Transcript Type II hypersensitivity target tissues

Chapter 23
Immediate hypersensitivity (Type I)
Trai-Ming Yeh, Ph.D.
Department of Medical Laboratory Science
and Biotechnology
College of Medicine
National Cheng Kung University
HYPERSENSITIVITY REACTIONS ARE BASED ON THE
CLASSIFICATION OF COOMBS AND GELL
Type I: Immediate hypersensitivity responses
Type II: Antibody-mediated reactions
Type III: Immune complexes
Type IV: Cell-mediated reactions
Anaphylaxis and urticaria
wheal and flare skin response
MOST ALLERGENS ARE PROTEINS
IgE is distinct from other
immunoglobulin
• IgE has four constant regions
of heavy chain
• IgE can bind to high-affinity
IgE receptors, FcεRI on mast
cells and basophils and lowaffinity FcεRII (CD23)on B
cells
• The half-life of IgE is short
(less than 2 days) compared
with that of other
immunoglobulins
IgE is digest in endosome while IgG is
protected by binding to the neonatal Fc
gamma receptor, FcγRn
TH2 Cytokines regulate the production of IgE
TH2 cytokines:
L-4 (IL13)
IL-5
IL-10
Both IgE and IgG4 are dependent
on IL-4
Tolerance to allergen by
inducing IgG4 blocking
antibody (hyposensitization)
Small quantities of inhalant
allergens cause hayfever, chronic
rhinitis, and asthma
Mast cells and basophils contain histamine
which is released during degranulation
Mucosal mast cells (MMCs) and
connective tissue mast cells (CTMCs)
have distinct granule proteases
In allergic individuals mast cells
can be recruited to the skin and
to the nose
Cross-linking of two FcεRI
receptors results in
degranulation and the
synthesis of newly formed
mediators
MULTIPLE GENES HAVE BEEN
ASSOCIATED WITH ASTHMA
IN DIFFERENT POPULATIONS
Skin test are used for diagnosis and investigation
Skin tests
• Prick test: 25-gauge needle, 0.1 μl of extract
into the dermis
• Intradermal injection 0.02-0.03 ml
• Patch test :10 μg allergen is applied on a gauze
pad 2.5 cm2, and the biopsy is carried out at 24
or 48 hours.
SEVERAL DIFFERENT PATHWAYS CAN CONTRIBUTE TO
THE CHRONICITY OF SYMPTOMS OF ALLERGY
Corticosteroids, which are an effective treatment for
most of the inflammation in asthma act at both stages
ALLERGENS CONTRIBUTE
TO ASTHMA
• Bronchoalveolar lavage (BAL) analysis
after allergen challenge demonstrates mast
cell and eosinophil products
• Major basic protein (MBP) is present in
biopsies of the lungs and can produce
epithelial change typical of asthma in vitro.
• Non-specific bronchial hyperreactivity
(BHR) is a major feature of asthma
• Nasal smear eosinophils are increased
Immunotherapy (or hyposensitization) is an
effective treatment for hayfever
NEW APPROACHES FOR
TREATING ALLERGIC DISEASE
• Modified forms of allergen-specific
immunotherapy.
• Adjuvants shift immune response to TH1
• DNA vaccine
• Humanized monoclonal anti-IgE
• Recombinant soluble IL-4R to block the
biological activity of IL-4
• Humanized monoclonal anti-IL-5 decreases
circulating eosinophils
Summary of Chapter 23 Immediate hypersensitivity (I)
• Hypersensitivity reactions are based on the
classification of Coombs and Gell.
• Historical observations have shaped our
understanding of immediate hypersensitivity.
• Most allergens are proteins.
• IgE is distinct from the other dimeric immunoglobulins.
• Allergens are the antigens that give rise to immediate
hypersensitivity and contribute to asthma.
• Mast cells and basophils contain histamine.
• Multiple genes have been associated with asthma in
different populations.
