L 18 P?L8SLnSl1lvl1?

LLA8nlnC C8!LC1lvLS
O 1he classlflcaLlon of hypersenslLlvlLy reacLlons
O 1he dlseases assoclaLed wlLh hypersenslLlvlLy reacLlons
O DndersLand Lhe mechanlsms of damage ln hypersenslLlvlLy reacLlons
O 1he meLhods for dlagnoslng condlLlons due Lo hypersenslLlvlLy
O 1he modes of LreaLlng dlseases due Lo hypersenslLlvlLy and Lhelr raLlonale

P?L8SLnSl1lvl1?
PypersenslLlvlLy reacLlons are made ln response Lo lnherenLly harmless 'envlronmenLal' anLlgens such as
pollen food and drugs
lL's an undeslrable reacLlon produced by Lhe normal lmmune sysLem 8eacLlons are normally damaglng
dlscomforLproduclng or someLlmes even faLal
lL requlres a presens|t|zed (lmmune) sLaLe of Lhe hosL le Lhe person has Lo have been exposed already
Lo Lhe allergen
lL can be dlvlded lnLo four Lypes l lv 1hese dlffer based on Lhe mechanlsms lnvolved and Lhe Llme Laken
for Lhe reacLlon
requenLly a parLlcular cllnlcal condlLlon (le dlsease) may lnvolve more Lhan one Lype of reacLlon
LA1D8LS
1 lL lnvolves anLlbodles ln Lype l (lgL) ll and lll (lgC)
2 lL lnvolves 1cells ln Lype lv
3 resenslLlzaLlon Lo anLlgen ls requlred
CLASSllCA1lCn
@pe Descr|pt|ve name In|t|at|on t|me
I lgL medlaLed hypersenslLlvlLy 230 mln
II AnLlbodymedlaLed cyLoLoxlc hypersenslLlvlLy 38h
III lmmune complexmedlaLed hypersenslLlvlLy 28h
IV CellmedlaLed hypersenslLlvlLy 2472h

1?L l P?L8SLnSl1lvl1?
ln Lhe ma[orlLy of allergles (Lype l) such as Lhose Lo food pollen and house dusL reacLlons occur because of
Lhe lndlvldual has become sens|t|zed Lo an lnoffenslve anLlgen Lhe a||ergen by produclng lgL
1
anLlbodles
agalnsL lL SubsequenL exposure Lo Lhe allergen Lrlggers acLlvaLlon of lgLblndlng cells (lncludlng masL cells and
basophlls whlch have Lhe c8l recepLor Lo blnd lgL) ln Lhe exposed Llssue leadlng Lo a serles of responses LhaL
are characLerlsLlc of allergy and are known as allerglc reacLlons


1
lgL dlffers from oLher abLs lsoLypes ln belng predomlnanLly locallzed ln Llssues 1he producLlon of lgL ls drlven
by 1h2 cells
CPA8AC1L8lS1lCS
IgLmedlaLed
Anaph|act|c An acuLe allerglc reacLlon Lo an anLlgen (eg bee sLlng) Lo whlch Lhe body has become
hypersenslLlve
Immed|ate hypersenslLlvlLy
lnduced by anLlgen called a||ergens
PlsLory Culnea plgs were senslLlzed wlLh egg albumln 1hen challenged 2 weeks laLer wlLh Lhe same
anLlgen ln 2 mlnuLes Lhey sLarLed wheezlng smooLh muscle conLracLlons and even deaLh
2
(when
lngesLed)
ALLL8CLnS
AnLlgens LhaL can sLlmulaLe |nappropr|ate IgL product|on 1hey enLer vla |nha|at|on or |ngest|on ALoplc
(allerglc) people have IgL ln serum
Lxamples nuLs seafood eggs cockroach penlclllln house dusL mlLe pollen spores caLs dogs eLc
MLCPAnlSM
l8S1 LxCSD8L
1 lrsL exposure Lo allergen
2 AnLlgen recognlLlon acLlvaLes 1h2 cells and Lhese wlll secreLe
Lhe cyLoklne lL4 (and lL3) lL4 wlll Lhen sLlmulaLe class
swlLchlng Lo lgL 8 cells
3 lgL 8 cells become memory and plasma cells lasma cells wlll
secreLe lgL
4 1he free lgL wlll blnd Lo c recepLors on masL cells (Llssue) and
basophlls (blood)
3

