Type I Hypersensitivity Reaction

Hypersensitivity ReactionTYPE IHirak Jyoti Talukdar and Abhineet Dey

Hypersensitivity: Immunologically mediated tissue injury Hypersensitivity is defined as a state of exaggerated immune response to an antigen.

Individuals who have been previously exposed to an antigen manifest detectable reactions to that antigen and are therefore said to be “sensitized”.

General Features1. Hypersensitivity reactions can be elicited by

exogenous environmental antigens or endogenous self antigens.

2. Results from failure of normal regulation of immune response.

3. Development of hypersensitivity diseases is often associated with the inheritance of particular susceptibility genes.

Classification1. Immediate or Type I Hypersensitivity Reaction2. Antibody Mediated or Type II Hypersensitivity

Reaction3. Immune Complex mediated or Type III

Hypersensitivity Reaction4. T-Cell Mediated or Type IV Hypersensitivity

Reaction

Immediate or Type I Hypersensitivity ReactionOr better known as, Allergies

Immediate or Type I hypersensitivity is a rapid immunological reaction occurring in a previously sensitized individual that is triggered by the binding of an antigen to IgE antibody on the surface of mast cells.

Also known as allergic reactions or allergies. Antigens causing them are allergens. Most immediate hypersensitivity disorders are caused by excessive TH2 responses and these cells stimulate IgE production in genetically susceptible individuals.

PHASES OF TYPE I HYPERSENSITIVITY REACTIONIMMEDIATE REACTION LATE-PHASE REACTIONManifested in minutes Manifested in 2-24 hours laterSubsides in few hours May last for several daysRelease of mast cell• Histamine• Leukotrienes: C4, D4• Prostaglandins: D2

Tissue infiltration by:• Neutrophils• Eosinophils• Basophils• Monocytes• CD4+ T Cells

Effects• Vasodilation• Increase Vascular

Permeability• Bronchoconstriction• Mucus-secretion

• Epithelial injury by inflammatory response

PHASES OF TYPE I HYPERSENSITIVITY REACTION (CONTD.)

Type I hypersensitivity reactionSequence of Events

Activation of TH2 Cells

Entry of antigen

Capture of antigen by dendritic cell

Presentation of antigen to naive CD4 + Helper T cells

T Cells differentiate to TH2 Helper Cells

Release of Cytokines by TH2 Cells upon subsequent encounter with antigen

Production of IgE Antibody

Cytokines produced by TH2 Cells

*IgE class switching B cells.*Development of

additional TH2 cells

IL4

*Development and activation of

EosinophilsIL5

*Enhances IgE production

*Acts on epithelial cells to stimulate mucus

secretion

IL13

Sensitization and Activation of Mast Cells Mast Cells express a high affinity receptor FcεRI

FcεRI: Specific for Fc-portion of antibody

IgE coated mast cells are said to be sensitized

Subsequent exposure of the IgE coated mast cell to the same antigen

Multivalent antigens bind to IgE antibody

Cross-linking of high-affinity IgE Fc receptor

Activate signal transduction pathway

Production of mediators

Release of Mediators

Mediators of Type-I Hypersensitivity ReactionMast cell activation leads to degranulation with the discharge of pre-formed or primary mediators that are stored in the granules and de novo synthesis and release of secondary mediators including lipid products and cytokines.

Preformed MediatorsMediators contained within the mast cell granules are the first to be released and can be divided into three categories:1. Vasoactive Amines

Eg. Histamine2. Enzymes

Eg. Neutral proteases (Chymase, Triptase), Acid Hydrolases

3. ProteoglycansEg. Heparin, Chondroitin Sulfate

Lipid Mediators These are Arachidonic Acid derived products. Reactions in the mast cell membrane lead to activation of Phospholipase A2 that converts membrane phospholipids to Arachidonic Acids, from which Leukotrienes and Prostaglandins are produced.1. Leukotrienes

Leukotrienes C4 and D4, Leukotriene B42. Prostaglandins

Prostaglandin D23. Platelet Activating Factor

These are not derived from Arachidonic Acid.

Cytokines These include TNF, Interleukin-1, Chemokines which promote leucocyte recruitment, Interleukin-4 which amplifies TH2 response.

Development of Allergies1. Susceptibility to type I hypersensitivity is

genetically determined. ATOPY-Increased propensity to develop

immediate hypersensitivity reactions. Atopic individuals have higher serum IgE levels

and more IL-4 producing TH2 cells. Inheritance of certain HLA alleles permits

reactivity to certain allergens.2. Environmental factors: Exposure to

environmental pollutants

Clinical ManifestationsSYSTEMIC ANAPHYLAXIS

LOCAL REACTIONS

Clinical Manifestation

• Vascular shock• Widespread edema• Breathing difficulty

• Reactions to environmental antigens – pollen, house dust

Example • Administration of antisera, drugs, enzymes

• Bee sting

• Urticaria• Allergic rhinitis(hay fever)• Bronchial asthma• Food allergy

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