AUTOIMMUNITY

Prof. Emad A Koshak

Professor and Consultant
nternal Medicine, Allergy & mmunology
King Abdulaziz University- Faculty of Medicine
The immune sysfem normoIIy
ocquires seIf foIeronce by cIonuI
deIetion of uutoreuctive T ceIIs
in fhe fhymus before birfh ond by
functionuI suppression of
ouforeocfive T ond 8 ceIIs of
Iofer sfoges of deveIopmenf.
The immune sysfem normoIIy
ocquires seIf foIeronce by cIonuI
deIetion of uutoreuctive T ceIIs
in fhe fhymus before birfh ond by
functionuI suppression of
ouforeocfive T ond 8 ceIIs of
Iofer sfoges of deveIopmenf.
8ockground on infIommofion 8ockground on infIommofion
The word infIommofion IiferoIIy meons
"burning."
InfIommofion occurs in
response fo o ronge of froumos
from sunburn ond wounds, fo
infecfion ond oufo-immune
condifions. Whofever fhe couse,
fhis process is bosicoIIy fhe
some....
InfIommofion occurs in
response fo o ronge of froumos
from sunburn ond wounds, fo
infecfion ond oufo-immune
condifions. Whofever fhe couse,
fhis process is bosicoIIy fhe
some....
"SHAPP" "SHAPP"
Poin
SweIIing
Heof
Pedness
Heof ond redness resuIf from diIofion of fhe
smoII bIood vesseIs in fhe injured oreo ond
increosed IocoI bIood fIow.
8ecouse bIood vesseIs become more permeobIe
during infIommofion, profein rich exudofe
escopes from bIood pIosmo fo fhe domoged fissue
ond couses sweIIing.
Poin is beIieved fo resuIf from such chemicoI
subsfonces os serofonin, specific cyfokines or
from fension of fissue over fhe infIomed oreo.
Aufoimmune
disorders ore o diverse
group of condifions,
which occur due fo
obnormoI sfimuIofion ond
signoIing wifhin fhe
immune sysfem. "SeIf"
versus "non-seIf"
recognifion is oIfered.
Aufoimmune
disorders ore o diverse
group of condifions,
which occur due fo
obnormoI sfimuIofion ond
signoIing wifhin fhe
immune sysfem. "SeIf"
versus "non-seIf"
recognifion is oIfered.
An oufoimmune
response occurs
becouse, for some
reoson, heIper T
ceIIs recogni;e o
ceII of fhe body
(or seIf ceII) os
foreign, ond mork
if for desfrucfion.
xompIes of
Aufoimmune
Diseoses:
uIfipIe scIerosis
yosfhenio grovis
(ocefyIchoIine recepfor
oufoonfibodies)
Aufoimmune neuropofhies
such os 0uiIIoin-8orr
Aufoimmune uveifis
Mervous Sysfem: Mervous Sysfem:
0osfroinfesfinoI Sysfem: 0osfroinfesfinoI Sysfem:
Crohns Diseose
UIcerofive coIifis
Primory biIiory cirrhosis
Aufoimmune hepofifis
Iood: Iood:
Aufoimmune hemoIyfic onemio
Pernicious onemio
Aufoimmune fhrombocyfopenio
eisho, o Iob/ferrier/sponieI mix, wos 3 yeors oId when
she wos diognosed wifh oufoimmunue hemoIyfic onemio in
Jonuory of I99Z.
AnfiphosphoIipid onfibody
$in: $in:
Psoriosis
Dermofifis herpefiformis
Pemphigus vuIgoris
VifiIigo
ndocrine: ndocrine:
D
Hoshimofo fhyroidifis
0roves diseoses
Addison diseose
DM
is on exompIe of on
oufoimmune
disorder in which
8efo ceIIs of fhe
poncreose show
desfrucfion.
(poncreofic befo-ceII
ouforeocfive T ceIIs ond
oufoonfibodies)
Type I (insuIin -
dependenf) diobefes
Type I (insuIin -
dependenf) diobefes
ndocrine: ndocrine:
0rove's Diseose 0rove's Diseose
0roves Diseose is on
oufoimmune condifion fhof
sfrikes more women fhon
men of o rofe of 7:I. If
offecfs fhe funcfioning of
fhe fhyroid ond couses
hyperfhyroidism, buf if
con oIso offecf fhe fissue
surrounding fhe eyes.
#eumutoIogy: #eumutoIogy:
SL
PA
Sysfemic SceIerosis
Dermofomyocyfis
Progressive
systemic
scIerosis
is on exompIe of on
oufoimmune
disorder in which
skin ceIIs show
exfensive dermoI
fibrosis.
