USMLE PRACTICE QUESTION #128
TOPIC: Immunology/Pathology
USMLE practice question #128 will test your knowledge about a highly tested immune system disorder.
I’m Paul Ciurysek, MD, founder of The USMLE Guys! This daily newsletter aims to provide super high-yield USMLE concepts commonly tested on exam day. All content is FREE! If you’d like more help with your USMLE preparation, please see the options at the bottom of today’s newsletter. Please share the newsletter with a friend if you’d like to support our efforts!
A 32-year-old woman presents with a 3-month history of fatigue, dry cough, and shortness of breath. She reports occasional joint pain and a recent onset of painful red nodules on her shins. Physical examination reveals bilateral crackles in the lungs. Chest X-ray shows bilateral hilar lymphadenopathy. Bronchoalveolar lavage reveals increased CD4+/CD8+ ratio. A transbronchial biopsy shows non-caseating granulomas. Which of the following immunological processes is most likely responsible for the formation of these granulomas?
A) Hyperactivation of CD8+ cytotoxic T cells releasing perforin and granzymes
B) Dysregulated activation of macrophages by persistent microbial antigens
C) Overexpression of IL-12 and subsequent Th1 polarization and IFN-γ release
D) Deficient regulatory T-cell activity leading to excessive Th2 responses
E) Excessive B-cell activation resulting in abnormal immunoglobulin deposition
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following immunological processes is most likely responsible for the formation of these granulomas?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Diagnose the condition; 2nd: Identify the immunological process underlying the granulomas.
Step 3: Read the vignette carefully and ask yourself: “Based on my diagnosis, the underlying immunological process of granuloma formation is ____________________________.”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
This 32-year-old woman presents with fatigue, dry cough, shortness of breath, and painful red nodules on her shins. Physical examination reveals bilateral crackles, and imaging shows bilateral hilar lymphadenopathy. Laboratory findings include an increased CD4+/CD8+ ratio in bronchoalveolar lavage, and biopsy shows non-caseating granulomas. These findings are classic for sarcoidosis, a systemic inflammatory disease characterized by granuloma formation in multiple organs, most commonly the lungs.
ANSWER CHOICES:
CHOICE A: Hyperactivation of CD8+ cytotoxic T cells releasing perforin and granzymes
Explanation: CD8+ T cells are involved in cytotoxic responses, particularly against intracellular pathogens or tumor cells, by releasing perforin and granzymes to induce apoptosis.
CHOICE B: Dysregulated activation of macrophages by persistent microbial antigens
Explanation: Persistent microbial antigens (e.g., from Mycobacterium tuberculosis or fungi) can drive macrophage activation and granuloma formation in infections. This process underlies caseating granulomas seen in tuberculosis.
CHOICE C: Overexpression of IL-12 and subsequent Th1 polarization and IFN-γ release
Explanation: IL-12 drives the differentiation of naïve CD4+ T cells into Th1 cells. Th1 cells secrete IFN-γ, which activates macrophages to form granulomas.
CHOICE D: Deficient regulatory T-cell activity leading to excessive Th2 responses
Explanation: Regulatory T cells suppress excessive immune responses, while Th2 responses are associated with allergic diseases and eosinophilic inflammation.
CHOICE E: Excessive B-cell activation resulting in abnormal immunoglobulin deposition
Explanation: Excessive B-cell activation can lead to conditions like autoimmune diseases or amyloidosis due to abnormal immunoglobulin deposition.
FINAL VERDICT…
CORRECT ANSWER: C) Overexpression of IL-12 and subsequent Th1 polarization and IFN-γ release
The pathogenesis of sarcoidosis involves overexpression of IL-12, which polarizes CD4+ T cells into the Th1 subtype. These Th1 cells secrete IFN-γ, which activates macrophages to form non-caseating granulomas. This process leads to the characteristic inflammatory lesions seen in sarcoidosis.
KEY CONCEPTS:
Sarcoidosis Pathophysiology:
Driven by a Th1-dominant immune response.
Overexpression of IL-12 polarizes CD4+ T cells into the Th1 subtype.
Th1 cells secrete IFN-γ, which activates macrophages to form granulomas.
Granuloma Formation in Sarcoidosis:
Non-caseating granulomas consist of tightly clustered macrophages surrounded by lymphocytes.
Macrophages activated by IFN-γ transform into epithelioid cells or multinucleated giant cells.
Granulomas help contain inflammation but can cause organ dysfunction if excessive.
Clinical Features of Sarcoidosis:
Commonly affects the lungs (bilateral hilar lymphadenopathy), skin (erythema nodosum), and eyes.
Symptoms include fatigue, cough, dyspnea, night sweats, and weight loss.
Diagnostic Findings:
Chest X-ray: Bilateral hilar lymphadenopathy.
BAL: Increased CD4+/CD8+ ratio.
Biopsy: Non-caseating granulomas.
Differential Diagnosis for Granulomas:
Caseating granulomas: Tuberculosis or fungal infections.
Non-caseating granulomas: Sarcoidosis, Crohn's disease, berylliosis.
1) 1-ON-1 STRATEGY SESSION: CLICK HERE TO SET UP YOUR 1-ON-1 STRATEGY SESSION
2) TEST-TAKING SKILLS & RESIDENCY MASTERCLASSES: LEARN ABOUT THE MASTERCLASSES HERE
3) ASSESSMENT EXAMS: CLICK FOR USMLE STEP 1, STEP 2, & CLINICAL SHELF EXAMS
4) USMLE DRILLS BOOKS: CLICK HERE FOR THE STEP 1 BOOK, OR HERE FOR THE STEP 2 CK BOOK.
See ya tomorrow 👋