Ch.

19–Di
sea
sesoft
heI
mmun
eSy
ste
m

I
. 19.
1Hypers
e ns it
iv i
ties
A.TypeIHype r se ns it
ivi
ties
1. Alle rgie soc curwhe nt hea n ti
bodyr es pon seiss os ev ereitc aus est i
ss ueda ma gea sitfight sof fape rce i
v ed
i
n fec ti
on ,ora ll
e rge n ,tha twoul do the rwi sebeha rml es st othebody( s uc ha spol lenorpe tda n de r)a n dis
clas sifi
e da saTy pe1hy pe rs ens i
t
ivity.
2. Ty pe1hy pers en s i
ti
v i
tybe gin swi t
hins e condsofe x pos urea ndla st
sha lftoon ehour .Ex :a n aphy la cti
cs hoc k
an da l
le rgicrhi niti
s .
3. Ty peI hy perse n siti
v i
tyr ea ctionsi nvolvei mmun ogl obul i
nE( IgE)a nti
bodya ga i
n sts olublea ntige n ,tri
gge ri
n g
ma stc ellde gra n ula t
ionr e l
e a si
ngc he mi calme dia tor ss uc ha s:histami ne ,serot on i
n ,a ndbr a dy k i
n in,
l
e uk ot ryine s,pr os tagla ndins ,a ndc ytok ines.Thec he mi cal me diatorsr eleas edbyma stc e l
lsc ol l
e c t
ive l
yc a us e
thei n fl
a mma t
iona nds ign sa n ds ympt omsa ssoc i
a tedwi t
ht ypeI hype rs ensiti
v i
tyr e ac t
ion s.Hi s tami n e
sti
mu late smuc uss ec r
e t
ioni nna sal pa ssage sa n dt e arforma t
ionf r
oml acrima l glan ds ,promot ingt her un n y
nos ea ndwa t
e rye ye sofa llergies.Intera cti
onofhi s tami newi t
hn ervee n dingsc a us esi t
c hinga n ds n ee zi
n g.
Thev a sodi l
ationc a us edbys everal oft heme diator sc anr esultinhiv es ,he ada che s, angioe de ma( s we l
l
ing
tha to fte na ffec tst hel i
ps ,throa t
, andt on gue ),an dhy pot en si
on( l
owbl oodpr es sur e ).Bron chi olec on s tr
iction
ca us e dbys omeoft hec he mi calme diatorsle adst owhe ez i
ng, dyspn e a(diffi
c ultybr eathing) ,c oughi n g,a nd,
i
nmor es eve rec as es ,c yan os i
s( bl
uis hc olortot hes kinormuc ousme mbr an es ).Vomi tingc anr e sultf r
o m
sti
mu lati
onoft hev omi tingc enterint hec erebe l
lumbyhi st
a min ea nds eroton i
n .Hi stami nec a na l
s oc aus e
relax ationofi n tes ti
n al smoot hmu s clesa nddiarrhe a .
4. Ty peI hy perse n siti
v i
tyr ea ctionsc a nbee it
herloc a li
z edors yst
e mic. Loc ali
ze dt y peI hype rs en s i
ti
v it
yr eac ti
on s
i
n clud eha yfe ve rr hiniti
s ,hive s,anda sthma .Sys temi ct ypeI hy pe r
se ns i
ti
vityre a cti
on sa rer efe rre dt oa s
an aphy lax i
sora n aphy l
a cti
cs hoc k.Al t
hougha na phy l
a xi
ss ha resma n ys ympt omsc ommonwi tht hel oc alized
typeI hy pe r
s en s i
tivi
tyr e action s,thes we ll
ingoft het on guea ndt rache a ,block ageofa i
rwa ys, da n ge rousdr op
i
nb loodpr es sur e ,a ndde ve lopme ntofs hoc kc anma kea n aphy laxi
se s pe ci
a l
lys e ve rea n dlife- thre a t
e ning. In
fac t
, de a thc anoc c urwi t
hinmi nute sofon setofs ign sa n ds ympt oms .
5. La te-pha ser ea ction si nty peI hype rse ns i
ti
vit
i
e sma yde ve l
op4–12hour sa ftert hee arl
ypha sea nda re
me d i
a tedbye os i
n ophi ls,ne ut r
oph il
s ,an dlymphoc y test hatha v ebe e nr ecruite dbyc he mot ac ti
cf ac t
or s
relea s edf r
omma stc ell
s. Ac tiv
a ti
onoft he ser ecrui tedc el
lslea dst other e l
eas eofmor ec he mi c a lme diator s
tha tc a us et i
ss ueda ma gea n dlate-pha ses ympt omsofs we l
l
inga ndr e dn essoft hes kin,c oug h i
n g, whe ez i
ng,
an dn a sa ldi
s cha rge .
B.TypeI
I(Cy tot ox i
c )Hy pe rs en siti
viti
e s
1. Ty peI Ihy pe rse ns i
tivityr eac ti
on sinv olveI gGa ndI gMa nti
bodi esdi r
ec teda gains tc e l
lulara ntige n s, l
e adin gt o
ce l
l da ma geme diate dbyot he rimmun es yst
e me ffe ctors.The s ea nti
bodi e sc a ne i
the ra cti
v a t
ec ompl eme n t
,
res ultingi na ni n fl
a mma toryr espon sea ndl ysi
soft het arge tedc el
l
s, ort he yc anbei n volvedi na ntibody -
de pe n de n tce l
l-me dia tedc ytotox i
city(ADCC)wi thc ytotoxicTc e l
l
s.
2. I
ns omec ases ,thea ntigenma yb eas e l
f-ant
ige n, i
nwhi c hc aset her e ac t
ionwoul da lsobede s cribe da sa n
aut oimmun edi s e as e.Inot he rcase s, antibodiesma ybi n dton atural
lyoc curring, bute xoge n ous ,c ell
-s urfac e
mol e c ule ss uc ha sa nti
ge n sa ssociatedwi thbloodt ypin gfoun donr e dbl oodc ell
s( RBCs ).Thi sle a dst ot he
coa tin goft heRBCsbya n t
ibodi es,a ctivati
onoft hec ompl e me ntc asc ade ,an dc ompl eme nt-me dia tedl ysisof
RBCs ,aswe l
l a sops on i
za ti
onofRBCsf orpha goc y t
os is.Twoe xampl e soft y peI I hype rs ens iti
v i
tyr e ac t
ion s
i
n vo l
v i
n gRBCsa rehe mol ytictrans fusionr ea ct
ion( HTR)a n dhe mol yti
cdi seas eoft hen ewbor n( HDN) .
3. ABOBl oodGr oupI n compa ti
bil
ity
a . Ther ec ogn i
tiont ha ti n
dividua lsha vedi ffer entbl oodt ype swa sf ir
s tde s cribe dbyKa rlL a nds te i
ne rin
thee a rly1900s ,ba se donhi sobs ervationt ha tse r
umf romon epe rsonc oul dc aus eac l
umpi ngof
RBCsf roma not he r.The ses t
udi esledL a n ds t
e i
ne rtot heide n ti
fi
ca t
ionoff ourdi s t
in ctbl oodt ype s .
Subs e que n tr ese arc hbyot he rs ci
e nt
istsde t
e rmin edtha tthef ourbl oodt ype swe reba s edont he
pres en c eora bse nc eofs urfac ec arbohy dra tes“ A”a n d“ B,”a ndt hispr ov i
de dt hef ou n da tionf ort he
ABObl oodgr oups ystemt ha tiss t
il
linus et oda y.
b . Thea ll
e lesf orAa ndBbl oodt y pesa rec odomi n anttoe achot her,a ndbot ha r
edomi na n tov e rblood
typeO. The re f
or e, i
n di
vidu alswi thge not ype sofAAorAOha vet ypeAbl ooda nde x pre s st heA
 ca rbohy dratea ntige nont hes ur f
a ceoft he irRBCs .Pe opl ewi thge not ype sofBBorBOha v et y
peB
blooda nde xpr e s st heBc a rbohy dra tea nt i
ge nont hes urfa c eoft he irRBCs .Thos ewi thage notype
ofABha vet y peABbl ooda nde xpr essbot hAa n dBc arbohy dr atea ntige nsont hes ur f
a ceoft heir
RBCs .F inall
y ,in div i
dua lswi thage not ypeofOOha vet y peObl ooda ndl a ckAa n dBc a r
bohy dra t
e
ont hes urfac eoft he irRBCs .
c.IgMa nti
bodi e si npl a smat ha tc ros s-rea ctwi thbl oodgr oupa n t
ige n sn otpr e sen tona ni ndivi
dua l
’s
ownRBCsa rec alledi s ohe ma gglut i
n i
n s.Isohe ma ggl utinin sa repr oduc e dwi thint hef irstfewwe eks
afte rbirtha ndpe r sistt hro u ghoutl if
e .The s ea ntibodi e sa r epr oduc e di nr e spon s et oe xpos uret o
en viron me ntal a ntige n sf romf ooda n dmi croor ga nisms .
