====== 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

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===== 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.

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===== 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.

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===== 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:
  * [[allergy:drugs:loratadine|H1 Antihistamines]]
  * [[cardio:drugs:epinephrine|Epinephrine]]

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===== 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:
  * [[endocrine:drugs:fluticasone|Corticosteroids]]
  * [[respiratory:drugs:montelukast|Leukotriene Modifiers]]

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===== Systemic Type I Reaction – Anaphylaxis =====

When mediator release becomes systemic:

  * Massive vasodilation
  * Capillary leak
  * Bronchospasm
  * Hypotension
  * Airway edema

First-line treatment:
  * [[cardio:drugs:epinephrine|Epinephrine]] (IM)

See:
  * [[allergy:clinical:anaphylaxis|Anaphylaxis Protocol]]

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===== 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 |

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===== 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:
  * [[allergy:immunology:hypersensitivity_types|All Hypersensitivity Types]]

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===== 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.