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Hypersensitivity

Dr. Yordan Khaedir, PhD


What makes us sick?

•  “enemies” in the environment in the form of


microbes and chemicals are constantly attacking
our bodies, disrupting homeostatis"
•  Sometimes immune system homeostasis is
disrupted on its own

It may It may
under-react as It may
over-react React to self
to antigens with human
immunodeficiency proteins as
such as with
with virus infection
autoimmune
allergies (HIV)
disease
Introduction
§  Hypersensitivity  (Immunological reaction)
refers to undesirable (damaging, discomfort-
producing and sometimes fatal) immune
reactions produced by the normal immune
system."
"
§  Hypersensitivity reactions: When an immune
response result in exaggerated OR in
appropriate reactions harmful to the host the
term hypersensitivity OR allergy used."

§  Hypersensitivity reactions require a pre-


sensitized (immune) state of the host."
"
Hypersensitivity classification
Hypersensitivity reactions: four types;"
§ Type I"
§ Type II"
§ Type III"
§ Type IV"
based on the mechanisms involved and time
taken for the reaction, a particular clinical
condition (disease) may involve more than
one type of reaction."
Hypersensitivity classification
•  Hipersensitivitas reaksi cepat ( hitungan detik,
menghilang dalam 2 jam )"
•  Hipersensitivitas reaksi intermediet ( hitungan jam,
menghilang dalam 24 jam)"
Onset •  Hipersensitivitas reaksi lambat ( terjadi sekitar 48
jam setelah terjadi pajanan)"

•  Tipe I (Reaksi IgE) atau Immidiate


hypersensitivity"
•  Tipe II (Reaksi sitotoksik) atau antibody-
mediated disorder"
Robert Coombs •  Tipe III (Reaksi kompleks imun) atau immune-
dan Philip HH complex mediated disorder"
Gell (1963) •  Tipe IV (Reaksi selular) atau cell-mediated
immune disorder"
Gel and Coombs classification of hypersensitivities "

Type I Type II Type III Type IV

IgG/IgM IgG Mediated T cell


IgE Mediated
Mediated

Immune Delayed
Classic Allergy rbc lysis complex Type
Disease Hypersensitivity
Type I, II and III Antibody Mediated

Type IV Cell Mediated


Type I Hypersensitivity

Ø  Commonly called allergy


Ø  Mediated by IgE antibodies produced by plasma cells in
response to stimulation of Th2 cells by an antigens.
Ø  The antigens that stimulate it are called allergens
(i.e. House dust, Pollens, Cosmetics, Insects, Clothing and Drug)
Ø  Exposure may be ingested, inhalation, injection or direct
contact.
Ø  Type I hypersensitivity reactions can be systemic (e.g.,
systemic anaphylaxis) or localized to a specific target
tissue or organ (e.g., allergic rhinitis, asthma).
Allergens
Phases:

•  sensitization
•  activation
•  effector
Busse and Lemanske NEJM Feb 2001. 344:350
Allergen

IgE production by B lymphocytes


(at the site of entry of antigen and draining
Lymphnodes)

IgE antibodies attach to


mast cells and basophils

This person is sensitized


to that allergen.

Memory cells are


generated
Re-exposure to the allergen

Binding of allergen to 2 adjacent IgE molecules


on the surface of a basophil or mast cell

Destortion of the cell membrane causing them


to degranulate

Release of vasoactive amines (histamine) into


the circulation
Primary Phase

Histamine

Increased
Increased Pruritus and
capillary
mucus secretion erythema
permeability

Watery nasal
Edema, facial
and conjunctival
puffiness
discharge
Secondary Phase

Secretion of leukotrienes and


prostaglandin

Stimulation of more white


blood cells

Generalized
inflammatory reaction
Mediators of Type I Hypersensitivity
Primary Mediators
Pre-formed mediators in granules
•  Histamine
•  Cytokines TNF-a, IL-1, IL-6.
•  Chemoattractants for Neutrophils and
Eosinophils
•  Enzymes
–  tryptase, chymase, cathepsin
–  changes in connective tissue matrix,
tissue breakdown
Type I Hypersensitivity
Secondary mediators
Mediators formed after activation

•  Leukotrien (lipid mediator)


•  Prostaglandins
•  Th2 cytokines- IL-4, IL-5, IL-13, GM-CSF
Allergy is characterized by a local or systemic
inflammatory response to allergens