d. At ran sfus i
onwi tha ni n co mpa t
ibleABObl oodt y pema yl e adt oas t
r on g, pote ntial
lyletha ltypeII
hy pe rse ns i
ti
v i
tyc y totox i
cr e spon sec all
e dhe mol ytict ra ns fus i
onr ea c ti
on( HTR) . Forins t
a nce ,i
fa
pe rs onwi tht ypeBbl oodr ec eivesat r
a ns fus i
onoft y peAbl ood, t
he ira nti
-Aa n t
ibodi eswi llbindto
an da gglut i
na tet het ran sfus e dRBCs .Ina ddi t
ion ,a ctivationoft hec l
a s sical compl eme ntc asc adewi l
l
l
e adt oas tron gi n fl
amma tor yr espon se ,an dt hec ompl e me n tme mbr an ea t
tac kc ompl ex( MAC)wi l
l
me diatema s siv ehe mol y
s isoft het rans f
us edRBCs .Thede brisf romda ma geda n dde s t
roy edRBCs
ca noc cludebl oodv e s selsi nt hea lveol ioft hel un gsa ndt hegl ome ruli ofthek idn ey s.Within1t o24
hour sofa ni n compa tiblet ra ns f
us ion ,thepa ti
en te x pe ri
e nc e sf e ver, chi l
ls,pr uri
tus( i
tching) ,
ur t
icari
a
(hive s),dy spn e a, he mogl o b i
n uria( he mogl obi nint heur i
n e ),a ndhy pot e ns i
on( lowbl oodpr es sure).I
n
themos ts eriousr e ac tions ,da n ge rous lylowbl oodpr e ss ur ec anl ea dt os hoc k ,mul ti-
orga nf ai
lure,
an dde a thoft hepa ti
e n t.
e. Hos pitals,me di c al ce nte r
s ,a nda s soc i
a tedc li
nica llabor a tor i
e st y pi
c a l
lyus ehe mov igil
anc es ystems
tomi n i
mi zet her i
s kofHTRsduet oc l
e ri
ca le rror. He mov i
gi l
a nc es y ste msa repr oc edu r
e stha ttrack
tran sfus i
oni n for ma tionf r
omt hedon ors our c ea ndbl oodpr oduc tsobt a inedt ot hef ol
low- upof
rec i
pi entpa ti
e n ts. He mov i
gi l
a nc es y stemsus edi nma nyc oun tri
e si de n ti
fyHTRsa ndt he i
rout come s
throughma n da tor yr e por ti
n g( e .
g., t
ot heF ooda ndDr ugAdmi n i
s t
ra ti
oni nt heUn i
te dSt ates),a n
d
thisi nforma ti
oni sv a l
ua blet ohe l
ppr ev ents uc hoc c urre nc e si nt hef utur e.
4. Rhf
act
ors
a. Thes ec on dmos tf re que n tl
yde scribe dRBCa n ti
ge nsa reRhf a ctor s, na me da fterther he sus
ma ca que( Ma ca c amul a t
ta )fa ctorsi de n t
if
ie dbyKa rl La nds teine ra n dAl ex ande rWe i
ne rin1940 .The
Rhs yste mofRBCa n tigen si st hemos tc ompl e xa ndi mmun oge ni
cbl oodgr oups ystem, wi t
hmor e
tha n50s pe c i
fic i
tie side nti
fiedt oda te.Ofa l
ltheRha n ti
ge n s ,theon ede sign atedRho( We iner)orD
(Fishe r-Ra ce)i st hemos ti mmun oge nic .Ce ll
sa rec lass i
fie da sRhpos iti
v e( Rh+)i ftheRho/ D
an ti
ge ni spr e s e ntora sRhn e ga ti
v e( Rh− )i ftheRho/ Da n ti
ge ni sa bs en t
. I
nc on t
ra sttot he
ca rbo hy dratemol e cul est ha tdi s t
ingui sht heABObl oodgr oupsa nda ret het arge tsofI gM
i
s ohe ma ggl utin i
n si nHTRs ,theRhf act ora n ti
ge n sa repr ot e ins.
b.L ikeABOi nc ompa ti
bi l
itie
s ,bloodt ran sfus i
on sf romadon orwi tht hewr on gRhf ac t
ora n t
igen sc an
ca us eat ypeI I hy pe rs e nsiti
v i
tyHTR. Howe ve r,inc on t
ra stt ot heI gMi s ohe ma ggl utini
n spr oduc ed
ea rl
yi nl i
fet hr oughe x pos ur et oe n vi
ron me n tala ntige ns ,pr oduc ti
onofa nti-Rhf a ctora ntibodies
requi rest hee x pos ureofa ni n dividua lwi thRh−bl oodt oRh+pos i
ti
v eRBCsa nda ctivat
ionofa
prima rya n t
ibodyr es pon se .
c. Rhf a ctorin compa t
ibili
tybe twe e nmot he ra ndf e tusc a na l
s oc aus eat y peI Ihy pe rsen si
ti
v i
ty
he mol yti
cr e ac tion ,re fe rr
e dt oa she mol yticdi s ea seoft hen e wbor n( HDN) . I
faRh−woma nc ar
ri
e sa
Rh+ba byt ot e rm, themo the r’simmun es y ste mc a nbee x pos e dt oRh+f etalr edbl oodc ell
s .
This
ex pos ur ewi l
l us ua l
lyoc cu rdur ingt hel a stt ri
me s t
e rofpr e gn an c ya nddur ingt hede l
iverypr oce ss.I
f
thise xpos ur eoc c urs ,theRh+f eta lRBCswi l
la ctiva teapr ima rya da ptivei mmun er espon sei nthe
mot he r,an da n ti
-Rhf ac torI gGa n ti
bodi e swi llbepr oduc e d. IgGa nt
ibodi e sa ret heon lyc l
a ssof
an ti
bodyt ha tc a nc ros st hepl ac entaf rommot he rt of etus ;howe ve r,inmos tca se s,thef ir
stRh+
ba byi sun affe c tedbyt he sea n ti
bodi e sbe ca us et hef i
rs te x pos uret ypic all
yoc cur sla t
ee noughi nt he
pre gn an cyt ha tthemot he rdoe sn o tha vet i
met omoun tas uffi
c i
e ntpr ima rya n ti
bodyr es pon se
be for etheba byi sbor n .
d.Ifas ubs eque n tpr egn an cywi thaRh+f e t
usoc c urs ,howe ve r,themot he r’ss ec on de xpos ur etothe
Rhf a ctora n ti
ge n sc aus esas trongs e con da rya ntibodyr e spon s et ha tpr oduc e sla r
ge rqua n ti
ti
esof
 an ti
- Rhf a ctorI gG. The s ea n t
ibodi e sc a nc ros st hepl a cen tafrommot he rt of e tusa ndc auseHDN, a
pot e nti
all
yl e tha lcon ditionf ort heba by .
e. Pr i
ort othede velopme nto ft ec hn ique sf ordi a gnos isa ndpr ev enti
on ,Rhf ac t
ori n compa tibi
li
tywa s
themos tc ommonc aus eofHDN, re sultingi nt hous a ndsofi n fantde a thse a chy ea rwor ldwide .For
thisr e ason , t
heRhf a ctorsofpr os pe c ti
vepa r
e ntsa rer e gula r
lys cre en ed, a ndt re atme nt
sha v ebe en
de v elope dt opr ev e ntHDNc aus e dbyRhi n compa ti
bi l
i
ty .Topr e v
e ntRhf ac tor-me dia tedHDN,
huma nRho( D)i mmun egl obul in( e .g.,RhoGAM)i sin jecte di nt
r aven ous lyori ntramus cularl
yin tot he
mot he rdur in gt he28t hwe e kofpr e gn a nc ya n dwi t
hin72hour sa fterde l
ive ry.Thi st rea t
me n tis
i
n i
tia t
e ddur i
n gt hef i
rs tpre gn an c ywi tha nRh+f etus .Thea nti-Rha nti
bodi esi nRho( D)i mmun e
globul i
nwi l
lbin dt ot heRhf a ctorofa n yf e t
a lRBCst ha tga i
na c ces stot hemot he r’
sbl oods tre am,
pre v enti
n gt he seRh+c el
lsf roma c ti
v a t
ingt hemot he r’spr ima rya n ti
bodyr es pon se.Wi thouta
prima rya n t
i-Rhf a ctora nti
bodyr e s pon se, then ex tpr egn a ncywi thaRh+wi l
lha vemi nima lri
s kof
HDN. Howe v er,themot he rwi l
l ne e dt ober etrea t
e dwi thRho( D)i mmun egl obul indu ri
ngt ha t
pre gn a n
c yt opr e ve ntapr ima r
ya n ti-Rha ntibodyr es pon set ha tcoul dt hre a tens ubs e que nt
pre gn a n
c ies .
C.Ty
peII
IHy pe rsen siti
v i
ties
1. Ac cu mula tionofi mmun ec ompl exe sint i
s suel e adst ot i
s sueda ma geme diate dbyot he rimmu nes ys tem
ef
fe ctors. Al oc ali
z edr ea cti
on( e x:subc ut an eoushe mor rha gewi the de maa ts iteofi nfe cti
on3- 10hr s. pos t
i
nje cti
onofr abbitwi thhor s es e rum)t on on - se l
fs e rumpr ote i
n swa sc all
eda nAr thusr ea cti
on .
AnAr thus
reac t
ionoc c urswhe ns olubl ea nti
g en sbi n dwi thI gGi nar atiot ha tr esultsint hea c cumul ati
onofa nti
ge n -
antibodya ggr egate sc all
e di mmun ec ompl e xe s.
2. TypeI IIhy pe rs ensiti
v i
tyr e ac t
ion sin volvet hei nte rac ti
on sofI gG( pr i
ma ril
y )
,IgM, an d, oc ca si
on a l
ly,I
gA1
antibodieswi tha ntige nt of ormi mmun ec ompl ex es .
