Prior Sensitization: IgE Coats the Mast Cell Surface
First allergen exposure primes IgE onto FcεRI receptors.
- FcεRI: Receptor (high-affinity IgE receptor)
- ~500k: IgE per cell (placeholder estimate)
- 1st contact: Priming exposure (no symptoms yet)
- Mast cell: Cell type (tissue-resident sentinel)
IgE production and receptor loading
Placeholder: B cells class-switch to IgE against the allergen.
Surface receptor saturation
Placeholder: FcεRI becomes densely coated with specific IgE.
Allergen Re-Exposure Cross-Links Surface IgE
Multivalent allergen bridges two or more adjacent IgE molecules.
- Re-exposure: Trigger (same allergen returns)
- 2 IgE: Min. bridge (placeholder threshold)
- Fab region: Binding site (allergen epitope contact)
- Seconds: Onset (placeholder timescale)
Multivalent allergen bridging
Placeholder: allergen epitopes span and link neighboring IgE-Fc complexes.
Receptor clustering
Placeholder: cross-linked receptors aggregate into signaling clusters.
Cross-Linking Triggers the Degranulation Cascade
Clustered receptors activate kinases and calcium signaling inside.
- Lyn/Syk: Kinase (placeholder signaling axis)
- Ca²⁺ influx: Second messenger (placeholder trigger)
- <1 min: Latency (placeholder estimate)
- Granule fusion: Outcome (commits to release)
Intracellular signal cascade
Placeholder: kinase activation propagates from receptor to granules.
Calcium-driven commitment
Placeholder: calcium flux commits granules to membrane fusion.
Granule Fusion Releases Histamine, Tryptase, Leukotrienes
Stored and newly made mediators burst out of the cell.
- Histamine: Preformed (stored in granules)
- Tryptase: Preformed (protease granule content)
- Leukotrienes: Newly made (lipid mediators, de novo)
- Exocytosis: Process (placeholder mechanism)
Preformed granule contents
Placeholder: histamine and tryptase are pre-packaged for instant release.
De novo lipid mediators
Placeholder: leukotrienes are synthesized rapidly after activation.
Mediators Spread Into Systemic Anaphylaxis
Circulating mediators cause vasodilation, edema, and bronchoconstriction.
- Vasodilation: Vessels (placeholder effect)
- Bronchoconstriction: Airway (placeholder effect)
- Urticaria: Skin (placeholder effect)
- Anaphylactic shock: Worst case (placeholder severity)
Vascular and airway effects
Placeholder: mediators act on distant vessels and smooth muscle.
Clinical progression
Placeholder: symptoms escalate from mild to systemic shock.
Placeholder: epinephrine reverses the cascade in emergency treatment.