Immunology USMLE Practice Questions
Immune system fundamentals and autoimmune diseases.
5 free immunology practice questions
Pick an answer and check it. After each question you get the same explanation StepGenie students see: the stem decoded clue by clue, the reasoning chain with its infographic, why every wrong option is wrong, and the trap the question was built around. Step 1 questions test mechanism; Step 2 CK questions ask for the next step.
A 2-year-old boy is brought to the physician due to fever, productive cough, and shortness of breath. Since birth, he has had recurrent respiratory infections requiring multiple courses of antibiotics. His immunizations are up to date, but he is in the 10th percentile for both height and weight. Temperature is 38°C (100.3°F). Physical examination reveals diffuse bilateral wheezing and cervical lymphadenopathy. Flow cytometric analysis of his serum using dihydrorhodamine fails to demonstrate fluorescence, indicating impaired oxidative burst in neutrophils. This patient is at greatest risk of infection with which of the following organisms?
Correct answer · C
Serratia marcescens
Decoding the stem
Step-by-step reasoning
Step 1 of 7
Recurrent infections since infancy plus failure to thrive point toward a primary immunodeficiency, not just isolated infections.
Step 2 of 7
The dihydrorhodamine (DHR) test assesses neutrophil oxidative burst; lack of fluorescence indicates impaired ROS production.
Step 3 of 7
Impaired oxidative burst is due to NADPH oxidase deficiency, the hallmark of chronic granulomatous disease (CGD).
Step 4 of 7
In CGD, neutrophils cannot effectively kill certain bacteria/fungi inside phagosomes because they lack sufficient reactive oxygen species.
Step 5 of 7
Patients are especially susceptible to catalase-positive organisms, which degrade their own hydrogen peroxide and deprive host cells of substrate for ROS generation.
Step 6 of 7
Classic catalase-positive pathogens in CGD include Staphylococcus aureus, Serratia marcescens, Nocardia, Burkholderia cepacia, Pseudomonas, and Aspergillus.
Step 7 of 7
Among the options, Serratia marcescens is the classic catalase-positive organism associated with CGD, making it the greatest infection risk.
Why not the others?
A. Enterococcus faecium
This option implies nosocomial, vancomycin-resistant enterococcal (VRE) infection, which commonly causes UTIs, endocarditis, or intra-abdominal infections, BUT it is not a classic catalase-positive pathogen linked to CGD susceptibility.
B. Actinomyces israelii
This option implies Actinomycosis (often cervicofacial with draining sulfur granules), a filamentous, anaerobic, catalase-negative Gram-positive organism, BUT CGD patients are especially vulnerable to catalase-positive pathogens, which this is not.
D. Streptococcus pneumoniae
This option implies encapsulated, catalase-negative Gram-positive diplococcus causing pneumonia, otitis media, meningitis, or sepsis. Increased risk of S. pneumoniae is typical in asplenia or humoral (B-cell) deficiencies, BUT here the defect is in neutrophil oxidative burst, pointing instead to catalase-positive organisms.
E. Clostridioides difficile
This option implies antibiotic-associated colitis due to disruption of gut flora and toxin-mediated diarrhea, BUT this is not primarily related to phagocytic oxidative burst defects and is more about prior antibiotic exposure and gut microbiome changes.
F. Streptococcus pyogenes
This option implies Group A streptococcal infections (pharyngitis, impetigo, cellulitis, necrotizing fasciitis), a catalase-negative organism, BUT CGD specifically predisposes to catalase-positive pathogens like Serratia rather than GAS.
Exam trap
The vignette emphasizes recurrent infections and poor growth, which may push you toward B-cell or T-cell disorders. The key is the dihydrorhodamine (DHR) test, which directly points to oxidative burst / NADPH oxidase and thus CGD—you must then recall the classic catalase-positive organisms, not just any common pediatric pathogen.
The bottom line
Chronic granulomatous disease (defective NADPH oxidase, impaired oxidative burst) → recurrent catalase-positive organism infections (eg, Staph aureus, Serratia, Burkholderia, Nocardia, Aspergillus).
An 18-year-old man is brought to the emergency department by his girlfriend due to an intensely pruritic rash on his penis that began about an hour ago. The rash developed shortly after their first episode of protected sexual intercourse. His girlfriend is asymptomatic. Five days ago, he visited a friend who had severe pruritus on the elbows, wrists, groin, and axillae and was treated with a regimen that required washing bedding, clothing, and towels in hot water. Two years ago, he developed an itchy rash around his mouth after blowing up balloons at a birthday party. He is breathing comfortably, and vital signs are within normal limits. Physical examination reveals multiple well-circumscribed, raised, erythematous plaques with mild excoriations extending from the base to the glans of the penis. The remainder of the examination is unremarkable. Administration of which of the following is the most appropriate next step in management?
