlbodles blnd Lo and block speclflc slLes on vlruses or exoLoxlns, Lhus
prevenLlng Lhese anLlgens from blndlng Lo recepLors on Llssue cells
AggluLlnaLlon - anLlbodles blnd Lhe same deLermlnanL on more Lhan one anLlgen
Makes anLlgen-anLlbody complexes LhaL are cross-llnked lnLo large laLLlces
Cell-bound anLlgens are cross-llnked, causlng clumplng (aggluLlnaLlon)
reclplLaLlon - soluble molecules are cross-llnked lnLo large lnsoluble complexes
Monoc|ona| Ant|bod|es
Commerclally prepared anLlbodles are used:
1o provlde passlve lmmunlLy
ln research, cllnlcal LesLlng, and LreaLmenL of cerLaln cancers
Monoclonal anLlbodles are pure anLlbody preparaLlons
Speclflc for a slngle anLlgenlc deLermlnanL
roduced from descendenLs of a slngle cell
Pybrldomas - cell hybrlds made from a fuslon of a Lumor cell and a 8 cell
Pave deslrable properLles of boLh parenL cells - lndeflnlLe prollferaLlon as well as Lhe ablllLy
Lo produce a slngle Lype of anLlbody
Ce||-Med|ated Immune kesponse
Slnce anLlbodles are useless agalnsL lnLracellular anLlgens, cell-medlaLed lmmunlLy ls needed
1wo ma[or populaLlons of 1 cells medlaLe cellular lmmunlLy
Cu4 cells (14cells) are prlmarlly helper 1 cells (1
P
)
Cu8 cells (18cells) are cyLoLoxlc 1 cells (1
C
) LhaL desLroy cells harborlng forelgn anLlgens
CLher Lypes of 1 cells are:
uelayed hypersenslLlvlLy 1 cells (1
uP
)
Suppressor 1 cells (1
S
)
Memory 1 cells
Importance of numora| and Ce||u|ar kesponses
Pumoral 8esponse
Soluble anLlbodles
1he slmplesL ammunlLlon of Lhe lmmune response
lnLeracL ln exLracellular envlronmenLs such as body secreLlons, Llssue fluld, blood, and
lymph
Cellular 8esponse
1 cells recognlze and respond only Lo processed fragmenLs of anLlgen dlsplayed Lhe surface
of body cells
1 cells are besL sulLed for cell-Lo-cell lnLeracLlons, and LargeL:
Cells lnfecLed wlLh vlruses, bacLerla, or lnLracellular paraslLes
Abnormal or cancerous cells
Cells of lnfused or LransplanLed forelgn Llssue
pp. )86)
CnA1Lk 21 - IMMUNL SS1LM 9

Ant|gen kecogn|t|on and MnC kestr|ct|on
lmmunocompeLenL 1 cells are acLlvaLed when Lhe v reglons of Lhelr surface recepLors blnd Lo a
recognlzed anLlgen
1 cells musL slmulLaneously recognlze:
nonself (Lhe anLlgen)
Self (a MPC proLeln of a body cell)
MnC rote|ns
8oLh Lypes of MPC proLelns are lmporLanL Lo 1 cell acLlvaLlon
Class l MPC proLelns
Always recognlzed by Cu8 1 cells
ulsplay pepLldes from endogenous anLlgens
C|ass I MnC rote|ns
Lndogenous anLlgens are:
uegraded by proLeases and enLer Lhe endoplasmlc reLlculum
1ransporLed vla 1A (transporLer assoclaLed wlLh anLlgen processlng)
Loaded onLo class l MPC molecules
ulsplayed on Lhe cell surface ln assoclaLlon wlLh a class l MPC molecule
C|ass II MnC rote|ns
Class ll MPC proLelns are found only on maLure 8 cells, some 1 cells, and anLlgen-presenLlng cells
A phagosome conLalnlng paLhogens (wlLh exogenous anLlgens) merges wlLh a lysosome
lnvarlanL proLeln prevenLs class ll MPC proLelns from blndlng Lo pepLldes ln Lhe endoplasmlc
reLlculum