AnkyIosing spondyIifis
oIor rosh oIor rosh
$ is fhe mosf
commonIy known
oufoimmune disorder.
This chorocferisfic
"bufferfIy" rosh is mode
worse by exposure fo
sunIighf.
Lupus is o pofenfioIIy
fofoI oufoimmune diseose
fhof sfrikes I in Z,000
Americons ond I0 fimes
os mony women os men.
Pheumofoid orfhrifis Pheumofoid orfhrifis
Among fhe mosf serious ond
disobIing fypes of orfhrifis, Z.I
miIIion Americons Iive wifh
rheumofoid orfhrifis.
Abouf one
ouf of seven
Americons exhibif
some form of
orfhrifis.
ony chronic infIommofory
diseoses hove been shown fo
occur preferenfioIIy in individuoIs
corrying cerfoin vorionfs of HC
(mojor hisfocompofibiIify
compIex) genes.
ony chronic infIommofory
diseoses hove been shown fo
occur preferenfioIIy in individuoIs
corrying cerfoin vorionfs of HC
(mojor hisfocompofibiIify
compIex) genes.
A 0enefic Connecfion7 A 0enefic Connecfion7
HC 0enes HC 0enes
There ore fwo cIosses of HLA onfigens:
cIoss I onfigens (HLA Cw)
cIoss II onfigens (HLA D# [und DQ & DP])
There ore:
ZZ differenf HLA A onfigens
4Z differenf 8 onfigens
9differenf Cw onfigens
I8 differenf DP onfigens
Pheumofoid orfhrifis (PA)
offecfs peripheroI joinfs ond
moy couse desfrucfion of
bofh corfiIoge ond bone. The
diseose offecfs moinIy
individuoIs corrying fhe D#
vorionf of HC genes.
This focf con Ieod fo beffer
prognoses ond in oiding
efforfs fo chonge immune
reocfions fhof invoIve fhe
DP4 vorionf whiIe Ieoving
ofher reocfions infocf.
Pheumofoid orfhrifis (PA)
offecfs peripheroI joinfs ond
moy couse desfrucfion of
bofh corfiIoge ond bone. The
diseose offecfs moinIy
individuoIs corrying fhe D#
vorionf of HC genes.
This focf con Ieod fo beffer
prognoses ond in oiding
efforfs fo chonge immune
reocfions fhof invoIve fhe
DP4 vorionf whiIe Ieoving
ofher reocfions infocf.
AnkyIosing spondyIifis
(8echferews Diseose), o joinf
infIommofion moinIy offecfing
fhe spine, occurs onIy in
individuoIs corrying o cerfoin
vorionf of HC moIecuIe
). uch evidence
suggesfs fhof moIecuIes
derived from microorgonisms
inferocf wifh fhe 8Z7
moIecuIe in cousing fhe
desfrucfive immune reocfions
AnkyIosing spondyIifis
(8echferews Diseose), o joinf
infIommofion moinIy offecfing
fhe spine, occurs onIy in
individuoIs corrying o cerfoin
vorionf of HC moIecuIe
). uch evidence
suggesfs fhof moIecuIes
derived from microorgonisms
inferocf wifh fhe 8Z7
moIecuIe in cousing fhe
desfrucfive immune reocfions
ndividuals with the # #
variant of MHC genes are
most susceptible to MS.
ndividuals with the # #
variant of MHC genes are
most susceptible to MS.
Multiple sclerosis (MS) Multiple sclerosis (MS)
Some popuIofions, such
os 0ypsies, skimos, ond
8onfus, never gef S.
Some popuIofions, such
os 0ypsies, skimos, ond
8onfus, never gef S.
Multiple sclerosis (MS) Multiple sclerosis (MS)
However, for suscepfibIe
popuIofions, if one person in o fomiIy
hos S, fhof persons firsf-degree
reIofives -- porenfs, chiIdren, ond
sibIings -- hove o one fo fhree
percenf chonce of geffing fhe
diseose.
However, for suscepfibIe
popuIofions, if one person in o fomiIy
hos S, fhof persons firsf-degree
reIofives -- porenfs, chiIdren, ond
sibIings -- hove o one fo fhree
percenf chonce of geffing fhe
diseose.
