Type IV Hypersensitivity – Delayed Type – 24-72h (Abbas pp 211)

This is referred to as delayed type hypersensitivity, and these occur as a result of T lymphocytes reacting, usually against self antigens  resulting in autoimmune diseases. Most autoimmune diseases are Type IV Hypersensitivity reactions.

Mechanisms of Tissue Injury

• Host is exposed to tissue antigen, which is broken down and is presented on APCs

• Naïve CD4+ cells recognise these peptides and differentiate into Th1 cells. Th1 cells migrate into the blood stream and remain as a pool of memory cells. Then when the host is presented with the same antigen again, the hypersensitivity reaction is started. Delayed because T cell activation is via APC and migration to infection site.

• Antigen re-presents, and are presented on APCs and Th1 cells interact with these  get activated. Th1 specific cytokines are released that induce local inflammation and activate macrophages. The macrophages along with other inflammatory cells cause tissue injury.

• A variant of Type IV reactions is when CD8+ T cells specific for antigens borne by autologous cells lyse these cells. The killing mechanism can be perforin-granzyme dependent or Fas-Fas ligand dependent.

• The Mantoux test works on Type IV Hypersensitivity reaction principle. The antigen is Mycobacterium TB + tuberculin. In TB, granuloma formation results because the infection cannot be eradicated, so granuloma causes functional impairment (Abbas pp211).

Category: Pathology Notes