REAKSI HIPERSENSITIVITAS

Febtarini, R, dr. Sp.PK

Bagian Patologi Klinik
FKU - UWKS

Jumat, 10-Januari-2014

ANATOMY OF THE IMMUNE SYSTEM

CELLS OF THE IMMUNE SYSTEM

Schematic diagram of structure of Ig

Glycoprotein
Polypeptide : 82-96%
Cbh : 2-14%

ANTIBODIES
STRUCTURE

CLASS

Ag can bind in pockets or grooves

or on extended surfaces in the
binding sites of Abs

 VON PIRQUET (1906)

Aktivitas berubah
Reaktivitas berubah
Energi berubah
atau : Reaksi abnormal oleh adanya suatu rangsangan

COCA DAM COOKE (1923)

Atopi : reaksi alergi yang dipengaruhi oleh faktor keturunan
(herediter)
SENSITISASI:
Membuat (sesorang) menjadi reaktif terhadap zat asing
HIPERSENSITIVITAS : Reaksi alergi
REAKSI IMUNOLOGIS
Antigen Antibody (Zat Anti)
Limfosit Sensitif
8

 ANTIGEN
Zat asing yang dapat merangsang pembentukan antibody
Antigen = Alergen
= Imunogen
= Atopen

SYARAT ANTIGEN

Umumnya protein asing

Berat molekul besar
Bentuk tetap
Mampu menginduksi pembentukan AB
Dapat dihancurkan oleh sel-sel tubuh
Penting jumlah optimal untuk dapat merangsang
pembentukan AB cukup tinggi

 HAPTEN
Zat Kimia
Berat Molekul (rendah) kecil
Bila bergabung dengan
protein badan Antigen

A
10

 REAKSI HIPERSENSITIFITAS
Menurut Gell & Coombs 4 type
Type I = Reaksi Cepat
= Reaksi Anafilaksis
= Reaksi Reagin Dependent
= Immediate Hypersensitivity R
Type II = Reaksi Sito-toksik
Type III = Reaksi Antigen-Antibody kompleks
Type IV = Cell Mediated Immun Reaction
11

Gell And Coombs Classification Of

Immune-mediated Allergic Response
TYPE

MECHANISM

MANIFESTATIONS

IgE dependent

Anaphylaxis,
urticaria

II

Complement-mediated
cytotoxicity

Cytopenias

III

Immune complex
deposition

Vasculitis /
nephritis

IV

Delayed-type
hypersensitivity

Dermatitis or
hepatitis

 REAKSI TYPE I

DASARNYA:

Ig E melekat pada dinding sel mast

Antigen terikat Fab dari Ig E
Terjadi degranulasi sel mast
Pengeluaran vasoaktif amin

Timbul gejala klinik : Vasodilatasi, Permeabilitas, Perdarahan , exudasi,

edema, obstruksi bronkus, kontraksi otot polos.

13

 CONTOH REAKSI TYPE I :

Asma Bronkial Ekstrinsik
Rinitis Alergika
Hay Fever (Demam Rumput)
Beberapa Jenis Urtikaria
Angioneurotik Oedema
Alergi Obat
Alergi Makanan
Gigitan Serangga
Anafilaksis Sistemik
Dermatitis Atopik
Eksim
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Allergy
(type I hypersensitivity mediated by IgE on mast cells)

 CARA ANTIGEN MASUK BADAN

Kontak langsung dengan permukaan kulit

Jalan nafas ( A. Inhalan)
Traktus Digestivus
Parenteral

MACAM ALERGEN:
Inhalan

: Debu Rumah, Tungau, Jamur, Tepung

Sari, Rumput, Serpih Kulit
: Susu, telur, ikan, kacang-kacangan

Ingestan
(Makanan)
Injectan : obat-obatan Penisilin, Streptomisin
(Parenteral)
Lain-lain : Virus/produk bakteri
Contactan : Obat-obatan, Zat-zat Kimia

16

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 REAKSI TYPE II

DASAR:

Yang berperan: IgG, IgM

Antigen pada dinding sel, dapat berupa Hapten
Antibody spesifik terikat pada antigen
Kadang-kadang mengikat Complement

Sel Lisis
18

Antigen
Red blood cell

Complement
Antibody

Antibody

Cytolysis

19

 CONTOH REAKSI TYPE II :

Alergi Obat/Zat Kimia Lain
Anemia Hemolitik
Purpura
Trombositopenia, Pansitopenia karena Alergi
obat/Zat kimia lain
Beberapa Penyakit Autoimun
Miastenia gravis
Thyroiditis Chronis
Acut Post Streptococcus G. Nephritis
20

Reaksi hipersensitifitas tipe 3

Reaksi kompleks imun (Ag-Ab) di
jaringan atau pembuluh darah
Ig G
Kompleks imunmengaktifkan
komplemenkemotaktik
faktormakrofag ke
jaringanmerusak jaringan

21

Ag-Ab Complex

Platelet
Aggregation

Microthrombi

Vasoactive
amine release

Complement
activation

Attract
Polymorphs

Release proteolytic
enzymes and
polycationic proteins
from granules
Figure 6.3 Type III Complex-mediated hypersensitivity

Anaphylatoxin

Histamin
release

22

 CONTOH KHAS R. TYPE III

Arthus Phenomen
Serum Sickness
Penyakit Autoimun

CONTOH DALAM KLINIK:

Rheumatoid Arthritis
Serum Sickness Syndrome
Alergi Obat
Peri Arteritis Nodosa
Sub Acut / Chronic G.N
Extrinsik Alergik Alveolitis

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 REAKSI TYPE IV

SKEMA:

Ikatan antara Ag oleh T Limfosit

Pelepasan Mediator dgn Aktivitas Biologis yang luas (MAF)
Akibatnya memperbesar Imun respons selluler
Akumulasi sel Macrophag & Leukocyt ke tempat reaksi

Nekrose Jaringan, Ulserasi lokal

24

 DASAR R. TYPE IV
Reaksi terjadi antara Ag. Spesifik dengan
limfosit sensitif
Pelepasan Lymphokins
Menimbulkan sitotoksik langsung tanpa
melibatkan lg & complement

CONTOH:
Sensitivitas reaksi thd TBC
Reaksi thd Transplantasi
Tumor Imunitas
Contact Dermatitis
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KARAKTERISTIK REAKSI HIPERSENSITIFITAS

Sering akut
Kronis
Rekuren (Kumat-kumatan)
Organ sasaran berubah
Satu (single) alergen bermacam-macam manifestasi klinik
Satu (single) manifestasi klinik : dapat disebarkan oleh banyak
alergen
ASMA
RINITIS

DERMATITIS
SYOK ANAFILAKSIS D.L.L
MACAM-MACAM
ALERGEN
ASMA

A. INHALAN
MAKANAN
OBAT-OBATAN
DLL
26

KARAKTERISTIK LAIN

Herediter (menurun)
Dapat diditeksi faktor-faktor pencetus
Intensitas: alergen dipengaruhi oleh faktor non alergen
Menunjukkan sifat hiperreaktif

DIAGNOSIS (ATAS DASAR):

ANAMNESIS: - Riwayat Penyakit - Faktor Pencetus
- Gejala (keluhan)
- Faktor Keluarga
- Perjalanan Penyakit
FISIK: Tergantung organ sasaran
Wheezing
Mukosa Hidung oedem
Urtika, syok, dll

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MACAM-MACAM TES:
Tes Kulit
Tes Provokasi Bronkial
Tes Latihan(Exercise)

LABORATORIUM PENTING
Jumlah Eosinofil
Kadar Ig E (Total/spesifik) dalam

PEMERIKSAN LAIN
X Foto: Thorax
Sinus Paranasalis
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MEDIATOR2 PENTING DALAM REAKSI HIPERSENSITIFITAS

