USMLE Step 1 Quiz
Practice Immunodeficiency Disorders in USMLE Step 1 with focused quiz questions that help you check what you know, review explanations, and build confidence with test-style prompts.
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A 5-year-old child living in a refugee camp is diagnosed with severe protein-energy malnutrition (kwashiorkor). The child has concurrent measles infection with complications of pneumonia and severe diarrhea. Physical examination reveals significant edema, skin lesions, and hair discoloration.
The severe course of this child's viral infection is primarily attributed to the impairment of which component of the immune system by malnutrition?
This quiz focuses on Immunodeficiency Disorders, giving you a quick way to practice the rules, question types, and explanations that matter most for USMLE Step 1.
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A 5-year-old child living in a refugee camp is diagnosed with severe protein-energy malnutrition (kwashiorkor). The child has concurrent measles infection with complications of pneumonia and severe diarrhea. Physical examination reveals significant edema, skin lesions, and hair discoloration.
The severe course of this child's viral infection is primarily attributed to the impairment of which component of the immune system by malnutrition?
Explanation: Severe protein-energy malnutrition has a profound negative impact on the immune system, but it most significantly impairs cell-mediated immunity. This is characterized by atrophy of the thymus, lymph nodes, and spleen, leading to a sharp decrease in the number and function of T-lymphocytes. This T-cell deficiency is the primary reason for the increased susceptibility to and mortality from intracellular pathogens like the measles virus.
A 1-year-old boy presents with opportunistic infections and failure to thrive. Flow cytometry shows normal numbers of CD4+ and CD8+ T-cells in the peripheral blood. However, when his lymphocytes are cultured with phytohemagglutinin (a T-cell mitogen), they fail to proliferate. B-cell and NK-cell numbers and function are normal.
The defective protein in this patient is most directly involved in which of the following cellular processes?
Explanation: This patient has a form of SCID characterized by the presence of T-cells that are non-functional. This specific presentation is classic for a defect in a protein involved in T-cell receptor (TCR) signaling, such as ZAP-70 or CD3. ZAP-70 is a tyrosine kinase that is recruited to the TCR complex upon antigen binding and is essential for initiating the downstream signaling cascade that leads to T-cell activation and proliferation. Its absence leads to T-cells that are present but unable to respond to stimuli.
A 32-year-old man presents with his fourth episode of bacterial pneumonia in two years. He has a history of bronchiectasis and chronic giardiasis. Serum protein electrophoresis shows markedly decreased levels of all immunoglobulin classes. Flow cytometry reveals a normal number of circulating B-lymphocytes.
Which of the following best describes the fundamental immunologic defect in this patient?
Explanation: This patient's presentation in adulthood with recurrent sinopulmonary and GI infections, along with panhypogammaglobulinemia despite a normal B-cell count, is characteristic of Common Variable Immunodeficiency (CVID). The core defect in CVID is a failure of B-lymphocytes to differentiate into immunoglobulin-secreting plasma cells and memory B-cells, leading to low antibody levels and impaired humoral immunity.
A 6-month-old boy is brought to the pediatrician for his third episode of otitis media in the past two months. He also had a recent episode of pneumonia caused by Streptococcus pneumoniae. Physical examination is unremarkable. Laboratory studies show very low levels of IgG, IgA, and IgM. Flow cytometry of peripheral blood reveals a normal T-cell count but an absence of CD19+ lymphocytes.
A defect in the gene encoding which of the following proteins is the most likely cause of this patient's condition?
Explanation: This patient's presentation of recurrent sinopulmonary infections with encapsulated bacteria, along with absent B-cells (CD19+) and panhypogammaglobulinemia, is classic for X-linked (Bruton) agammaglobulinemia. This condition is caused by a mutation in the Bruton tyrosine kinase (BTK) gene, which is essential for the maturation of pre-B cells into immature B-cells in the bone marrow.
A 10-year-old boy has a history of multiple episodes of life-threatening bacteremia caused by Streptococcus pneumoniae and Haemophilus influenzae. He also developed immune complex-mediated glomerulonephritis at age 8. Laboratory testing reveals that his serum is unable to effectively opsonize bacteria.
