USMLE Step 1 Hypersensitivity Reactions practice questions
Hypersensitivity reactions are immune responses that cause tissue damage rather than protection, classically organized into four types by the Gell and Coombs system based on the immune mechanism involved: Type I (IgE-mediated, immediate), Type II (antibody-mediated cytotoxicity or receptor modulation), Type III (immune complex-mediated), and Type IV (T cell-mediated, delayed). USMLE Step 1 emphasizes matching a clinical scenario to the correct mechanism rather than simply naming the disease.
A 24-year-old man is stung by a wasp while gardening. Within minutes he develops diffuse urticaria, lip swelling, wheezing, and a blood pressure of 78/44 mm Hg. He reports a similar but milder reaction to a wasp sting 2 years ago. Which of the following is the most likely mechanism of this patient's current presentation?
Patient Information Age: 34 years | Gender: F, self-identified | Site of Care: outpatient clinic History Reason for Visit/Chief Concern: "I've been so tired and my eyes look yellow." History of Present Illness: • 3-week history of progressive fatigue and dark urine • No recent travel, no new medications • History of systemic lupus erythematosus Physical Examination Temp: 37.1°C | Pulse: 104/min | Resp: 16/min | BP: 116/70 mm Hg Scleral icterus present, mild splenomegaly Diagnostic Studies Hemoglobin 8.2 g/dL, reticulocyte count elevated, indirect bilirubin elevated, peripheral smear shows spherocytes, direct antiglobulin (Coombs) test positive Which of the following is the most likely mechanism of this patient's anemia?
A 9-year-old boy is treated with an antivenom derived from horse serum after a snakebite. Ten days later, he develops fever, urticarial rash, arthralgias, and lymphadenopathy. Serum complement (C3, C4) levels are low. Which of the following is the most likely mechanism underlying this patient's findings?
A 28-year-old woman develops an intensely pruritic, erythematous rash with vesicles on the skin under a new nickel-containing belt buckle. The rash appeared approximately 2 days after she began wearing the belt and has slowly worsened. Which of the following is the most likely mechanism of this reaction?
A 37-year-old woman comes to the office because of a 3-month history of unintentional weight loss, heat intolerance, and palpitations. Examination shows a diffusely enlarged, non-tender thyroid gland and a fine resting tremor. Laboratory studies show a markedly decreased TSH and elevated free T4. Which of the following is the most likely mechanism of this patient's thyroid overactivity?
Hypersensitivity Reactions, answered
What's a quick way to remember the four types of hypersensitivity reactions for Step 1?
Many students use the mnemonic ACID: Anaphylactic/Allergic (Type I), Cytotoxic (Type II), Immune complex (Type III), and Delayed cell-mediated (Type IV). Anchoring each type to one classic disease example, rather than memorizing lists, tends to transfer better to vignette-based questions.
Is Type II hypersensitivity always destructive to the target cell?
No. Most Type II reactions are cytotoxic (as in autoimmune hemolytic anemia), but a subset involves antibodies that modulate receptor function without directly destroying the cell, either stimulating it (as with TSH receptor autoantibodies in Graves disease) or blocking it (as with acetylcholine receptor antibodies in myasthenia gravis).
How do I tell Type II and Type III reactions apart on an exam question?
Look at what the antibody is binding. In Type II, the antibody binds directly to an antigen fixed on a specific cell or tissue surface, producing a localized effect. In Type III, the antibody binds a soluble antigen while both are still circulating, forming complexes that deposit more diffusely in vessel walls, joints, and skin, often with associated hypocomplementemia.
Do I need to memorize every disease example under each hypersensitivity type?
It helps more to understand the underlying mechanism and timing (immediate IgE-mediated, antibody-cell-surface, immune complex, or delayed T cell-mediated) than to memorize an exhaustive disease list, since Step 1 vignettes typically test whether you can map a new clinical scenario to the correct mechanism rather than recall a name.
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