3. Sys temict y peI IIhy pe rs ens i
ti
v i
ty( se rums i
c kn e ss )oc c urswhe nimmun ec ompl ex esde pos itinv ari
ousbody
si
te s,resul ti
n ginamor ege ne rali
ze ds ys temi ci nfl
a mma toryr e spon se. The sei mmun ec ompl exesi nvol ven on
-s
e lfprote inss ucha sa n t
ibodi e spr oduc e di na n i
ma lsf ora rtif
icial pas siveimmun i
ty( s eeVa cc i
nes ),cer tai
n
drugs ,ormi crobia lan ti
ge n stha ta r
ec on tin uous lyr elea sedov ert i
medur i
ngc hron ici nfe cti
on s( e.g.,
s uba cute
bac teri
ale n do cardi t
is, chron i
cv i
ralhe pa ti
tis). Theme cha nismsofs e r
ums ickn essa res imilart othos e
des cri
be di nl oc al
iz edt y peI II
hy pers en siti
v i
tybuti n volvewi de s pre ada c tiv
a t
ionofma stc e l
ls,c ompl eme nt
,
neut r
ophi ls, an dma c ropha ge s ,whi chc a us e st issuede struc tioni na r
e ass uc ha st hek idn ey s,joi
n ts,an d
bl
oo dve ss e l
s .Asar es ultoft iss uede struc tion ,s ympt omsofs erums i
c kne ssi ncludec hill
s ,f
e ver,ras h,
vas culi
t
is, an da r
thr i
tis. De ve l
opme n tofgl ome rulon e phr i
ti
sorhe pa ti
ti
si sa lsopos sible.
4. Aut oimmun edi s
e a se ss uc ha ss yste micl upuse ry the ma t
os us( SL E)a ndr he uma toida rthriti
sc ana l
s o
i
nv olveda ma gingt ypeI IIhy pe rse nsiti
v i
tyr e a ctionswhe na uto- antibodi esf ormi mmun ec ompl exeswi ths e l
f
antigens .
D.Ty
peIVHy pe r
se n siti
v i
ti
es
1. TypeI Vhy pe rsen siti
v i
tyr ea ction sa reT- c ell-me diate dr ea ction st ha tca nin volvet iss ueda ma geme dia tedby
activatedma cropha ge sa n dc ytotox icTc e l
ls.
2. The set ype sofhy pe rse nsiti
vitiesc a nbeor ga n i
z edi n t
ot hr ees ubc ategor i
e sba se donT- ce l
ls ubtype ,ty peof
antigen, an dt her e sul ti
n ge ffec torme cha n ism.
a.F irs ttypeI Vs ubc a t
e gor y,CD4TH1- me diate dr ea ction sa r
ede s cri
be da sde lay ed-ty pe
hy pe rsen s i
ti
v i
ties( DTH) .Thes en s i
tiza ti
ons tepi n volv est hei n tr
oduc ti
onofa ntige nin tothes kina n d
pha goc ytos isbyl oc al an t
ige npr e se ntingc e l
ls( APCs ).TheAPCsa c t
iva tehe lpe rTc e l
ls,sti
mul ati
ng
clon a lprolif
e ra t
iona nddi f
fe ren ti
a ti
o ni n t
ome mor yTH1c e l
ls.Upons ubs e que nte xpos u r
et ot he
an ti
ge n,the ses en s i
t
iz edme mor yTH1c e ll
sr e l
e as ec y t
ok i
ne st hata ctivatema cropha ge s,and
ac ti
v atedma c ropha ge sa rer es pon siblef ormuc hoft het issueda ma ge .Ex a mpl e soft hi
sTH1-
me dia t
edhy pe rse n si
tivit
ya reobs e rve dint ube rcul i
nt heMa ntouxs kint es ta ndc on ta ctde rma ti
ti
s ,
suc ha soc c ur sinl atexa l
lergyr e ac ti
on s.
b. Se c on dt ypeI Vs ubc a tegor y,CD4TH2- me diate dr e action sr esultinc hron ica s thmaorc hron ic
all
e rgicr hiniti
s .Int hes ec ase s,thes ol ublea n t
ige ni sf i
rsti nha l
e d,res ulti
n gi ne os inophi lr
e cr
uitme n t
an da cti
va ti
onwi tht her el
e a seofc y tok i
n esa ndi n fl
a mma toryme dia t
or s.
c. Thi rdt ypeI Vs ubc a t
e gor y,CD8c ytot ox i
cTl ymphoc y te( CTL )-me diate dr e action sa rea s soc i
a ted
wi tht i
s s
uet ran spla ntr ejectiona n dc on tac tde rma titi
s( F i
gur e19. 8). Fort hisf or mofc el
l-me dia ted
 hype r
s ens it
iv i
t
y ,APCspr oc e s sa ndpr ese ntthea ntige nwi thMHCI ton aïveCD8Tc ells.
Whe n
the sen aï veCD8Tc e l
lsa rea ctiva ted, t
he ypr oliferatea n ddi ffer entiatein toCTL s .Ac t
ivatedTH1
ce l
lsc ana l
s oe nha n c et hea c ti
v ationoft heCTL s .Thea c ti
v ate dCTL st he nt arge ta ndin duc e
gra nzyme -me dia teda popt os isi nc ellspre sentingt hes amea ntige nwi thMHCI .The setarge tc el
ls
coul dbe“ se l
f”c e l
l
st ha tha vea bs or be dt hefor e i
gna ntige n( suc ha swi t
hc on tac tde rma ti
ti
sdu eto
pois oni vy), ort he yc ouldbet ra nspl an t
edt issuec ellsdi s pla yi
n gf ore igna n t
ige nf romt hedon or.
E.Hy pers
e ns i
tivi
tyPn eumon iti
s
1. Somedi sea sec aus e dbyhy pe rse ns i
tiv i
tiesa ren otc aus e de x clus ive l
ybyon et ype .F ore xa mpl e,
hy per sensitivi
typn e umon i
tis( HP) ,whi c hi sof tena noc c upa ti
on al ore nv i
ron me ntaldis ea s e, occurswhe nthe
l
un g sbe comei nf
la me dduet oa na ll
e rgi cr ea cti
ont oin ha leddus t, en dos por e s,birdf e athe rs ,bir
ddr oppi ngs ,
mol ds ,orc he mi cals. HPgoe sbyma n ydi ffe rentn ame sa ss oc i
a te dwi thv a r
iousf ormsofe xpos ur e.HP
as soc i
atedwi thbi rddr oppi ngsi ss ome ti
me sc al
ledpige onf a nc ier’sl un gorpoul trywor k e r’
sl ung—bot h
commoni nbi rdbr e e dersa n dha n dler s. Che e seha ndle r’
sdi s ea se ,fa rme r
’sl ung, s aun at a ke rs'disea se ,an d
hot -t
ubl un ga reot he rn a me sf orHPa s s oc i
a tedwi the xpos ur et omol dsi nv a r
iouse n viron me nts.
2. Pa thologya ssoc i
a te dwi thHPc a nbeduet obot htypeI II (
me dia tedbyi mmun ec ompl e xe s )a ndt y
peI V
(me diatedbyTH1c e ll
sa n dma c ropha ge s)hy pers ensit
iviti
es .Re pe atede xpos uret oa l
le rge n sca nc a us e
alveolit
isduet ot hef orma t
ionofi mmun ec ompl ex esint hea lve ola rwa lloft hel un ga c compa ni
e dbyf luid
ac cumul ation ,andt hef or ma ti
onofgr a n uloma sa n dothe rles i
on si nt hel un ga sar es ultofTH1- me dia t
e d
ma cropha gea cti
v ation .Al veol i
tiswi t
hf luida n dgra nul
omaf or ma tionr es ul
tsi npoorox y ge npe rfusi
oni nt he
alveoli,whic h,intur n ,ca nc aus es ympt omss uc ha scoughi n g, dy s pn ea ,chills,fev er,s we a ti
n g,my al
gia s ,
he ada che ,an dn aus ea. Sy mpt omsma yoc c ura squi cklya s2hour sa ftere x pos urea ndc a npe rsi
stf orwe eks
i
fle f
tun t
rea ted.
F. Di
agnos i
sofHy pe rse nsit
iv i
tie s
1. Diagn osisoft ypeI hy pe rs en sit
iviti
e si sac ompl e xpr oc essr e quirings e ve raldia gn os ti
ct es tsi na ddit
iont oawe l
l-
docume ntedpa ti
enthi s tory. Se rumI gEl e ve lsc a nbeme a
s ur ed, bute l
e va tedI gEa l
on edoe sn otc on f
ir
ma ll
ergic
di
se as e.
a. Aspa r
toft hepr oce s st oi de n ti
fyt hea n t
igensr e spon siblef orat ypeI re actiona ll
e rgy ,t
e st
ing
throughapr i
ckpun c tur es k i
nt es t(PPST)ora ni ntra de rma lte stc a nbepe rfor me d. PPSTi sc arri
e d
outwi t
ht hei ntroduc ti
ono fa l
le rge n sinas eri
e sofs upe rfi
c i
a ls ki
npr icksont hepa ti
e nt’
sba ckor
arms .PPSTsa rec on si
de re dt obet hemos tc on ve nien ta n dl ea ste x pen sivewa yt odi agn os e
all
e rgi
e s,a cc ordi ngt ot heUSJ oin tCoun ci
lofAl l
ergya ndt heEur ope anAc a de myofAl ler
gya nd
Immun ol
ogy .
b. Thes e con dt ypeoft es ti
n g, thei ntra derma ltes t,requi re si nje cti
oni n tot hede rmi swi t
has ma llne edl
e.
Thi sn eedl e, al
s ok nowna sat ube rculinn eedle, i
sa tt
a che dt oas yrin gec on ta i
n i
n gas ma ll
a moun tof
all
e rgen .Bot ht hePPSTa ndt hei ntra derma ltes tsa reobs erv edf or15–20mi nut e sf orawhe al-
flare
rea cti
ont ot hea l
lerge n s.Me a s ure me ntofa nywhe al (
ar ais ed, i
tchybump)a ndf lare( redne s s)wi thi
n
mi nute sin dic atesat ypeI h ype rs ens it
ivi
ty,andt hel arge rthewhe a l
- f
larer ea ction ,theg reate rt he
pa ti
e nt
’ss e n si
tivityt ot hea ll
e rge n.
