A 34-year-old man comes to the physician because of a persistent cough, night sweats, and a 5-kg (11-lb) weight loss over the past 3 weeks. He recently emigrated from Southeast Asia. Past medical history is negative, and he does not take any medications. Physical examination shows dullness to percussion and increased tactile fremitus over the right upper lung field. A sputum acid-fast stain is positive for several red, slender bacilli. A biopsy of a pulmonary nodule is performed.
Epithelioid histiocytes in the biopsy specimen have been activated by a cytokine primarily secreted by which of the following cell types?
The clinical presentation is highly suggestive of secondary (reactivation) tuberculosis. The host immune response to Mycobacterium tuberculosis involves a Type IV hypersensitivity reaction. In this process, macrophages first ingest the bacilli and secrete IL-12, which stimulates naive T cells to differentiate into Th1 cells. These Th1 cells then secrete Interferon-gamma (IFN-γ). IFN-γ is the critical cytokine that activates macrophages, increasing their phagocytic activity and inducing them to differentiate into epithelioid histiocytes and multinucleated Langhans giant cells, which form the core of the caseating granuloma.
Answer choice A: B lymphocytes, is incorrect. B lymphocytes are involved in humoral immunity (Type II and III hypersensitivity) and the production of antibodies. While they can be found in the periphery of granulomas, they do not secrete the IFN-γ required for macrophage activation and granuloma maturation.
Answer choice B: Cytotoxic T cells, is incorrect. CD8+ cytotoxic T cells play a role in killing infected cells directly. While they can secrete some IFN-γ, the primary driver of the delayed-type hypersensitivity response and the coordinated activation of macrophages in TB is the CD4+ Th1 subset.
Answer choice C: Eosinophils, is incorrect. Eosinophils are primarily involved in the immune response against helminthic (parasitic) infections and in Type I hypersensitivity (allergic) reactions. They are not a major component of the granulomatous response to M. tuberculosis.
Answer choice D: Macrophages, is incorrect. While macrophages are the cells that become activated and form the epithelioid histiocytes seen in the biopsy, they do not secrete the primary cytokine (IFN-γ) responsible for their own activation in this context. Macrophages secrete IL-12 to activate Th1 cells, but the question asks for the cell type that secretes the cytokine responsible for activating the biopsy-visualized cells (epithelioid histiocytes).
Key Learning Point
The formation of caseating granulomas in tuberculosis is a Th1-mediated Type IV hypersensitivity reaction. Th1 cells secrete Interferon-gamma (IFN-γ), which activates macrophages and promotes their transformation into epithelioid histiocytes and Langhans giant cells.
