HYPERSENSITIVITY

Fransiska M.C.
 Learning Objectives
After completion this chapter, you all will
be able to :
Describe the pathogenesis of the four types of
hypersensitivity
List examples of each type of hypersensitivity
Distinguish between the preformed and newly
formed mediators of type I hypersensitivity
Understand the mechanism of damages in
hypersensitivity reaction
 Protection from
Immune Response
infecting microorganism

Exaggerated immune response

that may harmful

HYPERSENSITIVITY
Hypersensitivity reactions produced by the
normal system immune
Hypersensitivity
is undesirable reaction produced by the
normal immune system that causes tissue
damage, and such response usually occurs in a
sensitized host when it encounter the same
antigen for the second time
Classification (Gell n Coombs) :
Type I Hypersensitivity anaphylactic
Type II Hypersensitivity citotoxic
Type III Hypersensitivity immune complex
disorders
Type IV Hypersensitivity delayed hypersensitivity
Characteristics of Hypersensitivity
Type Mechanism Effector Cells Immunoglobulin

I Rx hipersensitivitas Basophils/ Mast IgE

cepat Cells
II Antibodi thd sel Sel FcR IgG or IgM
(fagosit,NK)
III Kompleks Ag-Ab Sel FcR, IgG or IgM
komplemen,
kompleks imun
IV Rx hipersensitivitas T cells, -
lambat eusinofil,
neutrofil
Macrophages
 Type I Hypersensitivity
Dikenal dengan reaksi cepat, reaksi
anafilaksis, atau reaksi alergi terjadi
dalam hitungan menit setelah kontak
dengan alergen
Dalam tubuh individu yg mengalami, akan
beredar basofils atau sel mast jaringan yang
disensitisasi oleh IgE
Terjadi umumnya pada jaringan yang kaya
sel mast kulit, nasal membranes, lidah,
paru, GIT
 Mekanisme melibatkan 3 fase
1. Sensitisasi
2. Aktivasi/degranulasi
Influks Ca dlm sel mast

Pengaktifan fosfodiesterase dlm sitoplasma

Kadar cAMP turun

Granul berisi mediator bergerak ke permukaan sel

Terjadi eksositosis & isi granul dilepas keluar sel

3. Efektor
Type I Hypersensitivity
Hipersensitivitas tipe I
(anafilaksis)
Mast Cells or Basophils release vasoactive amines
Preformed & Newly Synthesized Mediators
Preformed Mediators
Histamine kontraksi otot polos
(bronkokontriksi), sekresi mukus meningkat, dll
Eosinophil Chemotactic Factor of Anaphylaxis
(ECF-A) migrasi granulosit & sel
mononuklear
Newly Synthesized Mediators
Prostaglandin peningkatan permeabilitas
vaskular, sekresi mukus, vasodilasi
Leukotriene kontraksi otot polos, vasodiltasi,
kemotatktik neutrofil
Sitokin (TNF) Aktivasi monosit, eusinofil,
demam
Manifestasi klinik Hipersensitivitas Tipe I :
Reaksi lokal:
Rinitis alergi
Asma
Dermatitis atopi, urtikaria
Reaksi sitemik:
Anafilaksis
Contoh :
Alergen umum, misal: makanan, debu, polen
Chimeric Ab, sediaan imunoglobulin, Ab beta
laktam (penisilin, sefalosporin), quinolon
 Pseudoalergi
Disebut juga anafilaktoid
Definisi : reaksis sistemik umum yang
melibatkan pengepasan mediator oleh sel
mast yang terjadi tidak melalui IgE
Mekanisme jalur efektor non imun
Contoh: media radiokontras, cairan
plasma, NSAID (aspirin, diklofenak, asam
mefenamat, ibuprofen), vankomisin,
quinolon
 Type II Hypersensitivity

Melibatkan antibodi IgG or IgM terhadap

molekul permukaan/komponen jaringan
Sel yang terlibat: komplemen, NK cell dan
makrofag
Pemicu normalnya adalah antigen
endogen, meskipun beberapa juga ada yg
eksogen
 Type II Hypersensitivity

Antibodi-dependent cell-
mediated cytotoxicity

Complement
activation
Common disease of Type II Hypersensitivity :

Transfusion reaction
Hemolytic anemia autoimmune
Drug Interaction (drug act as hapten)
Myasthenia gravis (antibodies form against
acetylcholine (Ach) nicotinic postsynaptic receptors
at the myoneural junction reduce muscle
strength)
Hemolytic disease of newborn (Rhesus system)
Hipersensitivitas tipe II
(Sitotoksik/Sitolitik)
Hemolytic disease of newborn
 Type III hypersensitivity
Known as immune complex hypersensitivity
Involves IgG or IgM antibodies
The antigen may be
exogenous (chronic bacterial, viral or parasitic
infections), or
endogenous (non-organ specific autoimmunity: e.g.
systemic lupus eythematosus, SLE)
The reaction may take 3-10 hours after exposure
to the antigen
It is mediated by soluble immune complexes
 Soluble antigen Body Antibody

IMMUNE RESPONSE

Small molecular soluble Large molecular insoluble

Immune complex intermediate molecular Immune complex
soluble Immune complex

Eliminate by
Deposit on the basement phogacytosis
of capillaries

Combine and activate complement system

Immune complex reaction
Normal mechanism :
Soluble immune complex stayed on circulation,
and will destroyed by phagocytosis
(Macrophage) no harmful

when it presipitate in the tissues it may harmful

and cause tissue damage

Factors that may affect the presipitation of immune

complex in the tissues :
Size of Immune complex
The affinity of immune complex
Phagocytosis function
Common disease of Type III Hypersensitivity :

Arthus reaction
Necrotic vasculitis
Glomerulonephritis because of Streptococcus
infection
Rheumatoid arthritis
Lupus Eritematosus Sistemik
Serum sickness
 Hipersensitivitas Tipe III
(Hipersensitivitas Kompleks Imun)
 Type IV Hipersensitivity

Known as Delayed Type Hypersensitivity (DTH) =

Cell Mediated Immunity
Involve T cell, monocyte and macrophage
antibodi involve in this reaction
T cytotoxic cause direct tissue damage
T helper activate monocyte & macrophage
antigen Dipresentasikan sel APC Type IV
(Antigen Presenting Cell)
Hypersensitivity
mechanism
Sel Th MHC II
Dependen

Melepas MIF, MAF & Mengaktifkan

IFN makrofag M
e
l
Sitokin (IL-1, IL-6, e
Menimbulkan IL-8, IL-12,IFN ) p
inflamasi & a
mnghancurkn Metabolit Oksigen Reaktif s
bakteri dan sel lain (Superoksid, Radikal
yg dianggap asing hidroksil, hidrogen peroksid,
protease & enzim2 lisosom
Hipersensitivitas Tipe 4
 Type IV Hypersensitivity

Common condition :
Contact Dermatitis
Granuloma Reaction
Tuberculin Test (tjd >20 jam stlh trpajan)
Tuberculin Test
Measurement of Mantoux
Thanks