SLCCnu LxCSD8L
1 8epeaLed exposure Lo allergen
2 AcLlvaLlon of masL cell by allergen cross||nk|ng to IgL
4
whlch ls
bound Lo c recepLors
3 lnduces degranulaLlon release of vasoacLlve subsLances
MLulA1C8S
PlsLamlne seroLonln eoslnophll
chemoLacLlc facLor neuLrohpll chemoLacLlc
facLor leukoLrlenes (and prosLaglandlns)
LffecLs of Lhese medlaLors are 1) lncrease ln
vascular permeablllLy 2) vasollaLlon and
smooLh muscle conLraLlon

2
Muscle conLracLlons so LlghL LhaL couldn'L breaLhe SysLemlc oedema followed by shock (low 8 and fallure
of vlLal organs)
3
1hey are now armed masL cells ready Lo release Lhelr granules ln Lhe nexL exposure
4
1wo anLlbodles need Lo be acLlvaLed by Lhe allergen
CCnSLCDLnCLS C 1?L l 8LAC1lCnS
SS@LMIC ANAnLAkIS
When reexposure Lo allergen Lrlggers an allerglc reacLlon Lhe effecLs are focused on Lhe slLe aL whlch masLcell
degranulaLlon occurs lf Lhe allergen enLers Lhe bloodsLream or ls rapldly absorbed by Lhe guL lL wlll acLlvaLe
masLcells LhaL are assoclaLed wlLh blood vessels 1hls acLlvaLlon causes a very dangerous syndrome known as
sstem|c anaph|ax|s
S?M1CMS clrculaLlng masLcell acLlvaLlon leads Lo poLenLlal faLal effecLs LhaL are generally known as
anaph|act|c shock
1 1he wldespread lncrease ln vascular permeablllLy ln Lurn leads Lo drasLlc fall ln 8
2 Alrways consLrucLlon leads Lo breaLh dlfflculLles
3 Swelllng of eplgloLLls can cause suffocaLlon
CADSL lL ls occaslonally seen ln humans allergens can be bee sLlngs penlclllln food (peanuLs or seafood)
S1ACLS
l Cenerallsed lLchlng (urLlcarla)
ll Swelllng away from Lhe sLlng (lnconLlnence)
lll ulfflculLy ln breaLhlng
lv all ln blood pressure loss of consclousness
18LA1MLn1S ln[ecLlon wlLh eplnephrlne 1hls wlll lead Lo relaxaLlon of smooLh muscles and reduces vascular
permeablllLy
LCCALI2LD ANAnLAkIS (Atop%
lL usually lnvolves a locallzed area of Lhe eplLhella aL Lhe slLe of enLry of Lhe allergen
ALLLkGIC knINI@IS (na fever%
Allergen enLry by lnhalaLlon (eg pollen) wlll acLlvaLe Lhe masL cells beneaLh Lhe nasal eplLhellum ln
areas such as con[uncLlve and nasal mucosa
S?M1CMS waLery eyes sneezlng coughlng and mucus

AS@nMA
ls a more serlous syndrome whlch ls Lrlggered by allergenlnduced acLlvaLlon lf submucosal masL cells
ln Lhe lower alrways
ALLL8CLnS pollen dusL vlruses lnsecL producLs eLc
MLCPAnlSM MasLcell degranulaLlon affecLlng Lhe lower resplraLory LracL
LLC1S S?M1CMS 1) bronchlal smooLh muscle consLrlcLlon 2) oedema 3) mucus producLlon
and 4) lnflammaLlon All Lhese lead Lo alrway obsLrucLlon and resplraLory dlfflculLles

CCD ALLLkGILS
1he crossllnklng of lgL (le acLlvaLlon of masL cells) happens along Lhe Cl LracLs due Lo Lhe lngesLlon
of Lhe allergen Powever Lhe allergen may spread Lo skln (le Wheal and flare reacLlon causes
readness ln Lhe skln)
LLC1S S?M1CMS Muscle consLrlcLlon and vasodllaLlon leadlng Lo vomlLlng and dlarrhea

uL1LC1lCn C 1?L l 8LAC1lCn
lnLradermal ln[ecLlon or scraLchlng
Wheal and flare reacLlon happens wlLhln 30 mlnuLes
4 SklnL LesL
4 ueLermlnaLlon of Lhe LoLal serum lgL
8adlolmmunosorbenL LesL (8AS1)
3

