HYPERSENSITIVITY

PROF.AGUSTINA TRI ENDHARTI.,Ph.D

FACULTY OF MEDICINE
UNIVERSITAS BRAWIJAYA
 HYPERSENSITIVITY

Tipe 1 ( Reaksi Anafilaksis)

Damage of the body Tipe II ( Reaksi Sitotoksik)
Tipe III ( Reaksi Imun Kompleks)
by immune response Tipe IV ( Reaksi Tipe Lambat)

Suatu Respons imun yang berlebihan dan yang tidak diinginkan karena dapat menimbulkan kerusakan jaringan tubuh
 Classification of Immunological Diseases

reaksi cepat,reaksi anafilaksis:

Reaksi yang segera timbul
sesudah alergen masuk kedalam
tubuh.

reaksi sitotoksis terjadi oleh

karena dibentuk antibodi IgG /
IgM

Abbas et al., 2009

 Classification of Immunological Diseases

reaksi kompleks imun yang terjadi akibat

endapan kompleks antigen-antibodi dalam
jaringan / pembuluh darah

reaksi lambat, kelainan inflamasi yang

sering bersifat ekzematosa dan
disebabkan oleh reaksi kulit terhadap
sejumlah bahan yang iritatif /alergenik,

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Type I Hypersensitivity

Known as “immediate hypersensitivity or anaphylactic hypersensitivity”

Respon to an antigen called allergen
Grasses, pollens, animal dander, drug, bee sting and foods
Mediated by IgE and mast cells
Clinical symptoms
Allergic rhinitis, sinusitis, hay fever, food allergies, bronchial asthma,
anaphylaxis
Abbas et al., 2017
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Type I Hypersensitivity

Production of IgE in response Allergen interaction with IgE on the surface of mast
to an allergen cells triggers the release of inflammatory mediators
10 Clinical Manifestations of immediate
hypersensitivity reactions
Clinical syndrome Clinical and pathologic manifestations

Allergic rhinitis, sinusitis (hay Increased mucus secretion;

fever) inflammation of upper airways, sinuses
Food allergies Increased peristalsis due to
contraction of intestinal muscles
Bronchial asthma Bronchial hyper-responsiveness caused
by smooth muscles contraction;
inflammation and tissue injury caused
by late phase reaction
Anaphylaxis (may be caused by Fall in blood pressure (shock) caused by
drugs, bee sting, food) vascular dilation; airway obstruction
due to laryngeal edema

Abbas et al., 2009

APC antigen presenting cell,, TCR T-cell receptor, Sel TH2 T
helper CD 4+ pajanan ulang, alergen berikatan silang dengan IgE
pada sel sel mast mengakibatkan:Degranulasi vesikel yang sudah
terbentuk sebelumnya (mediator primer: histamin,
• Diperantarai IgE
• Alergen
• produksi IgE
• berikatan spesifik dengan reseptor permukaan sel mast dan
basofil
Skin prick tests
15

• Reaksi hipersensitivitas tipe I => reaksi alergi yang terjadi karena

terpapar antigen spesifik yang dikenal sebagai alergen. Terpapar dengan
cara ditelan, dihirup, disuntik, ataupun kontak langsung.
• Perbedaan antara respon imun normal dan hipersensitivitas tipe I adalah
adanya sekresi IgE yang dihasilkan oleh sel plasma.
• Antibodi ini akan berikatan dengan respetor IgE pada permukaan jaringan
sel mast dan basofil.
• Sel mast dan basofil yang dilapisi oleh IgE akan tersensitisasi (fase sensitisasi),
karena sel B memerlukan waktu untuk menghasilkan IgE,
• Waktu yang diperlukan bervariasi dari 15-30 menit hingga 10-20 jam. Adanya
alergen pada kontak pertama menstimulasi sel B untuk memproduksi antibodi,
yaitu IgE.
• IgE kemudian masuk ke aliran darah dan berikatan dengan reseptor mastosit
dan basofil sehingga sel mastosit atau basofil menjadi tersensitisasi
17
 Type II Hypersensitivity
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Antibody against cells or extracellular matrix component in any

tissue that expresses the relevant target antigen
Mediated by IgG, IgM
Immune Processes involved:
Classical Complement Pathway, opsonization and phagocytosis
Phagocytosis via FcR and Complement receptor
ADCC via NK cells or eosinophils
Result → lysis on the target cell
OPSONIZATION DURING TYPE-II HYPERSENSITIVITY

Animation: IgG reacts with epitopes on the host cell membrane.

