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IMUNOPATOFISIOLOGY ASMA

EDDY MART SALIM


Sub Bag Alergi Imunologi Ilmu Penyakit Dalam FK Unsri/RSMH Palembang

DEFINISI ASMA
Inflamasi kronik saluran napas Hipereaktiviti bronkus terhadap

berbagai rangsangan
Penyempitan saluran napas difus

Derajat penyempitan bervariasi


Membaik spontan atau dengan pengobatan

KARAKTERISTIK ASMA
Penyakit kronik
Sifatnya variasi Obstruksi reversibel

Airway remodeling

Allergy may involve multiple target organs systemic:


Organ Disease

Respiratory tract . Asthma

Nose . Allergic rhinitis


Eye .. Allergic conjunctivitis Skin . Urticaria

Central Nervous System ..

Migraine

Neuro-musculosceletal Neuromyalgia Digestive tract Diarrhea Cardiovascular ... Anaphylactic shock

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 Asthma


Genetics
Risk Factors (for development of asthma)
Environmental

INFLAMMATION
Airway Hyperresponsiveness Airflow Obstruction

Risk Factors (for exacerbations)

Symptoms

Rangsangan Non IgE Mediated (virus, fisik, kimia, stres, dll)

Rangsangan IgE Mediated (alergen)

Aktivasi Sel

refleks akson neuropeptida

Mastosit, Sel epitel, Makrofag, Eosinofil, limfosit Limosit, Syaraf otonom Mediator inflamasi, Kontraksi otot polos, Kemotaksis

Respon granulositosit, netrofil, eusonofil, basofil


Mediator Inflamasi Edema saluran napas Infiltrasi seluler Fibrosis subepitelial Sekresi mucus Permeabilitas mukosa dan vaskuler Saluran nafas hiperaktif

ASMA

Mekanisme Inflamasi dan hiperreaktivitas bronkus

Genetic risk for asthma, allergic rhinitis, and atopic dermatitis


Odds ratio for the children to have a disease

4 3,5 3 2,5 2 1,5 1 0,5 0


Asthma Allergic rhinitis Atopic dermatitis Allergic disease in 1 parent

Asthma Rhinitis Dermatitis

Dold S, et al. Archives of Disease in Childhood 1992;67:1018-1022

Coincidence of asthma & atopic dermatitis genetic linkages

9 10 11 12 13 14 15 16 17 18 19 20 21 22 X

Atopic dermatitis

Asthma

Lawrence F, et al. Pediatrics 2003;111:608-616

Th1 / Th2 Skewing


Uncommitted T cell

Th1
Intracellular Pathogens Pathogens
(TNF, IFN gamma, IL-12) Promote inflammation & production & intracellular killing

Th2
Extracellular
(IL-4, 5, 10) Promote IgE eosinophil recruitment

Early Allergic Response


IL-5
Mast cell

Sneeze Itch

Histamine
EOSIN PGD2 Tryptase TNF

Mucus Smooth muscle

Congestion
ICAM-1

Arachidonic Acid

Late Allergic Response


Oedema Mucus Chemotaxis Sm muscle stim

5-LO

LT-A4

LT-C4
LT-D4 LT-B4
Chemotaxis

LT-E4

BHR
Eosinophilia

Mechanism of early and late phase allergic reaction


0
APC

8
Late phase

24
TNF- IL- IL-3 IL-4 IL-5 IL-8 GM-CSF IL-3 IL-4 IL-5 IL-6 IL-13 RANTES IL-4 IL-13 MIP-1
VCAM-1

48 (h)

Early phase

Very late phase

Epithelium
RANTES MCP-4 Eotaxin

Ag
FcRI

MBP, ECP, EDN, CLC etc

Mast cells
Th2 B cells Eos

MBP, ECP, EDN, CLC etc

IL-4
Th0

Histamin, PGD2, LTs etc

TNF- IL-4 IL-5 IL-8 GM-CSF MIP-1 MCP-3

Th2

RANTES Eotaxin IL-8 GM-CSF Endothelium PAF


ICAM-1 VCAM-1 E-selectin

Baso Histamin, LTC4

RANTES Eotaxin IL-8 GM-CSF PAF

Endothelium
Eos Th2 Baso

Eos