Immunology for USMLE Step 1

A 9-month-old boy has had recurrent otitis media, pneumonia and sinusitis with encapsulated organisms since around 6 months of age. Serum immunoglobulins of all classes are markedly reduced. Flow cytometry shows absent circulating B cells with normal T cell numbers. Tonsils are absent on examination. What is the underlying defect?

1. Deficiency of terminal complement components C5 to C9 Causes recurrent Neisseria infections specifically, with normal immunoglobulins and normal B cells.
2. A mutation in Bruton tyrosine kinase preventing B cell maturation correct Correct. X-linked agammaglobulinemia: BTK mutation arrests B cell development at the pre-B stage, so there are no mature B cells, no immunoglobulin of any class, and no lymphoid tissue. Symptoms begin around six months as maternal IgG wanes.
3. Defective class switching due to a CD40 ligand mutation That is hyper-IgM syndrome, where IgM is normal or HIGH and the other classes are low. B cells are present here would be the discriminator, and this child has none.
4. Failure of NADPH oxidase in phagocytes Chronic granulomatous disease, with catalase-positive organism infections and granulomata. Immunoglobulins are normal.
5. A defect in the common gamma chain of cytokine receptors That causes severe combined immunodeficiency, which presents earlier and far more severely, with absent T cells, opportunistic infections and failure to thrive.

The point: Onset around 6 months as maternal IgG falls, encapsulated organisms, absent B cells and absent tonsils is X-linked agammaglobulinemia. Contrast with common variable immunodeficiency, which presents in adolescence or adulthood with normal B cell numbers but poor antibody production.

Source: USMLE Content Outline — immunology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator

Four hours after a blood transfusion a patient develops fever, hypotension, flank pain and hemoglobinuria. Direct antiglobulin test is positive and free hemoglobin is detected in the plasma. Which hypersensitivity mechanism is responsible?

1. Type IV — T cell mediated delayed hypersensitivity Contact dermatitis, tuberculin reaction, graft rejection. It takes 48 to 72 hours and involves no antibody.
2. Type II — antibody binding to cell surface antigen with complement activation correct Correct. Acute hemolytic transfusion reaction from ABO incompatibility. Preformed IgM binds donor red cells and fixes complement through to the membrane attack complex, producing INTRAvascular hemolysis with hemoglobinuria.
3. Type III — immune complex deposition Serum sickness and post-streptococcal glomerulonephritis. Complexes deposit in vessel walls days later; they do not lyse transfused cells within hours.
4. Type I — IgE-mediated mast cell degranulation That is the anaphylactic transfusion reaction, classically in IgA-deficient recipients with anti-IgA. It gives urticaria, bronchospasm and shock WITHOUT hemolysis.
5. Non-immune osmotic lysis Would occur if cells were mixed with hypotonic fluid, and would not produce fever, flank pain or a positive direct antiglobulin test.

The point: Transfusion reactions by timing: anaphylactic (minutes, IgA deficiency), acute hemolytic (within an hour, ABO, type II), febrile non-hemolytic (1 to 6 hours, cytokines from donor leukocytes), TRALI (within 6 hours, donor anti-HLA), delayed hemolytic (days, anamnestic).

Source: USMLE Content Outline — immunology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator

A 5-year-old boy has had recurrent Staphylococcus aureus and Aspergillus infections with lymphadenitis and liver abscesses. Dihydrorhodamine flow cytometry shows failure of fluorescence on stimulation. Which defect does this identify?

1. Absent Bruton tyrosine kinase X-linked agammaglobulinemia: absent B cells and immunoglobulins, encapsulated and enteroviral infection, normal oxidative burst.
2. Terminal complement (C5 to C9) deficiency Recurrent Neisseria infection specifically, with a normal phagocyte burst.
3. NADPH oxidase deficiency in phagocytes correct Correct. Chronic granulomatous disease. Without the respiratory burst, phagocytes engulf organisms but cannot kill them, so catalase-POSITIVE organisms that destroy their own hydrogen peroxide survive. Dihydrorhodamine has replaced nitroblue tetrazolium as the test of choice.
4. Defective microtubule polymerisation in phagosome-lysosome fusion Chédiak–Higashi: giant granules, partial albinism, peripheral neuropathy.
5. Defective leukocyte integrin CD18 Leukocyte adhesion deficiency: delayed umbilical cord separation, recurrent infections WITHOUT pus, and a persistently high neutrophil count.

The point: Catalase-positive organisms to remember in CGD: Staphylococcus aureus, Serratia, Burkholderia cepacia, Nocardia, Aspergillus, Candida. Manage with prophylactic trimethoprim-sulfamethoxazole, itraconazole and interferon gamma.

Source: USMLE Content Outline — immunology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator