MCAT Microbiology and Immunology

Dr. Marta Reyes evaluates a 4-year-old boy with recurrent severe respiratory syncytial virus and adenovirus infections. Genetic testing reveals a homozygous loss-of-function mutation in TAP1, the transporter that delivers cytosolic peptides into the endoplasmic reticulum. Flow cytometry shows normal serum IgG, IgA, and IgM titers, normal CD4+ T-cell counts, normal B-cell counts, and a markedly reduced CD8+ T-cell compartment with poor thymic maturation. Bronchial biopsy during an active viral infection demonstrates widespread viral replication in respiratory epithelium with minimal lymphocyte infiltration. The patient has not had unusual problems with encapsulated bacterial infections such as Streptococcus pneumoniae, and routine childhood vaccines have produced protective antibody titers. Reyes notes that the patient's clinical pattern is asymmetric: severe susceptibility to viruses, near-normal handling of extracellular bacteria.

Which finding most directly explains the patient's recurrent severe viral infections despite intact antibody responses?

• A Antibody production is preserved, but virus-infected epithelial cells fail to load endogenous peptides onto MHC class I, so CD8+ cytotoxic T cells cannot recognize them. ✓ Correct
• B Helper T cells cannot activate macrophages without TAP1, so intracellular viruses persist while extracellular bacteria are still cleared by complement.
• C B cells require TAP1 for class switching, so the patient produces only low-affinity IgM and cannot neutralize viruses.
• D MHC class II loading is impaired, preventing presentation of viral antigens to CD8+ cytotoxic T cells.

Dr. Fei Liu's group develops a candidate vaccine against a soil-borne bacterium whose pathology is driven entirely by a secreted exotoxin. The vaccine consists of formaldehyde-inactivated toxoid combined with an aluminum hydroxide adjuvant. In a Phase I trial, vaccinated volunteers show high serum titers of toxoid-specific IgG starting at week 4, with clear class switching from initial IgM. Memory B cells specific for the toxoid persist at 6 months. When peripheral lymphocytes from vaccinees are challenged in vitro, proliferation occurs only when the toxoid is presented alongside autologous antigen-presenting cells; proliferation is abolished by anti-CD4 blocking antibodies but is unaffected by anti-CD8 blocking antibodies. Liu's team concludes that the vaccine elicits a robust adaptive response specifically targeting the secreted toxin rather than the bacterium itself.

Which immune mechanism is the primary basis of the vaccine's protective effect?

• A Cytotoxic CD8+ T cells lyse bacterial cells expressing the toxin gene before the toxin can be released.
• B Neutralizing IgG antibodies bind the secreted toxin in the bloodstream and block its interaction with host receptors. ✓ Correct
• C Memory CD8+ T cells produce IFN-$\gamma$ to activate macrophages that phagocytose the bacterium at the infection site.
• D Complement-mediated lysis of the bacterium via the alternative pathway clears the organism before toxin is released.

A 9-month-old boy presents with recurrent severe pyogenic infections caused by encapsulated bacteria. Laboratory workup shows undetectable serum IgG, IgA, and IgM, nearly absent peripheral B cells, and normal numbers and function of CD4+ and CD8+ T cells. Genetic testing confirms a loss-of-function mutation in BTK (Bruton tyrosine kinase), establishing the diagnosis of X-linked agammaglobulinemia.

Compared with his other infectious risks, which exposure would this patient be expected to handle most effectively?

• A Streptococcus pneumoniae bacteremia
• B Reactivation of latent varicella-zoster virus in a sensory ganglion ✓ Correct
• C Inhalation exposure to diphtheria exotoxin
• D Giardia lamblia colonization of the small intestinal lumen