Professional Documents
Culture Documents
SpKK
Tempat/Tgl lahir : Bondowoso, 7 September 1946
Alamat
: Jl. Gatot Subroto 230 Surakarta
Pendidikan
:
- Lulus dokter th 1972 FK.Unair
- Spesialis Penyakit Kulit & Kelamin th 1977 FK
Unair
Pendidikan tambahan :
- Pendidikan S III : Pasca sarjana Unair th lulus
th.2003
Pekerjaan/ Jabatan :
- Guru besar th 2004
- Ketua seksi alergi imunologi bag. I.Kesehatan
Kulit & Kelamin FK UNS th 1997-sekarang
- Anggota komite medik RSUD Dr.Moewardi th
2003-2008
- Ketua Program Sutudi I.Kesehatan Kulit &
Kelamin FK UNS th 1999-2003/ 2008-sekarang
Karya Ilmiah:
- 13 buah penelitian
- 17 Publikasi Ilmiah
- 3 Buku teks: 2 sbg kontributor dan 1 sbg
penulis utama
b.imunoprofilaksis (= imunisasi):
-pasif natural transplasental Ab transfer
artifisial tx Imunoglob
-aktif
natural infeksi
artifisial vaksinasi
II. Imunoterapi :
imuno supresi:-kortikosteroid
-cyclophosphamid
-azathioprin, dsb
anti alergi : antihistamin
Anti Histamin
Obat yang bekerja sbg antagonis terhadap
Histamin
Mediator patogenetik major pada berbagai peny
alergi
Dikeluarkan oleh sel mast dan atau basofil
setelah stimulus Ag degranulasi
Berasal dari a.a histidin, sekali terlepas darah
(2,5-5 mnt) reseptor histamin H1 pd jar tbh:
sel otot polos bronkus, usus halus dan pemb drh
Anti histamin
Reseptor H2: peran < H1 pada path.is peny alergi,
ANTIHISTAMIN
AH1 generasi lama (I=pertama)
generasi kedua=baru (non-sedating)
generasi ketiga
AH2
ANTIHISTAMIN 1 Gen I (1940):
- Klorfeneramin (CTM), difenhidramin, hidroxsizin, prometazin,
pirilamin, tripolidin.
- Efek sampng: sedativ ok larut dlm lemak shg sawar drh
otak,
konstipasi, disuria, serotomia, batuk, nausea dan vomitus
ok. memacu hambatan reseptor kolinergik,a-adrenergik
glaukoma (pd usia lanjut) ok efek midriasis
- Tidak digunakan lagi secara rutin utk peny alergik kec
hidroxsizin pada urtikaria kronik dan dermatitis atopik sbg anti
pru
ANTIHISTAMIN 1 Gen. II :
KORTIKOSTEROID
Pemahaman Tentang
Reaksi Alergi
Harijono Kariosentono*
PG. Konthen**
*Bag. I.Kes.Kulit & Kelamin FK UNS Surakarta
** Bag.I.Peny.Dalam FK Unair Surabaya.
Pendahuluan
Penyakit Alergi
Peny yang didasari oleh reaksi hipersensitivitas
terhadap benda asing dari lingkungan (alergen)
Bermanifestasi pada berbagai macam organ sasaran
Faktor yang mendasari
Genetik
Paparan alergen
Kondisi lingkungan
Atopi
Alergi
Manifestasi klinis penyakit atopi
Diperantarai IgE (Hipersensitifitas tipe I)
Contoh : asma, rinitis alergi, dermatitis atopi,
alergi makanan dll.