Correct answer · G
Oral cetirizine
Decoding the stem
Step-by-step reasoning
- 1
Penile rash starts within 1 hour after condom use → suggests immediate-type (Type I) hypersensitivity, not infectious etiology (which would take days).
- 2
Lesions are raised, well-circumscribed, erythematous plaques with intense pruritus → classic for urticaria (wheals) rather than eczema, herpes, or scabies.
- 3
History of rash around mouth after blowing up balloons → prior reaction to latex, establishing sensitization and making repeat latex exposure a likely trigger.
- 4
Protected intercourse implies probable latex condom exposure → with prior sensitization, re-exposure provokes localized contact urticaria on the penis.
- 5
He is breathing comfortably with normal vitals and no systemic signs (no wheeze, hypotension, GI symptoms) → localized urticaria, no anaphylaxis.
- 6
First-line therapy for uncomplicated urticaria is a second-generation oral H1 antihistamine (eg, cetirizine), which blocks histamine at H1 receptors with minimal sedation.
- 7
Therefore, the most appropriate next step is administration of oral cetirizine.
Why not the others?
D. Subcutaneous epinephrine
This option implies anaphylaxis (airway compromise, hypotension, systemic symptoms), which requires epinephrine, BUT this patient has isolated localized urticaria with stable vitals and no respiratory or cardiovascular involvement.
E. Oral famotidine
This option implies use of an H2 blocker as adjunctive therapy; H2 blockers can be added, BUT they are not first-line monotherapy and are less effective than H1 blockers for urticaria, and a second-generation H1 is directly indicated here.
F. Intravenous prednisone
This option implies systemic corticosteroid use for severe, refractory, or systemic allergic reactions, BUT this patient has mild, localized symptoms and should be treated first-line with an oral H1 antihistamine without steroid side effects.
A. Intravenous acyclovir
This option implies herpes simplex virus infection, which presents with painful vesicles/ulcers and systemic prodrome, BUT the patient has pruritic, raised plaques (wheals), rapid onset after exposure, and no vesicles or pain, making HSV unlikely.
B. Topical permethrin
This option implies scabies infestation, which causes intensely pruritic papules and burrows in typical locations (web spaces, wrists, axillae, groin) and requires washing bedding, BUT his lesions are acute wheals only on the penis after latex exposure, and he lacks the characteristic chronic distribution or household spread.
C. Oral cromolyn sodium
This option implies mast cell stabilization for chronic allergic conditions (eg, asthma, mastocytosis, food allergy prophylaxis), BUT cromolyn is not used for acute urticaria relief; H1 antihistamines like cetirizine are standard acute treatment.
Exam trap
The stem mentions a friend with scabies-type treatment and prior pruritic rash, tempting selection of permethrin or an infectious cause. However, the rapid onset after latex condom use and history of latex reaction (balloons) point to contact urticaria, not scabies or STI. Focus on timing, lesion morphology, and systemic stability to choose a second-generation oral H1 antihistamine rather than over-escalating to epinephrine or steroids.
The bottom line
Acute allergic contact urticaria from latex exposure presents with rapid-onset, intensely pruritic wheals; treat with second-generation oral H1 antihistamines (eg, cetirizine).
A 7-year-old boy is brought to the physician with a 5-day history of fever, malaise, and joint pain. Four weeks ago, he had a sore throat that resolved without medical treatment. His temperature is 38.6°C (101.5°F), and blood pressure is 84/62 mm Hg. Physical examination reveals several firm, non-tender subcutaneous nodules over the extensor surfaces near the elbows and on the dorsal aspect of both wrists. Both knees are warm to the touch. Cardiopulmonary examination shows bilateral basilar crackles and a blowing holosystolic murmur best heard at the cardiac apex. Laboratory testing demonstrates an erythrocyte sedimentation rate of 129 mm/h. The immune response seen in this patient is most likely due to the presence of which of the following?
Correct answer · E
M protein
Decoding the stem
Step-by-step reasoning
Step 1 of 6
Child has history of untreated sore throat 4 weeks ago → strongly suggests group A β-hemolytic Streptococcus (Strep pyogenes) pharyngitis.
Step 2 of 6
Latency of ~2–4 weeks between strep throat and new symptoms (fever, arthritis, murmur) points to a post-infectious immune complication, not ongoing infection.
Step 3 of 6
Current findings: migratory polyarthritis (knee involvement), subcutaneous nodules, and new mitral regurgitation murmur → classic Jones criteria for acute rheumatic fever.
