A neonate is born at 38 weeks gestation age via spontaneous vaginal delivery to a 40-year-old woman.  The mother was working in South America when she discovered that she was pregnant.  She had 2 days of fever associated with cough and swollen cervical glands, which resolved spontaneously at 12 weeks gestation prior to returning to the United States.  The mother has no current symptoms.  Neonatal examination shows weight and length at the 8th percentile, and head circumference below the 3rd percentile for age.  Heart and lung sounds are normal.  There is moderate hepatosplenomegaly.  Skin examination shows diffuse, dark-blue papules and nodules.  Serology from the mother and infant are attained.  Which of the following serology patterns is most consistent with a suspected congenital infection?

Pharmacology researchers develop a novel immunotherapy to treat malignancies.  In this therapy, T lymphocytes are harvested from patients with a malignancy and genetically modified to express a chimeric antigen receptor composed of an extracellular antigen recognition domain linked with an intracellular T-cell signaling domain.  These modified T cells are expanded ex vivo and then infused back into the patient, where they destroy the cancer cells.  In one of the experiments, they modify the chimeric antigen receptor to recognize CD19.  Use of this treatment is most likely to have which of the following potential complications?

A 34-year-old woman with end-stage kidney disease secondary to IgA nephropathy is undergoing kidney transplant from an unrelated living donor.  The patient receives induction immunosuppression with a rabbit antithymocyte globulin–based regimen immediately prior to the procedure.  The surgery is performed without complications, and maintenance immunosuppressive therapy is begun.  Ten days later, the patient experiences high fevers, generalized pruritic rash, and pain, redness, and swelling of the bilateral metacarpophalangeal joints, wrists, and knees.  The erythrocyte sedimentation rate is elevated.  Arthrocentesis of the involved joint yields synovial fluid with neutrophilic leukocytosis; there are no crystals and no bacteria on Gram stain.  Which of the following is most likely responsible for the increased synovial membrane permeability in this patient?

A 10-month-old boy is hospitalized for respiratory distress due to Pneumocystis jiroveci pneumonia.  The patient has had repeated episodes of otitis media and thrush; weight is below the 5th percentile.  Laboratory evaluation reveals normal levels of circulating B and T cells with low levels of all immunoglobulins.  Genetic testing reveals a rare autosomal recessive mutation resulting in a defect in the regulation of human leukocyte antigen gene transcription.  Flow cytometry of the patient’s peripheral blood compared with a healthy control is shown in the illustration below:

Which of the following processes is most likely to be impaired by this patient’s mutation?

A 36-year-old woman with fistulizing perianal Crohn disease comes to the office for a follow-up appointment.  Eight weeks ago, the patient began receiving intermittent injections of infliximab, a chimeric human-mouse monoclonal antibody targeted against tumor necrosis factor-alpha.  She reports improvement in fistula discharge and discomfort but has experienced fever, diffuse joint pain, and an itchy rash 5-7 days after each of the recent treatments.  The symptoms spontaneously resolve after 2-3 days.  The patient has no other medical conditions and has no history of drug allergies.  A delayed drug reaction due to formation of antibodies against foreign drug components is suspected.  Which of the following mechanisms is most likely responsible for resolution of these drug reactions?

An autopsy is performed on an 8-month-old infant after his unexpected death.  Prior to death, the patient had a 1-month history of poor feeding and intermittent fever, which progressed to severe lethargy and coma.  The infant was adopted soon after birth, and there is limited information about his family history beyond documentation of an uncomplicated pregnancy and delivery at term gestation.  Brain biopsy reveals leptomeningeal inflammation and is positive for Enterovirus by PCR.  This patient would have been most likely to have which of the following laboratory findings?

An 8-year-old boy is brought to the hospital due to severe headache and altered mental status.  An aggressive, high-risk neuroblastoma is diagnosed.  As part of his treatment, the patient will receive an autologous bone marrow transplant using stem cells obtained from his peripheral blood.  His pretransplant evaluation reveals a history of Epstein-Barr virus infection.  This patient is at greatest risk for which of the following after transplantation?

 10-year-old girl is brought to the office due to sneezing, rhinorrhea, and nasal congestion and itching.  The symptoms began 2 days ago after she arrived at a family farm for a summer vacation.  The patient has spent a few days visiting the farm during previous summer seasons.  She had no symptoms at her first visit 2 years ago but recalls having similar symptoms last year.  She has had no respiratory symptoms while residing in another state the rest of the year.  The patient has no prior medical conditions and takes no medications.  On physical examination, the nasal turbinates are enlarged and bluish; clear rhinorrhea is present.  Allergic response to a farm allergen is suspected.  Which of the following processes most likely occurred during the first farm visit 2 years ago?

Pharmacology researchers develop a novel monoclonal antibody medication to treat the wet form of age-related macular degeneration.  The antibody binds vascular endothelial growth factor, decreasing abnormal blood vessel formation in the subretinal space.  In a clinical trial, the medication is found to improve visual function.  During the next phase of the study, researchers use only the antigen binding fragment (Fab) of the antibody instead of the whole immunoglobulin.  Which of the following is most likely to be observed with use of the antibody fragments compared to the intact immunoglobulin?

A 40-year-old woman, gravida 4 para 4, comes to the clinic due to anemia.  A week ago, the patient was seen in the emergency department due to fatigue, shortness of breath, and increasingly heavy, irregular menses.  Laboratory evaluation showed a hemoglobin level of 5.4 g/dL.  After a transfusion with packed red blood cells, her follow-up hemoglobin level was 7.8 g/dL prior to discharge.  Since then, the patient’s energy and breathing have improved, and she has had no further menstrual bleeding.  However, yellowing of the eyes and face has developed over the last day.  Vital signs are normal.  Examination reveals scleral icterus.  There is no hepatosplenomegaly.  Laboratory results are as follows:

This patient’s current symptoms are most likely due to which of the following antibody-antigen reactions?

