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HYPERSENSITIVITY REACTIONS
Innocous materials can cause
hypersensitivity in certain
individuals
unwanted inflammation
damaged cells and tissues
ANTIBODY MEDIATED HYPERSENSITIVITY REACTIONS
HYPERSENSITIVITY REACTIONS
TYPE I
ALLERGY
TYPE II
TYPE III
Soluble antigen
Cell surface or matrix
antigen
Soluble antigen
IgE
Mast cell
Hay fever
Asthma
Systemic anaphylaxis
IgG
FcγR+ cells
NK, macrophage
Certain drug allergies
(penicillin)
IgG – immune complex
FcγR+ cells
Complement
Serum sickness
TYPE I HYPERSENSITIVITY
REACTION
ALLERGY
IgE
MAST CELL RESPONSE TO
SURFACE FcRεI CROSSLINKING
a
g b
I
I
TT
AA
MM
PLA2
foszfa tidil-kolin
LYSO-PC
arachidonsav
Fc eRI
I
T
A
M
MAPkináz
I
T
A
M
Lyn
II
TT
AA
MM
Syk
endoplazmás
retikulum
2
Ca +
5-lipoxigenáz
PIP2
PI-PLCg
DAG
IP3
foszfolipid
ciklooxigenáz
Ca 2+
PGD2
citokin gének
transzkripciója
LTC4
NFAT AP-1 NF-k B
PAF
szekretoros
granulum
2+
PKC Ca
Ca 2+
proteinek
(miozinkönnyűlánc)
foszforilációja
Ca 2+
szekréció
PGD2
EARLY MEDIATORS
LTC4
LTD4
LTE4
LATE MEDIATORS
mediátorok
citokinek
IL-3, IL-4,
IL-5, IL-6
TNFa
Biogenic amins – histamin
Enzymes – triptase, chymase,
carboxypeptidase
ALLERGENS USUALLY ENTER THE BODY VIA MUCOSAL
SURFACES AND THEY ARE PRESENT AT A LOW DOSE
DC
B cell
Th2
Th2
antigen
presentation
T cell priming
and polarization
allergic
response
 soluble proteins on te surface of small particles (pollen, dust mite „drops”)
 small molecular weight
 trans-mucosal entry, enzymatic activity
 low dose (ragweed: 1µg/year)
The enzymatic activity of some allergens enables penetration
of epithelial barriers
Der p1
A légutak intakt
epitéliuma
A Der p1 hasítja
az okkludint
A Der p1 –t felveszik
a DC-k, Th2-priming
A Der p1-specifikus
IgE a hízósejtekhez
kötődik
(LTB4, PGE2)
Copyright ©2005 American Society for Clinical Investigation
IMMUNE RESPONSES MEDIATED BY Th2 CELLS
DC
Bas
Th0
IL-4
ALLERGEN
Th2
C
D
4
0
mucosal
membranes
B
IL-13
CD40L
C
D
4
0
M
H
CII
B
IgE
Mechanism of the initiation of Th2 response
Immunology and Cell Biology (2008) 86, 637–638
GENETIC/ENVIRONMENTAL PREDISPOSITION TO
ALLERGY
Genetic factors
chromosome 11q
FcεRβ chain gene
chromosome 11q
IL-3-5 IL-9, IL-13
GMCSF
HLAII DRB1*015
Inproper
immunregulation
Th1/Th2 inbalance
regulation of IgE synthesis
high eosinophil counts
allergy
Environmental
factors
lack of tolerance
Treatment
Types of IgE-derived allergic response
SYNDROME
ALLERGENS
ROUTE OF ENTRY
systemic
anaphylaxis
drugs
anti-serum
peanuts
intravenous
Per os
acute
urticaria
bug bite
allergy test
subcutan
local increase in blood
flow and vascular
permeability
allergic
rhynitis
pollen
dust mite
drops
inhaled
irritation and edema of
nasal mucosa
airway inflammation
asthma
animal fur
pollen
dust mite
drops
inhaled
bronchial constriction,
increased mucus
production
food allergy
nut, peanuts,
fish, shellfish
milk, eggs
Per os
vomiting, diarrhea
pruritis (itching)
urticaria (hives)
anaphylaxia (rare)
RESPONSE
edema, increased
vascular permeability
tracheal occlusion
circulatory collapse,
death