A 15-year-old boy develops severe cardiomyopathy following myocarditis from Coxsackie virus and is placed on the cardiac transplant list.  Two weeks following his cardiac transplantation from a matched donor, he develops dyspnea on exertion.  Extensive evaluation is undertaken including cardiac catheterization and endomyocardial biopsy to assess for acute allograft rejection.  Which of the following histologic findings is most consistent with this diagnosis?

A 26-year-old man is brought to the emergency department due to fever and lethargy.  His girlfriend says the patient abruptly began experiencing fever, chills, vomiting, and diarrhea several hours ago, which were quickly followed by lightheadedness and lethargy.  He has no prior medical conditions other than an episode of epistaxis after a bar fight 3 days ago.  The patient does not smoke cigarettes or use injection drugs.  There is no history of exposure to sick contacts, and he has not eaten anything out of the ordinary.  Temperature is 38.9 C (102 F), blood pressure is 90/60 mm Hg, and pulse is 120/min.  Physical examination shows a diffuse, erythematous rash.  There is an anterior nasal packing in the left nostril, removal of which shows mild mucosal erythema with a purulent discharge.  Cardiopulmonary and abdominal examinations reveal no abnormalities, and signs of meningeal irritation are absent.  Which of the following processes is most essential in pathogenesis of this patient’s current condition?

A 44-year-old man with a chronic cough and progressive weight loss comes to the emergency department.  He has lost 5 kg (11 lb) over the past 3 months.  The patient recently emigrated from Southeast Asia.  Temperature is 37.4 C (99.3 F), blood pressure is 113/70 mm Hg, pulse is 78/min, and respirations are 18/min.  Chest x-ray reveals an apical left lung infiltrate.  Sputum Gram stain and cultures are negative.  However, culture of a lung biopsy specimen grows acid-fast bacilli.  Microscopy of the lung specimen is shown below.

Which of the following processes is most likely to contribute to formation of the finding indicated by the arrow?

A 25-year-old man comes to the office due to a 1-month history of increasing abdominal girth and swollen extremities.  His BMI is 32 kg/m².  Laboratory evaluation shows decreased serum albumin and hypercholesterolemia, and urinalysis reveals heavy proteinuria and fatty casts.  A renal biopsy shows findings consistent with focal segmental glomerulosclerosis.  Despite aggressive medical management, the patient requires a kidney transplant from his younger sister, who is a 5 out of 6 HLA antigen match.  As a part of his posttransplant immunosuppressive regimen, he takes a medication that inhibits lymphocyte proliferation by directly blocking interleukin-2 signal transduction.  This mechanism best describes which of the following drugs?

A 23-year-old woman is brought to the emergency department due to one day of fever, vomiting, diarrhea, and muscle pains.  The symptoms developed rapidly over the course of the day.  The patient is confused and unable to answer questions.  She has no known medical problems and takes no medications.  She lives with her boyfriend.  The patient’s temperature is 39.1 C (102.4 F), blood pressure is 88/50 mm Hg, pulse is 120/min, and respirations are 20/min.  A diffuse, erythematous, macular rash resembling a sunburn is noted on dermatologic examination; pelvic examination reveals a tampon in the vagina.  Laboratory results are as follows:

A pregnancy test is negative.  Activation of which of the following cells is most likely primarily responsible for this patient’s condition?

A 56-year-old woman with a history of heart failure is admitted to the hospital for orthotopic cardiac transplantation.  The patient developed biventricular failure due to idiopathic myocarditis.  She has had persistent New York Heart Association class IV symptoms refractory to maximal medical therapy and was placed on the transplant waiting list.  An ABO-compatible cadaveric heart is available for transplant with partial human leukocyte antigen (HLA) mismatch.  Cardiac transplantation is performed and the patient’s T lymphocytes quickly recognize the foreign HLA molecules of the transplant cells.  Inhibition of which of the following substances would specifically reduce the proliferation and differentiation of these T lymphocytes?

A 2-year-old boy is brought to the office due to recurrent infections.  He was born at term after an uncomplicated pregnancy.  His mother states, “My boy is always sick with something and is constantly on antibiotics.”  The patient has had multiple episodes of otitis media, skin infections, and pneumonia.  Incision and drainage of his skin infections revealed Staphylococcus aureus on bacterial culture but no purulence.  The infections usually resolve with prolonged antibiotic courses.  Laboratory testing reveals absent CD18 antigens on the surface of leukocytes.  This patient’s underlying condition is most likely associated with which of the following?

