Hypersensitivity Reactions — A Clear, Exam-Safe Guide (With Common Traps, Confusions, and Hidden Points)

Hypersensitivity reactions are frequently tested, not because they are difficult, but because examiners deliberately blur clinical appearances while testing underlying mechanisms. This guide focuses on mechanism-first thinking, which is how exams are written.

The Golden Rule (Most Important Exam Principle)

Hypersensitivity type is defined by the IMMUNOLOGICAL MECHANISM, not by how the disease looks clinically.

“Allergy-like” does not automatically mean Type I.“Chronic inflammation” does not automatically mean granuloma.

The Four Types — One-Line Core Definitions

Type	Core Mechanism	Key Effector
Type I	IgE-mediated mast cell degranulation	Mast cells
Type II	Antibody binds fixed cell surface antigen	Complement, NK cells
Type III	Immune complex deposition	Neutrophils
Type IV	T-cell–mediated, no antibodies	Th1 cells, macrophages

Mnemonic: ACIDAnaphylactic, Cytotoxic, Immune complex, Delayed

Type I Hypersensitivity — What It Must Have

Type I = IgE + mast cells + immediate reaction

Essential features

• IgE bound to mast cells/basophils

• Re-exposure → IgE cross-linking

• Histamine release

• Onset: minutes

Classic examples

• Anaphylaxis

• Allergic rhinitis

• Atopic asthma

• Urticaria

Exam trap 🚨

❌ “IgE is involved → must be Type I”✔ Wrong — IgE can appear in Type II (ADCC) as well

Type II Hypersensitivity — Why Opsonization & ADCC Are Type II

Defining feature:

Antibody binds directly to a cell or organism → cell is destroyed or function altered

Mechanisms

• Opsonization → phagocytosis

• Complement-mediated lysis

• ADCC (NK cells, eosinophils)

Key point (very high yield)

• IgE + eosinophils killing parasites = Type II (ADCC)

• NOT Type I, because:

  • ❌ no mast cells

  • ❌ no histamine

  • ✔ direct antibody-dependent killing

Examples

• Autoimmune haemolytic anaemia

• ITP

• Graves disease

• Myasthenia gravis

• Parasitic killing via eosinophils

Type III Hypersensitivity — Immune Complex Disease

Defining feature:

Antibodies bind soluble antigens → immune complexes deposit in tissues

Hallmarks

• IgG (± IgM)

• Complement activation

• Low C3 / C4

• Neutrophil-mediated inflammation

Classic examples

• SLE (primary mechanism)

• Post-streptococcal GN

• Polyarteritis nodosa

• Arthus reaction

• Serum sickness

Arthus Reaction (Important Correction)

• ❌ NOT Type II

• ✅ Type III

• Local immune complex vasculitis

• Occurs 4–8 hours after antigen injection in someone with high IgG

Type IV Hypersensitivity — Delayed, T-Cell Mediated

Defining feature:

No antibodies involved — entirely T-cell driven

Core features

• Th1 cells

• IFN-γ

• Macrophage activation

• Onset: 48–72 hours

Examples

• Contact dermatitis

• TB tuberculin (Mantoux) test

• Acute graft rejection

• Granulomatous diseases

Key exam distinction

• Looks “allergic” ≠ Type I

• Timing + lack of antibodies = Type IV

Granulomas — The Big Clarification

Are granulomas Type IV?

✅ Yes — all granulomas form via a Type IV (T-cell–mediated) mechanism

Do all Type IV reactions form granulomas?

❌ No

Why granulomas form

• Persistent antigen

• Th1 → IFN-γ

• Chronic macrophage activation

Diseases with granulomas

• Tuberculosis (caseating)

• Sarcoidosis (non-caseating)

• Crohn disease

• Berylliosis

• Foreign body reactions

Caseating vs Non-Caseating Granulomas

Feature	Caseating	Non-caseating
Central necrosis	Yes	No
Classic cause	TB	Sarcoidosis
Still Type IV?	Yes	Yes

🚨 Exam trap:❌ “All granulomas are caseating” → WRONG

SLE — Final, Exam-Safe Classification

Primary mechanism

✅ Type III hypersensitivity

• Immune complex deposition

• Low complement

• Granular immunofluorescence

• Nephritis, vasculitis

Secondary features

• Cytopenias (AIHA, thrombocytopenia) → Type II

Critical correction

❌ SLE does NOT form granulomasIf granulomas are present → think sarcoidosis, TB, Crohn, not SLE

High-Yield “Sorting Rules” for Exams

Ask these in order:

1. Are antibodies involved?

   • No → Type IV

   • Yes → Type I, II, or III

2. Is it immediate with mast cells?

   • Yes → Type I

3. Is antibody bound to a cell?

   • Yes → Type II

4. Are immune complexes depositing?

   • Yes → Type III

5. Are there granulomas?

   • Yes → Type IV

One-Line Exam Clinchers (Memorise)

• IgE + mast cells + minutes → Type I

• Antibody-coated cell being destroyed → Type II

• Immune complex deposition + low complement → Type III

• Delayed (48–72 h), no antibodies → Type IV

• Granuloma = Type IV

• SLE = Type III (± Type II), NEVER Type IV

Final Take-Home Message

Most hypersensitivity questions are not testing knowledge — they are testing discipline.If you ignore appearance and focus on mechanism, you will not be trapped.