HISTAMIN: - Dalam sel mast
- Kontraksi otot polos
- Dilatasi pembuluh darah - Permeabilitas
- Exudasi
- Oedema
LEUKOTRINE : - SRS-A (SlowReactinSubtance of Anaphylaxis)
- Kontraksi otot polos
SEROTONIN: - Dilatasi pemb. Darah - Permeabilitas
- Bronkus Obstruksi
Diagnosis:
Anamnesis
Lab: Ig.E, Eosinofil
Fisis
Faal Nafas
X-Foto
Tes Kulit
Tes Provokasi
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SHOCK ORGAN (ORGAN SASARAN)

Digunakan oleh DOERR (1922)
Artinya: Organ atau jaringan tempat timbulnya reaksi alergi
Misalnya: Penyakit Organ Sasaran
ASMA Jl. Nafas
URTIKA Kulit
RINITIS Hidung
MIGRAIN . S.S.P
DIARE .. Tract Digest
CONJUNCTIVITIS . Mucosa Mata
NEUROMIALGIA Sistem Neuro Musk
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The four types of hypersensitivity reaction

CYTOKINE
ADHESION MOLECULES

Bagian Patologi Klinik

FKU-UWKS
32

ANTIGEN

PSIKIS

Bakteri
Virus
Parasit
Zat-zat asing
Dll

STATUS NUTRISI

ALERGEN
IMUNOGEN

KLINIK
ALERGI
A.I.

GEN

R.I. ABNORMAL
(MENYIMPANG)

TERPAPAR
(PAPARAN)

R.I

PROTEKSI

IMUN
(KEBAL)

(EXOGEN)
FISIK

R.I.S R.I.H

S.I DEF

TERMIS
MEKANIS
RADIASI

SUB NORMAL

KELEMAHAN
UMUM
INAKTIVITAS
DLL

RADIASI
OBAT-OBATAN
ZAT-ZAT TOKSIS
DLL

01

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FUNGSI CYTOKINE
MENGATUR (REGULATE)
PERTUMBUHAN SEL
MEMACU AKTIFITAS SEL
PROSES INFLAMASI
PROSES IMUNITAS
TISSUE REPAIR
PROSES FIBROSIS
MORFOGENESIS
02

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Target cell effects

Costimulant of T
cells proliferation
IL-4

Cell
sources

Costimulant
of B cells
proliferation IL-5

+ IgA

IL4

Bone marrow
precursor cell
proliferation

myelopoiesis

IL5

Macrophage
activation and
differentiation

+ MHC class II

T cells

NK cells

+ Ig E
+ MHC class II
+ FcR epsilon

Mast cell proliferation

Eosinofil proliferation
03

35

Figure 7-4. Cell sources and target cell effects of IL-4 and IL-5

Target cell effects

Cell
sources

Inhibits T cell proliferation

and lymphokine production
Inhibits B cell proliferation
and antibody production

T cells

B cells

Inhibits early hematopoietic

stem cell replication
Transforming
Growth Factor

Attract macrophages

(TGF-)
macrophages

Platelets

Placenta, bone
and kidneys
04
Figure 7-4. Cell sources and target cell effects of TGF-

Inhibits natural killer

activity
Osteoclast activation in
bone
Stimulates and mobilizes
fibroblasts wound healing +
collagen, fibronectin and
collagenase
Suppresses proliferation of
epithelial cells, fetal
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hepatocytes, and endothelial
cells

T-Lymphocytes
lymphokine
production
IL-2 receptors

IFN
CSF

IL-2, IL-4
IFN-

IL-4
LDCF

B-Lymphocytes
Proliferate

IL-2

antibody production

TNF- and
TNF- (LT)
Macrophages
prostaglandins and
mediates cytocidal
activation
IL-1, IL-6,IL-8. GMCSF
Bone Marrow
Inhibits in vitro
hematopoiesis but
stimulates CSF in vivo

PMNs
Neutrophilia
Metabolic activation
chemoattracts
05
37

T-Lymphocytes
IFN
CSF
lymphokine
production

IL-2, IL-4
IFN-

IL-4, IL-5
LDCF

B-Lymphocytes
Proliferate

IL-2

antibody production

IL-1
and
Macrophages
prostaglandins and
cytocidal activation
IL-6, IL-8, GMCSF,
TNF, PA, I-CAM 1

