I | Immediate (IgE mediated) | Allergen binds to IgE on basophils or mast cells, resulting in release of inflammatory mediators | Within 1 hour (may be within 1–6 hours) | Penicillin anaphylaxis, angioedema Blood products Polypeptide hormones Vaccines Dextran |
II | Delayed; Cytotoxic | Cell destruction occurs because of cell-associated antigen that initiates cytolysis by antigen-specific antibody (IgG) and complement. Most often involves blood elements. | Typically >72 hours to weeks | Penicillin, quinidine, quinine, heparin, thiouracils, sulfonamides, methyldopa |
III | Delayed; Immune complex | Antigen–antibody (IgG or IgM) complexes form and deposit on blood vessel walls and activate complement. Result is a serum sickness-like syndrome or vasculitis. | >72 hours to weeks | May be caused by penicillins, sulfonamides, minocycline, hydantoins |
IV | Delayed; T Cell-mediated | Antigens cause activation of T lymphocytes, which release cytokines and recruit effector cells | >72 hours | |
| IVa | Th1 cells and interferon-γ, monocytes and eosinophils respond to the antigen | 1–21 days | Tuberculin reaction, contact dermatitis |
| IVb | Th2 cells, interleukin-4 and interleukin-5 respond to the antigen | 1–6 weeks | Maculopapular rashes with eosinophilia |
| IVc | Cytotoxic T cells, perforin, granzyme B, FasL respond to the antigen | 4–28 days | Bullous exanthems; fixed drug eruptions |
| IVd | T cells and interleukin-8 respond to the antigen | >72 hours | Acute generalized exanthematous pustulosis |