Food allergy, the beginning of allergic march1.

Prof Dr Ariyanto Harsono dr SpAK

CURICULUM VITAE

Tempat /tgl lahir : Kediri, 3- JuliAgama : Islam

Status Perkawinan: MenikahPendidikan

S-1: Lulus Dokter : FK UNAIR, 1972

S-2: Spesialis Anak : FK UNAIR, 1982

S-3: Program Pascasarjana UNAIR, 2004 Pendidikan tambahan : Sertifikat “Fellowship on Food Allergy”, Academisch Ziekenhuis Utrecht, Nederland, 1990-1991Jabatan sekarang : Guru Besar Ilmu Kesehatan

Anak, Dep IKA FK UNAIR/RSU Dr.Soetomo, Surabaya.

Konsultan Alergi/Imunologi: 1992

FOOD ALLERGY: The beginning of Allergic March

Prof DR Dr Ariyanto Harsono SpA(K)

Pendahuluan

1. Proses akan berlanjut dalam kehidupan bayi2. Sensitisasi terhadap protein makanan yang lain akan

terjadi

Umumnya Susu sapi adalah alergen pertama pada bayi

sekali respons IgE terhadap susu sapi terjadi

Alergen Makanan

• Buah• Susu• Telur• Ikan• Kacang

4 Macam alergen

5Prof DR Dr Ariyanto Harsono SpA(K)

Cross reactivity

• Terdapat Cross-reactivity antara alergen makanan apabila ada kesamaan struktur, yang kemudian mencetuskan reaksi simpang yang sama dengan alergen makanan yang asli.

• Contoh: antara beberapa shellfish, kacang-kacangan, ketimun, dan tree nuts.

J Allergy Clin Immunol. 2010;126:S1-58

Alergi Makanan

• Beberapa factor yang berpengaruh terhadap terjadinya alergi makanan:– Genetik– Lingkungan– Disfungsi Mucosa– Tipe dan dosis alergen makanan– Usia

GENETIC

If both parents had same allergy, risk of allergy in their

child will be increased up to 60-80%

Father Mother Father Mother Father Mother Father MotherSiblings

ChildRisk of allergy 5-15%

ChildRisk of allergy

Uptake Alergen di Usus

1. Alergen di uptake oleh subepithelial dendritic cells (DCs) melalui 2 jalur:DCs dapat meraih diantara enterocytes.sAlergen yang larut air dapat di uptake oleh fase cair endocytosis oleh enterocyte

dan dideposisi di lamina propria kemudian difagosit DCs. DCs bermigrasi dari lamina propria ke mesenteric lymph node (MLN), dimana alergen bisa di presentasikan pada naïve T cells.

2. Di Peyer's patch, M cells mempunyai spesifikasi uptake alergen tertentu, kemudian diserahkan pada DCs di ruang subepithelial. DCs ini bisa bergerak ke area interfollicular Peyer's patch untuk dipresentasikan ke T cells (hijau) atau interaksi dengan sel B (merah).

Pediatric allergy: principles and practice. 2nd edition

Fireman P, Slavin RG. Atlas of Allergies, 1991.

Mekanisme Alergi

SENSITIZATION ENHANCEMENT TRIGGERING

Aktivasi sel-selImuno-kompeten•Sel T•Sel B•Sel Mast•Sel Langer- hans

Aktivasi sel-selstruk-tural

•Sel endotel•Sel epitel

Aktivasi dan Rekruitmen

•Sel Mast•Eosinofil•Neutrofil•Basofil

Pelepasan mediator

Kerusakan epitel

Stimulasi neural

Dilatasi & peningkatan permeabilitas vaskulerl

Bronkokonstriksi

Perbaikan epitel

•Proliferasi fibroblast•Deposisi kolagen•Hipertropi/hiperplasia otot polos•Ekspansi vaskuler

Penyempitan saluran nafas bawah

Symptom alergi

Bronkus hiper-reaktif

ALERGEN

A B C D E

Imunopatologi alergi

Airway remodelling

11Prof DR Dr Ariyanto Harsono

SpA(K)

Trigger

Susu sapi

APC MHC-II Th0

IL-12 IL-2, IFN-γ

B-Cell

SEL PLASMASEL MEMORI

Memory Cells

AKTIVASI SEL-SEL IMUNOKOMPETEN OLEH ANTIGEN

Prof DR.dr. Ariyanto Harsono SpAK14(J Allergy Clin Immunol

1999;118:124-6)