Bone Marrow
hematopoiesis but
CSF

PMNs
Neutrophilia
Metabolic activation
06

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Table 7-1. Characterictic properties of cytokines

Cytokine

MW

IL-1

17,500

Macrophahes and others (see

Table 7-2)

Immunoaugmentation

Inflammatory and hematopoietic

IL-2

15,500

T Lymphocytes and LGL

T and B Cell growth factor

Activates T and NK cells

IL-3

14,000-28,000

T Lymphocytes

Hematopoetic growth factor

Promotes growth of early myeloid progenitor cells

IL-4

20,000

TH Cells

T and B cell growth factor; promotes

IgE reactions

Promotes Ig E switch and mast cell growth

IL-5

18,000

TH Cells

Stimulates B cells and eosinophils

Promotes IgA switch and eosinophilia

IL-6

22,000-30,000

Fibroblast and others

Hybridoma growth factor; augments

inflammation

Growth factor for B cell and polyclonal

immunoglobulin production

IL-7

25,000

Stromat cells

Lymphopoietin

Generates pre-B and Pre-T cells and is lymphocyte

growth factor

IL-8

8,800

Macrophages and others

Chemoattracts neutrophils and T

Lymphocytes

Regulates lymphocyte homing and neutrophil

infiltration

G-CSF

18,000-22,000

Monocytes and others

Myeloid Growth factor

Generates neutrophil

M-CSF

18,000-26,000

Monocytes and others

Macrophages growth factor

Generates macrophage

GM-CSF

14,000-38,000

T cells and others

Monomyelotic growth factor

Myelopoiesis

IFN

18,000-20,000

Leukocytes

Antiviral, antiproliferativee, and

immunomodulating

Stimulates macrophages and NK cells

Induce cell membran antigens (eg, MHC)

IFN

25,000

Fibroblasts

IFN

20,000-25,000

TNF

17,000

Macrophages and others

Inflammatory, immunoenhancing, and

tumorcidal

Vascular thromboses and tumor necrosis

LT=TNF

18,000

T-Lymphocytes

TGF-

25,000

Principal Cell Sources

Primary Type of Activity

Preeminent Effects

T-Lymphocytes and NK cells

Platelets, bone and others

41

Fibroplasia and immunosuppression

Wound healing and bone remodelling09

The main feature of the best-studied cytokines

Cytokine

Mol.wt

Cell source(s)

Main cell target(s)

IFN

40-50.000 (dimer)

T cells, NK cells

Lymphocytes,
monocytes, tissue cells

IL-1
IL-1

33.000
17.500

Monocytes, dendritic
cells, some B cells,
fibroblasts, epithelial
cells, endothelium,
asctrocytes, macrophages

Thymocytes, neutrophils,
T and B cells, tissue cells

IL-2

15.000

T cells

T cells, B cells,
monocytes

IL-3

15.000

T cells

Stem cells, progenitors

IL-4

15.000

T cells

B cells, Tcells

IL-5

? 15.000
(153 aminoacids)

T cells

B cells, eosinophils

IL-6

20.000

Macrophages, T cell,
fibroblasts, some B cells

T cells, B cells,
thymocyets, hepatocytes

IL-8
(Family)

8.000

Macrophages, skin cells

Granulocyte, T cells

TNF

50.000

TNF
(Lymphotoxin)

50.000

Macrophages.
lymphocytes

Fibroblasts, endothelium

Main actions
Immunoregulation, B cell
differentation, some antiviral
action
Immunoregulation,
inflammatory, fever

Proliferation, activation
Pan-specific colony stimulating
factor
Division and differentiation
Differentiation
Differentiation, acute phase
protein synthesis
Chemotaxis
Inflammation, catabolism
(cachexia), fibrosis, production
of other cytokines (IL-1, IL-6,
GM-CSF) and adhesion
molecules

42

Fig. 7.14 Summary of the main features of the best studied from study of cDNA sequences. Only the most important cytokines. In some cases10
the
molecular weight is derived targets and action are shown

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