ari reaksi alergi

8/13/2019 Ari Reaksi Alergi

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Prof.DR.dr.Harijono KS. SpKK

Tempat/Tgl lahir: Bondowoso, 7 September 1946Alamat : 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


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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


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APLIKASI OBAT IMUNOSUPRESI &

ANTI ALERGI

Pengobatan penyakit atau kelainan akibat

gangguan respons imun:

I. Pengobatan kausatif (terhadap agen

penyebab)

a.eliminasi agen: antibiotik, antivirus,antijamur, anti parasit dsb


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b.imunoprofilaksis (= imunisasi):

-pasif natural transplasental Ab transferartifisialtx Imunoglob

-aktif natural infeksi

artifisial vaksinasi

II. Imunoterapi :

imuno supresi:-kortikosteroid

-cyclophosphamid-azathioprin, dsb

anti alergi : antihistamin


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Anti Histamin

Obat yang bekerja sbg antagonis terhadapHistamin

Mediator patogenetik major pada berbagai penyalergi

Dikeluarkan oleh sel mast dan atau basofilsetelah stimulus Ag degranulasi

Berasal dari a.a histidin, sekali terlepas darah(2,5-5 mnt)reseptor histamin H1pd jar tbh:sel otot polos bronkus, usus halus dan pemb drh


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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-adrenergikglaukoma (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

ritus dan efek sedasinya yg ringan.


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ANTIHISTAMIN 1 Gen. II :

AKRIVASTIN, ASTEMIZOL, AZELASTIN, LORATADIN,KETOTIFEN, OKSATOMID DAN TERFENADIN

Afinitas dan selektrifitas thd reseptor H1 > tinggi dp gen I

Efek sedasinya minimal mgkn krn selektivitas thd R H1

perifer > daripada sentral

Dosis: eg loratadin = 10 mg 1 X/hari

ANTIHISTAMIN 1 Gen. III :

Setirizin metabolit asam karboksilat dari hidroksizindan

Fexofenadin metabolit aktif as karboksilat terfenadin


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KORTIKOSTEROID


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Pemahaman Tentang

Reaksi Alergi

Harijono Kariosentono*PG. Konthen**

*Bag. I.Kes.Kulit & Kelamin FK UNS Surakarta** Bag.I.Peny.Dalam FK Unair Surabaya.


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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

Salah bentuk dari imunopatologis


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Atopi

Kecenderungan respon peningkatan IgE

Adanya IgE spesifik terhadap suatu komponen

Secara praktis : tes kulit yang positif

Dipengaruhi faktor herediter

Alergi

Manifestasi klinis penyakit atopi Diperantarai IgE (Hipersensitifitas tipe I)

Contoh : asma, rinitis alergi, dermatitis atopi,

alergi makanan dll.


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Hipersensitifitas

Respon imun yang menyimpang/berlebihan

Antigen :

EksternalAutoantigen (self antigen) penyakit

autoimun

Ada 4 macam tipe : I, II, III, IV


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Four Types of Hypersensitivities

Type 1 = allergy


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The four types of hypersensitivity reactionThe four types of hypersensitivity reaction


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Gell And Combs Classification Of

Immune-mediated Allergic Response

TYPE MECHANISM MANIFESTATIONS

I IgEdependent

Anaphylaxis,

urticaria

IIComplement-mediated

cytotoxicityCytopenias

III Immune complexdeposition

Vasculitis /nephritis

IVDelayed-type

hypersensitivity

Dermatitis or

hepatitis


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Allergy(type I hypersensitivity mediated by IgE on mast cells)


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Epidemiologi

Penyakit alergi menjadi epidemi abad ke-21

Di negara maju :

Prevalensi

Atopi : 3040%

Asma : 510%

Rinitis : 1020 %

Alergi makanan : 13 %


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Clinical course of the disease


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The apperance of atopic eczema on the back of

a knee in a child allergic to rice and eggs


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Urticarial reaction to Penicillin


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*a contact-sensitizing agent is usually

a small molecule that penetrates the

skin then binds to self-proteins,making them look foreign

Can be caused by poison ivyand mango sapContact Dermatitis

DTH as a result of a contact-sensitizing agent*


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Changing of target organ in clinical allergy

