Hypersensitivity Reactions😍

Hypersensitivity Reactions

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  • Total types: Five.
  • Mnemonic for first four: ACID
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    • A: Anaphylaxis (Type 1).
    • C: Cytotoxic (Type 2) → Antibody against cells
    • I: Immune Complex Mediated (Type 3).
    • D: Delayed Cell mediated Response(Type 4).

Types Overview

Type
Examples
Type 1 (Anaphylaxis)

Immediate

IgE mediated,
Mast cell degranulation
- Allergies (dermatitis, rhinitis, conjunctivitis)
- Bronchial asthma (atopy - chromosome 5)
- Casoni test (Echinococcus)
- Drugs (penicillin)
- Theobald Smith phenomena, PK reaction

Mnemonic: ABCD (for examples)
Type 2 (Cytotoxic)

Antibody-mediated

Antibody vs cell surface/matrix Ag
- Myasthenia Gravis
- Blood transfusion reactions 
- Graves disease
- Goodpasture syndrome
- Immune hemolytic anemia (AIHA)
- ITP
- Rh incompatibility
- RHD
- Pemphigus
- Pernicious anemia
Mnemonic: "My blood group is Rh positive P"
Type 3 (Immune Complex)

Immune Complex Mediated

Ag-Ab complex deposition
- SLE
- Serum Sickness
- Shick test (C. diphtheriae)
- HSP (IgA vasculitis)
- Arthus reaction
- Raji reaction 
- Reactive arthritis
- PSGN (cola urine)
- PAN

Mnemonic: SHARP
Type 4 (Delayed)

Cell-mediated

T-cell mediated
• Granulomas
• Skin Tests:
◦ Mantoux Test (for Tuberculosis)
◦ Lepromin Test
• IBD (Crohn's Disease)
• Multiple sclerosis
• Contact Dermatitis:
◦ Worldwide common cause: Poison Ivy
◦ In India (especially among females):
▪ Detergent
▪ Artificial Jewellery (Nickel, Cadmium)
Type 5 (Stimulatory)

Receptor-mediated (Controv.)

Antibodies vs cellular receptors
- Myasthenia Gravis (AChR Ab), 
- Graves disease (TSHR Ab).

(If Type 5 not option, mark Type 2)

Controversial Entities/Combinations:

Condition
Hypersensitivity Type(s)
Rheumatoid Arthritis
Type 3 > Type 4

Scleromalacia Perforans → Type 3
Hypersensitivity Pneumonitis
Type 4 > 3
SLE
Type 2 and Type 3

Mnemonic:
Flip 'S' → 2,
Flip 'E' → 3
Transplant Rejection
ㅤ
• Hyperacute
Type 2
• Acute
Type 2 and Type 4
• Chronic
Type 4
 

Type 1 Hypersensitivity

First Exposure

  • Allergen interact with
      1. Naive CD4 T cells (via dendrtic cells) → Activate into Th2 cells
      1. B cells → Activated B cells
  • Activated B cell in turn interact with Th2 cells → Causes Isotype switching → B cell releases Allergen specific IgE
  • Allergen specific IgE binds to Mast cells remain ready for next exposure of allergen
  • Stain for mast cell → Toluidine blue
 
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Re Exposure

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Immediate Phase:

  • Occurs within minutes.
  • Allergen crosslinks IgE on mast cells.
  • This leads to a degranulation explosion.
  • Vasodilatation, vascular permeability, bronchoconstriciton, ↑ mucus produciton
  • Preformed Mediators
    • Histamine:
      • Earliest
      • Causes vasodilation and itching.
    • Tryptase:
      • Acts as a mast cell marker.
    • Protease
    • Enzymes
  • Others
    • Leukotrienes:
      • Cause bronchospasm and mucus production.
    • Prostaglandins

Late Phase:

  • Eosinophils and other inflammatory cells arrive.
  • Chemokines call in backup cells.
  • Epithelial damage, tissue damage, fibrosis
  • Occurs after a few hours.
  • Results in more inflammation and tissue damage.

Questions

  • Most important cell in
      1. Immediate phase → Mast cells
      1. Late phase → Eosinophils
      1. Overall → Mast cells
  • Earliest released → Histamine
  • Most important anitbody → IgE

Tests:

  • Skin test
  • ELISA for allergen-specific IgE

Examples:

  • Anaphylaxis (e.g., bee sting, food, drugs)
  • Allergic asthma
Type 2
Type 2
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