WBR0736

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Author [[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Immunology
Sub Category SubCategory::Hematology
Prompt [[Prompt::Neutrophils are considered the primary line of defense against bacterial infections and non-specific inflammatory processes. They are an important component of the innate immune response and are able to migrate by a process called chemotaxis. Chemotaxis requires complex intracellular signaling pathways that allow neutrophils to move towards chemoattractant molecules that drive them towards regions of inflammation. According to the image below, which of the following pathways is most likely involved in neutrophil chemotaxis?

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Answer A AnswerA::A
Answer A Explanation AnswerAExp::LTB4 plays a major role in neutrophil chemotaxis.
Answer B AnswerB::B
Answer B Explanation AnswerBExp::LTC4 and LTD4 are important to increase bronchial tone. They play a role in inflammatory bronchoconstrictive lung diseases, such as asthma.
Answer C AnswerC::C
Answer C Explanation AnswerCExp::The classical role of prostacyclin (PGI2) is the prevention of platelet aggregation. It also decreases vascular, bronchial, and uterine tonicity.
Answer D AnswerD::D
Answer D Explanation [[AnswerDExp::Prostaglandins share some characteristics with prostacyclin; they decrease vascular and bronchial tone. However, they have an opposing role in uterine tonicity, where they increase uterine tone. As such, prostaglandin analogs may be used in conjunction with other drugs to induce labor in pregnancy.]]
Answer E AnswerE::E
Answer E Explanation AnswerEExp::Thromboxane (TXA2) has an opposing role to prostacyclin in platelets. It increases platelet aggregation. Also, it increases both vascular and bronchial tonicity.
Right Answer RightAnswer::A
Explanation [[Explanation::Neutrophils are key components of the innate immune response. They are the first cells to respond to bacterial infections, areas of inflammation, and wound sites. To achieve adequate chemotaxis, which is defined as migration to sites of inflammation, intracellular signaling pathways, which are spacially and temporally regulated, help the neutrophil identify gradients of chemoattractants, such as LBT4, before it undergoes polarization and physical migration. Endogenous and exogenous chemoattractants allow the neutrophil to alter its morphological appearance to achieve polarization that aids in orientation during migration. Chemotaxis is thus an important feature of neutrophil activity. The pathway shown in the image is the arachidonic acid pathway that involves 2 main enzymes: Lipoxygenase which forms hydroperoxides to yield leukotrienes, and cyclooxygenase (COX), which forms endoperoxides. The 2 enzymes have significant roles in unrelated domains. In the pathway, LTB4 is an important neutrophil chemotactic agent.

Educational Objective: LTB4 is an important neutrophil chemotactic agent.
References: Nuzzi PA, Lokuta MA, Huttenlocher A. Analysis of neutrophil chemotaxis. Methods Mol Biol. 2007;370:23-36.
First Aid 2014 page 224 and 439]]

Approved Approved::Yes
Keyword WBRKeyword::Neutrophil, WBRKeyword::Chemotaxis, WBRKeyword::LTB4, WBRKeyword::Leukotriene, WBRKeyword::Arachidonic acid, WBRKeyword::Lipoxygenase, WBRKeyword::Inflammation, WBRKeyword::Chemoattractant
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