🧠 Granulomatous Inflammation for USMLE Step 1: Types, Causes, and Immune Mechanism
Granulomas are organized aggregates of macrophages and T cells that form in response to persistent pathogens or irritants. They’re a classic Step 1 topic because they appear in multiple disciplines: immunology, pathology, microbiology, and pharmacology.
You’ll be asked to:
Distinguish caseating vs non-caseating
Know the immune cells involved
Recognize key disease associations
🧬 What Is a Granuloma?
| Definition | Chronic inflammation with macrophages, epithelioid histiocytes, and giant cells |
| Core Cell Type | Activated macrophages (epithelioid cells) |
| Immune Response | Th1 → IFN-γ → macrophage activation (Type IV hypersensitivity) |
| Purpose | Wall off a persistent antigen or pathogen |
🔥 Caseating vs Non-Caseating Granulomas
| Type | Appearance | Associated Conditions |
|---|---|---|
| Caseating | Central necrosis (“cheese-like”) | TB, histoplasmosis, fungal infections |
| Non-Caseating | No necrosis, uniform macrophages | Sarcoidosis, Crohn’s disease, berylliosis |
🧠 Step 1 Tip:
Necrosis = infection, while non-necrotic = autoimmune or reactional
🧪 Immune Pathway Recap
Persistent antigen (e.g., mycobacteria) activates macrophages
Macrophages present antigen to CD4⁺ T cells via MHC II
Th1 cells release IFN-γ → macrophage activation
Activated macrophages become:
Epithelioid cells
Multinucleated giant cells
Surrounding T cells + fibroblasts form the granuloma capsule
🦠 Diseases That Form Granulomas
| Cause | Disease Example |
|---|---|
| Bacteria | Tuberculosis, leprosy, Bartonella henselae |
| Fungi | Histoplasma, Blastomyces |
| Inorganic | Berylliosis, silicosis |
| Autoimmune | Sarcoidosis, Crohn’s disease |
| Parasites | Schistosomiasis |
🧠 Mnemonics to Master
“Gran-U-Late = Gather Up Lymphocytes and Macrophages”
“CASEating = TB CASE”
📚 Histologic Buzzwords
| Term | Meaning |
|---|---|
| Epithelioid histiocytes | Macrophages with pink cytoplasm resembling epithelial cells |
| Langhans giant cells | Multinucleated macrophages with peripheral nuclei |
| Caseous necrosis | Amorphous granular debris typical of TB granulomas |
| Asteroid bodies | Star-shaped inclusions in sarcoid granulomas |
⚠️ Step 1 Clinical Clue
A 32-year-old African-American woman has bilateral hilar lymphadenopathy and non-caseating granulomas on biopsy. No evidence of TB. What’s the diagnosis?
✅ Answer: Sarcoidosis
✅ Mechanism: Non-caseating granulomatous inflammation
🎯 Call-To-Action
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Frequently Asked Questions (FAQs)
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Aim for 4-6 focused hours, ensuring you incorporate breaks to avoid burnout.
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Practice mindfulness techniques, take practice exams under realistic conditions, and maintain a balanced lifestyle.
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Set short-term goals, seek support from mentors, and reward yourself for small achievements.
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