Class ll MPC proLelns mlgraLe lnLo Lhe phagosomes where Lhe anLlgen ls degraded and Lhe
lnvarlanL chaln ls removed for pepLlde loadlng
Loaded Class ll MPC molecules Lhen mlgraLe Lo Lhe cell membrane and dlsplay anLlgenlc pepLlde
for recognlLlon by Cu4 cells
Ant|gen kecogn|t|on
rovldes Lhe key for Lhe lmmune sysLem Lo recognlze Lhe presence of lnLracellular
mlcroorganlsms
MPC proLelns are lgnored by 1 cells lf Lhey are complexed wlLh self proLeln fragmenLs
lf MPC proLelns are complexed wlLh endogenous or exogenous anLlgenlc pepLldes, Lhey:
lndlcaLe Lhe presence of lnLracellular lnfecLlous mlcroorganlsms
AcL as anLlgen holders
lorm Lhe self parL of Lhe self-anLlself complexes recognlzed by 1 cells
1 Ce|| Act|vat|on: Step Cne - Ant|gen 8|nd|ng
1 cell anLlgen recepLors (1C8s):
8lnd Lo an anLlgen-MPC proLeln complex
Pave varlable and consLanL reglons conslsLlng of Lwo chalns (alpha and beLa)
MPC resLrlcLlon - 1
P
and 1
C
blnd Lo dlfferenL classes of MPC proLelns
1
P
cells blnd Lo anLlgen llnked Lo class ll MPC proLelns
Moblle ACs (Langerhans' cells) qulckly alerL Lhe body Lo Lhe presence of anLlgen by mlgraLlng Lo
Lhe lymph nodes and presenLlng anLlgen
1
C
cells are acLlvaLed by anLlgen fragmenLs complexed wlLh class l MPC proLelns
ACs produce cosLlmulaLory molecules LhaL are requlred for 1
C
acLlvaLlon
1C8 LhaL acLs Lo recognlze Lhe self-anLlself complex ls llnked Lo mulLlple lnLracellular slgnallng
paLhways
CLher 1 cell surface proLelns are lnvolved ln anLlgen blndlng (e.g., Cu4 and Cu8 help malnLaln
coupllng durlng anLlgen recognlLlon)
10 CnA1Lk 21 - IMMUNL SS1LM

1 Ce|| Act|vat|on: Step 1wo - Cost|mu|at|on
8efore a 1 cell can undergo clonal expanslon, lL musL recognlze one or more cosLlmulaLory slgnals
1hls recognlLlon may requlre blndlng Lo oLher surface recepLors on an AC
Macrophages produce surface 87 proLelns when nonspeclflc defenses are moblllzed
87 blndlng wlLh Lhe Cu
28
recepLor on Lhe surface of 1 cells ls a cruclal cosLlmulaLory slgnal
CLher cosLlmulaLory slgnals lnclude cyLoklnes and lnLerleukln 1 and 2
uependlng upon recepLor Lype, cosLlmulaLors can cause 1 cells Lo compleLe Lhelr acLlvaLlon or
aborL acLlvaLlon
WlLhouL cosLlmulaLlon, 1 cells:
8ecome LoleranL Lo LhaL anLlgen
Are unable Lo dlvlde
uo noL secreLe cyLoklnes
1 cells LhaL are acLlvaLed:
Lnlarge, prollferaLe, and form clones
ulfferenLlaLe and perform funcLlons accordlng Lo Lhelr 1 cell class
rlmary 1 cell response peaks wlLhln a week afLer slgnal exposure
1 cells Lhen undergo apopLosls beLween days 7 and 30
LffecLor acLlvlLy wanes as Lhe amounL of anLlgen decllnes
1he dlsposal of acLlvaLed effecLor cells ls a proLecLlve mechanlsm for Lhe body
Memory 1 cells remaln and medlaLe secondary responses Lo Lhe same anLlgen
Cytok|nes
MedlaLors lnvolved ln cellular lmmunlLy, lncludlng hormonellke glycoproLelns released by
acLlvaLed 1 cells and macrophages
Some are cosLlmulaLors of 1 cells and 1 cell prollferaLlon
lnLerleukln 1 (lL-1) released by macrophages cosLlmulaLes bound 1 cells Lo:
8elease lnLerleukln 2 (lL-2)
SynLheslze more lL-2 recepLors
lL-2 ls a key growLh facLor, whlch seLs up a poslLlve feedback cycle LhaL encourages acLlvaLed 1
cells Lo dlvlde
lL ls used LherapeuLlcally Lo enhance Lhe body's defenses agalnsL cancer
CLher cyLoklnes ampllfy and regulaLe lmmune and nonspeclflc responses
Lxamples lnclude:
erforln and lymphoLoxln - cell Loxlns
Camma lnLerferon - enhances Lhe kllllng power of macrophages
lnflammaLory facLors
ne|per 1 Ce||s (1
n
)
8egulaLory cells LhaL play a cenLral role ln Lhe lmmune response
Cnce prlmed by AC presenLaLlon of anLlgen, Lhey:
Chemlcally or dlrecLly sLlmulaLe prollferaLlon of oLher 1 cells
SLlmulaLe 8 cells LhaL have already become bound Lo anLlgen
WlLhouL 1
P
, Lhere ls lmmune response
1
P
cells lnLeracL dlrecLly wlLh 8 cells LhaL have anLlgen fragmenLs on Lhelr surfaces bound Lo MPC
ll recepLors
1
P
cells sLlmulaLe 8 cells Lo dlvlde more rapldly and begln anLlbody formaLlon
8 cells may be acLlvaLed wlLhouL 1
P
cells by blndlng Lo 1 cell-lndependenL anLlgens
MosL anLlgens, however, requlre 1
P
cosLlmulaLlon Lo acLlvaLe 8 cells
CyLoklnes released by 1
P
ampllfy nonspeclflc defenses
CnA1Lk 21 - IMMUNL SS1LM 11

Cytotox|c 1 Ce||s (1
C
)
1
C
cells, or klller 1 cells, are Lhe only 1 cells LhaL can dlrecLly aLLack and klll oLher cells
1hey clrculaLe LhroughouL Lhe body ln search of body cells LhaL dlsplay Lhe anLlgen Lo whlch Lhey
have been senslLlzed
1helr LargeLs lnclude:
vlrus-lnfecLed cells
Cells wlLh lnLracellular bacLerla or paraslLes
Cancer cells
lorelgn cells from blood Lransfuslons or LransplanLs
8lnd Lo self-anLlself complexes on all body cells
lnfecLed or abnormal cells can be desLroyed as long as approprlaLe anLlgen and cosLlmulaLory
sLlmull (e.g., lL-2) are presenL
naLural klller cells acLlvaLe Lhelr kllllng machlnery when Lhey blnd Lo MlCA recepLor
MlCA recepLor - MPC-relaLed cell surface proLeln ln cancer cells, vlrus-lnfecLed cells, and cells of
LransplanLed organs
Mechan|sms of 1
C
Act|on
ln some cases, 1
C
cells:
8lnd Lo Lhe LargeL cell and release perforln lnLo lLs membrane
erforln causes cell lysls by creaLlng Lransmembrane pores
CLher 1
C
cells lnduce cell deaLh by:
SecreLlng lymphoLoxln, whlch fragmenLs Lhe LargeL cell's unA
8eleaslng Lumor necrosls facLor (1nl), whlch Lrlggers apopLosls
SecreLlng gamma lnLerferon, whlch sLlmulaLes phagocyLosls by macrophages
Cther 1 Ce||s
Suppressor 1 cells (1
S
) - regulaLory cells LhaL release cyLoklnes, whlch suppress Lhe acLlvlLy of
boLh 1 cells and 8 cells
uelayed-Lype hypersenslLlvlLy cells (1
uP
) - cells lnsLrumenLal ln promoLlng allerglc reacLlons
called JeloyeJ bypetseosltlvlty teoctloos
Camma delLa 1 cells - 10 of all 1 cells found ln Lhe lnLesLlnes LhaL are Lrlggered by blndlng Lo
MlCA recepLors
nomeostat|c Imba|ances of Immun|ty
Immunodef|c|enc|es
CongenlLal and acqulred condlLlons ln whlch Lhe funcLlon or producLlon of lmmune cells,
phagocyLes, or complemenL ls abnormal