Phagocytes then bind to the Fc portion of the IgG and discharge their
lysosomes
 MAC LYSIS DURING TYPE-II HYPERSENSITIVITY/REAKSI SITOTOKSIK
Animation: IgG or IgM reacts with epitopes on the host cell
membrane and activates the classical complement pathway.
Membrane attack complex (MAC) then causes lysis of the cell.
dibentuk antibodi jenis IgG atau IgM
terhadap antigen. Kelainan patologi terjadi
secara sekunder lewat 3 jalur :
a. Opsonisasi dan fagositosis
Dimediasi oleh komplemen serta reseptor
Fc. Sel-sel dapat mengalami lisis langsung
lewat komplemen C5-C9 membran attack
complex (MAC) .
 TYPE II HYPERSENSITIVITY
21 ANTIBODY DEPENDENT CELL MEDIATED CYTOTOXICITY

Animation: Antibodies react with epitopes on the host cell membrane and
NK cells bind to the Fc of the antibodies. The NK cells then lyse the cell with
pore-forming perforins and cytotoxic granzymes
22 EXAMPLES OF DISEASES CAUSED BY CELL
OR TISSUE SPESIFIC ANTIBODIES
 Autoimmune Hemolytic Anemia
 Autoimmune Thrombocytopenic Purpura
 Pernicious Anemia
 Pemphigus Vulgaris
 Acute Rheumatic Fever
 Myasthenia Gravis
 Grave Disease
 HUMAN ANTIBODY – MEDIATED DISEASES
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Type III Hypersensitivity
“Immune complex disease”
Soluble Ag-(IgG or IgM)  high titers of each required
Immune processes involved:
classical complement pathway
phagocytic cells
Common sites : blood vessel walls at site of turbulance or
high pressure ( kidney, and synovium of joint )
Result : vasculitis, arthritis and nephritis
25 IMMUNE COMPLEX MEDIATED HYPERSENSITIVITY

Pezzuto, 2003
 26 TYPE-III HYPERSENSITIVITY: IMMUNE COMPLEX

Ab-Ag Complexes Critical mediators appear to be

C5a-receptor and FcgRIII--probably present on mast
cells

Animation: Large quantities of soluble antigen-antibody complexes form in the

blood and are not completely removed by macrophages. These antigen-antibody
complexes lodge in the capillaries between the endothelial cells and the basement
membrane. The antigen-antibody complexes activate the classical complement
pathway and complement proteins and antigen-antibody complexes attract
leukocytes to the area. The leukocytes then discharge their killing agents and
promote massive inflammation. This leads to tissue death and hemorrhage
27 HUMAN IMMUNE COMPLEX-MEDIATED DISEASES

Immune complex Antigen involved Clinicopathologic

manifestation
Disease
Systemic lupus DNA, nucleoproteins Nephritis, arthritis,
erythematosus others vasculitis
Polyarteritis nodosa Hepatitis B virus surface Vasculitis
antigen
Poststreptococcal Streptoccocal cell wall Nephritis
glomerulonephritis antigen (s) ; may be
“planted” in glomerular
basement membrane
Serum sickness Various protein antigens Arthritis, systremic
vasculitis, nephritis
Arthus reaction Various protein antigens Cutaneous vasculitis

Abbas et al., 2009

28
Systemic Lupus Erythematosus (SLE)

Roitt et al.,2004
29 Type IV Hypersensitivity
Delayed type hypersensitivity (DTH) and T cell-mediated cytolysis
Occurs 48 – 72 hours after contact
Two phase:
Sensitization phase: produce memory Th1, no visible symptoms
Effector phase: activated macrophage
Contact : poison ivy, latex, nickel, jewelry, and cleaning product
Clinical example: TB skin test
30 Type IV Hypersensitivity

Abbas et al., 2004

31 Type IV Hypersensitivity
DTH sensitization phase

an
tig
en
Type IV Hypersensitivity
Effector phase: start 24 hrs, peak 48 hrs later

antigen
tipe lambat (delayed type
hypersensitivity),
• Reaksi tuberkulin (mantoux)
yang memuncak 48 jam setelah
injeksi antigen •
• Dermatitis kontak, penyakit
autoimun dan infeksi seperti
tuberkulosis, lepra
T CELL-MEDIATED IMMUNOLOGICAL DISEASES
34 Comparison of types of hypersensitivity
involving acquired responses

Roitt et al., 2004