Summary of Chapter 23 Immediate hypersensitivity (II)
• Skin tests are used for diagnosis and investigation.
• Several different pathways contribute to the chronic
symptoms of allergy.
• Allergens contribute to asthma.
• Immunotherapy can be used for hayfever and
anaphylactic sensitivity.
• New approaches are being investigated for treating
allergic disease.
• IgE antibodies play a critical role in defense against
helminths.
97年1月11日有一新聞報導衛生署核准的非類固醇
類止痛劑「Ketorolac」，自民國八十七年迄今，
國內「藥品不良反應通報系統」已有數十起有關
Ketorolac類藥物通報案件，已發生七例病人注射
含Ketorolac成分注射劑後產生過敏性休克案例，
其中四例更因此死亡。因此衛生署要求加註警語，
提醒醫護人員使用注射劑型Ketorolac成分藥品時，
需有急救設備備用，注射後半小時內應有人監控
病患的安全性。請說明此現象的免疫反應的機制，
就標示的重點回答。
Chapter 24
Hypersensitivity (Type II)
Trai-Ming Yeh, Ph.D.
Department of Medical Laboratory Science
and Biotechnology
College of Medicine
National Cheng Kung University
Type II hypersensitivity is mediated by IgG or IgM binding
to specific cell surface and extracellular antigens
1. Cells engage their
targets using Fc
and C3 receptors
2. Cells damage
targets by
exocytosis of their
normal immune
effector molecule
3. When the target is
host tissue that has
been sensitized by
antibody, the result
is damaging
1. Ab against blood
group Ag causes
transfusion
reactions
2. Cross-matching
ensures that a
recipient does not
have antibodies
against donor
erythrocyte.
ABO blood group system is of
primary importance
Genes coding for enzymes that
transfer terminal sugars to a
carbohydrate backbone cause
the different blood group ABO
The Rhesus system is a major cause of hemolytic disease of
the newborn (hemolytic disease of the newborn, HDNB)
HDNB is due to maternal IgG reacting against the
child's erythrocytes in utero
Autoantibodies against RBC
• Warm-reactive autoantibodies against
Rhesus system antigens, including
determinants of the RhC and RhE loci as
well as RhD cause accelerated clearance of
erythrocytes
• Cold-reactive autoantibodies IgM against I
Ag and fix complement strongly cause
erythrocyte lysis by complement fixation
Direct Coomb’s test (direct antiglobulin test, DAT);
to detect incomplete Ab on RBC surface)
Drug-induced reactions to
blood components occur in
three different ways
Type II hypersensitivity target
tissues
• Antibodies against basement membranes (collagen type
IV) produce nephritis in Goodpasture's syndrome
• Pemphigus is caused by autoantibodies to an intercellular
adhesion molecule desmoglein-1 and desmoglein-3,
components of desmosomes
Autoantibodies to neutrophil
cytoplasmic antigens (ANCAs)
• Cytoplasmic (c-ANCA against proteinase III) is
associated with Wegener's granulomatosis
• Perinuclear (p-ANCA against myeloperoxidase)
Antibodies against
acetylcholine receptors
(AchR) in Myathenia
gravis
Ab against voltage-gated
calcium channels or the
synaptic vesicle protein
synaptotagmin in
Lambert-Eaton
syndrome caused
defective release of
acetylcholine
Summary of Chapter 24 Hypersensitivity (Type II)
• Type II hypersensitivity is mediated by antibodies
binding to specific cells.
• Type II hypersensitivity reactions may target cells.
• Hemolytic disease of the newborn.
• Type II hypersensitivity reactions may target tissues.
• The role of autoantibodies in disease is not always
clear.
• Cytotoxic antibodies are increasingly being used for
therapeutic indications.
Important points needed to understand after class
• Understand the importance and the immunology
of the IgE-mediated hypersensitivity.
• Understand the diagnosis and treatment of allergy.
• Understand the role of type II hypersensitivity in
blood transfusion.