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