A 23-year-old man is referred to the gastroenterology clinic due to a 3-year history of recurring abdominal pain accompanied by cramps and diarrhea.  The patient has noticed an increased frequency of episodes lately with worsening pain.  He also says that his urine occasionally appears dark brown and his urine stream sometimes sputters.  Imaging studies reveal a colovesical fistula.  Biopsy obtained during colonoscopy shows chronic ileocolitis with discontinuous transmural inflammation and noncaseating granulomas.  When given the diagnosis of Crohn disease, the patient becomes skeptical and says, “There’s no way I’m getting a colostomy bag.”  He then refuses treatment and pursues a second opinion once his symptoms subside.  A second biopsy demonstrates reduced inflammation in regions of previously active ileocolitis.  An increase in which of the following cytokines is most likely responsible for this patient’s clinical regression?

A 14-year-old boy is brought to the emergency department by his mother after he develops a sudden rash.  He was trying to retrieve a baseball that had rolled under a log when he got stung by something.  By the time he told his mom, his body was covered in welts.  Within minutes, the patient’s face started to swell and he was having a hard time swallowing.  The patient’s blood pressure is 70/50 mm Hg and heart rate is 120/min.  Physical examination shows erythematous, raised plaques over the trunk, extremities, and face.  Lung auscultation reveals bilateral expiratory wheezes.  The mother is not aware of the child having any similar reaction in the past.  Which of the following most likely triggered this patient’s condition?

A 57-year-old man underwent lung transplantation for severe emphysema 2 years ago.  Over the last 6 months, he has had increasing exertional dyspnea and dry cough.  The patient has adhered to his medical regimen.  He does not smoke and has no exposure to secondhand smoke.  Physical examination shows scattered bilateral rales and end-expiratory squeaks.  Cardiac auscultation reveals no murmurs or additional sounds.  Spirometry demonstrates markedly decreased FEV1 compared with findings 6 months prior, although the FVC remains largely unchanged.  Chronic lung transplant rejection is suspected, and bronchoscopy with transbronchial biopsy is planned.  Histopathology is most likely to show injury predominantly involving which of the following structures?

A 34-year-old man is brought to the hospital by ambulance after being involved in a motor vehicle collision.  He was an unrestrained passenger and sustained considerable trauma.  On arrival to the emergency department, he is hypotensive and bleeding from several sites.  The patient receives an emergency blood transfusion as part of the resuscitation efforts.  Abdominal ultrasound reveals splenic laceration and blood in the peritoneal cavity.  On the way to the operating room, the patient develops difficulty breathing, chills, and pain in the chest and back.  Urine drainage from the Foley catheter was initially clear but now appears brown in color.  Which of the following is the most likely cause of this patient’s new findings?

A 7-year-old boy is brought to the emergency department by his parents for arthralgias.  He had a cough and runny nose last week but otherwise has been in good health.  Temperature is 37 C (98.6 F), blood pressure is 95/65 mm Hg, pulse is 92/min, and respirations are 20/min.  Physical examination shows raised, red-purple papules, some of which have coalesced, over the patient’s buttocks and thighs.  Auscultation of the lungs and heart is normal.  The abdomen is soft with normal bowel sounds.  The knees are tender but do not appear warm or swollen.  Urinalysis results are as follows:

Which of the following mechanisms is the most likely underlying cause of this patient’s renal findings?

A 45-year-old man comes to clinic for routine follow-up.  He has a history of end-stage renal disease due to autosomal dominant polycystic kidney disease, and he underwent a deceased-donor kidney transplant 4 years ago.  The patient has hypertension that initially resolved following the transplant but redeveloped 6 months ago.  Review of his recent laboratory studies reveals a progressive increase in serum creatinine levels over the last few months.  Urinalysis is within normal limits.  On ultrasonography, the transplanted kidney is reduced in size.  A biopsy of the graft is most likely to show which of the following?

A 32-year-old man is started on infliximab for treatment of refractory Crohn disease.  Ten days later, he develops joint pain and a pruritic skin rash.  Skin biopsy shows scattered areas of fibrinoid necrosis and neutrophil infiltration involving his small blood vessels.  Which of the following findings is most likely to accompany this patient’s condition?

