A 64-year-old man comes to the clinic due to several weeks of persistent cough, fever, and weight loss. He smokes a pack of cigarettes daily and drinks 10-12 beers on weekends. Chest x-ray reveals an infiltrate in the left upper lobe. The patient is prescribed broad-spectrum antibiotic therapy for both aspiration and community-acquired pneumonia, but his symptoms worsen despite taking the medication as prescribed. Sputum Gram stain does not reveal any organisms. Lung biopsy findings are shown in the image below: Which of the following substances is most important for driving the development of this patient's observed microscopic lesion?

Question

A 64-year-old man comes to the clinic due to several weeks of persistent cough, fever, and weight loss.  He smokes a pack of cigarettes daily and drinks 10-12 beers on weekends.  Chest x-ray reveals an infiltrate in the left upper lobe.  The patient is prescribed broad-spectrum antibiotic therapy for both aspiration and community-acquired pneumonia, but his symptoms worsen despite taking the medication as prescribed.  Sputum Gram stain does not reveal any organisms.  Lung biopsy findings are shown in the image below:  Which of the following substances is most important for driving the development of this patient's observed microscopic lesion?

Quizplus · Accepted Answer

11ec160b_37dd_d9f1_9249_239d78b7fdba_MD0001_00 This patient has cough, fever, weight loss, and an upper lobe lesion on chest x-ray, raising strong suspicion for active pulmonary tuberculosis. Mycobacterium tuberculosis cannot be visualized on Gram stain due to the high lipid content (mycolic acid) of its cell wall. Most cases are diagnosed by acid-fast sputum testing and culture, but tissue microscopy typically shows granulomas characterized by epithelioid histiocytes and multinucleated Langhans giant cells. Granulomas often form after tissue macrophages encounter pathogens or substances that cannot be easily digested or removed. M tuberculosis can evade intracellular killing by macrophages and reproduce within phagolysosomes. Infected macrophages present mycobacterial antigens to naïve CD4 helper T cells in pulmonary lymph nodes and secrete IL-12, which induces activated T helper cells to differentiate into T helper subtype 1 (Th1) cells. Proliferating Th1 cells migrate to sites of infection, where they release interferon-gamma, which activates macrophages, improves intracellular killing of ingested mycobacteria, and recruits additional macrophages by increasing production of tumor necrosis factor-alpha. Activated macrophages can also limit the spread of mycobacteria by differentiating into epithelioid and giant cells that surround residual foci of mycobacteria, trapping them inside the necrotic, cheese-like area of a caseating granuloma. (Choice A) C3a is a split product anaphylatoxin derived from C3. It stimulates the release of histamine by mast cells, which increases vascular permeability and vasodilation. (Choice B) Fibroblast growth factor has a variety of proliferative effects, including stimulation of angiogenesis and fibroblast proliferation during formation of granulation tissue. It does not have a primary role in the formation of granulomas. (Choice C) Granulocyte-macrophage colony-stimulating factor induces stem cell differentiation into monocytes and other granulocytes (eg, neutrophils, eosinophils). However, it does not induce granuloma formation. (Choice D) IL-4 is a cytokine that stimulates the differentiation of naïve CD4 T cells into the Th2 subset, which plays an important role in humoral immunity and allergic reactions by stimulating B-cell proliferation and isotype switching to IgE. (Choice E) Interferon-alpha is a primary mediator of the immune response to virus-infected cells. However, in contrast to interferon-gamma, it limits macrophage proliferation and does not drive granuloma formation. Educational objective: T helper subtype 1 cells release interferon-gamma, leading to the activation of macrophages, a process critical for control of Mycobacterium tuberculosis infection. Activated macrophages form mature phagolysosomes that destroy phagocytosed mycobacteria and can differentiate into epithelioid and Langhans giant cells to wall off extracellular mycobacteria within caseating granulomas. __________ References: Th1 and Th17 cells in tuberculosis: protection, pathology, and biomarkers. (http://www.ncbi.nlm.nih.gov/pubmed/26640327)

A 64-Year-Old Man Comes to the Clinic Due to Several