Hipersensitifitas
Respon imun yang menyimpang/berlebihan
Antigen :
Eksternal
Autoantigen (self antigen) penyakit
autoimun
Ada 4 macam tipe : I, II, III, IV
Type 1 = allergy
MECHANISM
MANIFESTATIONS
IgE dependent
Anaphylaxis,
urticaria
II
Complement-mediated
cytotoxicity
Cytopenias
III
Immune complex
deposition
Vasculitis /
nephritis
IV
Delayed-type
hypersensitivity
Dermatitis or
hepatitis
Allergy
(type I hypersensitivity mediated by IgE on mast cells)
Epidemiologi
Penyakit alergi menjadi epidemi abad ke-21
Di negara maju :
Prevalensi
Atopi
: 30 40%
Asma : 5 10%
Rinitis : 10 20 %
Alergi makanan : 1 3 %
R A
A R D O
Symptom severity
Eczema
4
8
Age (years)
Food
allergy
16
Asthma
32
64
Rhinitis
Faktor Genetik
Faktor Lingkungan
Sensitisasi alergen
Saudara kandung sedikit
Hidup terlalu bersih
Antibiotika pada usia < 2 th
Vaksinasi
Atopi
Defek organ target
Epitel saluran nafas
Kulit
Saluran cerna
Pencetus
Infeksi virus
Paparan alergen
Merokok
Polutan indoor / out door
Faktor Genetik
Allergen-specific IgG4
CD148
TLR2
Treg
DC
?
Prostanoid
receptor12
allergen
IL-109, TGF-10
B cell
IL4R
19,20
GATA3
STAT617
15
CD4 Thp
IL4
SOCS22
STAT6
18
IL135,6
IL13R121
CD4 Th2
Tbet
16
CD4 Th1
IFN-
Basophil
Mast cell
FcERI24
Exogenic factors :
POLLUTANT - ALLERGEN - VIRUS
Pollutant
O3, NO2,
SO2
Allergen
Mite
Pollen
Virus
Rhino
Virus
Dust Mite
ALLERGEN
10 min.
H1
IgE
SYNTHESIS
TH2
B
NON-IgE TRIGGERS
ACH noradrenalin
IFN
IL-4
IgE
Fc
ATTACHMENT
TO MAST
CELL
OEDEMA
+ + +
+ cGMP
MUCUS
SECRETION
cAMP
+
MEDIATORS
CROSS-LINKING
BY ALLERGEN
CALCIUM
INFLUX
C3a
C5a
DSCG
adrenalin steroids
Ca2+
PG, LT
BRONCHIAL
CONSTRICTION
CHEMOTAXIS
antihistamines
INHIBITORS
DEGRANULATION &
MEDIATOR RELEASE
VASCULAR
PERMEABILITY
Repeated exposure
to allergen
Activation of
mast cells :
release of mediators
Allergen
B cell
TH2 cell
IgE-secretine
B cell
Antigen activation
of TH2 cells and
stimulation of
IgE class switching
in B cells
Mediators
Cytokines
Immediate
hypersensitivity
reaction (minutes
after repeated
exposure
to allergen)
Late-phase
reaction (2-4 hrs
after repeated
exposure
to allergen)
IgE
Mast cell
Production of IgE
Vasoactive amines,
lipid mediators
First exposure
to allergen
IL-4
Late Phase
Allergic Reaction
(hours)
IL-4
APC
T cell
IL-4,IL-13 VCAM 9
Eotaxin
3
1
Th2
4
Antigen
IL-4, IL-13
CD40L
B cell
Eo-poesis
Eo survival
Eo activation
6
8
IgE
-1 3
L
I
,
IL-4
3,
1
, IL
4
L
I
IL-5
Histamine
TN
F-
8 Leukotrienes
Mast cell
Prostaglandins
PAF
Further wheezing
Sustained blockage
of the nose
Persistent inflammation
Tissue Eosinophils
Acute
Allergic Reaction
(minutes)
Vasc. permeability
Vasodilatation
Smooth muscle
