A 26-year-old man comes to the office due to myalgia, nasal congestion, and cough. Temperature is 38.3 C (100.9 F). Examination shows nasal and pharyngeal hyperemia. Rapid influenza antigen testing of nasopharyngeal secretions is positive. Within the infected cells of the patient's respiratory tract, viral proteins are degraded and attached to major histocompatibility complex class I molecules, which are then expressed on the cell surface for presentation to cytotoxic CD8⁺ lymphocytes. Which of the following enzymes is most essential to initiating this process?

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Quizplus · Accepted Answer

11ec160b_39fc_c1ca_9249_6b89a50fb1e1_MD0001_00 The cellular immune response to a viral pathogen (eg, influenza) requires the presentation of viral antigens to effector immune cells (eg, CD8⁺ lymphocytes). The ubiquitin proteasome pathway (UPP) is essential to this process because of its role in breaking down native and foreign intracellular proteins. Ubiquitin ligase initiates the UPP by recognizing specific protein substrates and catalyzing the attachment of ubiquitin. The proteins tagged with ubiquitin are then broken down by a proteasome to peptide fragments which can be recycled into amino acids. The peptide fragments produced during this process can also be coupled to major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum and then presented on the cell surface. Cytotoxic CD8⁺ lymphocytes recognize nonnative (eg, viral) proteins on infected cells and trigger apoptosis of the cell by activating the caspase cascade through the release perforin and granzyme (Choice B). (Choice A) Acid phosphatase is found in the lysosome of most cells and hydrolyzes organic phosphates, but it is not involved in antigen presentation. (Choice C) Guanylate cyclase is involved in the G-protein signaling cascade, which plays a crucial role in the activation and regulation of diverse physiologic processes (eg, smooth muscle relaxation, retinal phototransduction). (Choice D) Myeloperoxidase is a key component of the respiratory burst of neutrophils and is released into the phagocytic vacuole and extracellular space as part of the immune response to bacteria and other pathogens. Educational objective: An essential step in the activation of the cellular immune response to a virus is the breakdown of intracellular viral proteins by the ubiquitin proteasome pathway. This pathway is initiated by ubiquitin ligases, which recognize specific protein substrates and attach a ubiquitin tag. The target proteins are then degraded by a proteasome into peptide fragments, which are coupled with major histocompatibility complex class I proteins and presented on the cell surface for surveillance by cytotoxic CD8⁺ lymphocytes. __________ References: The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases. (http://www.ncbi.nlm.nih.gov/pubmed/16978533)

A 26-Year-Old Man Comes to the Office Due to Myalgia