Type I Hypersensitivity reaction
Dr.Pavulraj.S
M.V.Sc., scholar,
Division of Pathology
Indian Veterinary Research
Institute, India
Introduction
•Hypersensitivity -excessive, undesirable
reactions produced by the normal immune
system
•Hypersensitivity reactions require a pre-
sensitized (immune) state of the host
•1906 –Von Pirquetcoined term:
hypersensitivity
•Gell-Coombs Classified the reactions into four
types based on the mechanisms involved and
time taken for the reaction Hypersensitivity
reactions can be divided into four types: type
I, type II, type III and type IV
3 involve antibody-
•Type I (immediate): mediated by IgE(Mast
Cells)
•Type II: mediated by IgGor IgM
•Type III (immune complex disease): IgG&
complement
One involves antigen specific cells
•Type IV: Delayed type hypersensitivity, cell
mediated immune memory response. Type I
Hypersensitivity
TYPE I Hypersensitivity
•Type I hypersensitivity –immediate
oranaphylactichypersensitivity
•Immediate hypersensitivity is mediated byIgE
•The primary cellular component in this
hypersensitivity is the mast cell or basophil
•The reaction is amplified by neutrophilsand
eosinophils
•1902 -Charles Richet and Paul Portier
discoveredanaphylaxis
•The symptoms resulting from allergic
responses are known as anaphylaxis
•Includes: Hay fever, asthma, eczema, bee
stings, food allergies
•Exposure may be by ingestion, inhalation,
injection or direct contact
Allergens
•Allergens are nonparasiteantigens that can
stimulate a type I hypersensitivity response.
•Allergens bind to IgEand trigger degranulation
of chemical mediators
Characteristics of allergens
•Small 15-40,000 MW proteins
•Protein components –Often enzymes
•Low dose of allergen
•Mucosal exposure
•Most allergens promote a Th2 immune
Atopy
•Atopyis the term for the genetic trait to have
a predisposition for localized anaphylaxis
•Atopic individuals have higher levels of IgEand
eosinophils
Mechanisms of allergic response
Sensitization
•Repeated exposure to allergens initiates
immune response that generates IgEisotype
•Th2 cells required to provide the IL-4 required
to get isotypeswitching to IgE
Mechanisms of allergic response
Sensitization
•The IgEcan attach to Mast cells by Fcreceptor,
which increases the life span of the IgE
•Half-life of IgEin serum is days whereas
attached to FcεRit is increased to months
Mechanisms of allergic response
Fcε receptors (FcεR)
•FcεR1 -high affinity IgEreceptor found on
mast cells/basophils/activated eosinophils
•Allergen binding to IgEattached to FcεR1
triggers release of granules from the mast cell
Mechanisms of allergic response
Effector Stage of Hypersensitivity
•Secondary exposure to allergen
•Mast cells are primed with IgEon surface
•Allergen binds IgEand cross-links to activate
signal with tyrosine phosphorylation, Ca++
influx, degranulationand release of mediators
Mediators of Type I Hypersensitivity
Immediate effects
Histamine
Constriction of smooth muscles.
Bronchiole constriction = wheezing.
Constriction of intestine = cramps-diarrhea.
Vasodilationwith increased fluid into tissues
Causing increased swelling or fluid in mucosa.
Activates enzymes for tissue breakdown.
•Leukotrienes
•Prostaglandins
Secondary mediators
Mediators formed after activation
•Leukotrienes
•Prostaglandins
•Th2 cytokines-IL-4, IL-5, IL-13, GM-CSF
Continuation of sensitization cycle
•Mast cells control the immediate response
•Eosinophilsand neutrophilsdrive late or
chronic response.
•More IgEproduction further driven by
activated Mast cells, basophils, eosinophils
Localized anaphylaxis
•Target organ responds to direct contact with
allergen
•Digestive tract contact results in vomiting,
cramping, diarrhea
•Skin sensitivity usually reddened inflamed
area resulting in itching
•Airway sensitivity results in sneezing and
rhinitis or wheezing and asthma
Systemic anaphylaxis
•Systemic vasodilationand smooth muscle
contraction leading to severe bronchiole
constriction, edema, and shock
•Similar to systemic inflammation
Other types of anaphylaxis
Diagnostic tests for immediate
hypersensitivity
Skin (prick and intradermal) tests
•Measurement of total IgEand specific IgE
antibodies against the suspected allergens
•Total IgEand specific IgEantibodies are
measured by a enzyme immunoassay (ELISA)
•Increased IgElevels are indicative of an atopic
condition
•A genetic predisposition for atopic diseases
Intra dermal test
REFERENCES
•Brostoff, J., Scadding, G. K., Male, D., & Roitt, I. M. (1991). Introduction to
Immune Responses. In J.Brostoff, G. K. Scadding, D. Male, & I. M. Roitt
(Eds.), Clinical Immunology ( New York: Gower Medical Publishing)
•Gell, P. G. H. & Coombs, R. R. A. (1963). The classification of allergic
reactions underlying disease. In R.R.A.Coombs& P. G. H. Gell(Eds.),
Clinical Aspects of Immunology ( Blackwell Science)
•Shamberger, R. (2008). Types of Food Allergy Testing. Townsend Letter,
January, 71-72
•Kubyimmunology, Sixth edition
•Yamasaki, S. & Saito, T. (2005). Regulation of mast cell activation through
FcepsilonRI. Chem.Immunol.Allergy, 87, 22-31.