Hypersensitivity Reactions & Autoimmunity

Hypersensitivity Reactions & Autoimmunity

Gell & Coombs Classification

| Type | Mechanism | Example |

|------|-----------|--------|

| I (Immediate) | IgE → mast cell degranulation | Anaphylaxis, asthma, allergic rhinitis |

| II (Cytotoxic) | IgG/IgM against cell surface antigens | Autoimmune haemolytic anaemia, Graves', myasthenia gravis |

| III (Immune complex) | Antigen-antibody complex deposition | SLE, post-streptococcal GN, serum sickness |

| IV (Delayed/Cell-mediated) | T cell mediated (Th1/CTL) | TB (Mantoux), contact dermatitis, graft rejection |

Type I — Anaphylaxis

• Sensitisation: IgE produced → binds Fc╬ÁRI on mast cells/basophils
• Re-exposure: antigen cross-links IgE → degranulation → histamine, tryptase, leukotrienes
• Clinical: urticaria, angioedema, bronchospasm, hypotension (within minutes)
• Treatment: IM adrenaline 0.5 mg (1:1000) — first line; then IV fluids, chlorphenamine, hydrocortisone

Type III — SLE

• Loss of self-tolerance → autoantibodies against nuclear antigens (dsDNA, Sm antigen)
• Complement-activating immune complexes deposit in kidneys, skin, joints, choroid plexus
• Features: butterfly rash, photosensitivity, arthralgia, serositis, lupus nephritis, CNS disease
• Antibodies: ANA (sensitive), anti-dsDNA (specific, correlates with disease activity), anti-Sm (specific)

Central vs Peripheral Tolerance

• Central tolerance: T cells deleted in thymus (clonal deletion) if they bind self-MHC too strongly (negative selection)
• Peripheral tolerance: Treg suppression; anergy (T cell activation without co-stimulation); CTLA-4 (inhibitory)