2. TypeI IIhype rsen sit
ivi
tiesc anof te nbemi s dia gn os edbe caus eoft he irn on spe c i
fi
ci nflamma tor yn at
ur e.The
sympt omsa ree a si
lyv isible, butt he yma ybea ss ociatedwi tha nyofan umbe rofot he rdi se as e s.As t
ron g,
compr ehe nsivepa t
ien thi stor yisc ruc i
a ltopr ope ran da ccur atedi a gn os i
s. Te stsus edt oe s tablisht hedi a gn osis
ofhy pe rsens i
ti
v i
typn e umon iti
s( re sultingf romt ypeI I
I hype rse nsiti
vity )in cludebr on c hoa l
v eol arl avage( BAL ),
pul
mon aryfun ctiont es ts, andhi gh- re so l
ut i
onc omput e dtomogr a phy( HRCT) .
G.Tre a
tme n tsofHy pe rse nsiti
v iti
es .Al l
e rgicr e ac ti
on sc anbet re
a te dinv ar i
ouswa y s.
1. Pr eve nt
ionofa ll
er gicr e ac t
ion sc anbea chie ve dbyde s en si
tiz ation( hy pos e ns i
ti
z ati
on )t he ra py,whi chc a nbe
us edt or educ et hehy pe rse n sit
ivityr e ac ti
ont hroughr epe atedi n jec ti
on sofa ll
erge ns .Ex tre me l
ydi l
ute
con ce ntr
a t
ion sofk n owna ll
e rge n s( de te rmi ne dfromt hea ll
e rge nt e sts )a r
ei n jectedi n t
ot hepa t
ienta t
pre scri
be di nterva l
s( e.
g., we e kly )
.Thequa n ti
tyofa l
ler
ge nde li
ve re dbyt hes hot si ss l
owl yi nc reasedov era
builduppe riodun ti
l ane ffec ti
v edo s ei sde te rmin eda ndt hatdos ei sma intaine df orthedur a ti
onoft re a tme nt
,
whi chc a nla sty ears .Pa tien tsa r eus ua ll
ye n cour agedt or ema i
ni nt hedoc tor ’
sof ficef or30mi n utesa fter
rec ei
v i
ngt hei njec ti
oni nc a set hea ll
er ge n sa dmin i
steredc a us eas e ve res ys temi cr ea ction .Th ea l
l
e rgys hots
eli
c i
tthepr oduc ti
onofdi ffere nti nterleuk insa ndIgGa ntibodyr es pon se sin ste adofI gE. Whe ne x cessa ll
e r
ge n-
spe cifi
cIgGa nt
ibodi e sa repr oduc e da n dbi ndt ot hea ll
e rgen , t
he yc ana cta sbl oc kinga ntibodi esto
 neutrali
zet hea l
ler
ge nbe f
orei tca nbindI gEonma stcell
s .The r
ea ree ar
lys t
udi esus i
n gora l
th era pyf or
dese nsi
ti
z ati
onoff ooda l
lergiestha tarepr omising.The ses tudiesi n volvef eedingc hil
drenwhoha v ea l
lergi
es
ti
nya moun tsofthea l
l
e r
ge n( e.g.
,pe anutf l
our )orr el
atedpr ote i
nsov ert i
me .
2. Eme rge ncys ystemica na phy l
ax i
sist r
e atedi ni
ti
all
ywi tha ne pinephr inei nj
e ct
ion ,whichc anc o un teractthe
dropinbl oodpr e
ss ure.I
n divi
dua lswi t
hk nowns ev e
rea ll
ergie sof te nc arryas elf
-admi ni
steri
nga uto- i
n j
ec t
or
thatca nbeus edinc a seofe xpos uretot hea l
ler
ge n( e.
g.
, ani n sec tstingora c ci
den ta
l i
nge st
ionofaf oodt hat
caus esas evererea cti
on )
.Bys elf
-admi n i
ste r
inga ne pi
n ephr ines hot( ors ome t
ime stwo) ,t
hepa t
ien tc a
n
stemt her e act
ionlon ge nought os eekme dicalattenti
on.F ollow- upt re atme ntge ne ral
lyinvol
v esgi v i
ngt he
pati
e ntantihi
stamine sa nds low- acti
n gc orticosteroi
dsf ors e ve r
al da ysa ft
e rther eac t
iontopr e ve ntpot en t
i
al
l
a t
e-pha ser eacti
ons .Howe ver, t
hee ffec t
sofa nt
ihistaminea n dc or t
icos t
e roi
dt reatme nta r
en otwe llstudied
anda reus e dba sedont heor eti
ca lcons i
de rati
ons .
3. Treatme ntofmi l
dera l
lergicre acti
on sty pi
c all
yinvolvesa ntihistami n esa ndot he ra nt
i-i
n f
lamma torydr ugs .A
vari
etyofa nti
hist
ami nedr ugsa rea vai
lable, i
nbot hpr escriptiona n dov er-the-c ounters tr
ength s.The rea re
alsoan t
il
euk otri
enea n da nti
pros taglandindr ugst hatc anbeus edi nt ande mwi tha nti
hist
ami nedr ugsi na
combi ned( andmor ee ff
e cti
ve )the r
apyr egime .
4. Treatme ntsoft ypeI I
Ihype rsen si
tivi
ti
esi ncludepr e venti
ngf ur there xpos uret ot hea nti
gena n
dt heus eofa n
ti
-
i
n f
lamma t
or ydrugs .Somec on di
ti
on sc anber esol v
e dwhe ne xpos ur et othea nti
geni spr even t
e d. An t
i-
i
n f
lamma t
or ycorti
cos teroidinha l
e r
sc a na l
s obeus edt odi mi nishin fl
amma ti
ont oa l
lowl ungle sion st ohe al
.
Systemi cc ort
icosteroidtrea t
me nt,oralori ntravenous ,i
sa lsoc ommonf ort ypeI I
Ihype rsensi
tiviti
esa f
fec t
ing
bod ys yst
e ms .Treatme ntofhy pe r
s ensiti
vitypne umon it
isin clude sa voidi
n gthea l
lergen ,
alongwi tht he
pos si
blea ddit
ionofpr e scri
ptions teroidss uc ha spr ednison et or e duc einflamma ti
on .
5. Treatme ntoft ypeIVhy pe r
s ens i
ti
vit
iesin cl
ude sa n t
i
histami ne s,an ti
-inflamma torydrugs ,ana l
ge sics ,and, i
f
pos si
ble,eli
min at
ingfur t
he re xpos uret othea nti
ge n.

I
I
. 19.2Aut oi
mmun eDi sor de r
sAl t
hought hei mmun es ystempr ote ctsthebodybya ttackingi nvading“ en e
mi es”
(
pathogens),
ins omec ase s,thei mmun es ystemc a
nmi s t
ak enlyide nti
fythebody ’
sownc e l
l
sa st hee n emy ,resul
tingin
aut
oimmun edise ase.Aut oimmun edis eas esa rethoseinwhi cht hebodyi sa ttack edbyi tsowns pe c if
icada pti
veimmun e
r
e s
ponse.Innorma l,
he althys ta t
es,thei mmun es ys
temi nduc est ol era
n ce, whi chi sal ackofa na nti
-s e l
fimmun e
r
e s
ponse.Howe v er
,wi t
ha utoimmun it
y, t
he rei salossofi mmun et oler
a nce, andt heme cha nismsr e spon si
blef or
aut
oimmun edise a
s esinc l
udet ypeII,I
II
,an dI Vhy persensit
i
v i
tyr ea cti
ons .Aut oimmun edis eas esc anha veav ariet
yof
mixedsymptomst hatfl
a reupa nddisa ppe ar,ma kingdiagnos isdi ffi
cul
t.Thec aus esofa ut oimmun edi seas ea rea
combina
ti
onoft hei ndiv
idua l'
sge neti
cma k eupa ndthee ff
ec tofe nvir
on me nta li
n f
luen ces, sucha ss un li
ght, i
n f
e ct
i
on s,
medicat
i
on s,
a nde nvi
ron me n t
a lchemi cals.
A.Or gan -
Spe cif
i
cAut oimmun eDi sea se s
1. Ce l
iacdis e
a se-i slargelyadi s eas eofthes ma lli
nte stine,al
thoughot herorga nsma ybea f
fec ted.Pe oplein
thei
r30sa nd40s ,andc hil
dr ena remos tcommon l
ya ffect
e d,butc e l
i
a cdise asec anbe gina ta nya ge. I
t
result
sfromar e ac t
i
ont opr ot ei
n s,common l
yc a l
l
e dgl uten, f
oun dma inl
yi nwhe at,ba r
l
e y ,rye,a nds ome
othergra i
ns.
a. Ca us e:Thedi seas eha ss ever
algen eti
cc a us es(pr edispos i
ti
ons )an dpoor lyun de rst
o od
environ me nt
alinf
lue nce s.One xpos uret ogl uten ,
thebodypr oduc e sv ari
ousa ut oan t
ibodi esa nda n
i
n f
l
a mma toryrespon se.Thei nfl
amma toryre s ponsei nt hes ma l
lintestinelea dst oar e duc ti
onint he
dept hoft hemi crovil
lioft hemuc osa ,whi chhi n
de rsa bs orptiona ndc anlea dtowe ightl ossa nd
ane mi a.Thedi sea sei sa l
s ocharacteri
z edbydi a r
rheaa nda bdomi na lpa i
n,s ympt omst ha tareof t
en
mis diagn ose dasi rr
itablebowe ls
y ndrome .
b. Di agn os i
s :Diagnos i
sofc el
iacdiseasei sa cc ompl i
she df roms e
rologic altestsfort hepr e senc eof
pri
ma ri
lyIgAa nti
bodi est oc ompon entsofgl ut en,t
het r
a ns gl
ut i
nami na see nzyme ,anda utoantibodi
es
toe ndomy si
um, ac on n ecti
vetissues urroun di ngmus clef i
be rs.Se r
ologi caltestsa rety picall
y
fol
l
owe dupwi the ndos copya ndbiops yoft heduode n al muc osa.
c. Tr ea tme n t:Celi
acdi s easei str
eatedwi t
hc ompl eter emov a lofgluten -containi
n gf ood sf romt hedi et
,
whic hr es ul
tsinimpr ove ds ymptomsa n dre duc edr i
s kofc ompl icati
on s.Ot hert he ore ti
cal
appr oac he sincl
udebr e ed i
nggrainstha tdon otcon t
a i
nt hei mmun ologicall
yr ea ctivec ompon e ntsor
dev elopingdi etarys upple me nt
stha tcon taine nzyme st ha tbr eakdownt hepr ot e i
nc ompon entsthat
caus et hei mmun er e spo nse.
