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?

Question

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?

Quizplus · Accepted Answer

This young woman's rapid-onset high fever, confusion, neck stiffness, and petechial rash likely indicate bacterial meningitis due to Neisseria meningitidis infection. Although healthy, college-aged individuals are at high risk for a single episode of bacterial meningitis, this patient's recurrent pneumonia and previous meningitis suggest an underlying immune system impairment. Culture results from her previous infections are unknown, but the leading cause of pneumonia and meningitis is Streptococcus pneumoniae. The major virulence factor for both N meningitidis and S pneumoniae is a polysaccharide capsule, which allows the bacteria to evade the following host defenses: Phagocytosis: Capsules have a negative charge, which repels the negative charge of the phagocyte surface. Capsules are also hydrophilic, which reduces surface tension at the interface between the capsule and the phagocyte, making engulfment more difficult. Opsonization: Capsules cover underlying antigenic epitopes on the bacterial cell membrane, which limits immunoglobulin binding. This impairs immunoglobulin-mediated opsonization and classical complement pathway activation. Therefore, initial control of encapsulated bacterial infections is largely dependent on the alternative complement cascade, which is triggered when autoactivated C3 lands on the bacterial cell and undergoes amplification. The alternative pathway generates the opsonin C3b (which increases bacterial phagocytosis), but it primarily kills encapsulated bacteria via the creation of membrane attack complexes (MACs). MACs form pores in the bacterial surface, leading to membrane destabilization and osmotic lysis. Therefore, patients who have defects in the complement proteins that generate the MAC (C5-C9) are at risk for recurrent, life-threatening infections from encapsulated bacteria. (Choice A) DiGeorge syndrome causes T-cell lymphopenia due to congenital absence of the thymus and parathyroid glands. Absent T-cells cause recurrent viral and fungal infections, not recurrent bacteremia. (Choice B) Excessive IgE production is seen in hyperimmunoglobulin E syndrome. Although recurrent sinopulmonary infection is common, patients also have severe eczema and recurrent abscesses. (Choice C) Impaired neutrophil chemotaxis is seen in leukocyte adhesion defects, which prevent neutrophil extravasation and migration to areas of infection. Although recurrent bacterial infection is common, patients often have a variety of other findings (eg, absence of pus, delayed umbilical cord separation, impaired wound healing). (Choice E) Chronic granulomatous disease is an X-linked immunodeficiency due to impaired NADPH oxidase, which prevents neutrophils from generating an oxidative burst. Although recurrent pneumonia is common, meningitis is not. In addition, infections associated with this defect are caused by certain catalase-positive organisms (eg, staphylococci), not encapsulated bacteria (eg, N meningitidis). Educational objective: Deficiency of the complement factors that form the membrane attack complex (C5-C9) results in recurrent infections of the lung and meninges by encapsulated bacteria (eg, Streptococcus pneumoniae, Neisseria meningitidis).

An 18-Year-Old College Student Is Hospitalized Due to a High