type IV hypersensitivity
Summary
Type IV hypersensitivity is a delayed, T-cell-mediated (not antibody-mediated) immune reaction that develops 48-72 hours after antigen exposure. It involves CD4+ Th1 cells activating macrophages or CD8+ cytotoxic T cells directly killing target cells. Classic examples include contact dermatitis, tuberculin skin test (PPD), and graft-versus-host disease.
Detail
Type IV hypersensitivity, also called delayed-type hypersensitivity (DTH), is unique among the four Gell-Coombs classifications because it is mediated by T lymphocytes rather than antibodies. There are two main mechanisms: (1) CD4+ Th1 cells recognize antigen presented by APCs via MHC II, releasing IFN-gamma to activate macrophages, which cause tissue damage through granuloma formation and inflammation (seen in tuberculin reaction, granulomatous diseases like TB and sarcoidosis, contact dermatitis from poison ivy or nickel); (2) CD8+ cytotoxic T lymphocytes directly recognize antigen via MHC I and kill target cells through perforin/granzyme-mediated apoptosis (seen in type 1 diabetes mellitus destruction of pancreatic beta cells, multiple sclerosis, graft-versus-host disease, and transplant rejection).
The timeline is critical for boards: reaction develops 48-72 hours after re-exposure to antigen, distinguishing it from immediate (type I, minutes), antibody-mediated cytotoxic (type II, hours), and immune complex (type III, hours) reactions. No antibody involvement means it cannot be transferred via serum; it can only be transferred via sensitized T cells (adoptive transfer).
Clinical correlations include the PPD/tuberculin skin test (used to screen for TB exposure), contact dermatitis (poison ivy, nickel, latex), granulomatous inflammation in TB and sarcoidosis, chronic transplant rejection, graft-versus-host disease, and autoimmune conditions like type 1 diabetes, multiple sclerosis, and Hashimoto thyroiditis (mixed mechanisms). Histologically, granulomas with epithelioid macrophages and giant cells are hallmark findings in chronic Th1-driven reactions like TB and sarcoidosis.
Mnemonic: Type IV = 4 T's = T cells, Transplant rejection, TB skin test, Touching (contact dermatitis).
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- Kaplan USMLE Step 1 Immunology Lecture Notes
- Janeway's Immunobiology
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