 2. Thy r
oidDi se ase
a. Gr av esdi se as ei st hemo s tc ommonc aus eofhy pe r t
hy roidismi nt heUn it
e dSt a te s. Sy mpt omsof
Gr av esdi s ea s er e sultf r
omt hepr oduc tionoft hy roid- stimul atingi mmun oglobul i
n( TSI )a l
soc al
led
TSH- r
e ce pt ora n t
ibody .TSI targe tsa ndbi n dst ot her ec eptorf ort hy r
oi ds ti
mul a ti
n gh o rmon e( TSH) ,
whi c hi sn a tur all
ypr oduc edbyt hepi tuitarygl an d. TSI ma yc aus ec on fl
icti
n gs ympt omsbe ca usei t
ma ys timul atet het hy roidt oma k et oomuc ht hy roidhor mon eorbl ockt hy roidhor mon epr oduc ti
on
en ti
r el
y ,ma k i
n gdi agn os i
smor edi ff
i
c ult.Si gn sa nds y mpt omsofGr a ve sdis eas ei nc ludehe a t
intole r
a nc e ,rapi da ndi rregul arhe artbe at, we i
ghtl os s,goi ter( as wol lent hyroidgl a n d, pr otrudi ng
un de rt hes k i
noft het hroa ta nde x opht ha lmi a( bul gin ge yes )of tenr e
fe rredt oa sGr a ve s
opht ha l
mopa thy .
b. Ha s himot o’sdi s e asea l
s oc a l
ledc hron icl y mphoc y ti
ct hy roiditisist hemos tc ommonc a us eof
hy pot hy roidis m. Pa tien t
swi thHa s himot ot hy roiditisof t ende ve lopas pe ctrumofdi ffere ntdi sea ses
be c aus et he ya remor el i
ke l
yt ode velopa ddi tion al aut oimmun edi se ase ss uc ha sAddi s ondi se ase
(disc us se dl ate ri nthi ss ec ti
on ),ty pe1di abe tes, rhe uma t
oida rthr i
tis,an dc e l
i
a cdi s e as e.Ha s hi
mot o
thy roiditi
si saTH1c ell
-me dia t
e ddi se a set ha toc c urswhe nt het hyr oi
dgl andi sa t
t ac ke dbyc ytotoxic
lymphoc ytes ,ma cropha ge s, an da u toan tibodi e s.Thi sa utoimmun er espon s ele adst on ume rous
sy mpt omst ha ti nc l
udegoi ter,c oldi ntole ran ce ,mus c l
ewe ak ne ss, painful an ds ti
ffj oin ts,de pr ession,
an dme mor yl os s.
3. TypeI di
a be tes .J uv en il
edi abe tes,ort ype1di abe tesme lli
tus , i
sus ua ll
ydi a gn os edi nc hildr ena n dy oun g
adults.I
tisaT- ce ll
-de pe n den ta utoimmun edi sea sec hara cte ri
z e dbyt hes e lecti
v ede struc tionoft heβc e l
ls
ofthei sl
etsofL a nge rha n sint hepa nc rea sbyCD4TH1- me di atedCD8Tc e l
l
s ,an t
i-β-ce lla ntibodi e s ,and
ma cropha gea c ti
v i
ty .The rei sa l
soe vide nc et ha tv iral i
n f
e ction sc anha v ee itherapot en ti
a ti
n gori n hi bit
oryr ol
e
i
nt hede ve lopme n toft ype1di a bete s( T1D)me l
li
tus .Thede struc ti
onoft heβc e l
lsc aus e sal a c kofi nsulin
produc ti
onbyt hepa nc re as.InT1 D, β- ce l
l de struc tionma yt akepl ac eov ers eve ralye ars, buts ympt omsof
hype r
glyce mi a, ex tremei n crea seint hirsta ndur in ation ,we i
ghtl os s,a nde xtr emef ati
gueus ua llyha v ea
sudde non se t,an ddi agn osisus ua l
l
ydoe sn otoc c urun t
ilmos tβc e l
lsha vea l
re adybe e nde stroy e d.
4. Autoimmun eAddi sondi s eas e. De struc ti
onoft hea dr ena lgl an ds( thegl an dsl yi
n ga bov et hek i
dn ey stha t
produc egl uc oc orticoi ds , min era l
oc orticoids ,a nds e xs t
e roids )i sthec a us eofAddi sondi s ea se , alsoc all
ed
pri
ma rya dr en alin suf f
ic i
e n cy( PAI )
. Toda y, upt o80%ofAddi s ondi s e asec a sesa redi agn os e da s
autoimmun eAddi sondi se as e( AAD) , whi chi sc aus edbya na utoimmun er e spon set oa dr e na ltiss ue s
disr
upt i
nga dr ena lfun c tion .Dis ruptionofa dr en al f
un ctionc a us e simpa iredme ta boli
cpr oc e ss e st ha tr equire
norma l s
te roidhor mon el eve l
s ,cau sings i
gn sa n ds ympt omst hr oughoutt hebody .Thea dr e na lcor te xc ell
s
aretarge t
e d, de s t
roy ed, a ndr e place dwi thf i
br oust i
s suebyi mmun e -me diatedi n f
lamma tion .Ins omepa ti
e nt
s,
atleast90%o fthea dr en a lcor texisde s troye dbe fores ympt oms .Sy mpt omsofAADi nc ludewe a kn e ss,
naus ea,de cr eas eda ppe ti
te, we ightl oss ,hy pe rpigme n tati
on ,hy pe rka l
e mi a( el
e va t
e dbl oodpot a ss i
uml e ve l
s)
,
hypon atremi a( de c re as edbl oods odi uml e vels),hy pogl yc e mi a( de cre as edl e v
e lsofbl oods uga r
) ,hy pot ens i
on
(decrea s
e dbl oodpr es s ure )
, an emia , l
ymph oc ytos is( de c r
e a se dl eve l
sofwhi tebl oodc e l
ls), an df a ti
gue .
Un dere xtremes tre ss ,s uc ha ss urge r
y ,ac cide nta ltra uma , ori nfec t
ion ,pa t
ie n
tswi thAADma ye x pe rie
n cea n
adrena lcri
s i
st ha tc aus e st hepa ti
en ttov omi t,ex pe rien cea bdomi na lpa in,ba ckorl egc ra mps ,a nde ven
severehy pot en sionl e a dingt os hoc k .
B.Sy
stemi
cAut oimmun eDi se as e s
1. Multi
ples c l
e ros is–( MS)i sa na utoimmun ec entra l ne r
v ouss ys temdi s ea set ha taffec t
st hebr aina n ds pinal
cord.L esi
on sinmul tiplel oc a t
ion swi thint hec ent r
a l ne rvouss ys tema r eaha l
lma r
kofmul tiples cle ros i
sa n d
arec ause dbyi n fi
ltrationofi mmun ec ell
sa cros st hebl ood- bra i
nba rrier. Thei mmun ec e l
lsi n cludeTc el
lsthat
promot ein fl
a mma tion ,de my eli
na t
ion ,an dn eur onde ge n era ti
on ,allofwhi c hdi sruptn eur on a ls i
g na li
n g.
Sympt omsofMSi nc l
udev i
sua l di
s turba n ces ;mus c l
ewe a kn es s;diffi
c ultywi t
hc oordin ationa ndba l
a n c
e ;
sensa t
ionss u cha sn umbn e ss ,pri
c k l
ing, or“ pin sa ndn ee dle s ”
; an dc ogn it
ivea ndme mor ypr obl ems .
2. My asthen i
agr a vis–Aut oa ntibod i
e sdi re cteda ga in sta c etylc hol i
ner e ce ptor s( AChRs )int hes y na pt i
cc leftof
neuro mus c ularj un ction sl e adt omy a sthe niagr a vis .An ti-AChRa ntibodi e sa rehi gh- affi
nityI gGsa n dt heir
synthes i
sr e quire sa c ti
v a tedCD4Tc el
lst oi ntera c twi tha nds timul a t
eBc ells
. On cepr oduc ed ,thea n t
i
-AChR
anti
bodi es.Thee ffe ctofa n t
i-ACh Ri se xtre memus cl
ewe a kn e ssa n dpot e n t
i
a l
lyde atht hr oughr e spi rat
or y
arrestins ev erec a se s. An ti-
AChRa n t
ibodi esa ffec tn e uromus culart ra ns mis si
onbya tlea s tth re e
me cha ni
sms :
 a. Compl eme n tbin din ga nda c t
ivationa tthen e uromus c ula rjun cti
on
b. Ac ce l
e ra t
e dAChRe ndoc ytosisofmol ec ule sc r
os s -l
ink e dbya n tibodi es
c.F un ction al AChRbl oc k i
ng ,whi chpr e ve ntsn or ma la c ety l
c holinea tta
c hme n tto, a nda ctivationof ,
AChR
3. Psor i
asisisas kindi se aset ha tc aus esi tchyors or epa tche soft hick ,r
e ds ki
nwi ths i
l
v erys cal
e sone lbows ,
knee s,scalp, ba c k, f
a ce, pa lms , f
e e t
, ands ome ti
me sot hera r ea s. Somei ndi v
idua l
swi thps ori
as isa lsoge ta
for
mofa rthriti
sc a l
ledps or iati
ca rthrit
i
s, inwhi cht hej ointsc a nbe comei n flame d.Ps or i
a s i
sr esultsf romt he
compl exin terpl aybe twe enk era ti
n oc yt
e s,de ndriti
cc e ll
s ,andTc e l
ls,a ndt hec y t
ok inespr oduc edbyt hes e
vari
ousc ell
s .Inapr oc es sc al
ledc e l
lturn ov er,s ki
nc e ll
st ha tgr owde e pint hes k inriset ot hes urfa ce .