SClu - severe comblned lmmunodeflclency (SClu) syndromes, geneLlc defecLs LhaL produce:
A marked deflclL ln 8 and 1 cells
AbnormallLles ln lnLerleukln recepLors
uefecLlve adenoslne deamlnase (AuA) enzymes
MeLabollLes leLhal Lo 1 cells accumulaLe
SClu ls faLal lf unLreaLed, LreaLmenL ls wlLh bone marrow LransplanLs
Acqu|red Immunodef|c|enc|es
Podgkln's dlsease - cancer of Lhe lymph nodes leads Lo lmmunodeflclency by depresslng lymph
node cells
Acqulred lmmune deflclency syndrome (AluS) - crlpples Lhe lmmune sysLem by lnLerferlng wlLh
Lhe acLlvlLy of helper 1 (Cu4) cells
CharacLerlzed by severe welghL loss, nlghL sweaLs, and swollen lymph nodes
CpporLunlsLlc lnfecLlons occur, lncludlng pneumocysLls pneumonla and kaposl's sarcoma

12 CnA1Lk 21 - IMMUNL SS1LM

AIDS
Caused by human lmmunodeflclency vlrus (Plv) LransmlLLed vla body flulds - blood, semen, and
vaglnal secreLlons
Plv enLers Lhe body vla:
8lood Lransfuslons
ConLamlnaLed needles
lnLlmaLe sexual conLacL, lncludlng oral sex
Plv:
uesLroys 1
P
cells
uepresses cell-medlaLed lmmunlLy
Plv mulLlplles ln lymph nodes LhroughouL Lhe asympLomaLlc perlod
SympLoms appear ln a few monLhs Lo 10 years
ALLachmenL
Plv's coaL proLeln (gp120) aLLaches Lo Lhe Cu4 recepLor
A nearby proLeln (gp41) fuses Lhe vlrus Lo Lhe LargeL cell
Plv enLers Lhe cell and uses reverse LranscrlpLase Lo produce unA from vlral 8nA
1hls unA (provlrus) dlrecLs Lhe hosL cell Lo make vlral 8nA (and proLelns), enabllng Lhe vlrus Lo
reproduce and lnfecL oLher cells
Plv reverse LranscrlpLase ls noL accuraLe and produces frequenL LranscrlpLlon errors
1hls hlgh muLaLlon raLe causes reslsLance Lo drugs
1reaLmenLs lnclude:
8everse LranscrlpLase lnhlblLors (AZ1)
roLease lnhlblLors (saqulnavlr and rlLonavlr)
new drugs LhaL are currenLly belng developed, whlch block Plv's enLry Lo helper 1 cells
Auto|mmune D|seases
Loss of Lhe lmmune sysLem's ablllLy Lo dlsLlngulsh self from nonself
1he body produces auLoanLlbodles and senslLlzed 1
C
cells LhaL desLroy lLs own Llssues
Lxamples lnclude mulLlple sclerosls, myasLhenla gravls, Craves' dlsease, 1ype l ([uvenlle) dlabeLes
melllLus, sysLemlc lupus eryLhemaLosus (SLL), glomerulonephrlLls, and rheumaLold arLhrlLls
Mechan|sms of Auto|mmune D|sease
lneffecLlve lymphocyLe programmlng - self-reacLlve 1 and 8 cells LhaL should have been
ellmlnaLed ln Lhe Lhymus and bone marrow escape lnLo Lhe clrculaLlon
new self-anLlgens appear, generaLed by:
Cene muLaLlons LhaL cause new proLelns Lo appear
Changes ln self-anLlgens by hapLen aLLachmenL or as a resulL of lnfecLlous damage
lorelgn anLlgens resemble self-anLlgens:
AnLlbodles made agalnsL forelgn anLlgens cross-reacL wlLh self-anLlgens
nypersens|t|v|ty
lmmune responses LhaL cause Llssue damage
ulfferenL Lypes of hypersenslLlvlLy reacLlons are dlsLlngulshed by:
1helr Llme course
WheLher anLlbodles or 1 cells are Lhe prlnclple lmmune elemenLs lnvolved
AnLlbody-medlaLed allergles are lmmedlaLe and subacuLe hypersenslLlvlLles
1he mosL lmporLanL cell-medlaLed allerglc condlLlon ls JeloyeJ bypetseosltlvlty
