HYPERSENSITIVITY DISORDERS

Hypersensitivity, in context of immunology, denotes untoward and inappropriate immunological response to a foreign antigen involving antigen-specific antibodies and memory cells.

1. Type I (IgE mediated) reactions, also termed allergy, are triggered by the binding of an allergen to specific or reaginic IgE antibodies attached on the surface receptors of circulatory basophils and tissue mast cells. (Ch 8.4.1)

2. Type II (cytotoxic) reactions are characterized by abnormal binding of IgM or IgG antibodies to self­antigens, modified by external insult, (e.g. drugs or infections), with complement activation and consequent target tissue injury. Discussed in relevant chapters, these reactions are usually tissue-specific, e.g. autoimmune hemolytic anemia or thrombocytopenia (target antigen­cell membrane), myasthenia gravis (target antigen- acetylcholine receptor) or Graves' disease (target antigen-TSH receptors).

3. Type III (immune-complex) reactions involve formation of soluble antigen-antibody complexes, which are either removed to reticuloendothelial organs or deposited at target tissues, e.g. glomerular basement membrane, skin and synovium. Immune-complex mediated complement activation leads to attraction of polymorphs at these sites with local inflammatory reactions and tissue damage, i.e. Arthus reaction; or more systemic and widespread reactions, i.e. serum sickness. Other common examples of these reactions are proteinuria in nephrotic syndrome and vasculitis syndromes, e.g. Henoch-Schonlein purpura.

Serum sickness presents as fever, arthralgia, urticaria, lymphadenopathy and proteinuria, usually after 7-14 days of the administration of animal-derived antisera, e.g. equine anti-snake venom, anti-tetanus serum, etc. or drugs, e.g. penicillin, cephalosporins, etc.

4. Type IV (delayed hypersensitivity) reactions are mediated by antigen-specific T cells and macrophages, due to recognition of antigen-peptide on antigen processing cells by T memory cells and release of inflammatory cytokines. These reactions peak after 24-48 hours of antigen exposure and include tuberculin reactions, contact dermatitis, transplant rejection and graft versus host disease, etc.

8.4.1