Nor ma l
l
y, t
hi spr oc es st ak esamon th.I
nps orias i
s ,a sar es ultofc ytok i
nea c t
ivation ,ce l
l turnov erha ppe nsin
j
us taf ewda ys .Thet hic ki nfl
a me dpa tc he sofs k i
nt ha ta rec ha ra cterist
icofps or i
a si
sde ve l
opbe c aus ethe
ski
nc e l
l
sr iset oof ast.
4. Rhe uma toida rthriti
sThemos tc ommonc hr on i
ci n fl
a mma tor yj ointdi sea s eisr he uma toida r
thr i
tis( RA)a nd
i
tiss ti
ll
ama jorme dical cha l
l
e ngebe caus eofun s olve dque s ti
on sr e l
atedt ot hee nv i
ron me ntala ndge ne ti
c
caus esoft hedi se ase .RAi nvolv est ypeI I
Ihy pe rs en siti
v i
tyr ea ction sa ndt hea ctiva t
ionofCD4Tc e ll
s,
result
inginc hr on icr elea seoft hei nfl
amma t
or yc y tok ine sIL -1, I
L -6, an dtumorn e cros i
sf a c t
or-α( TNF -α).The
acti
v a
tedCD4Tc e l
lsa lsos t
imul atet hepr oduc tionofr he uma t oidf a ct
or( RF )a n t
ibodi esa nda n ti
c ycli
c
cit
rull
i
n at
e dpe ptidea n t
i
bodi e s( anti-CCP)t ha tfor mi mmun ec ompl e xes. I
n crea se dle ve l
sofa c ute -pha se
protei
n s,suc ha sC- reac ti
v epr ote i
n( CRP) ,area l
s opr oduc e da spa rtoft hei nfl
a mma torypr oc e ssa nd
parti
cipatei nc ompl eme n tfixa t
ionwi tht hea ntibodi esont hei mmun ec ompl ex es .Thef or ma t
ionofi mmun e
compl exe sa n dr eac ti
ont ot hei mmun ef ac t
or sc aus ea ni nflamma torypr oc essi nj oints ,pa rt
i
c ularlyint he
han ds,f
e et, an dl egs .Di agn osisofRAi sba s edone l
e v atedl e ve l
sofRF ,a nti
-CCP, qua ntitati
veCRP, a ndthe
erythrocytes e dime nta t
ionr ate( ESR)( modi fiedWe ste rgre n). I
na ddi ti
on ,ra di
ogr a phs ,ul t
ra soun d, orma gn et
ic
resona ncei ma gin gs c an sc ani de nti
fyjoi ntd ama ge ,s uc ha se ros i
on s,al os sofbon ewi t
hi nthej oin t,and
narrowingofj oin tspa ce.
5. Sys te
mi cLupusEr ythe ma tos us( SLE)–a utoa n tibodi e sa tt
a c kma n yor ga ns .
a. Theda ma gea ndpa thologyofs yste mi cl upuse rythe ma tos us( SL E)i sc aus edbyt ypeI I
I
hy pe rs en siti
vityr ea cti
on s .Aut oa n t
ibodi espr oduc edi nSL Ea redi re cteda ga i
n stn uc l
ea ra nd
cy topl as mi cpr ot ein s.An ti-nucle ara ntibodi es( ANAs )a repr ese nti nmor etha n95%ofpa ti
e ntswi th
SL E, 16wi tha ddi ti
on a lau toa nt
ibodi e sin cludi nga nti-doubl e –s t
ran de dDNA( ds -DNA)a n da nt
i-Sm
an ti
bodi e s( an t
i
bodi est os ma l
ln uc l
e arr i
bon uc l
eopr ot e i
n ).An ti
-ds - DNAa n da n ti
-Sma ntibodi esa re
un iquet opa ti
en tswi t
hSL E; t
hus ,the i
rpr e se nc eisi n clude dint hec lass if
icationc rit
eri
aofSL E.
Ce l
lula rinte ractionwi tha utoa ntibodi esl ea dst on uc le ara ndc el
lula rde s tr
uc ti
on ,wi t
hc ompon ents
rele as eda fterc e l
l de athl ea di
ngt ot hef or ma ti
onofi mmun ec ompl e
x es .
b. Be c aus ea ut oa ntibodi esi nSL Ec ant a rge tawi dev ariet yofc ell
s ,s ympt omsofSL Ec a noc curin
ma nybodyl oc a t
ion s .Howe ver,themos tc ommons ympt omsi n c l
udef a t
igue ,fe v erwithn oot he r
ca us e ,ha irlos s,a n das un li
ght- se ns i
ti
v e" but te rf
ly"orwol f-ma sk( l
upus )r asht ha tisfoun dina bout
50%ofpe oplewi thSL E. Th era s hismos tof te ns ee nov ert hec he ek sa n dbr idgeoft hen os e,but
ca nbewi de s prea d. Ot he rs ympt omsma ya ppe arde pe n dingona ff
e cteda rea s. Thej ointsma ybe
affe cte d, l
e adingt oa rt
hr i
tisoft hef i
n ge rs, ha n ds ,wr i
s ts, an dk ne e s.Ef f
e ctsont hebr a i
na ndn ervous
sy ste mc anl edt ohe ada c he s,numbn e ss , t
ingl i
ng, se izur e s,visi
onpr oble ms , an dpe r
s on ali
tyc ha nges.
The rema ya l
s obea bdomi nalpa i
n ,na us e a,v omi ti
n g, a rrhy t
hmi a s ,shor tne ssofbr eath, an dbl oodi n
thes put um. Effec tsont hes ki
nc anl e adt oa dditi
on a la re asofs k i
nl es i
on s ,an dv asocon s tri
c t
ionc an
ca us ec olorc ha nge sint h ef i
nge rswhe nt he ya rec ol d( Ra ynaudphe nome non ).Ef f
ec tsont he
kidn e ysc anl e adt oe de mai nthel e gsa ndwe i
ghtga in.Adi a gnos i
sofSL Ede pe n dsoni de nti
ficati
on
off ou rof11oft hemos tc ommons ympt omsa ndc on f i
rme dpr oduc tionofa na rrayof
aut oa n ti
bodi e sun iquet oSL E.Apos i
tivet es tforANAsa l
on eisn otdi a gn os t
ic.

I
I
I
. 19.
3Or ganTranspla
n t
ati
onandRe ject
i
on
A.Tr
ans pl
antReject
ion
1. Re sul
tfr
omt iss
ues,or
gan s
,orbl
oodtr
anspl
ant
sthatar
en otcompa
ti
bl
ewit
htheti
ssue
softher
eci
pi
ent
.
The yarerecogni
zedasn on-
sel
fandatt
acke
d.
2. Inordertoreducerej
ect
ion,t
hebestpossi
bl
ema t
chissoughtandi
mmunosuppr
essi
vedr
ugsareus
ed.
 a
. Autogr
afts-t
issuesfromthesameperson
b
.Isograf
ts-ti
ssuesfromgen e
ti
cal
l
yiden
ti
c a
ltwi
ns
c
. Al
logra
fts-ti
ssuesfromnon-ge
neti
cal
l
yidenti
cal
per
sons
d
.Xenogr af
ts-ti
ssuesf r
omorgani
smsofdif
fere
ntspe
cie
s
B.Graf
t-versus-Hos tDi sea se( GVHD) .
Af or mofr e j
ecti
on, GVHDpr i
ma ri
lyoc cur si
nr e cipientsofbon ema rr
ow
t
ransplantsa ndpe ri
phe ralbloods temc e l
ls.GHVDpr ese ntsaun iques ituati
onbe ca us et het r
an spl
a ntedt i
ssueis
capableofpr oduc i
ngi mmun ec el
ls;APCsi nt hedon at
e dbon ema rr
owma yr ecogn izet hehos tc el
lsa sn on-sel
f,
l
eadi
n gtoa c
tivat
ionoft hedon orc yt
otox i
cTc el
ls.On c
ea ctivat
e d, t
hedon or’sTc ell
sa tt
a ckther ecipientc el
l
s,
causi
nga c ut
eGVHD
C.TheF utureofTr a nsplan t
ation
1. Hi s t
orical
lyspe a k
ing, thepr acti
ceoft ransplant
ingt i
ssues —a n dthec ompl i
c ati
on st hatc ana ccompa nys uch
proc edures—i sar e l
a t
ivel
yr ecen tde vel
opme nt.Itwa snotun ti
l1954t hatthef i
rs tsucc essful o
rga n
transplantat
ionbe twe e ntwohuma nswa sa c
hiev ed. Yett hefieldofor ga nt rans plantat
ionha spr ogress
e d
rapidlysincet hattime .
2. Non e t
he l
ess, t
hepr act i
ceoft ra
n splanti
ngn on-se l
ft i
ssue sma ys oonbe comeobs olete.Sc i
en t
istsa r
en ow
attempt i
n gtode velopme thodsb ywhi chn ewor ga n sma ybegr owni nv i
trof roma nindivi
dua l
’sown
ha rv
e stedc el
lst ore placeda ma ge dora bnorma lon es.Be c a
us eor gan spr oduc edi nthiswa ywoul dcon tai
n
thein div
idual’
sownc ell
s,theyc ouldbet r
ansplan t
e dintot hei ndivi
dua lwithoutr i
s kforre j
ec t
ion.