A 12-month-old boy is evaluated for an eczematous rash.  Medical history is significant for several severe respiratory infections that required hospitalization.  Complete blood count shows white blood cells at 9,000/mm³ and platelets at 40,000/mm³.  The platelets seem abnormally small and deformed on the peripheral blood smear.  Which of the following is the most likely diagnosis?

A 68-year-old man comes to the emergency department with a 2-day history of fever, chills, and productive cough.  His temperature is 38.9 C (102 F), blood pressure is 108/52 mm Hg, pulse is 102/min, and respirations are 26/min.  Crackles and bronchial breath sounds are heard over the right lower lung.  There is dullness to percussion over the same area.  Chest x-ray reveals right lower lobe consolidation and a right-sided pleural effusion.  The patient is started on the appropriate treatment, and a diagnostic thoracentesis is performed that shows an uncomplicated parapneumonic effusion.  When a sterile sample of the inflammatory exudate is experimentally introduced into normal human tissue, rapid neutrophil locomotion is observed.  Which of the following components of the exudate is most likely responsible for this observed effect?

A 3-year-old girl is brought to the office after developing fever and a sore throat.  The patient recently entered day care, and similar symptoms have been reported in several of the other children.  Physical examination shows exudative pharyngitis and enlarged anterior cervical lymph nodes.  A rapid antigen detection test confirms the diagnosis of streptococcal throat infection.  Her condition resolves with antibiotic therapy.  Several weeks later, she is re-exposed to Streptococcus pyogenes.  The bacteria penetrating beyond the surface epithelium are immediately coated with preformed IgG antibodies.  Which of the following substances acts in the most similar manner to IgG antibodies to facilitate phagocytosis?

An 18-year-old college student is hospitalized due to a high fever and confusion.  According to the patient’s roommate, the symptoms started about 6 hours ago.  The patient was feeling well this morning except for some nausea.  She has had several episodes of pneumonia in the past and had bacterial meningitis a year ago, which was treated with ceftriaxone.  Temperature is 39.1 C (102.4 F), blood pressure is 104/70 mm Hg, and pulse is 110/min.  The patient is lethargic but is able to follow simple commands and give single-word answers with prompting.  Physical examination reveals a petechial rash on the trunk and extremities, including the palms and soles.  Neck stiffness and photophobia are also noted.  Which of the following primary immune system impairments is most likely responsible for this patient’s recurrent infections?

A 34-year-old woman comes to the office for tuberculosis evaluation.  The patient was advised to have tuberculosis testing after her father, who came to visit from Haiti a week ago and had been living with her, was found to have active pulmonary tuberculosis.  She has no history of tuberculosis or any other chronic medical conditions and takes no medications.  Tuberculin skin testing is performed and results 48 hours later are negative.  Eight weeks later, the patient returns for follow-up and says she feels healthy and has had no fever, cough, shortness of breath, or weight loss.  Physical examination shows no abnormalities.  Repeat tuberculin skin testing reveals significant skin induration around the injection site at 48 hours.  Chest radiograph reveals no parenchymal opacities, pleural effusion, or enlarged lymph nodes.  Which of the following immune effector cells are most important for control of the pathogen responsible for this patient’s skin findings?

A 24-year-old recent immigrant from Africa describes a long history of weight loss, night sweats and nagging cough.  Imaging and biopsy of the lungs reveal numerous apical granulomas with central caseous necrosis.  Surrounding the necrotic areas are large cells with abundant pale cytoplasm.  Which of the following surface markers is most specific for those cells?

A 23-year-old woman comes to the physician with migratory joint pains involving her hands and knees.  Physical examination shows bilateral tenderness in her wrists and proximal interphalangeal joints.  There is also a malar skin rash and generalized lymphadenopathy.  A urinalysis reveals proteinuria.  Further evaluation shows that the patient’s lymphocytes contain a mutated and functionally defective Fas gene product.  Which of the following immunologic mechanisms is most likely impaired in this patient as a result of this molecular defect?

An 8-year-old male is brought to his pediatrician’s office by his mother.  The child has had a runny nose, sore throat, cough, and low-grade fever for the past 24 hours.  The patient’s mother recalls that several of the child’s friends have been ill recently with similar symptoms.  The mother asks whether the child will need antibiotics for his condition.  His pediatrician recommends symptomatic therapy and feels that his illness is most likely of viral etiology.  Cytotoxic CD8+ lymphocytes are able to kill virus-infected nasal epithelial cells once sensitized.  Cytotoxic CD8+ lymphocyte receptors recognize foreign proteins on the epithelial cell surface.  Foreign proteins are presented on the epithelial cell surface by MHC molecules.  These MHC molecules comprise which of the following components?