Dendritic cell

Eosinophile

Neutrophile

Ariyanto Harsono MD PhD 16

11Ariyanto Harsono MD PhD

Prof DR.dr. Ariyanto Harsono SpAK

VACCINATION

ACTIVATIONANTIGEN SPECIFIC

B CELL

GENERATION OF MEMORY

ACTIVATED CD4

+ Th-2 CELL IL-4

DIFFERENTIATION

& AFFINITYMATURATION

ANTIBODY SECRETING PLASMA CELLS

ANTIGEN PROCESSING &PRESENTATION

MHC Class II B CELL IMMUNOGLOBULINE

T CELL RECEPTOR ANTIGEN

B CELL

IL-5,IL-13

Cow’s Milk Protein

Cow’s Milk epitope

IgE mediated: Asthma, Rhinitis, Dermatitis Atopic, Urticaria, Abdominal colic

Mast Cells and basophiles involve in allergic reaction in the context of antigen-IgE Prof DR.dr. Ariyanto Harsono SpAK

IgGIgG mediated: Protein loosing enteropathy, Gastro-intestinal haemorrhage

IgMIgM mediated: Protein loosing enteropathy, Gastro-intestinal haemorrhage

SensitiSensitisasi didalam kandungansasi didalam kandungan

• SelSelT T telah berespons pada janin umur 22 telah berespons pada janin umur 22 minggu.minggu.

• SelSel T T pusar telah berespons pada waktu pusar telah berespons pada waktu lahirlahir– mite ~ 47 %– telur, susu sapi ~ 75 %– Sedikit IFN dan banyak IL-4 & 10

• IgE IgE waktu lahirwaktu lahir– Susu sapi, gandum, telur.

BAKTIVASI SEL-SEL STRUKTURAL

Nature Rev Immunol 2003; 3: 867-78

Neutrophil

Eosinophil

23Prof.DR.dr. Ariyanto Harsono SpAK

Chemotactic

Chemotactic…

CPELEPASAN MEDIATOR

Granule contents:Histamine,TNF-Proteases, Heparin, ECF, NCF Lipid mediators:

ProstaglandinsLeukotrienes

Cytokine production:Specifically IL-4, IL-13

D EFEK PELEPASAN MEDIATOR PADA TARGET ORGAN

Nature Rev Immunol 2004: 3:234-23730Prof DR Dr Ariyanto Harsono

SpA(K)

Target Organ

IgE-mediated disorder Non IgE-mediated disorder

Gastro-intestinal

Respiratory Tract Multi-system

Urticaria and angioedemaAtopic Dermatitis

Oral Allergy SyndromeGastrointestinal anaphylaxisAllergic eosinophilic gastroenteritis Asthma; Allergic Rhinitis Food-induced anaphylaxisFood associated, exercise-induced anaphylaxis

Atopic DrmatitisDermatitis Herpetiformis

ProctocolitisEnterocolitisAllergic eosinophilic- gastroenteritisEnteropathy syndromeCeliac Disease

Heiner Syndrome

Clinical Manifestation E Symptoms

32Prof DR Dr Ariyanto Harsono SpA(K)Prof DR Dr Ariyanto Harsono SpA(K)

Target organ Unusual Clinical manifestation

•Skin

•ENT

•Respiratory

•Gastrointestinal

•Multi system

Vasculitis; Fixed Skin Eruption

Chronic Serous Otitis Media

Chronic Pulmonary disease (Heiner Syndrome)

Hypersensitivity pneumonitis

Constipation; Gastroesophageal reflux

Irritability/Sleeplessness in infants; colic, Arthropathy;

Nephropathy; Thrombocytopenia

Unusual Clinical Manifestation

Unusual Manifestation

Prof DR Dr Ariyanto Harsono SpA(K) 46

Natural History of Food Allergy

• Kebanyakan anak alergi menjadi toleran terhadap susu sapi, kedelai, dan telur dalam beberapa tahun.

• Anak yang lebih besar (15 tahun) dan dewasa umumnya tidak mengalami toleransi imun.

• Alergi kacang, ikan, dan kerang lebih persisten. • Food hypersensitivity di usia dini (i.e. Susu sapi,

telur, kacang) adalah faktor resiko menjadi alergi makanan tambahan, Atopik Dermatitis, dan asma.

Induksi Toleransi Oral

T-cells regulation:

1. Intra Epithelial Lymphocytes: berasal dari ekstra thymus, TCR terbatas, dapat mengenali alergen, mempunyai fungsi sitolitik.

2. Lamina Propria Lymphocytes: berasal dari thymus, TCR/CD3 terbatas-memediasi signal di mukosa..

Anergy/Tolerance: Formula HA

: Imunoterapi: Probiotik

TReg TGF-

KesimpulanAlergi adalah hipersensitifitas tipe ISensitisasi pertama biasanya Susu Sapi

kemudian makanan lain. Kaskade inflamasi alergi melibatkan interaksi

sel dendritik, limfosit, sel Mast, esinofil, neutrofil beserta mediatornya

Thank You55

Food allergy, the beginning of allergic march1.

Health & Medicine

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