3. Ana l
ternati
vea pproa cht hatisga i
ningr enewe dr es ear
c hi nt
e r
e sti
sge neticmodi f
icati
onofdon oranima l
s,
suc ha spigs ,topr ovidet ran
s pl
a nt
a bleorganst ha tdon ote l
ici
ta nimmun er es pon seint her ecipient
.The
appr oachi nvolvese xcisi
ngthege ne sinthepig( int hee mbr yo)t hata remos tre spons i
blefort her ej
ecti
on
rea ct
iona ft
ert r
a nsplan ta
tion.Fi
n di
ngt he s
ege ne sa nde ff
e cti
velyre mov i
n gt he mi sac ha l
l
en ge, however .
So
tooisi denti
fyinga ndn eutral
i
z i
ngr i
sk sfromv ir
al se quenc e sthatmi ghtbee mbe dde dint hepi gge n
ome ,
pos i
n gar i
skf orinfe cti
oni nthehu ma nrecipi
ent.

I
V. 19.4I
mmun ode fi
ci
e nc i
esa reinhe ri
ted( pri
ma r
y)ora cqui red( sec on dary)dis order sinwhi che l
eme nt
sofhos timmun e
de
fensesaree i
th erabs entorf uncti
on all
yde fecti
ve .
A.Pr i
maryImmun ode fi
ci
e ncyPr ima r
yi mmun ode fi
c i
e nci
e s, whichn umbe rmor et ha n250, arec aus edbyi nhe ri
ted
def
ect
sofe ithern on spe ci
fi
cin nateors pe cif
ica da pti
vei mmun ede fenses .Inge n e r
al,pa t
ien t
sbor nwi thpr i
ma r
y
i
mmun ode f
ic i
e ncy( PI
)c ommon l
yha vea nincre ase ds us ce pti
bil
itytoi n
fec tion.
1. TChr onicGr a nuloma tousDi seas eThec ause sofc hron icgr anuloma tousdi s eas e(CGD)a r
ed efec tsi
nt he
NADPHox i
das es yst
e mofpha goc yt
icc e l
ls,i
n cludingn eutrophilsa n
dma cr
opha ge s,t
ha tpre ven tthe
produc ti
onofs upe r
ox i
der adicalsinpha golysos ome s.Thei nabil
ityt opr oduc es upe roxider adicalsimpa i
rsthe
an t
iba cterialactivi
tyofpha goc yt
e s.Asar e sult,i
n f
e cti
on si npa t
ien tswi thCGDpe r
s i
stlonge r,l
e adingt oa
chr on i
cloc a li
nfla
mma t
ionc a l
l
edagr a nuloma . Mi croorga nismst ha ta r
et hemos tc ommonc a use sof
infec ti
onsi npa tientswi t
hCGDi nc udeAs
l pergill
uss pp.,St aphyloc oc c
usa ureus ,Chr omoba cte r
ium
violac eum, Serrati
ama rces cens,a ndSa l
mon ell
at y phimur ium.
2. X- Lin kedAga mma gl
obul i
n emiaDe fi
c i
en ciesinBc el
l
sduet ode fe cti
vedi f
ferentiati
onl eadt oal a ckof
spe c if
ica nti
bodypr oduc ti
onk nowna sX- l
i
n keda ga mma globuline mia.In1952, Ogde nC. Brutonde s cr
ibed
thef i
rstimmun ode f
ic
ien cyinabo ywhos eimmun es yste mf ai
ledt oproduc ea n ti
bodi es.Thisd ef
e ctis
inhe rit
edont h eXc hromos omea ndisc ha racte ri
z edbyt hea bs en ceofi mmun ogl obulininthes e r
um; itis
ca l
ledBr utonX- l
inkeda ga mma globulinemi a(XL A) .Thede f
ecti
v ege ne,BTK, inXL Ai sn owk n ownt oe ncode
at yros i
nek inasec all
edBr ut ontyro si
n ek i
n ase( Bt k).I
npa ti
entswhos eBc ell
sa reun abletopr oduc es uffi
cien
t
amo un tsofBt k,theB- ce l
lma turati
ona nddi ff
e re nti
ati
onha l
tsatt hepr e -B- cellstageofgr owt h.B- ce l
l
ma turati
ona nddi ffe
re nt
iati
onbe yondt hepr e-B- ce l
lstageofgr owt hisr e quiredf orimmun oglobul i
n
prod ucti
on .Pa t
ien t
swhol a cka nti
bodypr oduc t
ions uff
e rfromr ec urrentin fecti
on sa l
mos te xclusivelyduet o
ex t
ra ce l
l
ula rpathoge n stha tcaus epy oge n i
cin fections: Ha emophi l
usin fl
ue n zae,St reptococ cuspn e umon iae,
S. py oge ne s,andS. aureus .Beca usec e l
l-me diate dimmun it
yisn otimpa ired,the sepa tientsa ren ot
pa rti
c ul
arlyv ulnerabletoi nfecti
on sc aus edbyv i
rus esori n tr
ace l
lularpa thoge ns.
3. Se lec ti
veI gADe fici
en cy.Themo stc ommoni n he ri
tedf ormofi mmun ogl obuli
nde fic
ien cyiss e l
ec t
i
v eIgA
de fi
c i
e ncy, af
fec t
i
n ga bouton ein800pe ople .I
n dividualswi ths el
e c ti
veIgAde fi
c i
en cypr oduc en or ma ll
e vel
s
ofIgGa ndI gM, buta r
en ota bl
et opr oduc es ecre toryIgA. I
gAde ficien
c ypr edispos est hes eindividua l
st olung
an dg astroint
e sti
na l
infecti
on sforwhi c hs e cr
e toryI gAi sn orma ll
ya nimpor tantde f
e nseme cha n
ism. I
nfecti
ons
 i
nt helungsa n dga strointe stina ltrac tcani nv olv eav ari
e tyofpa t
hoge n s, i
ncludin gH. i
n f
l
ue nza e,S.
pneumon i
ae , Mor ax ell
ac atarr ha l
is,S. aure us ,Gi ardialambl i
a ,orpa thoge ni
cs tr
a insofEs che ri
chiac oli.
4. SevereCombi n e dI mmun ode fi
cien cy( SCI D)
a . Pa tie ntswhos uffe rfr oms everec ombi ne dimmun ode fi
c i
e n cyha veB- cella ndT- c el
ld efe ctst ha t
impa i
rT- ce l
l depe n de nta ntibodyr es pon s esa swe l
l asc el
l-me diat
e di mmun ere spon se s. Pa ti
e nts
wi t
hSCI Da ls oc an n otde ve l
opi mmun ologica lme mor y,s ov ac c i
nespr ov i
det hemn opr ot ec ti
on ,and
li
v ea tt
e n ua t
e dv acc ine s( e.g.,
forv ari
c e l
la-zos t
e r,me as l
e sv ir
us , r
ota virus, pol i
ovi
rus )c ana c t
ua l
ly
c aus et hei n fectiont he ya rei nten dedt opr e ven t.Themos tc ommonf ormi sX- l
i
n kedSCI D, whi ch
a cc oun tsf orn e arly50%ofa l
lca sesa n doc curspr i
ma ri
lyinma les.Pa ti
e ntswi t
hSCI Da ret y picall
y
dia gn os e dwi thint hef ir
s tfe wmon thsofl ifea f
t erde velopin gs e vere, ofte nl i
fe-t
hr eaten i
n g,
oppor tun isti
ci nfe ctionbyCa ndidas pp. ,Pn eumoc ys ti
sj i
rov ecii,orpa thoge nics t
rainsofE. c oli
.
b . Wi tho utt re atme nt,ba bieswi t
hSCI Ddon otty picall
ys urv i
v ein f
a ncy. I
ns omec ase s,abon ema rrow
tran s plan tma ys uc c es sfull
yc or rectt hede f
e ctsinl y mphoc ytede velopme n tthatle adt ot heSCI D
phe n oty pe ,byr epla c i
n gt hede fec t
i
v ec ompon en t.Howe ve r,t
hi str
e a tme nta pproa chi sn otwi thout
risks , asde mon stra tedbyt hef amousc aseofDa v i
dVe tter(1971–1984) ,be tterk nowna s“ Bubbl e
Boy ”. Ve tte r
, apa t
ie ntwi thSCI Dwhol ivedi napr ot ectivepl asti
cbubbl et opr evente xpos ur et o
oppo rtun isti
cmi crobe s,re ce i
vedabon ema rrowt ra nspla ntfromhi ss ister. Be caus eo fal a ten t
Eps te i
n -Ba rrv irusi n f
e ctioni nhe rbon ema rr
ow, howe ve r
, hede v
elope dmon onuc l
eos isa n ddi e dof
Bur kittlymphomaa tt hea geof12y e ars.
B.Sec
on daryImmun ode fici
e nc y
1. Seco n
da ryImmun ode f
icien cyoc cur sasar e s ulta na cqui redi mpa irme n toff un ctionofBc el
ls,Tc e l
ls, orbot h.