Step 4 of 6
Pathogenesis of ARF: type II hypersensitivity with antibodies formed against streptococcal antigens that cross-react with host tissues (molecular mimicry).
Step 5 of 6
The key virulence factor driving this molecular mimicry is Strep pyogenes M protein, which shares epitopes with myosin and other cardiac/joint tissues.
Step 6 of 6
Therefore, the immune response seen in this patient (cross-reactive autoantibodies causing carditis and arthritis) is most likely due to M protein.
Why not the others?
A. Hyaluronic acid capsule
This option implies the hyaluronic acid capsule of Strep pyogenes, which helps evade phagocytosis, BUT it is poorly immunogenic and not the main driver of cross-reactive antibodies causing rheumatic fever.
B. TSST-1
This option implies toxic shock syndrome toxin-1 from Staph aureus, which causes toxic shock syndrome (fever, rash, hypotension, multi-organ failure), BUT this child has post-strep carditis and arthritis, not acute superantigen toxicity.
C. IgA protease
This option implies IgA protease made by organisms like S. pneumoniae, H. influenzae, Neisseria, enabling mucosal colonization, BUT these enzymes do not cause molecular mimicry or rheumatic fever–type autoimmune sequelae.
D. CAMP factor
This option implies CAMP factor of Streptococcus agalactiae (group B strep), associated with neonatal meningitis and sepsis, BUT this patient’s syndrome is post–group A strep pharyngitis with rheumatic heart disease features, unrelated to CAMP factor.
Exam trap
The test-taker may see “Strep-related” and reflexively choose any GAS virulence factor (like hyaluronic acid capsule). The key is to recall which specific factor mediates molecular mimicry and ARF—M protein, not the capsule or other enzymes.
The bottom line
Acute rheumatic fever from group A strep: anti–M protein antibodies cross-react with heart, joints, skin (type II hypersensitivity) causing migratory arthritis and carditis.
A 65-year-old man presents 7 days after bilateral total knee arthroplasty with dark discoloration and blistering on the abdomen. His medications include simvastatin, aspirin, and low-molecular-weight heparin. Vital signs are within normal limits. Skin examination reveals multiple coalescing blisters with areas of necrosis around the umbilicus. Laboratory studies show a platelet count of 32,000/mm3. Which of the following is the most likely underlying cause of this patient’s symptoms?
Correct answer · C
Antibody formation against heparin-PF4 complex
Decoding the stem
Step-by-step reasoning
Step 1 of 6
Patient received low-molecular-weight heparin after orthopedic surgery, a common prophylaxis and classic context for HIT.
Step 2 of 6
About 5–10 days after starting heparin, some patients form IgG antibodies against the heparin–platelet factor 4 (PF4) complex.
Step 3 of 6
These immune complexes bind platelets via Fc receptors, causing platelet activation rather than simple destruction.
Step 4 of 6
Activated platelets promote thrombosis (including in microvasculature of skin) while being consumed, leading to thrombocytopenia (platelets 32,000/mm³).
Step 5 of 6
Microvascular thrombosis in the skin at injection sites causes painful purpura, blisters, and necrosis on the abdomen.
Step 6 of 6
Thus the underlying mechanism is antibody formation against the heparin-PF4 complex, not primary platelet destruction alone or vitamin deficiency.
Why not the others?
A. Anti-desmoglein antibody formation
This implies pemphigus vulgaris, which causes flaccid bullae and erosions on skin and mucosa, BUT it is not linked to heparin use, thrombocytopenia, or necrotic lesions at injection sites.
B. Deficiency in ADAMTS13 activity
This implies TTP, causing MAHA, neurologic symptoms, fever, renal injury, and thrombocytopenia, BUT there is no mention of hemolytic anemia, schistocytes, or neuro signs; timing after heparin strongly favors HIT.
D. Antibody-platelet antigen complex formation
This implies immune thrombocytopenic purpura (ITP) with isolated thrombocytopenia due to platelet destruction, BUT ITP does not typically cause localized necrotic skin lesions at drug injection sites and is not specifically tied to heparin exposure/timing.
E. Deficiency in vitamin K
This causes impaired synthesis of clotting factors II, VII, IX, X, C, S leading to bleeding (elevated PT/INR), BUT would not cause severe thrombocytopenia or localized necrotic skin lesions after heparin administration.
F. Decreased production of GpIb
This suggests Bernard–Soulier syndrome, a congenital platelet adhesion defect with mild thrombocytopenia and bleeding from childhood, BUT this patient developed acute severe thrombocytopenia and necrotic lesions after heparin exposure, not lifelong bleeding symptoms.