AnLllgL ln agarose beads Lo deLecL anLlgenlgL blndlng
lMMLulA1L Anu LA1LPASL 8LAC1lCnS
1he lnflammaLory response afLer lgLmedlaLed masLcell
acLlvaLlon occurs as an lmmedlaLe reacLlon (seconds) and a
laLe reacLlon (812h) 1hese reacLlons can be dlsLlngulshed
cllnlcally
1he |mmed|ate response ls caused by Lhe dlrecL effecLs on
blood vessels and smooLh muscle of rapldly meLabollzed
medlaLors such as hlsLamlne released by masLcells
1he |ate phase response ls caused by Lhe effecLs of an lnflux
of lnflammaLory leukocyLes (eoslnophlls and basophlls)
aLLracLed by chemoklnes and oLher medlaLors (recrulLmenL)
released by masL cells durlng and afLer laLephase response

1PL8A?
1 Avold allergen
2 PyposenslLlzaLlon
Cradually lncrease exposure Lo allergen
lgC response predomlnaLes and clears allergen before lL blnds Lo lgL on masL cells
3 AnLlhlsLamlne (pharmacologlcal)
8lnds Lo hlsLamlne recepLors on mucosa






3
A kAS@ test ls a blood LesL used Lo deLermlne Lo whaL subsLances a person ls allerglc 1hls ls dlfferenL from a skln allergy LesL whlch
deLermlnes allergy by Lhe reacLlon of a persons skln Lo dlfferenL subsLances 1he suspecLed allergen ls bound Lo an lnsoluble maLerlal and
Lhe paLlenLs serum ls added lf Lhe serum conLalns anLlbodles Lo Lhe allergen Lhose anLlbodles wlll blnd Lo Lhe allergen 8adlolabeled anLl
human lgL anLlbody ls added where lL blnds Lo Lhose lgL anLlbodles already bound Lo Lhe lnsoluble maLerlal 1he unbound anLlhuman lgL
anLlbodles are washed away 1he amounL of radloacLlvlLy ls proporLlonal Lo Lhe serum lgL for Lhe allergen
1?L ll P?L8SLnSl1lvl1?
1he mechanlsm lnvolves an anLlbodymedlaLed cyLoLoxlc hypersenslLlvlLy 1hls lnvolves an anLlbodymedlaLed
desLrucLlon of cells 1he anLlbody blnds nk cells neuLrophlls eoslnophlls and macrophages vla Lhe c recepLor
and Lhese secreLe cyLoLoxlns afLer Lhe anLlbody recognlzes Lhe anLlgen" on Lhe cell surface

IgG and IgM on Lhe cell surface or exLracellular maLrlx Llssue
Ant|boddependent ce||med|ated ctotox|c|t (ADCC% le nC1 phagocyLosls buL opsonlsaLlon and
acLlvaLlon of Lhe complemenL sysLemMAC
6
(C3b)
1?L ll P?L8SLnSl1lvl1? ulSLASLS
18AnSDSlCn 8LAC1lCnS
1he effecL of donor red blood cells when Lhey are exposed Lo reacLlve anLlbodles ln hosL whlch are agalnsL Lhe
donor blood group anLlgens



A8C 8LCCD GkCU INCCMA@I8ILI@
A8C lncompaLlblllLy ls an lmmune sysLem reacLlon LhaL occurs when blood from Lwo dlfferenL and
lncompaLlble blood Lypes are mlxed LogeLher 1he Lypes are based on small subsLances (molecules) on Lhe
surface of Lhe blood cells ln people who have dlfferenL blood Lypes Lhese molecules acL as lmmune sysLem
Lrlggers (anLlgens) Lach person has a comblnaLlon of Lwo of Lhese surface molecules 1ype C lacks any
molecule eople who have one blood Lype form proLelns (anLlbodles) LhaL cause Lhelr lmmune sysLem Lo
reacL agalnsL oLher blood Lypes 8elng exposed Lo anoLher Lype of blood can cause a reacLlon 1hls ls lmporLanL
when a paLlenL needs Lo recelve blood (Lransfuslon) or have an organ LransplanL 1he blood Lypes musL be
maLched Lo avold an A8C lncompaLlblllLy reacLlon


