Type I Hypersensitivity (IgE-Mediated)

Type I hypersensitivity is an immediate, IgE-mediated immune reaction that occurs upon re-exposure to a sensitizing allergen.

Examples:

Allergic rhinitis
Urticaria
Atopic asthma
Anaphylaxis

Phase 1 – Sensitization (First Exposure)

Initial exposure does NOT usually produce symptoms.

Step-by-step:

1) Allergen enters tissue (pollen, food protein, etc.)
2) Dendritic cells process and present antigen via MHC II
3) Naïve CD4+ T cells differentiate into Th2 cells
4) Th2 cells release:
     * IL-4 → Class switching to IgE
     * IL-13 → IgE production and mucus production
     * IL-5 → Eosinophil activation
5) B cells produce allergen-specific IgE
6) IgE binds FcεRI receptors on mast cells and basophils

Result:

Mast cells are now "armed" with allergen-specific IgE.

No symptoms yet.

Phase 2 – Re-Exposure (Effector Phase)

Upon re-exposure:

1) Allergen cross-links IgE molecules on mast cell surface
2) Calcium influx occurs
3) Rapid degranulation

This produces the immediate allergic reaction.

Early Phase Reaction (Minutes)

Mediators released:

Histamine
Tryptase
Leukotrienes (LTC4, LTD4, LTE4)
Prostaglandins
Platelet-activating factor

Physiologic effects:

Vasodilation → erythema
Increased vascular permeability → edema, urticaria
Bronchoconstriction → wheezing
Mucus secretion → rhinorrhea
Sensory nerve activation → pruritus

Clinical examples:

Sneezing
Hives
Bronchospasm
Hypotension (anaphylaxis)

Primary drug target:

Late Phase Reaction (Hours)

Occurs 4–8 hours after initial reaction.

Mediated by:

Eosinophils
Th2 cytokines
IL-4, IL-5, IL-13
Ongoing leukotriene production

Effects:

Sustained airway inflammation
Persistent congestion
Chronic allergic symptoms

Primary drug target:

Systemic Type I Reaction – Anaphylaxis

When mediator release becomes systemic:

Massive vasodilation
Capillary leak
Bronchospasm
Hypotension
Airway edema

First-line treatment:

Epinephrine (IM)

See:

Anaphylaxis Protocol

Key Immunologic Components

Component	Role
IgE	Binds mast cells and basophils
FcεRI receptor	High-affinity IgE receptor
Th2 cells	Drive IgE production
IL-4 / IL-13	Promote class switching to IgE
IL-5	Eosinophil recruitment
Mast cells	Immediate mediator release
Eosinophils	Late-phase inflammation

Contrast With Other Hypersensitivity Types

Type	Mechanism	Example
I	IgE-mediated	Anaphylaxis
II	IgG/IgM against cell surface	Hemolytic anemia
III	Immune complex deposition	Serum sickness
IV	T-cell mediated (delayed)	Contact dermatitis

See:

All Hypersensitivity Types

Board Pearls

Type I reactions require prior sensitization.
Histamine drives early symptoms.
Leukotrienes contribute to sustained bronchoconstriction.
Eosinophils dominate late-phase inflammation.
Epinephrine is the only first-line treatment for anaphylaxis.