Exam trap
Skin necrosis can suggest warfarin-induced protein C deficiency or autoimmune bullous disease; however, the key is timing and exposure to heparin plus severe thrombocytopenia, which specifically indicates HIT via anti–heparin-PF4 antibodies.
The bottom line
Heparin-induced thrombocytopenia (HIT): anti–heparin-PF4 IgG → platelet activation → thrombosis, thrombocytopenia, and skin necrosis at heparin injection sites.
A 51-year-old woman with hyperlipidemia presents with a 1-month history of progressive fatigue. By the end of the day, she feels too tired to cook dinner or carry a laundry basket up the stairs. She also reports intermittent double vision that develops after reading for prolonged periods and improves with rest. Her only medication is pravastatin. On physical examination, she has bilateral ptosis. Muscle strength is 5/5 in all extremities initially but declines to 4/5 after several minutes of sustained effort. Sensation to light touch is intact, and deep tendon reflexes are normal. Which of the following best describes the pathogenesis of this patient’s condition?
Correct answer · A
Type II hypersensitivity reaction
Decoding the stem
Step-by-step reasoning
Step 1 of 6
The patient has fluctuating, fatigable weakness (normal strength initially → weaker with repeated use) affecting proximal and ocular muscles (ptosis, diplopia).
Step 2 of 6
Symptoms worsen with prolonged activity (reading, carrying objects) and improve with rest, which is characteristic of a neuromuscular junction postsynaptic disorder.
Step 3 of 6
Normal sensation and deep tendon reflexes rule out peripheral neuropathies and motor neuron diseases, narrowing the diagnosis to myasthenia gravis rather than neuropathy or myopathy.
Step 4 of 6
Myasthenia gravis is caused by autoantibodies directed against postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction.
Step 5 of 6
These antibodies mediate Type II (antibody-mediated) hypersensitivity, leading to receptor internalization, complement-mediated damage, and decreased end-plate potentials, producing fatigable weakness.
Step 6 of 6
Therefore, the best description of the pathogenesis is a Type II hypersensitivity reaction against the postsynaptic ACh receptor.
Why not the others?
B. Peripheral nerve demyelination
This option implies disorders like Guillain-Barré or chronic inflammatory demyelinating polyneuropathy, which cause ascending weakness, reduced/absent reflexes, and often sensory symptoms, BUT this patient’s sensation and reflexes are normal and weakness is fatigable with ocular involvement, fitting myasthenia gravis instead.
C. Impaired acetylcholine release
This option implies presynaptic disorders such as Lambert-Eaton myasthenic syndrome or botulism, which show proximal weakness improving with repeated use and are often associated with autonomic symptoms or malignancy; BUT here weakness worsens with use and ocular involvement is prominent, favoring postsynaptic myasthenia gravis, not impaired ACh release.
D. Adverse drug effect
This option implies statin-induced myopathy or another drug toxicity, which would cause fixed myalgias/weakness (not fluctuating), elevated CK, and no fatigability pattern or isolated ocular findings; BUT her weakness is clearly activity-dependent with diplopia and ptosis, classic for an autoimmune neuromuscular junction disorder, not a pravastatin side effect.
E. Anterior horn cell destruction
This option implies diseases like amyotrophic lateral sclerosis or poliomyelitis, which cause progressive weakness and atrophy, often with fasciculations and hyperreflexia or mixed UMN/LMN signs, BUT this patient has normal reflexes, no atrophy or fasciculations, and distinctly fatigable weakness with ocular involvement, inconsistent with anterior horn cell disease.
Exam trap
The presence of a statin (pravastatin) tempts you to blame an adverse drug effect (statin myopathy). However, the key clues—fatigable weakness, ptosis, diplopia improving with rest, and normal reflexes/sensation—point squarely to myasthenia gravis, which is a Type II hypersensitivity against postsynaptic ACh receptors.
The bottom line
Myasthenia gravis: autoantibodies (type II hypersensitivity) against postsynaptic ACh receptors cause fatigable weakness, ptosis, and diplopia improving with rest.
Source: StepGenie question bank. Questions are written by StepGenie, not taken from NBME or USMLE materials, and are chosen for this page by how students actually performed on them (first-attempt accuracy on StepGenie). Selection last refreshed September 5, 2026.
Keep going on Immunology
A free account includes 5 Visual QBank questions a day in practice blocks you build by subject and organ system, plus 10 Pattern Mastery questions a day.
About Immunology
Master innate and adaptive immunity, immunodeficiencies, autoimmune disorders, hypersensitivity reactions, and transplant immunology. AI-powered explanations help clarify complex immune pathways.