6
Membrane aLLack complex
CLlnlCAL MAnlLS1A1lCn
naemo|s|s of k8C whlch ls complemenLed medlaLed 1hls wlll lead Lo 1) haemog|ob|n re|eased ln
blood and 2) haemoglobln wlll be converLed Lo blllrubln
8|||rub|n |s Loxlc ln hlgh amounLs and also glves Lhe yellow characLerlsLlc colour ([aundlce or yellow
skln)
naemog|ob|nur|a
7

ever nausea chllls


PALMCL?1lC ulSLASLS
nALMCL@IC DISLASL C NLW8CkN (nDN8%
1hls occurs when Lhe moLher makes lgC anLlbodles speclflc for 8hsus or 8h blood group anLlgen expressed on
Lhe 88C of her foeLus
A 8h moLher of a 8h+ foeLus can become lmmunlzed Lo feLal 88C LhaL enLer Lhe maLernal clrculaLlon aL Lhe
Llme of dellver (a loL of bleedlng) 1hus ln a subsequenL pregnancy wlLh 8h+ foeLus lgC
8
anLl8h anLlbodles can
cross Lhe placenLa and damage Lhe foeLal 88Cs






DkUGINDUCLD nALMCL@IC ANALMIA
An example of 1ype ll dlseases ln whlch Lhe drug blnds Lo Lhe cell surface and serves as a LargeL for anLldrug
lgC anLlbodles LhaL cause desLrucLlon of Lhe cell
lL ls caused by cerLaln ant|b|ot|cs 1he anLlbloLlc Lhen ls broken down ln small molecules (by meLabollsm) and
blnd Lo 88C surface 1hen Lhe anLlbloLlc parLlcle wlll acL llke a hapten ant|gen
9
and Lhus wlll lnduce lgC
anLlbodles Lo blnd Lo Lhe hapLen anLlgen 1he anLlbloLlc" lgC anLlbody blndlng leads Lo acLlvaLlon of
comp|ementmed|ated haemo|s|s
An1l8lC1lCS penlllln cephalosporln sLrepLomycln (fungl)
18LA1MLn1 wlLhdraw of drug

7
ls a condlLlon ln whlch Lhe oxygen LransporL proLeln hemoglobln ls found ln abnormally hlgh concenLraLlons ln Lhe urlne 1he condlLlon ls
ofLen assoclaLed wlLh hemolyLlc anemla ln whlch red blood cells (88Cs) are desLroyed Lhereby lncreaslng levels of free plasma
hemoglobln 1he excess hemoglobln ls fllLered by Lhe kldneys whlch release lL lnLo Lhe urlne glvlng urlne a red color
8
lgM anLlbodles cannoL cross Lhe placenLa
9
a small molecule LhaL can ellclL an lmmune response only when aLLached Lo a large carrler such as a proLeln
AD1ClMMDnL
10
ulSLASL vlA 1?L ll
GCCDAS@UkL'S
SNDkCML

Ant|bod|es to certa|n basement membrane prote|ns 1he anLlbody blnds Lo Lhe basemenL
membrane collage of rena| glomerull and pu|monar alveoll causlng acLlvaLlon of Lhe
|eukoctes (monocyLes neuLrophlls basophlls and masL cells) and Lhe release of Lhelr
chemoklnes ln addlLlon Lhe blndlng of Lhe abs can also cause a local acLlvaLlon of
comp|ement And as a flnal resulL Lhe Llssue wlll be severely damaged

MAS@nLMIA
GkAVIS

ln Lhls case Lhe anLlbodles are auLoanLlbodles agalnsL Lhe nlcoLlnlc acet|cho||ne receptors
aL Lhe NMI As a resulL neuromuscular transm|ss|on |s b|ocked (le no sLlmulaLlon Lo
muscles) 1he flnal sympLom ls extreme weakness

LMnIGUS

AnLlbodles Lo ce|| [unct|ons (desmosomes) SympLoms a loL of bllsLerlng on Lhe skln
affecLed (chlcken wlre appearance)

DIA8L@LS

AnLlbodles agalnsL |s|et ce|| ant|gens lnsulln gluLamlc acld decarboxylase (CAu) and
Lyroslne phosphaLlse (lA2)


1?L lll P?L8SLnSl1lvl1?