The acidification of lysosomes within antigen presenting cells is prevented in an experimental setting.  Affected cells show impaired interaction with T lymphocytes upon antigen exposure.  This impaired interaction is most likely the result of decreased cell surface expression of which of the following molecules?

A 13-month-old boy is brought to the clinic after repeated infections for the past 4 months, including otitis media, pneumonia, and erysipelas.  Although his infections have been responsive to treatment, his father is concerned about the number of infections.  The patient also has persistent diarrhea, and a recent stool antigen detection assay was positive for Giardia lamblia.  An immunoglobulin panel demonstrates very low serum levels of all immunoglobulin types.  Intradermal injection of Candida antigens results in a large indurated nodule within 48 hours.  This patient’s lymph nodes most likely lack which of the following structures?

A 5-year-old boy is undergoing a partial hepatectomy to treat a poorly draining liver abscess.  He has a history of recurrent skin abscesses.  Cultures from his liver abscess are growing Staphylococcus aureus, which is sensitive to the current antibiotic regimen, but the abscess has failed to improve.  Genetic analysis reveals an inactivating mutation affecting a neutrophil oxidase enzyme.  This patient most likely has an increased risk of infection with which of the following organisms?

A 64-year-old man comes to the clinic due to several weeks of persistent cough, fever, and weight loss.  He smokes a pack of cigarettes daily and drinks 10-12 beers on weekends.  Chest x-ray reveals an infiltrate in the left upper lobe.  The patient is prescribed broad-spectrum antibiotic therapy for both aspiration and community-acquired pneumonia, but his symptoms worsen despite taking the medication as prescribed.  Sputum Gram stain does not reveal any organisms.  Lung biopsy findings are shown in the image below:

Which of the following substances is most important for driving the development of this patient’s observed microscopic lesion?

Immunoglobulins of different classes have different structures.  Some immunoglobulins have long hinge regions between the Fab and Fc regions, whereas others lack the hinge region, as shown in the image below:

The hinge region provides movement flexibility to the Fab regions.  This is most likely to affect which of the following immunoglobulin properties?

An 18-month-old boy is evaluated for recurrent infections.  He has been hospitalized 3 times with pneumonia since age 3 months.  He has also had multiple skin infections requiring treatment with antibacterial and antifungal agents.  During his last episode of pneumonia, he developed a large pleural effusion, which was drained.  The pleural fluid revealed numerous neutrophils containing a large number of intact gram-positive cocci.  The microorganisms responsible for this patient’s recurrent infections most likely produce which of the following virulence factors?

A 2-year-old boy is being evaluated for persistent diarrhea. He seemed healthy until he was about 6 months old and has since experienced 4 episodes of otitis media and 3 episodes of pneumococcal pneumonia. He was at the 50th percentile for weight and height at 6 months but is now at the 25th percentile for height and 10th percentile for weight. He is referred for upper gastrointestinal endoscopy, and Giardia lamblia is isolated from duodenal aspirates. Further workup shows very low serum levels of all immunoglobulin types. Flow cytometry of this patient’s peripheral blood is most likely to show deficiency of cells bearing which of the following markers?

A 44-year-old man with diabetic nephropathy undergoes a renal transplant.  One week later, he develops low-grade fever, body aches, and decreased urine output.  Temperature is 37.2 C (99 F), blood pressure is 124/76 mm Hg, and pulse is 88/min.  Physical examination shows mild tenderness over the graft on palpation.  Serum creatinine is 2.2 mg/dL, an increase from 1.2 mg/dL two days ago.  Arterial and venous Doppler studies reveal adequate graft perfusion.  Graft biopsy demonstrates dense interstitial infiltration by mononuclear cells.  Which of the following is the most likely cause of this patient’s current condition?

A 19-year-old woman is brought to the emergency department after a motor vehicle collision.  The patient’s medical history includes celiac disease and 3 episodes of pneumonia.  Her blood pressure is 80/45 mm Hg and pulse is 130/min.  Physical examination reveals pallor, and ultrasound shows a splenic laceration.  She receives a blood transfusion with O-negative packed red blood cells.  During transfusion, the patient develops facial swelling, generalized hives, and shortness of breath.  Which of the following is the most likely diagnosis in this patient?

