IMUNOLOGI

Hipersensitivitas dan
Alergi

Pendahuluan
 Sistem imun  proteksi

 Overproteksi  merusak jaringan  kematian

jaringan

 Hipersensitivitas (atau reaksi hipersensitivitas)

adalah reaksi berlebihan, tidak diinginkan karena
terlalu sensitifnya respon imun

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 Klasifikasi Hipersensitivitas
 Coombs and Gell classification

1-Type I - immediate ( atopic, or anaphylactic) (mediated

by IgE antibodies)
2-Type II - antibody-dependent (IgG and IgM)
3-Type III - immune complex (IgG and IgM
antibodies)
4-Type IV - cell-mediated or delayed (cell-mediated
response).

The hypersensitivity reactions

Figure 12-2

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 Type I - immediate (or atopic, or anaphylactic)

 Reaksi hipersensitivitas tipe I adalah reaksi alergi karena paparan

antigen spesifik (alergen).

 Paparan melalui kontak langsung, tertelan, terhirup atau injeksi

 Reaksinya diperantarai oleh IgE antibodies dan menyebabkan

pelepasan cepat histamine, tryptase, arachidonate oleh basophils
dan mast cells.
 Respon inflamasi segera terlihat (within seconds to minutes)
 Symptoms vary from mild irritation to sudden death from
anaphylactic shock.

 Treatment usually involves epinephrine, antihistamines, and

corticosteroids

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 TYPE I HYPERSENSITIVITYHistamine
leukotrien
ECF-A NCF
etc

Re-
exposure
First degranulation
exposure
o
Y oo o
YY  o
o
Y oo o
o o
Y o
o o
o o o
Y o oo
Plasma Specific o
cell IgE Mast cell

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 Some examples:
 Allergic asthma

 Allergic conjunctivitis

 Allergic rhinitis ("hay fever")

 Anaphylaxis

 Angioedema

 Urticaria (hives)

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 Fig 1

Mechanism:
 The mechanism of reaction involves preferential production of
IgE, in response to certain antigens (allergens).
 IgE has very high affinity for its receptor on mast cells and
basophils.
 A subsequent exposure to the same allergen cross links the cell-
bound IgE and triggers the release of various
pharmacologically active substances
 Cross-linking of IgE Fc-receptor is important in mast cell
triggering. Mast cell degranulation is preceded by increased
Ca++ influx, which is a crucial process; ionophores which
increase cytoplasmic Ca++ also promote degranulation,
whereas, agents which deplete cytoplasmic Ca++ suppress
degranulation.

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 Ig E melekat dengan mast cell kemudian terpapar dengan
alegen spesifik  crosslinking , degranulasi sel mast 
mediator , reaksi biokimia, aktivasi enzim metiltransferase
dan serin esterase.
Reaksi fosfatidil inositol  inositol trifosfat, diasilgliserol dan
peningkatan ion Ca intrasitoplasmik

Memudahkan reaski fusi membran granulasi , pelepasan

mediator histamin , heparin, eosinophil chemotatic factor ,
netrofil chemotatic factor, platelet, leukotrin 
vasodilator , peningkatan permeabilitas , edema dan
mukosa hipersekresi lendir

Bentuk mediator & gejala yg timbul

Tabel 7.1. mediator/agen yang dibebaskan oleh mast sel dan gejala yang timbul
Mediator Gejala
Bentuk mediator lama
Histamin Broncho konstriksi, sekresi mukus, vasodilatasi
Permiabilitas vaskuler
Tryptase Proteolysis
Kininogenase Kinin dan vasodilatasi, permiabilitas vaskuler, edema
ECF-A (tetrapeptida) Produksi eosinofil dan neutrofil
Bentuk mediator baru
Lekotrine B4 Edema dan rasa sakit
Leukotrine C4, D4 Sama seperti histamin tetapi lebih kuat
Prostalglandin D2 Edema dan rasa sakit
PAF(platelet activation Agregasi platelet dan pembebasan heparin, mikrotrombi
factor)

