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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
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FOOD ALLERGY: The beginning of Allergic March
Prof DR Dr Ariyanto Harsono SpA(K)
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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
Prof DR Dr Ariyanto Harsono SpA(K)
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Alergen Makanan
• Buah• Susu• Telur• Ikan• Kacang
4
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4 Macam alergen
5Prof DR Dr Ariyanto Harsono SpA(K)
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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
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Alergi Makanan
• Beberapa factor yang berpengaruh terhadap terjadinya alergi makanan:– Genetik– Lingkungan– Disfungsi Mucosa– Tipe dan dosis alergen makanan– Usia
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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 25-30%
ChildRisk of allergy
40%
ChildRisk of allergy 40-60%
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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
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Fireman P, Slavin RG. Atlas of Allergies, 1991.
Mekanisme Alergi
SENSITIZATION ENHANCEMENT TRIGGERING
Prof DR Dr Ariyanto Harsono SpA(K)
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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
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Prof DR Dr Ariyanto Harsono SpA(K)
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Susu sapi
APC MHC-II Th0
IL-1
Th-2
Th.1
IL-12 IL-2, IFN-γ
B-Cell
IL-4
IL-5
SEL PLASMASEL MEMORI
IL-6
IL-10
A
Memory Cells
13Prof DR Dr Ariyanto Harsono SpA(K)
AKTIVASI SEL-SEL IMUNOKOMPETEN OLEH ANTIGEN
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Prof DR.dr. Ariyanto Harsono SpAK14(J Allergy Clin Immunol
1999;118:124-6)
Th1
Dendritic cell
Eosinophile
Neutrophile
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Prof DR Dr Ariyanto Harsono SpA(K)
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Ariyanto Harsono MD PhD 16
11Ariyanto Harsono MD PhD
Prof DR.dr. Ariyanto Harsono SpAK
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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
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Mast Cells and basophiles involve in allergic reaction in the context of antigen-IgE Prof DR.dr. Ariyanto Harsono SpAK
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IgGIgG mediated: Protein loosing enteropathy, Gastro-intestinal haemorrhage
Prof DR Dr Ariyanto Harsono SpA(K)
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IgMIgM mediated: Protein loosing enteropathy, Gastro-intestinal haemorrhage
Prof DR Dr Ariyanto Harsono SpA(K)
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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.
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BAKTIVASI SEL-SEL STRUKTURAL
Nature Rev Immunol 2003; 3: 867-78
Neutrophil
Eosinophil
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23Prof.DR.dr. Ariyanto Harsono SpAK
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Chemotactic
24Prof.DR.dr. Ariyanto Harsono SpAK
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25Prof.DR.dr. Ariyanto Harsono SpAK
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Chemotactic…
26Prof.DR.dr. Ariyanto Harsono SpAK
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Chemotactic…
27Prof.DR.dr. Ariyanto Harsono SpAK
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CPELEPASAN MEDIATOR
28Prof DR Dr Ariyanto Harsono SpA(K)
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Granule contents:Histamine,TNF-Proteases, Heparin, ECF, NCF Lipid mediators:
ProstaglandinsLeukotrienes
Cytokine production:Specifically IL-4, IL-13
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D EFEK PELEPASAN MEDIATOR PADA TARGET ORGAN
Nature Rev Immunol 2004: 3:234-23730Prof DR Dr Ariyanto Harsono
SpA(K)
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Target Organ
IgE-mediated disorder Non IgE-mediated disorder
Skin
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
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32Prof DR Dr Ariyanto Harsono SpA(K)Prof DR Dr Ariyanto Harsono SpA(K)
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Prof DR Dr Ariyanto Harsono SpA(K)
33Prof DR Dr Ariyanto Harsono SpA(K)
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Prof DR.dr. Ariyanto Harsono SpAK
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Prof DR.dr. Ariyanto Harsono SpAK
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36Prof DR Dr Ariyanto Harsono SpA(K)
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Prof DR.dr. Ariyanto Harsono SpAK
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Prof DR.dr. Ariyanto Harsono SpAK
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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
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Unusual Manifestation
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Unusual Manifestation
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Unusual Manifestation
Prof DR.dr. Ariyanto Harsono SpAK
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CE
Prof DR Dr Ariyanto Harsono SpA(K)
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Unusual Manifestation
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Prof DR.dr. Ariyanto Harsono SpAK
Unusual Manifestation
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Prof DR Dr Ariyanto Harsono SpA(K)
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Prof DR Dr Ariyanto Harsono SpA(K) 47
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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.
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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..
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IEL
LPL
CD23
Anergy/Tolerance: Formula HA
: Imunoterapi: Probiotik
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IgA
TReg TGF-
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Prof DR Dr Ariyanto Harsono SpA(K)
53Prof DR Dr Ariyanto Harsono SpA(K)
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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
54Prof DR Dr Ariyanto Harsono SpA(K)
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Thank You55
Prof DR Dr Ariyanto Harsono SpA(K)