USMLE PRACTICE QUESTION #119

TOPIC: Immunology

Dec 31, 2024

USMLE practice question #119 will test your ability to link a commonly tested developmental disorder to its immunological defect(s).

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A 3-week-old male infant is brought to the emergency department due to new-onset seizures. The infant was born at term via spontaneous vaginal delivery, and his neonatal course was complicated by feeding difficulties and frequent infections. Physical examination reveals dysmorphic facial features, including a small jaw and low-set ears. Laboratory studies show hypocalcemia and lymphopenia. Further evaluation reveals a cardiac defect and the absence of a thymic shadow on chest radiography. Genetic testing confirms a microdeletion on chromosome 22q11.2. Which of the following immunologic abnormalities is most likely to predispose the infant to recurrent infections?

A) Impaired class switching of immunoglobulins
B) Reduced numbers of circulating B lymphocytes
C) Defective phagocyte NADPH oxidase activity
D) Decreased production of interleukin-17 by T helper cells
E) Impaired development of mature T lymphocytes

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 immunologic abnormalities is most likely to predispose the infant to recurrent infections?”

Step 2: Is this a first-, second-, or third-order question?
Answer: 3rd order. 1st: Make a diagnosis; 2nd: Identify the immunological relationship to the diagnosis, and 3rd: Identify the consequences of the immunological defect.

Step 3: Read the vignette carefully and ask yourself: “Based on my diagnosis and the affected immunological structure, the most likely consequence is __________”

Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.

GENERAL ANALYSIS

The 3-week-old male infant presents with seizures, dysmorphic facial features, hypocalcemia, lymphopenia, and a cardiac defect. The absence of a thymic shadow on chest radiography and confirmation of a 22q11.2 microdeletion strongly suggest DiGeorge syndrome (22q11.2 deletion syndrome). This syndrome is characterized by defective development of the thymus, parathyroid glands, and heart due to abnormal development of the third and fourth pharyngeal pouches.

ANSWER CHOICES:

CHOICE A: Impaired class switching of immunoglobulins

Explanation: This mechanism occurs in conditions like hyper-IgM syndrome, where B cells fail to undergo class switching due to defective T-cell help.

Why Incorrect: While humoral immune defects can occur in DiGeorge syndrome due to impaired T-cell help, the primary defect is in T-cell development, not immunoglobulin class switching.

CHOICE B: Reduced numbers of circulating B lymphocytes

Explanation: This describes primary B-cell deficiencies such as X-linked agammaglobulinemia.

Why Incorrect: DiGeorge syndrome primarily affects T cells due to thymic hypoplasia; B-cell numbers are typically normal, although their function may be secondarily impaired due to reduced T-cell help.

CHOICE C: Defective phagocyte NADPH oxidase activity

Explanation: This mechanism is characteristic of chronic granulomatous disease (CGD), which leads to recurrent infections with catalase-positive organisms.

Why Incorrect: DiGeorge syndrome does not involve defects in phagocyte function or NADPH oxidase activity.

CHOICE D: Decreased production of interleukin-17 by T helper cells

Explanation: IL-17 is produced by Th17 cells and plays a role in mucosal immunity and defense against extracellular pathogens.

Why Incorrect: While T-cell function is impaired in DiGeorge syndrome, the primary issue is the reduced number of mature T cells due to thymic hypoplasia, not specifically IL-17 production.

CHOICE E: Impaired development of mature T lymphocytes

Explanation: The lack of a functional thymus leads to T-cell lymphopenia.

Why Correct: DiGeorge syndrome is caused by thymic hypoplasia or aplasia, which results in impaired T-cell development. The thymus is essential for the maturation of T lymphocytes (T cells), which are critical for cell-mediated immunity; affected individuals are more susceptible to recurrent infections, particularly those caused by intracellular pathogens (e.g., viruses, fungi, and certain bacteria).

FINAL VERDICT…

CORRECT ANSWER: E) Impaired development of mature T lymphocytes

The most likely immunologic abnormality predisposing this infant with DiGeorge syndrome to recurrent infections is impaired development of mature T lymphocytes, leading to reduced cell-mediated immunity. This defect arises from thymic hypoplasia or aplasia caused by the 22q11.2 microdeletion. Consequently, these patients are highly susceptible to infections that require robust T-cell responses for clearance.

KEY CONCEPTS:

DiGeorge Syndrome Pathogenesis:
- Caused by a 22q11.2 microdeletion.
- Results in defective development of the third and fourth pharyngeal pouches.
- Leads to thymic hypoplasia/aplasia (impaired T-cell development), parathyroid hypoplasia (hypocalcemia), and cardiac defects.
Immunologic Defect:
- Impaired maturation of T lymphocytes due to thymic hypoplasia.
- Results in reduced cell-mediated immunity and increased susceptibility to intracellular pathogens (e.g., viruses, fungi).
Classic Features:
- Hypocalcemia (seizures due to parathyroid dysfunction).
- Cardiac anomalies (e.g., conotruncal defects like tetralogy of Fallot).
- Recurrent infections due to T-cell deficiency.
- Absence of a thymic shadow on chest X-ray.
Diagnosis:
- Confirmed via genetic testing for 22q11.2 microdeletion.
Management:
- Calcium supplementation for hypocalcemia.
- Infection prevention and treatment.
- Potential thymus transplant or hematopoietic stem cell transplantation in severe