contraction
Mucus secretion
Wheezing
Urticaria
Sneezing, rhinorrhea
Conjunctivitis
Early phase
APC
MBP, ECP,
EDN, CLC etc
FcRI
Th2 B cells
Eos
Histamin, PGD2,
LTs etc
Th0
TNF-
IL-4
IL-5
IL-8
GM-CSF
MIP-1
MCP-3
ICAM-1
VCAM-1
E-selectin Eos
Epithelium
RANTES
MCP-4
Eotaxin
MBP, ECP,
EDN, CLC etc
IL-3
IL-4
IL-5
IL-6
IL-13
RANTES
Th2
RANTES
Eotaxin
IL-8
GM-CSF
Endothelium
PAF
TNF-
IL-
IL-3
IL-4
IL-5
IL-8
GM-CSF
Mast cells
48 (h)
Late phase
Ag
IL-4
24
Baso
Histamin, LTC4
IL-4
IL-13
MIP-1
VCAM-1
RANTES
Eotaxin
IL-8
GM-CSF
PAF
Endothelium
Th2
Baso
Eos
CD40L
(CD154)
CD28
TCR
CD4
Sel B
IL-4R
CD40
B7-1
(CD80)
MHC II
PLA2
Preformed mediators
Histamine
Heparin
Tryptase
(Chymase)
Kininogenase
CO
Mast Cell
TNF-
TGF-
(IL-3, 4, 5)
(IL-13)
PGD2
5-LO
LTC4
LTD4
LTE4
Glands
Vessel
Itch
Recruit reflexes
Sneezing
Malaise
Mucus
secretions
Vasodilatation
Mucosal Thickening
Permeability
Watery rhinorrhea
LTB
Pre-formed
and in
granules
Synthesized
upon mast
cell activation
Eosinophils
have Fce
receptors
Bronchoconstriction
Lipid mediators
(e.g., PAF, PGD2, LTC4)
Intestinal
hypermotility
Activated
mast cell
(or basophil)
Cytokines
(e.g., TNF)
Lipid mediators
(e.g., PAF, PGD2, LTC4)
Enzymes
(e.g., tryptase)
Inflammation
Tissue
damage
Can be fatal.
Allergy to insect
venom, drugs,
foods and
Disease
Migraine
Neuro-musculosceletal Neuromyalgia
Digestive tract Diarrhea
Cardiovascular ... Anaphylactic shock
macrophage
-
IL-12
CD4+ve
Helper
T cell
Th1
Delayed
hypersensitivity
Th1
IL-2
IFN
+
IFN
IgG1
Th
IL-4
+
eosinophil
Th2
Th2
IL-5
- --
IL-4, IL-13
eosinophil
B
- --
Dendritic cell
MHC/
peptide
T Cell Differentiation
During Human Immune
Responses
(Immune Deviation)
IgE, IgG4
Mast cell*
Weak
binding
TH0
Strong
binding
TH0
TH2
TH1
IL-12
Th0
Th1
IL-2
IFN-gamma
TNF-beta
IL-2
IL-4
IFN-gamma
IL-4
Th2
IL-4
IL-5
IL-6
IL-10
IL-13
IFN-gamma
Eosinophilia
Mast Cell
IgE / IgG
Thus,
usually,
either TH1
or TH2
dominates
and the
other is
very low
Ringkasan
Organ sasaran penyakit alergi bermacam-macam
Etiologi : genetik, alergen, lingkungan
Mekanisme : hipersensitifitas tipe I
Peranan penting : IgE, sel mast, basofil, eosinofil
Hipotesis higiene : alergi merupakan respon TH 2
KORTIKOSTEROID
Hormon, disintesa kortek Adrenal
Efek
Mineralokortikoid : - Aldosteron
Glukokortikoid : - Hidrokortison (Kortisol)
Anti Inflamasi
Imunosupressi
Metabolisme : Glukoneogenesis
Lipolisis
Naik
Protein breakdown
Timbunan calsium turun
Sintetik
Osteoporosis
Kortikosteroid
(KS))
Sintesa Protein :
Transkripsi DNA
Translasi m RNA
GRE +
Transkripsi
GRE :
(GlucoCorticoid
Response Element)
GRE (-)
Transkripsi
Mekanisme
kerja Kortikosteroid
TERIMA KASIH