A deficiency in which of the following would best explain this patient's susceptibility to both pyogenic bacterial infections and immune complex disease?
Explanation: C3 is the central component of the complement system. Its cleavage product, C3b, is the most important opsonin, facilitating phagocytosis of encapsulated bacteria. A C3 deficiency therefore leads to recurrent, severe pyogenic infections. Additionally, C3b plays a key role in clearing immune complexes from the circulation. Its deficiency allows these complexes to deposit in tissues like the kidney, causing diseases such as glomerulonephritis.
A 3-day-old male infant develops jitteriness and facial twitching. His serum calcium level is 6.8 mg/dL (normal 8.5-10.5 mg/dL). Physical examination reveals low-set ears, a small mouth, and a harsh holosystolic murmur best heard at the left sternal border. A chest X-ray shows an absent thymic shadow. He develops a severe respiratory syncytial virus infection at 2 months of age.
This patient's immunodeficiency is a direct consequence of the malformation of which of the following embryonic structures?
Explanation: The patient's constellation of findings (hypocalcemia, cardiac defects, dysmorphic facies, and absent thymus) is characteristic of DiGeorge syndrome, caused by a 22q11.2 deletion. This deletion results in the failed development of the third and fourth pharyngeal pouches, which give rise to the thymus and parathyroid glands, leading to T-cell deficiency and hypoparathyroidism, respectively.
A 4-month-old infant presents with failure to thrive, chronic diarrhea, and extensive oral candidiasis. The complete blood count shows severe lymphopenia. Family history is significant for a maternal uncle who died in infancy from a severe infection. Further analysis shows profoundly decreased T-cell, B-cell, and NK-cell counts.
The accumulation of which of the following metabolites is most likely responsible for the lymphocyte toxicity in this patient?
Explanation: This patient has severe combined immunodeficiency (SCID). The specific pattern of T, B, and NK cell deficiency suggests adenosine deaminase (ADA) deficiency, an autosomal recessive form of SCID. ADA is crucial for the purine salvage pathway. Its deficiency leads to the accumulation of adenosine and deoxyadenosine, which are converted to toxic metabolites like deoxyadenosine triphosphate (dATP) that inhibit DNA synthesis and are particularly toxic to lymphocytes.
A 3-week-old infant presents with fever and redness and swelling around the base of the umbilical cord. The umbilical stump separated just this morning. The CBC shows a white blood cell count of 45,000/mm³ with a neutrophil predominance. A biopsy of the inflamed tissue reveals a dense infiltrate of inflammatory cells but a notable absence of pus.
A mutation affecting the expression of which of the following molecules is the most likely cause of this infant's condition?
Explanation: The presentation of delayed umbilical cord separation, recurrent skin/mucosal infections without pus formation, and marked leukocytosis points to Leukocyte Adhesion Deficiency Type 1 (LAD-1). This disorder is caused by a defect in the gene for the β2 integrin subunit, CD18. This defect prevents neutrophils from adhering to the vascular endothelium and migrating into tissues to fight infection.
A 2-year-old boy is evaluated for recurrent ear infections and severe eczema. His mother notes that he bleeds for a long time after minor scrapes. Laboratory studies reveal a platelet count of 40,000/mm³ with abnormally small platelets. Immunoglobulin levels show low IgM and normal IgG.
The protein mutated in this patient's condition is primarily involved in which of the following cellular functions?
Explanation: The clinical triad of thrombocytopenia (with small platelets), eczema, and recurrent infections is characteristic of Wiskott-Aldrich syndrome (WAS). This X-linked disorder is caused by a mutation in the WAS gene, which encodes the Wiskott-Aldrich syndrome protein (WASp). WASp is crucial for the rearrangement of the actin cytoskeleton in hematopoietic cells, linking cell surface receptor signaling to cellular responses like T-cell activation and platelet formation.
A 1-year-old boy presents with a history of recurrent sinopulmonary infections and an episode of Pneumocystis jirovecii pneumonia. Serum analysis shows markedly elevated IgM levels, but IgG, IgA, and IgE levels are undetectable. B-cell and T-cell counts are normal.
The most common genetic defect responsible for this condition disrupts the interaction between T-helper cells and which of the following cells?