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 Diagnosis dan pengobatan

 Diagnosis:
 Uji intradermal

 Uji ELISAmengukur total IgE

 Pengobatan:
 Antihistamin

 Sodium kromalinmencegah degranulasi mast sel

 hiposensitisasi

Type II - antibody-dependent
 Karena terjadinya respon imun thd antigen maka timbul antibodi.
 Antibodi kmdn mengikat antigen self pd sel tubuh sndiri atau antigen
asing yang terabsorbsi kedalam sel.
 Zat kimia eksogen yang bersifat haptens dapat terikat denga
membran dan menimbulkan reaksi hipersensitivitas tipe II

 IgM atau IgG mengikat antigen tersebut mengaktifkan jalur klasik

komplemen (dengan maksud untuk eliminasi sel yang
mempresentasikan antigen asing)  inflamasiMAClisis

 Phagocytes and NK cells may also play a role (ADCC).

 The reaction takes hours to a day.

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 Examples
 Autoimmune haemolytic anaemia
 Pernicious anemia
 Immune thrombocytopenia
 Transfusion reactions
 Hashimoto's thyroiditis
 Graves' disease
 Myasthenia gravis
 Farmer's Lung
 Hemolytic disease of the newborn

 Reaksi yg terjadi pada transfusi darah

 Reaksi hemolitik

 Anemia hemolitik akibat obat.

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 Golongan Antigen Antibodi Gol Drah yg
darah dapat
diterima
AB A dan B Tidak ada A,B.AB.O(pe
anti Aatau B nerima
universal)
B B Anti A B.O
A A Anti B A,O
O Tdk ada AntiA dan O (donor
Anti B universal)

 Sel darah dirusak oleh adanya antibodi.

 Apabila gol darah tdk sesuai pada saat transfusi :
 Gol B ditarnsfusi pada gol A, maka antigen B yg
terdapat pada dalam darah akan bereaksi dengan
antiB pada serum penerima.
 Reaksi ag-ab  merangsang reaksi aktivasi komplemen ,
menyebabkan hemolisis sel darah merah donor pada
saat masuk ke dalam tubuh penerima transfusi.

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 Mekanisme

Lab Diagnosis

Diagnostic tests include detection of circulating

antibody against the tissues involved and the
presence of antibody and complement in the lesion
(biopsy) by immunofluorescence

Obat : antiinflamasi

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 Type III - immune complex (agregasi IgM/IgG
dengan antigen)

In type III hypersensitivity:

 Kompleks Ag-Ab yang terbentuk didarah dapat terdeposit di
jaringan (kulit, ginjal dan persendian, paru-paru)  memicu
respon imun melalui aktivasi komplemen jalur klasik


 The reaction takes hours to days to develop

Examples:

 Immune complex glomerulonephritis

 Rheumatoid arthritis
 Serum sickness
 Subacute bacterial endocarditis
 Symptoms of malaria
 Systemic lupus erythematosus
 Arthus reaction

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  Immune complex formation may occur as a result
of :
 Autoimmune diseases (RA)
 Persistence infection (Hepatitis virus)
 Repeated inhalation of antigenic materials

MECHANISM
Step 1

Large quantities of
soluble antigen-
antibody complexes
form in the blood and
are not completely
removed by
macrophages.

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 Step 2

These antigen-
antibody complexes
lodge in the
capillaries between
the endothelial cells
and the basement
membrane.

Step 3

These antigen-
antibody complexes
activate the classical
complement
pathway leading to
vasodilatation.

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 Step 4

The complement proteins and antigen-antibody complexes

attract leukocytes to the area.

Step 5
The leukocytes
discharge their
killing agents and
promote massive
inflammation. This
can lead to tissue
death and
hemorrhage.

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 size of the immune complex, time, and place
determine if this reaction will occur or not

Localized depositions of immune complexes

within a tissue cause type III hypersensitivity

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 Serum Sickness

- Is
a disease caused by the injection of large doses of a
protein antigen into the blood and characterized by the
deposition of antigen-antibody complexes in blood vessel
walls, especially in the kidneys and joints.

