Review Question - QID 106769

Pulmonary tissue destruction in tuberculosis is caused by a delayed type IV hypersensitivity reaction. Macrophages with ingested tuberculosis bacilli are activated by CD4+ effector T cells.

Delayed type IV hypersensitivity reactions are immune responses mediated by CD4+ effector T cells. Macrophages with engulfed bacilli display tuberculosis antigens on MHC II class molecules, which are recognized by antigen-specific CD4+ effector T cells. The activation of these T cells leads to the production of IFN-gamma, a cytokine that stimulates macrophages to form phagolysosomes towards engulfed bacteria and secrete large amounts of tumor necrosis factor (TNF). TNF leads to the recruitment of monocytes that differentiate into epithelioid histiocytes; these, in turn, wall off the organisms into the characteristic caseating granulomas seen in tuberculosis. This immune response is the primary mechanism for tissue destruction in pulmonary tuberculosis.

Hauck et al. review the efficacy of the tuberculin skin test, which utilizes the delayed type IV hypersensitivity reaction seen in tuberculosis infection. A purified protein derivative of tuberculosis antigen is injected into the dermis, and antigen presentation to memory CD4+ effector T cells leads to the characteristic inflammatory reaction with erythema and induration at the site of injection.

Clifford et al. performed a systematic review to identify potential cytokine biomarkers that could be used to monitor the success of anti-tuberculous treatment. The most promising biomarker was TNF-alpha, which demonstrated a consistent reduction during treatment in several studies. This methodology would be limited in patients undergoing TNF-alpha inhibitor therapy for inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, or psoriasis.

Figure A is a chest radiograph demonstrating pulmonary tuberculosis and right upper lobe cavitation (white arrow).

Incorrect Answers:
Answer 1: Tuberculosis bacteria do not secrete proteolytic enzymes. Such pathology is seen with proteases released by group A streptococcus species in necrotizing fasciitis.

Answer 2: This form of tissue destruction is termed autophagy, a self-destructive process implicated in a number of neurodegenerative diseases such as Parkinson’s disease.

Answer 4: The immunologic process described is a type III hypersensitivity reaction, which mediates tissue destruction in a number of autoimmune diseases including systemic lupus erythematosus.

Answer 5: Reactive oxygen species are utilized by the immune system as a mechanism of killing pathogens, but it is not the primary cause of tissue destruction in pulmonary tuberculosis.