Explanation: This presentation is classic for X-linked hyper-IgM syndrome. The underlying defect is a mutation in the gene for CD40 ligand (CD40L) on activated T-helper cells. The interaction between CD40L on T-cells and CD40 on B-cells is essential for B-cell isotype switching and formation of germinal centers. Without this interaction, B-cells can only produce IgM, leading to high levels of IgM and a deficiency of IgG, IgA, and IgE.
A 25-year-old woman with a history of recurrent sinus infections, pneumonia, and chronic diarrhea requires a blood transfusion for anemia. Shortly after the transfusion begins, she develops shortness of breath, hives, and hypotension. The transfusion is stopped immediately.
This patient most likely has an underlying deficiency of which of the following immunoglobulins?
Explanation: This patient's history of recurrent mucosal infections (sinopulmonary, GI) suggests selective IgA deficiency, the most common primary immunodeficiency. The anaphylactic reaction to a blood transfusion is a key clinical clue. Some individuals with IgA deficiency produce anti-IgA antibodies (of the IgE class). When transfused with blood products containing IgA, they can experience a severe, life-threatening allergic reaction.
A 7-year-old girl is brought to a neurologist for progressive difficulty with balance and coordination. Physical examination reveals cerebellar ataxia, abnormal jerky eye movements, and multiple telangiectasias on her conjunctivae. She has had several episodes of pneumonia and sinusitis. Laboratory tests show low levels of IgA and IgG.
The mutated gene product in this disorder is primarily involved in which of the following cellular processes?
Explanation: The combination of cerebellar ataxia, oculocutaneous telangiectasias, and immunodeficiency is diagnostic of Ataxia-Telangiectasia. This autosomal recessive disorder is caused by a mutation in the ATM gene. The ATM protein is a serine/threonine kinase that functions as a crucial sensor of DNA double-strand breaks, orchestrating cell cycle arrest and DNA repair. Defective DNA repair contributes to both the neurologic degeneration and the immunodeficiency.
A 4-year-old boy presents with recurrent skin and soft tissue infections. His parents note that he has unusually light skin, silvery hair, and is very sensitive to sunlight. On physical examination, he has nystagmus. A peripheral blood smear reveals giant, azurophilic granules within his neutrophils.
The underlying genetic defect in this syndrome directly impairs which of the following cellular pathways?
Explanation: The combination of partial oculocutaneous albinism, recurrent pyogenic infections, and giant granules in leukocytes is characteristic of Chédiak-Higashi syndrome. This autosomal recessive disorder is caused by a mutation in the lysosomal trafficking regulator (LYST) gene. The defective LYST protein disrupts intracellular vesicle formation and transport, leading to impaired fusion of phagosomes with lysosomes in neutrophils, which compromises their ability to kill ingested microbes.
A 3-month-old boy presents with oral thrush, persistent diarrhea, and failure to thrive since birth. His lymphocyte count is markedly decreased. Flow cytometry analysis of his peripheral blood shows absent T-cells and NK cells, but a normal number of B-cells.
The mutated protein in the most common form of this disorder is a shared component of the receptors for which of the following cytokines?
Explanation: This patient has severe combined immunodeficiency (SCID) with a T- B+ NK- phenotype, which is characteristic of X-linked SCID. This is the most common form of SCID and is caused by a mutation in the gene encoding the common gamma chain (γc). This protein is a critical subunit of the receptors for several interleukins, including IL-2 (essential for T-cell proliferation) and IL-7 (essential for T-cell and NK-cell development).
An 8-year-old girl is evaluated for a chronic, intensely pruritic rash consistent with eczema. She has a history of recurrent staphylococcal skin abscesses that are noted to be non-erythematous and minimally tender. She also has two rows of teeth due to retained primary teeth. Laboratory studies show marked eosinophilia and a serum IgE level >20,000 IU/mL.
A mutation in a gene encoding which of the following signaling proteins is the most likely cause of this patient's condition?