A 2-year-old boy is brought to the emergency department due to wheezing and difficulty breathing.  The patient had been trick-or-treating with his parents and ate several packs of candy containing peanuts.  After he receives an intramuscular epinephrine injection, his symptoms resolve.  At a follow up appointment, an allergy specialist places droplets of various allergens on the patient’s skin and punctures the epidermis at each site.  After 15 minutes, the skin at the site with peanut extract is erythematous with a raised, itchy bump that improves by the time the family leaves the office.  Three hours later, the parents notice increased swelling at the puncture site.  Which of the following is most likely involved in this secondary reaction?

A 32-year-old woman comes to the allergy clinic due to a recurrent skin rash.  The patient has had several episodes of itchy, erythematous, vesicular eruptions on her hands over the past several months.  She works at a hair salon and is often exposed to hair dye and other beauty products.  The patient has no other medical conditions and takes no medications.  She undergoes patch testing, during which several allergens found in common cosmetic products are mounted on nonocclusive tape strips applied to her upper back.  Skin findings developed after 2 days of application and are shown in the exhibit.  Which of the following processes most likely occurred in this patient to enable the development of the observed skin reaction?

A 1-year-old boy is brought to the office for medical evaluation.  The patient was recently diagnosed with type 1 diabetes mellitus.  He has also had chronic diarrhea, failure to thrive, and eczematous dermatitis since early infancy.  Small bowel biopsy reveals villous atrophy and extensive lymphocytic infiltration.  Immunologic testing shows significantly increased serum immunoglobulins and decreased IL-10 and transforming growth factor-beta levels.  Genetic testing reveals a missense mutation affecting FOXP3.  Which of the following is the most likely cause of this patient’s current condition?

A 36-year-old woman comes to the clinic due to a rash for the past 3 days.  The rash started on the patient’s torso and spread to the extremities.  She has not had a similar rash previously.  The patient feels mildly feverish but has no other symptoms.  Medical history is notable for multiple sclerosis and associated trigeminal neuralgia.  Medications include a recombinant anti-B-cell antibody that was started a year ago and carbamazepine, which the patient has been on for the past 2 weeks.  Temperature is 38 C (100.4 F), blood pressure is 118/86 mm Hg, and heart rate is 86/min.  Examination shows a rash on the chest, abdomen, back, and proximal extremities, as shown in the exhibit.  Conjunctivae are clear bilaterally, and oropharyngeal examination is unremarkable.  The remainder of the examination is normal.  This patient’s rash is most likely caused by which of the following?

A 38-year-old woman comes to the office due to abdominal pain.  For the last 2-3 weeks, she has had increasingly severe abdominal pain associated with watery diarrhea.  The patient has a history of Crohn disease treated for the last year with adalimumab, which has controlled the symptoms until now.  Vital signs are normal except for a temperature of 37.8 C (100 F).  Examination shows moderate tenderness in the right lower quadrant with no peritoneal signs.  Laboratory results show an undetectable trough adalimumab level.  Which of the following is the most likely explanation for this patient’s worsening symptoms?

A 10-month-old boy is brought to the office due to recurrent sinopulmonary infections for the last several months.  The infections were caused by encapsulated bacteria, and the patient was also recently hospitalized due to Pneumocystis jiroveci pneumonia.  He was born at full term after an uneventful pregnancy.  Family history is significant for a maternal uncle’s early childhood death due to severe infection.  Genetic testing of the patient reveals missense mutation of the CD40 ligand gene.  Interaction between which of the following immune components is most likely impaired in this patient?

A 10-year-old boy is brought to the emergency department by his parents due to increasing lethargy and high fever for the past 12 hours.  The boy was well last night but was sluggish this morning.  Over the day, his activity level and responsiveness diminished.  The patient was treated for Neisseria meningitidis bacteremia 2 years ago.  He has received all routine vaccinations and is developing normally.  Temperature is 39.6 C (103.3 F).  On examination, the patient appears ill and is poorly responsive.  He is tachycardic, but heart sounds are otherwise unremarkable.  Lungs are clear to auscultation.  Numerous purple bruise-like markings and petechiae are noted over his extremities, which have diminished capillary refill.  Blood samples are drawn for total complement (CH50) and alternative complement (AH50) measurement.  Which of the following sets of results is most likely to be found in this patient?

A 43-year-old man visiting the United States from Thailand comes to the emergency department due to 10 days of hemoptysis.  He also has had night sweats but reports no fever or weight loss.  Temperature is 37.7 C (99.9 F), blood pressure is 118/68 mm Hg, pulse is 86/min, and respirations are 18/min.  Physical examination shows right-sided rhonchi and crackles.  Chest x-ray shows an infiltrate in the right upper lobe.  Sputum samples from 3 consecutive days are also obtained.  After 72 hours of tuberculin skin test (TST) placement, there is no induration at the site; however, 2 of 3 sputum sample smears reveal acid-fast bacilli.  Which of the following best explains the negative TST in this patient?

A 7-year-old boy is admitted to the hospital after his adoptive parents brought him to the emergency department due to fatigue and pallor.  Laboratory evaluation reveals pancytopenia with an absolute neutrophil count consistent with severe neutropenia.  Bone marrow examination reveals signs of aplastic anemia, and subsequent genetic testing reveals a congenital genomic defect in DNA repair leading to chromosomal instability.  A bone marrow transplant is required for treatment.  The patient’s only living relatives are an identical twin brother and older sister who were both adopted by the same parents.  He also has stored umbilical stem cells that were harvested after birth.  Which of the following is the best bone marrow transplantation method for this patient?