Key Topics Covered
Why Study Immunology with StepGenie?
- AI-Powered Explanations: Get personalized, Socratic explanations when you're stuck on complex immunology concepts.
- Adaptive Learning: Questions automatically adjust to target your weak areas in immunology.
- Spaced Repetition Flashcards: Reinforce high-yield immunology facts with our FSRS-powered flashcard system.
- Pattern Recognition: Master classic immunology presentations through keyword recognition drills.
Related Articles
Chronic Granulomatous Disease: Organisms, DHR & Treatment
Chronic granulomatous disease means phagocytes ingest microbes but cannot mount a respiratory burst. Expect catalase-positive infections, granulomas, and abnormal DHR/NBT.
Autoimmune Mechanisms: Type II vs III vs IV Hypersensitivity
Lupus nephritis points to type III hypersensitivity: immune complexes, low complement, and granular immunofluorescence. The key board trap is Goodpasture’s linear pattern.
Q-Bank Breakdown: HLA associations with disease — Why Every Answer Choice Matters
Ankylosing spondylitis links to HLA-B27, but the bigger test skill is knowing why DR3, DR4, B8, and DQ2 belong to other autoimmune diseases instead.
Immunology study guides
Chediak-Higashi Syndrome Mnemonic: The CHEDIAK Acronym
Chediak-Higashi clicks faster when you anchor it to partial albinism, giant granules, and recurrent Staph/Strep infections from an AR LYST defect.
Serum Sickness (Type III): Triad, Timing & Low C3/C4
Serum sickness shows up days to weeks after a foreign protein or new drug with fever, rash, and joint pain. Lock in the timing, mechanism, and key clues.
Job Syndrome (Hyper-IgE) Mnemonic: FATED & Flowchart
Spot Job syndrome fast: eczema, recurrent cold staph abscesses, retained baby teeth, and coarse facies point to STAT3 loss, low Th17, and high IgE.
Complement Deficiencies: USMLE Table and Mnemonics
Vague stem? Match the broken complement arm fast: early classical gives lupus-like disease, C3 gives severe pyogenic infections, and terminal defects mean Neisseria.
Wiskott-Aldrich Syndrome: Triad, Ig Pattern & USMLE Mimics
Eczema plus infections is not enough. Small platelets, thrombocytopenia, and the low-IgM/high-IgA-IgE pattern separate Wiskott-Aldrich from look-alikes.
T-Cell Activation Mnemonic: 3 Signals, Anergy & CTLA-4
T cells need more than antigen recognition to activate: B7-CD28 costimulation prevents anergy, and cytokines steer differentiation into Th subsets.
Th1 vs Th2 Immune Responses: Type 1 vs Type 2 Immunity
Th1 means macrophages, granulomas, and delayed hypersensitivity; Th2 means IgE, eosinophils, and asthma. Lock in the cytokines and board clues fast.
Immunology — Frequently Asked Questions
What are the four hypersensitivity reactions and how do you tell them apart?
Type I is immediate and IgE-mediated, as in anaphylaxis and atopy. Type II is antibody-mediated against cell surface antigens, as in autoimmune hemolytic anemia. Type III is immune complex deposition, as in serum sickness and lupus nephritis. Type IV is T-cell mediated and delayed, as in contact dermatitis and the tuberculin skin test.
How do you localise an immunodeficiency from the infection pattern?
Recurrent encapsulated bacterial infections beginning after maternal antibody wanes suggest a B-cell or antibody defect. Severe viral, fungal and opportunistic infections suggest a T-cell defect. Recurrent Neisseria infections point to a terminal complement deficiency. Catalase-positive organisms with granulomas point to chronic granulomatous disease.
What immunology topics are highest-yield for Step 1?
Hypersensitivity reactions, primary immunodeficiencies grouped by infection pattern, transplant rejection timing, autoantibodies and their disease associations, complement pathway defects, and the major cytokines with their sources and actions. Autoantibody associations are heavily tested because they let a vignette be solved from a single laboratory line.
How does the timing of transplant rejection identify the mechanism?
Hyperacute rejection occurs within minutes from preformed antibodies. Acute rejection occurs within weeks to months and is primarily T-cell mediated, which is why it responds to increased immunosuppression. Chronic rejection develops over months to years with fibrosis and vascular narrowing. Graft-versus-host disease is distinct, with the graft attacking the host.
Are the immunology practice questions on this page free?
Yes. The 5 questions above come from StepGenie's question bank and can be answered here without an account, with the full explanation shown after each one. From the link under the set you can try three more Immunology questions in the dashboard preview, also without an account; a free account is what lets you choose the system and keep going.