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 Serum sickness

Systemic Lupus Erythmatosus

 The disease is characterized by the presence of
autoantibodies , which form immune complexes with
autoantigens and are deposited within the kidney
glomeruli

 The resulting type III hypersensitivity is responsible

for the glomerulonephritis
(Inflammation of blood capillary vessels in the
glomeruli)

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 Type IV Hypersensitivity (delayed)

 takes two to three days to develop.

Unlike the other types, it is not antibody mediated
but rather is a type of cell-mediated response.
 Contoh klasik reaksi hipersensitivitas IV tuberculin
(Montoux) reaction

 Reaksi mencapai puncak setelah 48 jam injeksi

antigen (PPD/Purified Protein Derivative or old
tuberculin).
 Reaksi ditandai dengan eritema dan induratio
(penebalan kulit)

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 Some clinical examples:
 Contact dermatitis (poison ivy rash, for example)

 Temporal arteritis

 Symptoms of leprosy

 Symptoms of tuberculosis

 Transplant rejection

 Type IV hypersensitivity is involved in the pathogenesis of

many autoimmune and infectious diseases:
 Tuberculosis
 Leprosy
 Blastomycosis
 Histoplasmosis
 Toxoplasmosis
 Leishmaniasis
 Granulomas due to infections and foreign antigens.

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  Another form of delayed hypersensitivity is contact
dermatitis (poison ivy (figure 6), chemicals, heavy
metals, etc.) in which the lesions are more papular

 Type IV hypersensitivity can be classified into three

categories depending on the time of onset and
clinical and histological presentation

Type
Fig 5
Reaction
time
Clinical Histology Antigen and site
appearance

lymphocytes, followed by epidermal ( organic chemicals,

contact 48-72 hr eczema macrophages; edema of poison ivy, heavy metals,
epidermis etc.)

local lymphocytes, monocytes, intradermal (tuberculin, lepromin,

tuberculin 48-72 hr
induratio macrophages etc.)

persistent antigen or foreign

macrophages, epitheloid and
granuloma 21-28 days hardening body presence (tuberculosis,
giant cells, fibrosis
leprosy, etc.)

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 Mechanism:
 The mechanism includes T lymphocytes and
monocytes and/or macrophages.
 Cytotoxic T cells (Tc) cause direct damage
whereas helper T (TH1) cells secrete
cytokines which activate cytotoxic T cells,
recruit and activate monocytes and
macrophages, which cause the bulk of the
damage
 The delayed hypersensitivity lesions mainly contain
monocytes and a few T cells.

Diagnosis
 Diagnostic tests in vivo include delayed cutaneous
reaction (e.g. Montoux test )

 In vitro tests for delayed hypersensitivity include

mitogenic response, lympho-cytotoxicity and IL-2
production.

 Corticosteroids & other immunosuppressive agents

are used in treatment.

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 The hypersensitivity reactions
Figure 12-2

Tabel 7.4. Perbandingan beberapa tipe hipers ensitiviti menurut reaksi yang timbul
Parameter Tipe I Tipe II Tipe III Tipe IV
(anafilaktik) (sitotoksik) (imun komplek) (delay)
Antibodi IgE IgG, IgM IgG, IgM Absen
Antigen Exogenous Permukaan sel Agen mudah larut Jaringan/organ
/biologik
Waktu respon 15-30 menit menit- jam 3-8 jam 48-72 jam

Gejala Kemerahan, Lysis dan erithema, edema, Erythema dan

seperti terbakar nekrosis nekrosis pembengkakan

Histologi Basofil dan Antibodi dan komplemen dan Monosit dan

eosinofil komplemen neutrofil limposit
Sel-T
Ditransfer dg Antibodi Antibodi
Contoh Allergik, Eritroblastosis, antibodi Tes
asthma, hay nefritis SLE, penyk paru tuberkulin,
fever racun
tanaman,
granuloma

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 Tipe Nama lain Mediated Mekanisme onset contoh
Hipersensiti by
vitas

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