D R O

AR A D RA D O

A = Asthma R = Rhinitis D = Dermatitis O = other clinical manifestations


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Symptom Severity Versus Age

0 1 2 4 8 16 32 64

Age (years)

Symptom

severity

Eczema Food

allergy

Asthma Rhinitis


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Atopi

Reaksi alergi / inflamasi yang dimediasi oleh Th2

Faktor Lingkungan

Sensitisasi alergen

Saudara kandung sedikitHidup terlalu bersihAntibiotika pada usia < 2 th

Vaksinasi

Pencetus

Infeksi virus

Paparan alergen

MerokokPolutan indoor / out door

Faktor Genetik

Adanya alele HLA spesifik

Polimorfisme FcRI-Polimorfisme gena IL-4Polimorfisme CD14

Polimorfisme lokus lainnya

Defek organ target

Epitel saluran nafas

Kulit

Saluran cerna


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Faktor Genetik

Interaksi faktor genetik-alergen-lingkungan penyakit alergi

Gen-gen penyandi atopi :

Interleukin Protein MHC

Reseptor IgE berafinitas tinggi

Efektor Imunologi

Kromosom 5Q31-33, 11Q13, 13Q12-14


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Pollutant

O3, NO2,

SO2

Exogenic factors :

POLLUTANT - ALLERGEN - VIRUS

Allergen

Mite

Pollen

Virus

Rhino

Virus


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Dust Mite


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What are the

characteristics of

allergens?

It is not fully understood how

or why, but these type of

antigens tend to stimulate IL-4production; IL-4 production

tends to lead to more IL-4

production . IL-4 favors class

switching to IgE


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Induction and effector mechanisms in Type I HypersensitivityInduction and effector mechanisms in Type I Hypersensitivity

Allergy and Anaphylaxis


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Allergy and Anaphylaxis

TH1

TH2

B

cAMP

cGMP

++++

+

ALLERGEN

IgE

SYNTHESIS

ATTACHMENT

TO MAST

CELL

CROSS-LINKING

BY ALLERGEN

CALCIUM

INFLUX DEGRANULATION &

MEDIATOR RELEASE

VASCULAR

PERMEABILITY

CHEMOTAXIS

BRONCHIAL

CONSTRICTION

MUCUSSECRETION

OEDEMA

SKIN TEST

NON-IgE TRIGGERS

noradrenalinACH C3aC5a

IFN

IL-4

IgE

Ca2+

adrenalinDSCG

steroids

antihistamines

PG, LT

MEDIATORS

INHIBITORS

10 min.

Fc

S f t i i di t


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Sequence of events in immediate

hypersensitivity reactions

Antigen activation

of TH2 cells and

stimulation of

IgE class switching

in B cells

First exposureto allergen

Production of IgEFirst exposure

to allergen

Repeated exposure

to allergen

Activation ofmast cells :

release of mediators

CytokinesVasoactive amines,

lipid mediators

Late-phase

reaction (2-4 hrs

after repeated

exposure

to allergen)

Immediate

hypersensitivity

reaction (minutes

after repeated

exposure

to allergen)

Allergen

B cell

TH2 cell

IgE-secretine

B cell

IgE

Mast cell

Mediators

Mekanisme seluler dan molekuler pada reaksi alergi


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Mekanisme seluler dan molekuler pada reaksi alergi

IL-4 IL-4+ +

8

12

3

6

5

7

8

+

8

8

48

9

APC

T cell

Th2

Antigen

IgE

B cell

Mast cell

IL-4,IL-13 VCAMEotaxin

Eo-poesisEo survivalEo activation

IL-4, IL-13

CD40L

Histamine

Leukotrienes

Prostaglandins

PAF

Vasc. permeabilityVasodilatation

Smooth musclecontraction

Mucus secretion

Tissue Eosinophils

Late PhaseAllergic Reaction

(hours)

Further wheezingSustained blockage

of the nosePersistent inflammation

Acute

Allergic Reaction(minutes)

WheezingUrticaria

Sneezing, rhinorrheaConjunctivitis

Mechanism of earl and late phase


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Mechanism of early and late phaseallergic reaction

