A 2-week-old infant is brought to the emergency department due to fever, lethargy, grunting, and poor feeding. The patient was born at full term after an uneventful pregnancy and has had no prior medical issues. Blood samples are obtained for culture, and the patient is hospitalized for broad-spectrum antibiotic therapy. Cultures grow Escherichia coli. The patient's condition developed in part due to exposure to bacterial lipopolysaccharide, which stimulates NF-kB-induced transcription of inflammatory cytokines such as TNF-alpha, IL-1, and IL-6. This bacterial component most likely interacted with the patient's immune cells via which of the following?

Question

A 2-week-old infant is brought to the emergency department due to fever, lethargy, grunting, and poor feeding.  The patient was born at full term after an uneventful pregnancy and has had no prior medical issues.  Blood samples are obtained for culture, and the patient is hospitalized for broad-spectrum antibiotic therapy.  Cultures grow Escherichia coli.  The patient's condition developed in part due to exposure to bacterial lipopolysaccharide, which stimulates NF-kB-induced transcription of inflammatory cytokines such as TNF-alpha, IL-1, and IL-6.  This bacterial component most likely interacted with the patient's immune cells via which of the following?

Quizplus · Accepted Answer

Dendritic cells and macrophages are phagocytic antigen-presenting cells that have an important role in both the innate and adaptive immune responses. As part of their innate immune function, they express pattern recognition receptors (PRRs) on their surfaces that recognize 2 major categories of ligands: Damage-associated molecular patterns (DAMPs) are intracellular components (proteins, phospholipids, DNA) released by host cells when they are damaged by inflammation or infection. Pathogen-associated molecular patterns (PAMPs) are microbial components conserved across numerous species that are generally required for microbial survival. One of the most common PAMPs is lipopolysaccharide, a component of the outer membrane of all gram-negative bacteria (eg, Escherichia coli). Lipopolysaccharide binds to a type of PRR called a toll-like receptor, which contains an extracellular ligand-binding domain, a transmembrane domain, and a cytoplasmic domain that conducts transcription signals to the nucleus via NF-kB. NF-kB signaling promotes transcription of proinflammatory cytokines (eg, TNF-alpha, IL-1, IL-6, IL-12), leading to local inflammation, immune cell recruitment, and systemic effects (eg, fever, malaise, lethargy, poor feeding). It also stimulates antigen-presenting cells to increase phagocytosis, antigen display, and expression of costimulatory molecules (eg, CD80/86) for T- and B-cell activation, thereby triggering a strong adaptive immune response. (Choice A) Beta-2 integrin (CD18) helps leukocytes migrate from the bloodstream to tissue by binding to intercellular adhesion molecule-1 on the extracellular matrix of the endothelium. It also helps macrophages, neutrophils, and natural killer cells generate complement receptors, which recognize and phagocytose foreign peptides. (Choice B) The Fc receptor (CD16) on phagocytic cells binds to opsonized (eg, IgG-bound) foreign pathogens, leading to phagocytic destruction. The Fc receptor on natural killer cells mediates their ability to destroy infected or cancerous cells by antibody-dependent cellular cytotoxicity. (Choice C) L selectin (CD62L) is a lymphocyte adhesion molecule that binds to a ligand on the venule endothelium, which allows lymphocytes to leave the bloodstream and enter secondary lymphoid tissue. (Choice D) Major histocompatibility complex class II molecules are on antigen-presenting cells; they present antigens to the T cell receptor on CD4 cells. (Choice E) Mannose-binding lectin is a PRR that recognizes microbial carbohydrates and activates the lectin complement pathway. Educational objective: Pattern recognition receptors (PRRs) are part of the innate immune response; they recognize damaged host proteins or conserved microbial molecules and trigger inflammation. Toll-like receptors, a type of PRR on macrophages and dendritic cells, recognize lipopolysaccharide and promote the release of inflammatory cytokines (eg, IL-1/6/12, TNF-alpha) via NF-kB signaling. __________ References: Pattern recognition receptors and inflammation. (http://www.ncbi.nlm.nih.gov/pubmed/20303872)

A 2-Week-Old Infant Is Brought to the Emergency Department Due