WBR0276

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [2])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Pulmonology, SubCategory::General Principles
Prompt	[[Prompt::A 28-year-old man presents to the physician’s office for routine pre-employment check-up. During history-taking, the patient states that he grew up in Asia and immigrated to USA at the age of 20. The physician administers an intradermal injection of tuberculin skin test in the patient's left forearm, and the patient is instructed to follow-up in 2 days. When the patient returns, the site of his injection demonstrates a 16 mm erythematous, raised induration. Upon further questioning, the patient denies receiving a BCG vaccine in the past. When the patient asks why he did not develop any symptoms of his infection, the physician states that the majority of immunocompetent individuals are capable of containing the infection without developing any symptoms. Which of the following immunological changes occurs to contain this patient's infection?]]
Answer A	AnswerA::Eosinophils activate macrophages to phagocytose the infectious agent
Answer A Explanation	AnswerAExp::T-cells activate macrophages to phagocytose the tubercle bacillus
Answer B	AnswerB::The infectious agent undergoes phagocytosis by alveolar macrophages
Answer B Explanation	AnswerBExp::Activated macrophages fuse and become multinucleated giant cells that constitute a granuloma to phagocytose and contain the infection
Answer C	AnswerC::Infected macrophages release IL-2 and IL-4
Answer C Explanation	AnswerCExp::Infected macrophages release IL-12, which stimulates the formation of Th1 cells. IL-1 activates the Th1 cells and leads to fever. Th1 cells initiate the cell-mediated immunity needed to kill ''M. tuberculosis''.
Answer D	AnswerD::Destruction by cytotoxic T-cells results in coagulative necrosis.
Answer D Explanation	AnswerDExp::Destruction by cytotoxic T-cells results in caseous, not coagulative, necrosis.
Answer E	AnswerE::Activated neutrophils fuse to become multinucleated giant cells
Answer E Explanation	AnswerEExp::Activated macrophages, not neutrophils, fuse to become multinucleated giant cells.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Following primary infection with M. tuberculosis, the immunity of healthy individuals follows a sequence of events that result in the development of a tuberculous granuloma to contain the infection The sequence of tuberculous granuloma formation: Tubercle bacillus Mycobacterium tuberculosis undergoes phagocytosis by alveolar macrophages (processing of bacterial antigen). Infected macrophages present the antigen to CD4 -T cells in association with class II antigen sites. Infected macrophages release IL-12 which stimulates the formation of Th1 class cells and IL-1, which causes fever, and activates Th1 cells. Th1 cells release IL-2, gamma interferon, and migration inhibitory factors. Infected macrophages are killed by the host immunity, which is orchestrated by T-cell immunity and executed by non-infected macrophages. Activated non-infected macrophages fuse and become multinucleated giant cells that constitute a granuloma to phagocytose and contain the infection Cellular debris results in the formation of a caseous necrosis in the center of a granuloma, where lipid from the cell wall of killed M. tuberculosis result in the formation of the cheese-like appearance of caseous necrosis. Educational Objective: Tuberculous granuloma formation is a specialized form of chronic inflammation which is either caused by infections such as Tuberculosis or systemic fungal infections or by non-infectious causes such as Sarcoidosis or Crohn’s disease. References: Ladel CH, Szalay G, Riedel D, et al. Interleukin-12 secretion by Mycobacterium tuberculosis-infected macrophages. Infect Immun. 1997;65(5):1936-8. Grosset J. Mycobacterium tuberculosis in the extracellular compartment: an underestimated adversary. Antimicrob Agents Chemother. 2003;47(3):833-6. First Aid 2014 page 134]]
Approved	Approved::Yes
Keyword	WBRKeyword::Pulmonary tuberculosis, WBRKeyword::Tuberculosis, WBRKeyword::TB, WBRKeyword::Cough, WBRKeyword::Fever, WBRKeyword::Night sweats, WBRKeyword::Weight loss, WBRKeyword::Phagocytosis, WBRKeyword::Macrophages, WBRKeyword::Cell-mediated immunity, WBRKeyword::Th1, WBRKeyword::T-cells, WBRKeyword::Caseating necrosis, WBRKeyword::Caseous necrosis, WBRKeyword::Necrosis, WBRKeyword::Types of necrosis
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