Seco n
da ryimmun ode f
icien cie sc a nbec a use dby :
a . Sy s temi cdi sor de rss uc ha sdiabe t
e sme l
li
tus ,ma l
n utri
tion, he pa t
it
i
s ,orHI Vi n fecti
on
b .I mmun os uppr es sivet reatme ntss uc ha sc yt
ot oxicc he mot he ra py,bon ema rrowa bl
a t
ionbe fore
tran s plan ta t
ion ,orr a diationt he rapy
c . Pr olo nge dc ri
ti
c alil
ln es sd uet oin fection ,surge ry, ort raumai nt hev e ryy oun g,elde r
ly,orhos pitali
zed
pa tien ts
2. Unli
kepr i
ma ryi mmun ode f
ic i
e n ci
e s,whi chha v eage ne ti
cba s i
s ,sec on da r
yimmun ode fi
cien ci
esa reof ten
rever
sibl
ei ft heun de rlyi
n gc aus ei sr esolv ed. Pa ti
e ntswi ths e con da ryimmun ode fi
c ienciesde v elopa n
i
ncreas e
ds us c ept ibil
itytoa not he rwi s
ebe ni
gni nfec t
ionbyoppor tun i
s ti
cpa thoge nss ucha sCa ndi das pp.,P.
j
ir
ove ci
i,andCr ypt os por idi
um.
3. HIVinfecti
ona ndt hea ss oc i
a te da c quiredi mmun ode fi
c i
e nc ys y ndr ome( AIDS)a ret hebe st-
k nown
seconda ryimmun ode fici
e nc i
e s .AIDSi sc ha ra cterizedbypr of oun dCD4T- ce l
l l
y mphope nia(d ec rea sei n
l
ymphoc ytes ).Thede cre as ei nCD4Tc e ll
sist her e sultofv ariousme c ha n
is ms ,i
n c l
udingHI V- induc ed
pyroptosis(at ypeofa popt os i
st h ats ti
mul a
te sa nin f
lamma tor yr espon se),viral cy topa t
hice ffec t,an d
cytot
ox i
cit
yt oHI V- i
nfe cte dc e ll
s.
4. Themos tc ommonc a us eofs ec on daryi mmun ode fi
cien cywor l
dwi dei ss e
v e r
ema lnutri
ti
on ,whi cha ffe ct
s
bothinnatea n da da ptivei mmun i
ty .Mor er es ea rcha ndi nforma ti
ona r
en eede df ort hemor ec ommonc auses
ofsecon daryi mmun ode fici
e n c y;howe ve r,t
hen umbe rofn ewdi sc ove ri
e sinAI DSr esearchf a re xc ee dst hat
ofanyot hers inglec a us eofs e con da r
yimmun ode fi
cien cy.AI DSr e sea rchha spa idof fe xtreme l
ywe l
l i
nt e r
ms
ofdiscove r
ie sa n dt r
e atme n t
s ; i
nc rea s
e dr es ea rchi ntot hemos tc ommonc a us eofi mmun ode fi
c i
e n cy,
ma l
nutri
ti
on , woul dl i
k elybea sbe n efici
al.

V. 19.
5Ca ncerImmun obi
ologya ndImmun ot
herapy.I
tisknownt hatt
heimmun es yst
emc anrecogni
zeandde stroy
ca
ncerouscell
s,ands omer esear
c hersa n
dimmun ologi
stsa l
sobe l
i
eve,basedont heresultsofthei
rexperi
me nts,that
manycancersa r
ee l
i
mi nat
edbyt hebody ’
sownde fe
n sesbe f
oretheycanbec omeahe al
thpr obl
em.Thisideaisn ot
uni
ver
sall
yacc e
ptedbyr esearchers,howe ve
r,andne e
dsf ur
therinve
sti
gati
onf orveri
fi
cat
ion.
A.Ce ll
-MediatedRes ponsetoTumor s
1. Ce ll
-mediatedimmun er esponsescanbedi re
c t
eda gai
nstcancerc el
l
s ,
ma nyofwhi chdonotha vethe
n ormalcompl ementofs el
f-pr
otei
ns,mak i
ngthemat ar
getforel
i
mi nati
on.Abn ormalcance
rc el
lsma ya ls
o
pr esen
ttumora nt
i
gen s.Thesetumora nti
gensa r
en otapartofthes creeni
ngpr ocessusedtoe l
i
min ate
lymphoc ytesdurin
gde v
e l
opme nt
;t
hus ,
e venthoughtheyares e
lf-ant
igens,t
he ycans t
i
mulatea n
ddr ive
ada pti
veimmun eresponsesa gai
nstabnormal ce
ll
s.
 2. Pres entati
onoft umora ntige nsc ans t
imul aten aï vehe lpe rTc ell
st obe comea cti
v atedbyc ytok i
n ess ucha s
I
L -
1 2a nddi fferen t
iatein toTH1c el
ls.TH1c e l
lsre l
ea sec y t
ok ine st ha tc a na cti
v at
en atura lk i
l
ler( NK)c e l
l
sa nd
enha ncet hek i
ll
ingofa c ti
v atedc yto toxicTc e l
l
s .Bot hNKc e l
lsa ndc ytotoxicTc ellsc anr e cogn i
z ea ndt arget
canc erce l
lsa ndi n
duc ea popt osist hrought hea c ti
onofpe r f
or i
n sa n dgr an zyme s .I
na ddition ,ac ti
vated
cytotoxi
cTc el
lsc anbi n dt oc el
l-
s urfac epr oteinsona bn or ma lc ell
sa n dinduc ea popt os i
sbyas econ dk il
l
ing
me cha ni
s mc a
ll
e dt heCD95( Fas )c yt
ot ox icpa thwa y.
3. Des pit
et he seme cha nismsf orremov i
n gc anc erousc ell
sf romt hebody ,can cerr ema i
n sac ommonc aus eof
dea t
h.Un for tuna tel
y ,ma li
gn anttumor st e ndt oa c ti
ve l
ys uppr e sst hei mmun ere spon s ei nv a ri
ouswa ys .I
n
somec an c ers,thei mmun ec ell
st he ms elve sa rec anc erous .I
nl e uk e mi a,l
y mphoc ytest ha twoul dn orma l
l
y
faci
li
tatethei mmun er es pon s ebe comea bn orma l
.Inot he rc a nc ers ,thec anc erousc ell
sc a nb ecomer e si
stant
toinduc t
ionofa popt os i
s .Thi sma yoc curt hrought hee xpre s sionofme mbr anepr oteinst ha tshutof f
cytotoxi
cTc el
lsort hatin duc er eg ulator yTc e l
l
st ha tc ans hutdowni mmun er espon s e s.
4. Theme c ha nismsbywhi c hc ance rc el
lsa l
te rimmun er espon s esa res ti
l
l noty etfullyun de rstood, andt hisisa
verya cti
vea reaofr e sear ch.
B.Ca
nce
rVa c ci
ne s.The r
ea ret wot ype sofc a nce rv a cci
n es:pr eve nti
v ea ndt he rape uti
c .
1. Prev ent
ivev acc i
n esa reus edt opr e ven tc an cerfromoc cur ring, whe reast he rape uti
cv ac cine sa reus e dto
tr
ea tpatien tswi thc a nce r.Mos tpre ven ti
v ec a nce rvac cinest arge tv i
ral i
nfec t
ionst ha ta rek nownt olea dto
canc er.
The s einc l
udev a cc i
n esa ga i
n sthuma npa pill
oma virus( HPV)a ndhe patit
isB, whi chhe l
ppr even t
cervicalan dl i
ve rca nce r,re spe ct
ive l
y.
2. Mos tthe rape uticc an cerv ac ci
nesa reint hee xpe ri
me n tals tage .The ye xploittumor -spe c i
fica n ti
ge nst o
sti
mul atet hei mmun es y ste mt os e lectivelya ttackc anc erc e l
ls. Spe cif
ica l
l
y ,t
he ya imt oe n ha n ceTH1f un cti
on
andi nt
e r
a c t
ionwi t
hc ytotox icTc ell
s ,whi c h,intur n,res ult
si nmor ee f
fe cti
vea t
tac kona bn orma ltumorc el
ls.
I
ns omec a ses,r esea r
c he rsha veus edge ne t
ice ngine eringt ode ve lopa nt
itumorv acc i
n esi na na pproa ch
si
mi l
artot ha tus edf orDNAv accine s.Thev a cci
n ec on tai
n sar ec ombi na ntplas midwi thge n esf ortumor
anti
ge ns;the ore ti
ca l
ly,thet umorge newoul dn otinduc en e wc a nc erbe caus eitisn otf un cti
on al
, butitc ould
tr
ickthei mmun es ys t
emi ntot ar
g etingt het umorge nepr oduc ta saf ore i
gni nvade r
.
a. Thef i
rstF DA- a ppr ov edt he rape ut i
cc a ncerv ac cinewa ss ipule uce l
-T( Prov en ge ),a ppr ov edin2010
tot re atc ertai
nc a sesofpr os tatec an cer.Thisun c on ve n t
ion al vacc i
n eisc us tomde s igne dus ingt he
pa tient’
sownc e l
ls. APCsa rer e mov edf romt hepa t
ie nta n dc ult
ur edwi that umor -
s pe cifi
cmol ecule;
thec e
ll
sa r
et he nr eturnedt ot hepa t
ient.Thisa ppr oa c ha ppe a rstoe nha ncet hepa tient’simmun e
re spon s ea ga i
n stt hec an ce rc ell
s .
b. An othe rthe rape ut i
cc a nce rva c ci
n e( tal
imoge n elahe rpa repv e c,alsoc a l
ledT- VECorI ml ygic)wa s
a ppr ove dbyt heF DAi n2 015f ort reatme ntofme lan oma , af ormofs kinc anc e r.Thi sv a cci
n e
c on tai
nsav ir
ust ha tisinjec t
edi ntot umor s,whe rei tinf ectsa n dlyse sthet umorc e l
ls.Thev ir
usa ls
o
induc esar espon s einl e
s i
on sort umor sbe s i
de st hos ei ntowhi c hthev ac cinei sin j
e c t
e d,indi
c ati
ng
tha titiss ti
mul a ti
n gamo r ege n e ral(asoppos e dtol oc al)a n t
itumori mmun er es pon s eint hepa ti
e nt
.