CnA1Lk 21 - IMMUNL SS1LM 13

Immed|ate nypersens|t|v|ty
AcuLe (Lype l) hypersenslLlvlLles begln ln seconds afLer conLacL wlLh allergen
Anaphylaxls - lnlLlal allergen conLacL ls asympLomaLlc buL senslLlzes Lhe person
SubsequenL exposures Lo allergen cause:
8elease of hlsLamlne and lnflammaLory chemlcals
SysLemlc or local responses
1he mechanlsm lnvolves lL-4 secreLed by 1 cells
lL-4 sLlmulaLes 8 cells Lo produce lgL
lgL blnds Lo masL cells and basophlls causlng Lhem Lo degranulaLe, resulLlng ln a flood of
hlsLamlne release and lnduclng Lhe lnflammaLory response
Loca| 1ype I kesponses
8eacLlons lnclude runny nose, lLchlng reddened skln, and waLery eyes
lf allergen ls lnhaled, asLhmaLlc sympLoms appear - consLrlcLlon of bronchloles and resLrlcLed
alrflow
lf allergen ls lngesLed, cramplng, vomlLlng, and dlarrhea occur
AnLlhlsLamlnes counLeracL Lhese effecLs
System|c kesponse: Anaphy|act|c Shock
8esponse Lo allergen LhaL dlrecLly enLers Lhe blood (e.g., lnsecL blLe, ln[ecLlon)
8asophlls and masL cells are enllsLed LhroughouL Lhe body
SysLemlc hlsLamlne releases may resulL ln:
ConsLrlcLlon of bronchloles
Sudden vasodllaLlon and fluld loss from Lhe bloodsLream
PypoLenslve shock and deaLh
1reaLmenL - eplnephrlne ls Lhe drug of cholce
Subacute nypersens|t|v|t|es
Caused by lgM and lgC, and Lransferred vla blood plasma or serum
CnseL ls slow (1-3 hours) afLer anLlgen exposure
uuraLlon ls long lasLlng (10-13 hours)
CyLoLoxlc (Lype ll) reacLlons
AnLlbodles blnd Lo anLlgens on speclflc body cells, sLlmulaLlng phagocyLosls and
complemenL-medlaLed lysls of Lhe cellular anLlgens
Lxample: mlsmaLched blood Lransfuslon reacLlon
Subacute nypersens|t|v|t|es
lmmune complex (Lype lll) hypersenslLlvlLy
AnLlgens are wldely dlsLrlbuLed Lhrough Lhe body or blood
lnsoluble anLlgen-anLlbody complexes form
Complexes cannoL be cleared from a parLlcular area of Lhe body
lnLense lnflammaLlon, local cell lysls, and deaLh may resulL
Lxample: sysLemlc lupus eryLhemaLosus (SLL)
De|ayed nypersens|t|v|t|es (1ype IV)
CnseL ls slow (1-3 days)
MedlaLed by mechanlsms lnvolvlng delayed hypersenslLlvlLy 1 cells (1
uP
cells) and cyLoLoxlc 1
cells (1
C
cells)
CyLoklnes from acLlvaLed 1
C
are Lhe medlaLors of Lhe lnflammaLory response
AnLlhlsLamlnes are lneffecLlve and corLlcosLerold drugs are used Lo provlde rellef
Lxample: allerglc conLacL dermaLlLls (e.g., polson lvy)
lnvolved ln proLecLlve reacLlons agalnsL vlruses, bacLerla, fungl, proLozoa, cancer, and re[ecLlon of
forelgn grafLs or LransplanLs
14 CnA1Lk 21 - IMMUNL SS1LM

Deve|opmenta| Aspects
lmmune sysLem sLem cells develop ln Lhe llver and spleen by Lhe nlnLh week
LaLer, bone marrow becomes Lhe prlmary source of sLem cells
LymphocyLe developmenL conLlnues ln Lhe bone marrow and Lhymus
1
P
2 lymphocyLes predomlnaLe ln Lhe newborn, and Lhe 1
P
1 sysLem ls educaLed as Lhe person
encounLers anLlgens
1he lmmune sysLem ls lmpalred by sLress and depresslon
WlLh age, Lhe lmmune sysLem beglns Lo wane