Explanation: This clinical presentation is characteristic of autosomal dominant Hyper-IgE Syndrome (Job syndrome). The syndrome is caused by a dominant-negative mutation in the STAT3 gene. STAT3 is a critical transcription factor in the signaling pathways of multiple cytokines, including IL-6 and IL-23. Defective STAT3 signaling impairs the development of Th17 cells, which are crucial for neutrophil recruitment and mucosal defense, leading to recurrent 'cold' abscesses and chronic mucocutaneous candidiasis.
A 28-year-old woman presents with recurrent episodes of swelling of her face and hands. She also reports episodes of severe abdominal pain. The swelling is non-pitting and is not associated with itching or hives. Her father has a similar condition. She is currently asymptomatic.
A deficiency of which of the following proteins is the most likely cause of this patient's symptoms?
Explanation: Recurrent angioedema without urticaria (hives) is the hallmark of hereditary angioedema (HAE). This condition is most commonly caused by a deficiency or dysfunction of C1 inhibitor. C1 inhibitor normally regulates the complement, contact (kallikrein-kinin), and fibrinolytic pathways. Its deficiency leads to unchecked activation of kallikrein, resulting in excessive production of bradykinin, a potent vasodilator that causes the characteristic angioedema.
A 65-year-old man with severe rheumatoid arthritis has been treated with high-dose prednisone for the past 6 months. He develops a fever, productive cough, and shortness of breath. A chest X-ray reveals a new infiltrate, and sputum culture grows Nocardia asteroides. He is diagnosed with pulmonary nocardiosis.
The medication this patient is taking predisposes him to this type of opportunistic infection primarily by impairing the function of which of the following?
Explanation: High-dose corticosteroids like prednisone are potent immunosuppressants that primarily affect cell-mediated immunity. They inhibit T-cell activation and proliferation by decreasing the transcription of numerous cytokine genes (e.g., IL-2) and inducing T-cell apoptosis. This suppression of T-cell function makes patients vulnerable to opportunistic pathogens like Nocardia, which require a robust cell-mediated immune response for clearance.
A 9-month-old girl presents with failure to thrive and recurrent infections, including oral thrush and Pneumocystis jirovecii pneumonia. Laboratory analysis shows a severe deficiency of CD4+ T-cells. However, her CD8+ T-cell and B-cell counts are normal. Further studies show that her antigen-presenting cells fail to express HLA-DR molecules on their surface.
The primary defect in this condition impairs the expression of which of the following molecules?
Explanation: This condition is Bare Lymphocyte Syndrome Type II, an autosomal recessive form of combined immunodeficiency. It is caused by mutations in genes encoding transcription factors required for the expression of MHC class II molecules (like HLA-DR). The absence of MHC class II on antigen-presenting cells in the thymus prevents the positive selection of CD4+ T-helper cells, leading to a profound deficiency of these cells and severe immunodeficiency.
A 6-month-old infant presents with severe oral candidiasis and failure to thrive. Laboratory evaluation reveals a complete absence of circulating T-cells and B-cells. However, the number of natural killer (NK) cells is normal.
The function of the defective protein in this patient is essential for which of the following fundamental immunologic processes?
Explanation: The phenotype of absent T-cells and B-cells with normal NK cells (T- B- NK+) is characteristic of SCID caused by a defect in V(D)J recombination. This process is mediated by the RAG1 and RAG2 enzymes and is essential for creating the diverse repertoire of T-cell receptors (TCR) and B-cell receptors (BCR). Without functional RAG proteins, lymphocytes cannot assemble their antigen receptors and thus cannot complete their development.
A 72-year-old man is diagnosed with multiple myeloma after presenting with bone pain and fatigue. Over the next year, he is hospitalized twice for bacterial pneumonia. Laboratory studies show a monoclonal spike of IgG kappa protein and suppressed levels of normal polyclonal immunoglobulins.
What is the primary mechanism underlying this patient's increased susceptibility to bacterial infections?
Explanation: In multiple myeloma, malignant plasma cells proliferate and produce a large quantity of a single, non-functional monoclonal antibody (M-protein). This process suppresses the function and proliferation of normal B-cell clones, leading to a profound decrease in the production of all other functional polyclonal immunoglobulins (hypogammaglobulinemia). This lack of antibody diversity is the primary reason for the increased risk of infections, particularly from encapsulated bacteria.