M$
In S, fumor necrosis focfor-oIpho
(TNF-), inferLeukin , ond
Ieod fo fhe ocfivofion of mosf
peripheroI T-CeIIs (moinIy CD4 memory)
by promofing o persisfenf infroceIIuIor
coIcium increose vio fwo independenf
signoIing pofhwoys.
omiIy members wifh
oufoimmune diseoses moy inherif
ond shore o sef of obnormoI
genes, oIfhough fhey moy
deveIop differenf oufoimmune
diseoses.
fher genefic connecfions:
(APL), frodifionoIIy ossociofed
wifh rheumofic oufoimmune diseoses
such os SL (Iupus onficooguIonf)
APL hos been idenfified os o
"common fhreod" in fomiIies where of
Ieosf one member suffers from on
oufoimmune disorder.
ntipospoIipid untibody ntipospoIipid untibody
ntipospoIipid untibody syndrome
W(APS) is ossociofed wifh recurrenf
cIoffing evenfs (fhrombosis):
Wpremofure sfroke CVA
Wrepeofed miscorrioges
WPhIebifis
WVenous fhrombosis (cIof in fhe vein)
WpuImonory fhromboemboIism
WAIso ossociofed wifh Iow pIofeIef or
bIood eIemenfs fhof prevenf bIeeding.
ow to estabIish the iagnosis
W History: characteristic symptoms
W Classical physical findings and signs
W aboratory:
General: CBC, ESR, CRP, C3, C4, gG
Specific auto-antibodies
Hormonal assay
Radiological
? HA
Whof ore some of fhe
freofmenfs for
oufoimmune diseoses7
Diminishing of fhe
ocfivify of fhe
immune sysfem
This necessifofes o deIicofe boIonce,
confroIIing fhe disorder whiIe
moinfoining fhe bodys obiIify fo
fighf diseose in generoI.
Drugs mosf commonIy used
ore corficosferoid drugs.
CycIosporin A (CsA) inhibifs o
signoI fronsmission pofhwoy in
T Iymphocyfe ceIIs.
Treatment
1- MetaboIic controI:
a. Graves' disease: antithyroid drugs, surgical, radiation
b. Hashimoto's thyroiditis: Thyroxin.
c. Pernicious anemia: vitamin B12.
d. DDM: insulin
- AntiinfaIamtory and cytotxic drugs:
Nonsteroidal antiinflamatory (NSAD)
Corticosteroids
Cytotoxic drugs: Cyclophosphamide, Azothioprine, Cyclosporin
- Thymectmy:
Myasthenia gravis after anticholinesterase
4- PIasmapheresis or PIasma exchange:
GBS, SE, Goodpasture's
5- SpIeenectomy:
Hemolytic anemia, TP
6- Intravenous GammagIobuIin therapy
GBS, Dermatomyositis
7- Cytokines and inhibitors: anti-TNF
ntruvenous immunogIobuIin
IVI0 fheropy is used in fhe
freofmenf of vorious
oufoimmune diseoses fo reduce
circuIofing immune compIexes.
Anofher freofmenf
opprooch is fo monipuIofe
immune sysfem messenger
moIecuIes coIIed cyfokines.
Anofher freofmenf
opprooch is fo monipuIofe
immune sysfem messenger
moIecuIes coIIed cyfokines.
exompIes:
Inferferons
ond
InferLeukins
exompIes:
Inferferons
ond
InferLeukins
Cytoines
Are Iow moIecuIor moss profeins,
secrefed by Iymphocyfes, which ocfivofe
ofher immune sysfem ceIIs fo reguIofe:
CeII 0rowfh,
CeII Acfivofion,
InfIommofion,
Immunify,
Tissue Pepoir,
ibrosis ond
orphogenesis.
Some cyfokines (for exompIe,
IL-8) ore oIso chemofocfic for
specific ceII fypes, ond ore
coIIed "cemoines".
umpIe of infIummution und cytoines
Tumor necrosis focfor-o TNFu:
PeIeosed by mocrophoges, increoses
voscuIor permeobiIify, odhesion moIecuIe
expression on bIood vesseI endofheIium,
increoses HC expression, pIofeIef
ocfivofion (cIofs keep infecfion from fhe
bIood, ond direcf producfs fo fhe
Iymphofic sysfem).
If fhe infecfion reoches fhe
bIood, TM-o couses sepfic shock ond
deofh. PeIeose info joinfs Ieods fo
Pheumofoid orfhrifis.
New treutments
Use o chimeric monocIonoI onfibody
ogoinsf TM-o, or o new drug,
fonercepf, which is o recombinonf
profein wifh TM recepfor ond fhe
consfonf region of on onfibody.
8Iocking TM-o shows greof promise
os o new freofmenf for PA.
Thanks