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-5

IL-8GM-CSF

IL-3IL-4IL-5IL-6IL-13RANTES

IL-4IL-13MIP-1 RANTESEotaxin

IL-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 p hase

IL-4

Endothelium

Epithelium

Endothelium

VCAM-1

Th2 B cells

Ag

Mast cells

FcRI

Th2

Th0

Eos EosBaso

Baso

Eos

Th2

Histamin, LTC4

APC

Immediate and late skin reactions


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Immediate and late skin reactions

I t k i t l Th2 d l B


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Interaksi antara sel Th2 dan sel B yang

diperlukan untuk sintesis IgE spesifik

Sel T Sel B

IL-4 IL-4R

CD40CD40L(CD154)

CD28

TCR

CD4

B7-1(CD80)

MHC II


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Mast CellPreformed mediators

Histamine TNF-

Heparin TGF-Tryptase (IL-3, 4, 5)(Chymase) (IL-13)

Kininogenase

PLA2 AA + PAF

CO 5-LO

PGD2 LTC4LTD4LTE4

LTB

Mlanges of mast cell mediators

Nerves

Itch

Recruit reflexes

Sneezing

Malaise

Glands

Mucus

secretions

Vessel

Vasodilatation

Mucosal Thickening

Permeability

Watery rhinorrhea

Mast cell and its mediators


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Compounds Released from EosinophilsLike mast cels,

Eosinophilshave Fce

receptors

Biologic effects of mediators of


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Biologic effects of mediators of

immediate hypersensitivity

Biogenic amines(e.g., histamines)

Lipid mediators

(e.g., PAF, PGD2, LTC4)

Vascular leak

Broncho-constriction

Broncho-constriction

Intestinalhypermotility

Inflammation

Tissuedamage

Enzymes(e.g., tryptase)

Cytokines

(e.g., TNF)

Lipid mediators(e.g., PAF, PGD2, LTC4)

Activatedmast cell(or basophil)

All t d d t f ll t


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Allergy symptoms depend on route of allergen entry

Can be fatal.

Allergy to insect

venom, drugs,

foods and


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macrophage


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T Cell Differentiation

During Human Immune

Responses

(Immune Deviation)

Th2 Th2

Th

Th1

Th1

B

+ IL-2IFN

IgG1

IFN

Delayedhypersensitivity

CD4+veHelperT cell

IL-12

High dose antigene.g. DPT, viral orbacterial infection

MHC/peptide

IL-4+

IL-5MHC/

peptide

Dendritic cell

Low dose antigene.g. allergens

IL-4, IL-13

B

IgE, IgG4

eosinophil

eosinophil

Mast cell*

Differentiation of Naive CD4+ T Cells into


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Differentiation of Naive CD4 T Cells into

Subsets of Effector Cells

Pathogensinfluence

cytokines that

affect TH0

differentiation

into TH1 or T

H2

Amount of antigen presented and TCR binding strength


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g p g g

influence TH0 differentiation into TH1 or TH2

Weak

binding

TH0

TH2

Strong

binding

TH0

TH1


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IL-12

IL-4

Th0

Th1

Th2

IL-2

IFN-gamma

TNF-beta

IL-4

IL-5

IL-6IL-10

IL-13

IFN-gamma

Cell mediated cytotoxicityMacrophage activation

B cell help

Eosinophilia

Mast Cell

IgE / IgG

Transplantation tolerance (?)

IL-2

IL-4

IFN-gamma


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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 TH2


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KORTIKOSTEROID

Hormon, disintesa kortek Adrenal Efek Mineralokortikoid : - Aldosteron

Glukokortikoid : - Hidrokortison (Kortisol)

Anti Inflamasi

Imunosupressi Sintetik

Metabolisme : Glukoneogenesis

Lipolisis Naik

Protein breakdown

Timbunan calsium turun Osteoporosis


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M k i


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Mekanisme

kerja Kortikosteroid


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Efek Imunosupresi Steroid

1. Proses transkripsi Menurunkan

Molekul pro Inflamasi

2. Menekan Replikasi & Pergerakan sel

Monositopenia, eosinopenia,limfositopenia

TERIMA KASIH


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TERIMA KASIH

ari reaksi alergi

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