A 28-year-old woman with a history of seasonal allergic rhinitis and asthma develops acute angioedema of the lips and tongue after eating shellfish at a restaurant. Serum tryptase is elevated. Regarding the pathophysiology of this reaction, all of the following are mechanisms of Type I hypersensitivity EXCEPT:

Question

Accepted Answer

B. Complement-mediated lysis of mast cells and basophils via C5a activation. ## Type I Hypersensitivity Pathophysiology in Anaphylaxis ### Clinical Context The patient presents with **acute anaphylaxis** (angioedema, elevated tryptase) — a severe Type I hypersensitivity reaction. The question asks which mechanism is **NOT** part of Type I pathophysiology. ### Correct Mechanisms of Type I (Options 0, 1, 3) ```mermaid flowchart TD A[Antigen exposure]:::outcome --> B[Cross-links FcεRI on mast cell]:::action B --> C[Tyrosine kinase activation
Phospholipase C activated]:::action C --> D[Increased intracellular Ca²⁺]:::action D --> E{Mediator release}:::decision E -->|Preformed| F[Histamine, Tryptase
Heparin, Chymase]:::outcome E -->|Newly synthesized| G[Leukotrienes, Prostaglandins
Thromboxane, PAF]:::outcome F --> H[Immediate symptoms
Minutes]:::outcome G --> H ``` **Key Point:** Type I hypersensitivity involves two phases of mediator release: | Phase | Mediators | Timing | Source | |-------|-----------|--------|--------| | **Immediate (Preformed)** | Histamine, tryptase, heparin, chymase | Seconds–minutes | Mast cell granules | | **Late (Newly Synthesized)** | Leukotrienes (LTC₄, LTD₄, LTE₄), prostaglandins (PGD₂), PAF | 4–12 hours | De novo synthesis from arachidonic acid | **High-Yield:** The signal transduction cascade: 1. Antigen cross-links FcεRI → Lyn and Syk tyrosine kinase activation 2. Phospholipase C (PLC) activation → IP₃ + DAG 3. IP₃ → intracellular Ca²⁺ release → exocytosis of granules 4. DAG → PKC activation → further mediator synthesis ### Why Option 2 Is Incorrect **Complement-mediated lysis of mast cells is NOT a mechanism of Type I hypersensitivity.** **Clinical Pearl:** Complement activation (especially C5a) does NOT lyse mast cells; rather, **C5a is a potent mast cell activator** and acts as a chemoattractant. C5a can trigger mast cell degranulation directly, but this is **not a lysis mechanism** — it is activation-induced release. **Distinction:** - **Type I:** IgE-mediated, FcεRI cross-linking → mast cell activation and degranulation - **Type II:** IgG/IgM + antigen on cell surface → complement activation → **cell lysis** (e.g., hemolytic transfusion reaction, Graves' disease) - **Type III:** Immune complexes → complement activation → tissue inflammation **Warning:** Do not confuse complement activation (which occurs in Type II and Type III) with Type I pathophysiology. Type I is primarily **non-complement-dependent** — it relies on FcεRI signaling, not Fc receptors that activate complement. **Mnemonic:** **Type I = IgE + FcεRI; no complement needed.** Type II and III involve complement. [cite:Robbins 10e Ch 6]

Answer

A. Activation of phospholipase C leading to increased intracellular calcium and degranulation

Answer

C. Release of newly synthesized mediators such as leukotrienes and prostaglandins

Answer

D. Cross-linking of FcεRI receptors on mast cell surface by multivalent antigen

Explanation

Type I Hypersensitivity Pathophysiology in Anaphylaxis

Clinical Context

Correct Mechanisms of Type I (Options 0, 1, 3)

Why Option 2 Is Incorrect

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Phase	Mediators	Timing	Source
Immediate (Preformed)	Histamine, tryptase, heparin, chymase	Seconds–minutes	Mast cell granules
Late (Newly Synthesized)	Leukotrienes (LTC₄, LTD₄, LTE₄), prostaglandins (PGD₂), PAF	4–12 hours	De novo synthesis from arachidonic acid