6 Gallucci - Non-atopic IgE-mediated Disease

Obj. 1

Distinguish between atopic and non-atopic IgE mediated pathologies.

➡ Atopic

• Inherited (genetic predisposition)

• Allergens = inhalants + ingestants

• Hyperirritable tissues present

• Examples: rhinitis, asthma, dermatitis

➡ Non-Atopic

• NOT inherited

• Allergens = ingestants + injectants

• No hyperirritable tissues

📌 “Not inherited… allergens are ingestants and injectants”

Obj. 2

Describe how non-atopic IgE mediated disease allergens are usually delivered.

👉2 main routes:

1⃣ Ingested

• Foods

• Drugs

2⃣ Injected

• Parenteral drugs

• Insect venom

Obj. 3

List the most common types of non-atopic IgE allergens.

🍽 Foods

• Peanuts

• Nuts

• Fish

• Eggs

💊 Drugs

• Any drug (hapten or complete immunogen)

🐍 Venoms

• Bee

• Wasp

• Ant

Obj. 4

Identify the symptoms of non-atopic IgE mediated pathologies.

• Anaphylaxis (systemic, severe)

• Urticaria (hives)

• Angioedema

Obj. 5

Define the terms: Sensitization, Early Phase, and Late Phase as they relate to non-atopic IgE mediated disease.

• Sensitization

👉 Sensitization

• First exposure

• No symptoms

• Immune system produces IgE

Obj. 5

Define the terms: Sensitization, Early Phase, and Late Phase as they relate to non-atopic IgE mediated disease.

• Early Phase

👉 Early Phase

• 0–30 minutes (max ~60 min)

• Caused by preformed mediators (histamine)

Obj. 5

Define the terms: Sensitization, Early Phase, and Late Phase as they relate to non-atopic IgE mediated disease.

• Late Phase

👉 Late Phase

• 3–4 hours later (max 6–12 hrs)

• Caused by:

  • Leukotrienes

  • Cytokines

  • Inflammatory cells

Obj. 6

Describe how mast cells are activated.

📌 Requires cross-linking of IgE by allergen

Steps:

1. Allergen binds IgE

2. Cross-linking occurs

3. Mast cell degranulates

4. Mediators released

Obj. 7

Describe at least one early and one late phase mast cell product.

☀ Early Phase

• Histamine

• Other preformed mediators

🌙 Late Phase

• PAF

• Leukotrienes

• Arachidonic acid metabolites

• Cytokines

Obj. 8

Summarize the three basic pathologies of non-atopic IgE mediated disease and how mast cell mediators cause them.

1⃣ Anaphylaxis

• Systemic reaction

• Mast cell mediators →

  • Vasodilation → hypotension

  • Bronchoconstriction

2⃣ Urticaria (Hives)

• Skin swelling + itching

• Histamine → ↑ vascular permeability

3⃣ Angioedema

• Deeper tissue swelling

• Same mechanism as urticaria but deeper

Obj. 9

Describe and contrast an anaphylactoid response with anaphylaxis.

❗Anaphylaxis vs Anaphylactoid

1⃣ Anaphylaxis

• IgE-mediated

• Requires:

  • Sensitization

  • Re-exposure

• Mech: IgE cross-linking

✅ Simpler

1. First exposure → make IgE

2. IgE binds mast cells

3. Second exposure → allergen cross-links IgE

4. Mast cell degranulates

👉 This is immune + requires sensitization

2⃣ Anaphylactoid

• NOT immune-mediated

• No sensitization required

• Mast cells activated directly

• Mech: Direct Mast cell activation

  • ✍The mast cell releases histamine WITHOUT IgE involvement

✅ No IgE, no prior exposure needed

Instead:

• A substance DIRECTLY triggers the mast cell

• Causes immediate degranulation

📌 “No sensitization necessary… mast cells just being mast cells”

Summary

• Non-atopic = NOT inherited IgE allergy

• Allergens = foods, drugs, venom

• Early = histamine

• Late = leukotrienes + inflammation

• Anaphylaxis = immune

• Anaphylactoid = NOT immune