1he paLhology ls caused by Lhe deposlLlon of anLlgenanLlbody aggregaLes (or |mmune comp|exes) ln
parLlcular Llssues and slLes
11

lmmooe complexmeJloteJ bypetseosltlvlty teoctloos Joe to lotqe omooots of petslsteot lmmooe complexes lo
tlssoes ooJ otqoos
MLCPAnlSM
1 1he anLlgenanLlbody complex (soluble) deposlLs on Lhe Llssue
2 1hls wlll acLlvaLe Lhe compllmenL paLhway
C3a C4a ad CSa releases leads Lo
l masL cell degranulaLlon (lnflammaLory responses)
ll C3a and C3a aLLracL neuLrophlls whlch kllls nearby cells by lyLlc
enzymes
C3b also acLs as opsonln for neuLrophlls (phagocyLosls)
MAC
12
lnvolved ln cell kllllng Loo




10
AgalnsL own cells 1hese cells are orlglnally hldden (sequesLed) and for Lhls reason Lhe anLlbodles wlll noL be able Lo recognlze Lhem as
own
11
lmmune complexes are generaLed ln all anLlbody responses buL Lhelr paLhogenlc poLenLlal ls only lnduced when Lhe small complexes
are noL ellmlnaLed afLer Lhe lmmune response and clearance of Lhe lnfecLlon
12
Membrane aLLack complex
1?L lll P?L8SLnSl1lvl1? ulSLASLS
LCCALlZLu 8LAC1lCnS
Ak@nUS kLAC@ICN 1rlggered when Lhe deposlLlon of lmmune complex happens on Lhe sk|n or
|ung Llssue

AGA8 CCMLLk AcLlvaLes complemenL neuLrophlls and anaphylaLoxlns are lnvolved

Lk@nLMA AND CLDLMA 8edness and swelllng Can be caused by an |nsect b|te

AkMLk'S LUNGS 1hls person ls exposed Lo hlgh doses of |nha|ed a||ergens and lmmune
complexes are deposlLed ln Lhe wa||s of a|veo|| 1hls leads Lo accumulaLlon of
fluld proLeln and cells ln Lhe wall causlng slow bloodgas lnLerchange and
compromlslng lung funcLlon

CLnL8ALlZLu 8LAC1lCnS
1hls ls due Lo clrculaLlng lmmune complexes
SLkUM SICkNLSS 8esulLs from Lhe ln[ecLlon of poor| catabo||zed forelgn proLelns lnLo
b|oodstream
13


An1lCLnS penlclllln amoxlclllln horse serum proLelns (anLldlphLerla Loxln)

S?M1CMS fever rashes redness swelllng may lnvolve lnflammaLlon of Lhe
glomerull of Lhe kldneys

SS@LMIC LUUS
Lk@nLMA@CSUS (SLL%
AuLoanLlbodles are agalnsL Lo se|f ant|gens and ln Lhls case Lhe LargeLs are
DNA h|stones and k8Cs 1he lmmune complexes are deposlLed on blood
vessels kldneys [olnLs skln hearL lungs bralns

lL wlll acLlvaLe Lhe complemenL paLhway and resulLlng ln Llssue damage

lL occurs more ln females (101) beLween 2040 years old And a sympLom ls
Lhe buLLerfly rash on Lhe cheeks

1?L lv P?L8SLnSl1lvl1?

lL ls ce||med|ated (by 1h) noL humoral le anLlbodles are noL lnvolved Also known as de|aedtpe
hpersens|t|v|t (D@n% Slgns are vlslble afLer 2472h afLer anLlgen lnLroducLlon ln Lhe hosL
lL ls lmporLanL ln conLrolllng cerLaln lnfecLlons such as schlsLosomes (paraslLes) and Luberculosls lL may also
lead Lo granuloma formaLlon
14



