A 37-year-old woman is evaluated for progressive shortness of breath and dry cough. The patient has seasonal allergies and takes no medications. There is no significant family history. On physical examination, the lungs are clear to auscultation. Chest imaging studies reveal pulmonary infiltrates and hilar adenopathy. The patient undergoes lung biopsy; the findings are shown below. Which of the following sets of immune cells and cytokines is most likely responsible for the development of this patient's pathologic findings?

Question

A 37-year-old woman is evaluated for progressive shortness of breath and dry cough.  The patient has seasonal allergies and takes no medications.  There is no significant family history.  On physical examination, the lungs are clear to auscultation.  Chest imaging studies reveal pulmonary infiltrates and hilar adenopathy.  The patient undergoes lung biopsy; the findings are shown below.  Which of the following sets of immune cells and cytokines is most likely responsible for the development of this patient's pathologic findings?

Quizplus · Accepted Answer

11ec160b_37dc_ef8e_9249_97e477eaa245_MD0001_00 This patient with dyspnea and dry cough has pulmonary infiltrates and hilar adenopathy; this presentation suggests pulmonary sarcoidosis. The biopsy specimen with multiple, noncaseating granulomas-characterized by a central collection of tightly clustered epithelioid macrophages with abundant pink cytoplasm surrounded by a rim of mononuclear cells-confirms the diagnosis. Multinucleated giant cells, formed by macrophage fusion, are discernable at higher magnification. Sarcoidosis is thought to result from a dysregulated cell-mediated immune response to an unidentified antigen, which causes the formation of granulomas. Cell-mediated immunity is stimulated by production of IL-12 from activated antigen-presenting cells. IL-12 stimulates CD4+ helper T cells to differentiate into the Th1 subtype. Th1 cells then secrete IL-2 and interferon-γ (IFN-γ). IL-2 stimulates the autocrine proliferation of Th1 cells and furthers Th1 recruitment. IFN-γ activates macrophages and promotes granuloma formation. Activated macrophages and T cells also produce tumor necrosis factor-alpha, further assisting in leukocyte recruitment and granuloma maintenance. (Choice B) Th1 cells are central to cell-mediated immunity. However, IL-5 is a product of Th2 cells. Moreover, IL-10 is a cytokine involved in the downregulation of immune responses. (Choices C, D, and E) Th2 cells are involved in humoral immunity and defense against extracellular parasites. Asthma, a Th2-driven disease, causes dyspnea and cough but is not associated with granuloma formation. Cytokines involved with asthma include IL-4 and IL-5, which are secreted by Th2 cells. IL-4 promotes B-cell class switching to form IgE antibodies, and IL-5 promotes eosinophil production and activation. IL-3 is also involved in asthma (as it promotes survival of mast cells) but mainly supports the growth and differentiation of bone marrow stem cells. Educational objective: Sarcoidosis is characterized by noncaseating granulomas due to dysregulated cell-mediated immunity. Activated antigen-presenting cells produce IL-12, which stimulates the differentiation of Th1-type CD4⁺ cells. Th1 cells produce IL-2 and interferon-γ, which stimulate Th1 cell proliferation and macrophage activation, respectively.

A 37-Year-Old Woman Is Evaluated for Progressive Shortness of Breath