Allergy and Hypersensitivity

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Chapter 13 Allergy and Hypersensitivity
The book defines allergy as an IgE response to
innocuous antigens (i.e., a type I
hypersensitivity)(we will use this
definition) Others define all hypersensitivities
as allergies (i.e., types I to type
IV) Hypersensitivity is an immune reaction to
innocuous antigens that results in tissue injury
and/or disease An antigen that causes allergy is
an allergen
Can you defineallergen,immunogen,antigen?
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Four Types of Hypersensitivities
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Allergy (type I hypersensitivity mediated by IgE
on mast cells)
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Dust Mite
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Mast cell degranulation by antigen (allergen)
cross-linking of FceR-bound IgE
Eosinophils and basophils may also participate
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What are the characteristics of allergens?
It is not fully understood how or why, but these
type of antigens tend to stimulate IL-4
production Il-4 production tends to lead to more
IL-4 production. IL-4 favors class switching to
IgE
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The enzymatic activity of a dust mite fecal
protein allows it to penetrate epithelial tight
junctions and induce a TH2 response
Skip this slide
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Both Genetics and the Environment play a
significant roles in determining who has
allergies and which kind of allergy.
Certain allergies and autoimmunity can be mapped
to specific gene loci.
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Genetics and Environment are important for the
development of allergies
Susceptibility genes for asthma (certain alleles
make individuals more susceptible to allergies)
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Genetics and Environment are important for the
development of allergies
The hygiene hypothesis of allergy induction
contends that too clean of an environment and
lack of infections during childhood (along with a
genetic susceptibility) promote a bias of the
immune system toward TH2 and IgE
Atopy a increased tendency toward type I
hypersensitivity (IgE allergies)
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Mast cell activation (degranulation) has many
effects
Mast cells are most common near epithelial
surfaces (e.g., skin, lungs, gut). Most IgE is
on mast cells, not in the blood
Why? Normally IgE responses are associated with
worm infestations. These responses help evacuate
the places where the worms often live.
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Compounds Released from Mast Cells upon
activation antigen (allergen) binding on the
surface IgE
Pre-formed and in granules
Synthesized upon mast cell activation
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Compounds Released from Eosinophils
Cytokine-activated Eosinophils have Fce receptors
(FceR)
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Allergy symptoms depend on route of allergen entry
Can be fatal. Allergy to insect venom, drugs,
foods and
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TH2-mediated chronic airway obstruction
(asthma)
Type IV hypersensitivity because TH2 involvement
Type I hypersensitivity because IgE-mediated
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Allergy treatments
desensitization
Reverse TH1/TH2 balance (2006)
make IgG response to compete with IgE
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Type II hypersensitivity (IgG-mediated
anti-cell-associated antigen response) is
rare Immune response to certain drugs (e.g.,
penicillin) where drug binds to cell surface and
antibody cause removal of the cells (usually by
macrophages).
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Type III hypersensitivity
Type I, II, III are Immediate-type
hypersensitivities
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Serum Sickness (immune complexes in the blood)
(Type III hypersensitivity)
Symptoms are delayed while a primary immune
response develops (symptoms occur quickly if the
response is a secondary response). Symptoms ensue
from the activation of complement by
antigen-antibody complexes and other reactions
(mast cells). Symptoms include fever, rash,
arthritis and glomerulonephritis. Usually, serum
sickness is self-limiting.
Skin test before anti-venom
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Type IV hypersensitivity
Also known as delayed-type hypersensitivity (DTH)
See figure 13.16 (slide 15) (generally associated
with type I allergy
The tuberculin reaction is a positive result in
the TB skin test all of us have had
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Delayed-type hypersensitivity is mediated by T
cells
(Type IV hypersensitivity)
mango sap
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Delayed-type hypersensitivity (DTH) (e.g.,
tuberculin skin test)
TH1 from a previous immunization (memory)
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Chemical Mediators of DTH
A positive tuberculin skin test is a DTH reaction
Before the distinction between TH1 and TH2 (circa
1990), there was TH cell and TDTH. TH is now TH2
and TDTH is now TH1
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DTH as a result of a contact-sensitizing agent
Contact Dermatitis
Can be caused by poison ivy and mango sap
a contact-sensitizing agent is usually a small
molecule that penetrates the skin then binds to
self-proteins, making the protein look foreign
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