Type I Hypersensitivity reaction

Dr.Pavulraj.SM.V.Sc., scholar,

Division of PathologyIndian 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 Pirquet coined 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 IgG or 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 or anaphylactic hypersensitivity

• Immediate hypersensitivity is mediated by IgE• The primary cellular component in this

hypersensitivity is the mast cell or basophil• The reaction is amplified by neutrophils and

eosinophils

• 1902 - Charles Richet and Paul Portier discovered anaphylaxis

• 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 nonparasite antigens that can stimulate a type I hypersensitivity response.

• Allergens bind to IgE and 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

• Atopy is the term for the genetic trait to have a predisposition for localized anaphylaxis

• Atopic individuals have higher levels of IgE and eosinophils

Mechanisms of allergic responseSensitization

• Repeated exposure to allergens initiates immune response that generates IgE isotype

• Th2 cells required to provide the IL-4 required to get isotype switching to IgE

Mechanisms of allergic responseSensitization

• The IgE can attach to Mast cells by Fc receptor, which increases the life span of the IgE

• Half-life of IgE in serum is days whereas attached to FcεR it is increased to months

Mechanisms of allergic responseFc ε receptors (FcεR)

• FcεR1 - high affinity IgE receptor found on mast cells/basophils/activated eosinophils

• Allergen binding to IgE attached to FcεR1 triggers release of granules from the mast cell

Mechanisms of allergic responseEffector Stage of Hypersensitivity

• Secondary exposure to allergen• Mast cells are primed with IgE on surface• Allergen binds IgE and cross-links to activate

signal with tyrosine phosphorylation, Ca++ influx, degranulation and release of mediators

Mediators of Type I HypersensitivityImmediate effects

HistamineConstriction of smooth muscles.Bronchiole constriction = wheezing.Constriction of intestine = cramps-diarrhea.Vasodilation with increased fluid into tissuesCausing increased swelling or fluid in mucosa.Activates enzymes for tissue breakdown.

• Leukotrienes• Prostaglandins

Primary MediatorsPre-formed mediators in granules

• Histamine• Cytokines TNF-α, IL-1, IL-6.• Chemoattractants for Neutrophils and

Eosinophils• Enzymes – Tryptase, Chymase, Cathepsin – Changes in connective tissue matrix, tissue

breakdown

Secondary mediatorsMediators 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• Eosinophils and neutrophils drive late or

chronic response.• More IgE production 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 vasodilation and 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 IgE and specific IgE

antibodies against the suspected allergens• Total IgE and specific IgE antibodies are

measured by a enzyme immunoassay (ELISA) • Increased IgE levels 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

• Kuby immunology, Sixth edition• Yamasaki, S. & Saito, T. (2005). Regulation of mast cell activation through

FcepsilonRI. Chem.Immunol.Allergy, 87, 22-31.