Local symptoms:
•  Nose: swelling of the nasal mucosa (rhinitis allergy)
•  Eyes: redness and itching of the conjuctiva
•  Airways: bronchoconstriction, wheezingàasthma
•  Ears: pain , feeling fullness
•  Skin: rashes, hives, contact dermatitis

Systemic allergic symptoms:


•  Called anaphylaxis
•  Depending of the rate of severity à edema,
hypoytension, coma and even death
Type II (Cytotoxic) Hypersensitivity

Ø  Type II hypersensitivity also known as cytotoxic hypersensitivity


and may affect a variety of organs and tissues

Ø  The antigens are normally endogenous, although exogenous


chemicals (haptens) that an attach to cell membranes can also
lead to type II hypersensitivity

Ø  The reaction time is minutes to hours

Ø  Type II hypersensitivity involves IgG or IgM antibody-mediated

Ø  IgM or IgG immunoglobulin react with cell-surface antigens to


activate the complements system and produce direct damage
of the sell surface
Type II examples
•  Transfusion reactions
•  Erythroblastosis fetalis
•  Autoimmune hemolytic anemia,
agranulosis, thrombocytopenia
•  Drug reactions
Myasthenia gravis Graves disease
Type III HYPERSENSITIVITY
(Immune complex-mediated hypersensitivity)

Ø  The reaction may take 3 - 10 hours after exposure to the


antigen.
Ø  Involve reactions against soluble antigens circulating in serum
Ø  Usually involve IgM, IgG antibodies
Ø  Antibody-antigen immune complexes (Medium complexes) are
deposited in organs, activate complement, and cause
inflammatory damage.
Ø  The reaction may be general (e.g., serum sickness) or may
involve individual organs including skin (e.g. systemic lupus
erythematosus reaction, kidneys (e.g. lupus nephritis), joints
(e.g. rheumatoid arthritis) or other organs.
Pic.1 The crippling distortion of joints characteristic of rheumatoid arthritis

Pic.2 The characteristic facial rash of systemic lupus erythematosus


Hypersensitivity Type III Reactions

Local Reactions Systemic Reactions

v  Arthus Reaction: v  Serum Sickness:


ü It is named for Dr. Arthus. ü Systemic inflammatory response
ü Inflammation caused by the to deposited immune complexes at
deposition of immune many areas of body.
complexes at a localized site. ü Few days to 2 weeks after
ü Clinical Manifestation is : injection of foreign serum or drug it
Hypersensitivity Pneumonitis results in :
Fever, Urticaria, Artheralgia,
Eosinophila, Spleenomegally, and
Lymph adenopathy
Arthus Reaction
Acute Serum Sickness

Days after Antigen Injection


Type IV Hypersensitivity
Type IV (Delayed or Cell-Mediated) Hypersensitivity

Ø  Delayed hypersensitivity is a function of T Lymphocytes, not


antibody (the only type that is not antibody-mediated)
Ø  It is called delayed because its onset may vary, it starts hours
(or Days) after contact with the antigen and often lasts for
days.
Ø  There are two different types of reactions capable of causing
tissue injury in this way

1. Delayed type hypersensitivity is mediated by CD4 helper T


cells
2. Cell mediated cytotoxicity, is mediated by CD8 T cells
Dua bentuk mekanisme kerusakan jaringan pada
reaksi hipersensitivitas tipe-IV

A.  Reaksi CD4+ (kadang sel CD8+) berespon terhadap


antigen dengan melepas sitokin yang menstimulasi
inflamasi dan aktivasi fagosit, berakibat pada
kerusakan jaringan.
B. Pada penyakit tertentu, CD8+ cytolytic T
lymphosites (CTLs) bersifat langsung
membunuh sel.
Delayed type hypersensitivity (DTH)

DTH is a type of immune


response classified by
Th1 and macrophage
activation that results in
tissue damage.

DTH can be the result of


Chronic infection or
Exposure to some antigens.
Further reading

•  Kumar V, Abbas AK, Fausto N, Aster JC.


Robbins and Cotran Pathologic Basis of
Disease.8th ed. Elsevier Saunders: China.
2010.
•  Bratawidjaja KG, Rengganis I. Imunologi
Dasar.11th ed. Badan Penerbit Fakultas
Kedokteran Universitas Indonesia: Jakarta.
2014: 321-330.
•  Abbas AK, Lichtman AH, Pillai S. Cellular
and Molecular Immunology. 7th ed. Elsevier
Saunders: Philadelphia. 2012: 407-444.
ありがとう !!