Type I (immediate) hypersensitivity mediator: Which immunoglobulin class is the principal mediator of Type I hypersensitivity reactions such as anaphylaxis, allergic rhinitis, and many food allergies?

Introduction / Context:
Type I hypersensitivity reactions are rapid, IgE-dependent responses to allergens, involving mast cells and basophils. Correctly identifying the antibody class at the core of this mechanism is essential for understanding allergy diagnostics and therapies (e.g., anti-IgE treatment).

Given Data / Assumptions:

• Allergen exposure leads to class-switching to IgE in susceptible individuals.
• IgE binds FcεRI on mast cells and basophils with high affinity.
• Cross-linking of receptor-bound IgE by allergen triggers degranulation.

Concept / Approach:
IgE-coated effector cells release histamine, leukotrienes, prostaglandins, and cytokines upon allergen-induced cross-linking, producing immediate symptoms such as wheal-and-flare, bronchospasm, and anaphylaxis. Other isotypes (IgG, IgM, IgA, IgD) are not primary mediators of this immediate, mast cell–dependent pathway.

Step-by-Step Solution:
Identify the hypersensitivity type: Type I (immediate). Recall the effector mechanism: IgE bound to FcεRI on mast cells. Select IgE as the central immunoglobulin mediator. Confirm that other isotypes do not trigger this pathway.

Verification / Alternative check:
Clinical desensitization protocols and anti-IgE monoclonal antibodies reduce free IgE and FcεRI occupancy, alleviating allergic manifestations—evidence for IgE centrality.

Why Other Options Are Wrong:
IgG mediates other hypersensitivity types (e.g., II, III); IgM is early humoral responder; IgD is mainly a B-cell receptor; IgA protects mucosa rather than mediating immediate hypersensitivity.

Common Pitfalls:
Confusing IgE with IgG-mediated late-phase or complement-related reactions; timing and cellular players distinguish these categories.

Final Answer:
IgE.