13
uue Lo drug senslLlvlLy 1he drug ls poorly meLabollzed and small parLlcles are lefL ln Lhe blood
14
lncompleLe clearance of paLhogen leads Lo overproducLlon of cyLoLoxlc cells Pardenlng of Lhe cells
MLCPAnlSM
ln Lhe senslLlzed lndlvual
1 AnLlgen ls processed by AC and presenLed on MPC class ll Lo 1C8 on 1P1 cell 1he
anLlgen normally has enLered Lrough Llssue and lL needs Lo meeL an ACs 1hls AC
Lhen needs Lo Lravel Lo Lhe lymph node so lL can presenL lL or Lhls reason u1P ls
'delayed'
2 1hen acLlvaLed 1h1 cells secreLe prolnflammaLory cyLoklnes And also recrulLmenL of
more 1 cells and macrophages Lo slLe of anLlgen occurs MlgraLlon of new leukocyLes
also Lakes lLs Llme
3 lnflammaLlon aL slLe of anLlgen exposure

u1P 8LAC1lCn
(1) AnLlgen ln Llssue enLers afferenL lymphaLlc vessel and ls
LransporLed Lo lymph node
(2) uC presenLs anLlgen Lo Cu4 1 cells whlch are sLlmulaLed Lo
become 1h cells (1h1)
(3) 1h recognlze anLlgen presenL on monocyLes and release
1n
1n acLs on Lhe endoLhellum Lo recru|t monoctes and @h
ce||s from b|ood
1h cells also secreLe ln and lL2 (LogeLher wlLh 1n) and
act|vates t|ssue macrophage and recru|ted monoctes Lo
become efflclenL aL kllllng paLhogens
AnLlgen ls processed by Llssue macrophages (ACs) and ln Lurn
wlll sLlmulaLe 1h1 cells Lo secreLe



Chemok|nes

8ecrulL macrophages Lo slLe of anLlgen deposlLlon
IN 1 lnduces expresslon of vascular adheslon molecules
2 AcLlvaLes macrophages lncreaslng release of lnflammaLory medlaLors

@N and @N


1 Cause local Llssue desLrucLlon
2 lncrease expresslon of adheslon molecules on local blood vessels
IL3] GMCS SLlmulaLe monocyLe producLlon by bone marrow sLem cells
1?L lv P?L8SLnSl1lvl1? ulSLASLS
CCN@AC@ kLAC@ICN
lL ls lnduced by nlckel cosmeLlcs polsonlvy 1hese wlll be leaklng anLlgens LhaL wlll reach Lhe lymph node vla
clrculaLlon
l8S1 CCn1AC1 Lhe small molecules wlll peneLraLe Lhe skln and con[ugaLe Lo self proLelns
13
1hls resulLs ln
senslLlzaLlon
SLCCnu CCn1AC1 1he anLlgen ls presenLed Lo senslLlzed 1h1 cells by ACs 1hen 1h1 wlll secreLe cyLoklnes
LhaL wlll ln Lurn lead Lo lnflammaLlon

@U8LkCULIN kLAC@ICN
lL ls a skln LesL used Lo deLermlne Lhe presence of 1dLh cells Lo Luberculosls Also used Lo check Lhe lmmune
sLaLus of vacclnaLed populaLlons
llLraLe from old 18 culLures and ln[ecLed lnLradermal
8LSDL1S Lrthema (redness) and harden|ng (lnduraLlon) afLer 23 days lndlcaLes LhaL Lhere has been a
prev|ous exposure Lo Luberculln




13
lmporLanL LhaL Lhese small parLlcles of anLlgen are bound Lo a self proLeln so lL wlll be carrled
De|aed hpersens|t|v|t react|ons

@pe keact|on t|me C||n|ca| appearance n|sto|og Ant|gen and s|te

Contact (D@n%

4872h

eczema

1cells (secreLe 1n Lo
aLLracL macrophages eLc)


epldermal
@ubercu||n 4872h Local hardenlng 1 cells monocyLes and
macrophages

lnLradermal
(Luberculln)
Granu|oma 2128 days Pardenlng Macrophages glanL cells 1
cells flbrosls
erslsLenL anLlgen
(lncompleLe
clearance)