allergy & hypersensitivity Hajeer
Transcript of allergy & hypersensitivity Hajeer
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Allergy and Hypersensitivity
Ali Hajeer
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What is Hypersensitivity or Allergy?
Hypersensitivity: is an excessive immuneresponse which leads to tissue or organ
damage or dysfunction.The trigger is often an innocuous antigen.
Allergy: is a hypersensitive response to anenvironmental antigen. Such as asthma, hay
fever, dermatitis and anaphylaxis.
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Four types of
hypersensitivity
Type I hypersensitivity: Immediate hypersensitivity,IgE mediated.
Type II hypersensitivity: Cytotoxic hypersensitivity,IgG mediated.
Type III hypersensitivity: Immune complex mediatedhypersensitivity.
Type IV hypersensitivity: Delayed typehypersensitivity, cell mediated (Th1)
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Four Types ofHypersensitivities
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Impact ofallergic diseases
Allergic condition Estimated number
affected (million) USA
Allergic rhinitis 19.6
Chronic sinusitis 32.5
Contact dermatitis & eczema 5.8
12Skin rashes
Asthma 9-12
Anaphylaxis 1-2
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Immunobiology defines allergy as an IgE
response to innocuous antigens (i.e., a type Ihypersensitivity)
Others define all hypersensitivities as allergies(i.e., types I to type IV)
An antigen that causes allergy is an allergen
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Hypersensitivity
Excessive immune response in a sensitized individual(atopic) leading to tissue damage.
Types of Hypersensitivity:
Types I, II, III Immediate, Antibody-mediated.
Type IV Delayed, T cell-mediated.
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Type I hypersensitivity
It is the most common type
It is mediated by IgE
It occurs immediately and disappear rapidly The major problem is functional disorder
rather than tissue damage
The main components are: Allegens Allergen and Antibody (IgE) complex
FcIER on mast cells
FcEIRI on basophils
Eosinophils
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The mechanisms of type I hypersensitivity
1. Allergy induced period
2. Allergy stimulated period
3. Effector period
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Allergy induced period
Allergen entry
Allergen is recognized by BCR on nave Blymphocytes
B cell activation by Th2 cells through IL-4
Production of IgE antibodies
IgE binds to FcIRI on mast cells and basophils
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Allergy stimulated period second exposure
Antigen binding to the IgE on mast cells
Cross-link the FcRI on mast cell
Mast cell activation
Release of mast cell mediators (degranulation) Existing mediators such as histamine Newly synthesized mediators such as leukotrines,
prostaglandins and cytokines.
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Mast cell degranulation by antigen (allergen)
cross-linking ofFcIR-bound IgE
Eosinophils and basophils
may also participate
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Effector period
Is the effect of the mediators
Leukotrines: Increase vascular permeability, vasodilationand smooth muscle contraction
Cytokines e.g. TNF : IL-3 activates eosinophils
IL-4 stimulates T helper
TNF promotes inflammation
Histamine: Increase vascular permeability and smooth
muscle contraction
Chemokines: attracts macrophages
Platelet activating factor: platelet activation
Proteases: cause tissue damage (last step)
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Early phase reaction: occurs within minutes mainly byhistamine, increase vascular permeability,vasodilation and smooth muscle contraction
Late phase reaction: occurs within hours induced bythe synthesis and release of leukotrines,prostaglandines, cytokines, chemokines from theactivated mast cells, inflammation and eosinphils, Tcells and neutrophils infiltration.
Effector period continued
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Compounds Released fromMast Cells upon activation
[antigen (allergen) binding on the surface IgE]
Pre-formed and
in granules
Synthesized
upon mast cell
activation
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Sensitization against allergens andtype-I hypersensitivity
B
cell
Histamine,
tryptase,kininegenase,
ECFA
Leukotriene-B4, C4, D4,
prostaglandin D, PAFNewly
synthesized
mediators
TH2
Mast cells
Plasma
cellIgE
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Allergy (type I hypersensitivity mediated by IgE on mast cells)
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Why? Normally IgE responses are associated with
worm infestations. These responses help evacuate the
places where the worms often live.
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
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DustMite
fecal pellet
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The enzymatic activity ofa dust mite fecal protein allows it to
penetrate epithelial tight ju
nctio
ns and indu
ce a TH2 respo
nse
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What are the characteristics ofallergens?
It is not fully understood howor
why, but these type ofantigens
tend to stimulate IL-4production; Il-4 production
tends to lead tomore IL-4
production. IL-4 favors class
switching toIgE (cause allergy)
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Both Genetics and the Environment play a significant roles
in determining who has allergies and which kind ofallergy.
Certain allergies and autoimmunity can be mapped to specific gene loci.
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GeneticsGenetics and EnvironmentEnvironment are important for the development ofallergies
Susceptibility genesSusceptibility genes for asthma (certain alleles make
individuals more susceptible to allergies)
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The hygiene hypothesishygiene hypothesis
ofallergy induction
contends that too clean of
an environment and lackof
infections during childhood
(along with a geneticsusceptibility) promote a
bias of the immune system
toward TH2 and IgE
GeneticsGenetics and EnvironmentEnvironment are important for the development ofallergies
Atopy: a increased
tendency toward type I
hypersensitivity (IgE
allergies)
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Allergy symptoms depend on route ofallergen entry
Can be fatal.Allergy to insect
venom, drugs,
foods and
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Type I hypersensitivity because IgE-mediated
TH2-mediated chronic
airway obstruction
Type IV hypersensitivity
because TH2 involvement
(asthma)
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Allergy treatments
make IgG response
to compete with IgE
desensitizationReverse TH1/TH2 balance(2006)