IMUNOPATOFISIOLOGY
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Transcript of IMUNOPATOFISIOLOGY
IMUNOPATOFISIOLOGY ASMA
EDDY MART SALIM
Sub Bag Alergi Imunologi Ilmu Penyakit Dalam FK Unsri/RSMH Palembang
DEFINISI ASMADEFINISI ASMA Inflamasi kronik saluran napas
Hipereaktiviti bronkus terhadap
berbagai rangsangan
Penyempitan saluran napas difus
Derajat penyempitan bervariasi
Membaik spontan atau dengan pengobatan
KARAKTERISTIK ASMAKARAKTERISTIK ASMA
Penyakit kronik
Sifatnya variasi
Obstruksi “reversibel”
Airway remodeling
Allergy may involve multipletarget organs systemic:
Respiratory tract ………………. Asthma
Nose ……………………………. Allergic rhinitis
Eye …………………………….. Allergic conjunctivitis
Skin ……………………………. Urticaria
Central Nervous System …….. Migraine
Neuro-musculosceletal ……… Neuromyalgia
Digestive tract ………………… Diarrhea
Cardiovascular ………………... Anaphylactic shock
Organ Disease
Patofisiologi Asma
• Adanya obstruksi saluran napas yang reversibel, membaik secara spontan atau dengan pengobatan.
• Adanya inflamasi alergi saluran napas
• Adanya hiperreaktivitas bronkus yang meningkat terhadap berbagai rangsangan.
Mechanisms Underlying the Definition of AsthmaMechanisms Underlying the Definition of Asthma
Risk Factors(for development of asthma)
Risk Factors(for development of asthma)
INFLAMMATIONINFLAMMATIONINFLAMMATIONINFLAMMATION
AirwayAirway
HyperresponsivenessHyperresponsiveness
AirwayAirway
HyperresponsivenessHyperresponsiveness Airflow ObstructionAirflow ObstructionAirflow ObstructionAirflow Obstruction
Risk FactorsRisk Factors(for exacerbations)(for exacerbations) Risk FactorsRisk Factors(for exacerbations)(for exacerbations)
SymptomsSymptomsSymptomsSymptoms
Genetics Environmental
Mastosit, Sel epitel, Makrofag, Eosinofil, limfosit
Limosit, Syaraf otonomrefleks aksonneuropeptida
Mediator inflamasi, Kontraksi otot polos, Kemotaksis
Respon granulositosit, netrofil, eusonofil, basofil
Mediator Inflamasi
Edema saluran napasInfiltrasi seluler
Fibrosis subepitelialSekresi mucus
Permeabilitas mukosa dan vaskuler
Saluran nafas hiperaktif
ASMA
Aktivasi Sel
Rangsangan IgE Mediated (alergen)
Rangsangan Non IgE Mediated (virus, fisik, kimia, stres, dll)
Mekanisme Inflamasi dan hiperreaktivitas bronkus
Genetic risk for asthma, allergic rhinitis, and atopic dermatitis
Genetic risk for asthma, allergic rhinitis, and atopic dermatitis
0
0,5
1
1,5
2
2,5
3
3,5
4
AsthmaRhinitisDermatitis
Allergic disease in 1 parent
Od
ds r
ati
o f
or
the c
hild
ren
to h
ave a
dis
ease
Asthma Asthma Allergic AtopicAllergic Atopic rhinitis dermatitisrhinitis dermatitis
Dold S, et al. Archives of Disease in Childhood 1992;67:1018-1022
Coincidence of asthma & atopic dermatitis genetic linkages
Coincidence of asthma & atopic dermatitis genetic linkages
Lawrence F, et al. Pediatrics 2003;111:608-616
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X Y
Atopic dermatitisAtopic dermatitis AsthmaAsthma
Th1 / Th2 Skewing
Th1Th2
Intracellular Pathogens Extracellular Pathogens
(TNF, IFN gamma, IL-12) (IL-4, 5, 10)
Promote inflammation & Promote IgE production &
intracellular killing eosinophil recruitment
Uncommitted T cell
HistamineHistamine
PGD2PGD2
TryptaseTryptase
TNFTNF
IL-5IL-5
EOSINEOSIN
Early Allergic ResponseEarly Allergic Response
SneezeSneeze
ItchItch
MucusMucus
Smooth Smooth musclemuscle
CongestionCongestion
ICAM-1ICAM-1
Mast cell
Arachidonic Acid
LT-A4
LT-B4
LT-C4
LT-D4
LT-E4
Chemotaxis
Oedema
Mucus
Chemotaxis
Sm muscle stim
BHR
Eosinophilia
5-LO
Late Late Allergic Allergic ResponseResponse
Mechanism of early and late phase allergic reaction
Mechanism of early and late phase allergic reaction
0 1 6 8 24 48 (h)0 1 6 8 24 48 (h)
RANTESEotaxin
IL-8GM-CSF
PAF
TNF-IL-4IL-5IL-8GM-CSFMIP-1MCP-3
TNF-IL-
IL-3IL-4IL-5IL-8GM-CSF
IL-3IL-4IL-5IL-6IL-13RANTES
IL-4IL-13MIP-1
RANTESEotaxinIL-8GM-CSFPAF
RANTESMCP-4Eotaxin
ICAM-1VCAM-1E-selectin
Histamin, PGD2,LTs etc
MBP, ECP,EDN, CLC etc
MBP, ECP,EDN, CLC etc
Early phase Late phase Very late phase
IL-4
Endothelium
Epithelium
Endothelium
VCAM-1
Th2 B cells
Ag
Mast cells
FcεRI
Th2
Th0
Eos EosBaso
Baso
Eos
Th2
Histamin, LTC4
APC