A 3-year-old boy experiences recurrent sinusitis and an episode of severe pneumonia.  As part of his evaluation, Candida extract is injected intradermally.  Forty-eight hours later, he returns to the clinic with a firm nodule measuring 16 mm in diameter where the extract was injected.  Which of the following cell types is most likely responsible for the reaction observed in this patient?

A 5-year-old boy with severe, recurrent respiratory infections is undergoing evaluation.  Sputum studies reveal intracellular bacteria.  Further testing shows that the patient’s T cells lack the IL-12 receptor.  Supplementation with which of the following substances would most likely improve this patient’s condition?

A researcher identifies a group of malignant epithelial cells in the sigmoid colon that have decreased their surface expression of MHC class I antigen.  Which of the following immune effector cell types is most likely to kill the transformed epithelial cells?

A 21-year-old woman comes to the office due to recurrent episodes of self-limited, colicky abdominal pain.  She also had an episode of facial swelling that resolved spontaneously.  The patient has no other significant past medical history and takes no medications.  Examination is unremarkable.  Evaluation shows that her complement protein C1, even when not attached to an antigen-antibody complex, is excessively cleaving C2 and C4.  Which of the following is most likely increased in this patient?

A 3-year-old boy is brought to the emergency department with breathing difficulty and drooling that have worsened rapidly over the last 8 hours.  He has no chronic medical conditions.  Temperature is 39.4 C (102.9 F).  Examination shows a toxic-appearing patient leaning forward while sitting on the bed; he has inspiratory stridor and suprasternal retractions.  There are pooled oral secretions, and the patient is unable to swallow.  Which of the following is the greatest risk factor for this patient’s condition?

A 46-year-old man presents to your office with a slowly growing neck mass.  The mass is stony hard on palpation and seems to be fixed to the adjacent tissues.  After initial evaluation, combination chemotherapy is prescribed to the patient.  Several weeks later the mass significantly decreases in size, and biopsy demonstrates many shrunken eosinophilic cells within the tumor.  Which of the following substances released from mitochondria most likely triggered the observed cellular changes?

An 18-year-old man is evaluated for recurrent episodes of shortness of breath, wheezing, runny nose, and watery eyes.  The patient reports that his symptoms have recently worsened since he started training outdoors for an upcoming marathon.  He does not use tobacco, alcohol, or illicit drugs.  Skin testing is performed to determine symptom triggers.  A pricking device is used to apply allergen extract underneath the skin.  After 15 minutes, the patient develops raised, erythematous plaques with surrounding erythema at the application site.  Which of the following mediators is the first to be released during the pathogenesis of this patient’s skin findings?

A 61-year-old man comes to the emergency department due to fever, chills, and a productive cough with thick, blood-tinged sputum for the past several days.  His temperature is 38.8 C (102 F), blood pressure is 90/60 mm Hg, and pulse is 110/min.  On examination, the patient is lethargic and ill appearing.  Bronchial breath sounds and crackles are present in the right lung.  Blood and sputum cultures grow Klebsiella pneumoniae.  It is determined that the bacteria express a lipopolysaccharide on their outer membrane surface that stimulates toll-like receptors in the inflammatory cells.  This in turn leads to degradation of the IκB inhibitor protein, which normally binds to a latent transcription factor found in the cytoplasm.  Which of the following factors is most likely to be directly activated by the removal of this inhibitor protein?

A 72-year-old woman is brought to the emergency department from a nursing facility due to fever, chills, and hypotension.  The patient has a history of diabetes mellitus, ischemic stroke, and neurogenic bladder.  She has an indwelling urinary catheter.  Temperature is 38.8 C (102 F), blood pressure is 80/40 mm Hg, and pulse is 130/min.  The patient is lethargic and disoriented.  Her extremities are warm, and her breathing is rapid and shallow.  Lungs are clear on auscultation and there are no heart murmurs.  There is left costovertebral angle tenderness.  The urine in her catheter appears cloudy.  Her leukocyte count is elevated with left shift, and urinalysis shows pyuria and bacteruria.  Which of the following chemical mediators is most responsible for this patient’s current condition?