Mediators of Inflammation Overview
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Mediators of Inflammation Overview

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Questions and Answers

What triggers the rapid degranulation of mast cells?

  • Decreased blood flow and smooth muscle contraction
  • Neuropeptides and mechanical pressure
  • Increased temperature and electrical signals
  • Physical injury and binding of antibodies (correct)

    • What is the primary function of serotonin in the body?

  • Vasodilation in response to trauma
  • Neurotransmitter function in the gastrointestinal tract (correct)
  • Anti-inflammatory mediator in allergic reactions
  • Receptor antagonist for histamine

    • Which receptors do antihistamine drugs primarily target?

  • H1 receptors on microvascular endothelial cells (correct)
  • C3 receptors on immune cells
  • H2 receptors in the gastrointestinal tract
  • B2 receptors on smooth muscle

    • What mediates the vasoactive effects of histamine?

    <p>Binding to H1 receptors on endothelial cells</p> Signup and view all the answers

    What process releases arachidonic acid from membrane phospholipids?

    <p>Phospholipase A2 activity</p> Signup and view all the answers

    Which of the following best describes the role of leukotrienes in inflammation?

    <p>They stimulate vascular and cellular reactions.</p> Signup and view all the answers

    In humans, where is serotonin primarily found as a mediator?

    <p>In platelets and the gastrointestinal tract</p> Signup and view all the answers

    What role does histamine play in relation to venules in inflammation?

    <p>It increases permeability by producing interendothelial gaps.</p> Signup and view all the answers

    Which of the following best describes the nature of mediators of inflammation?

    <p>They can be secreted by cells or generated from plasma proteins.</p> Signup and view all the answers

    What process allows for the rapid secretion of stored mediators from cells during inflammation?

    <p>Granule exocytosis</p> Signup and view all the answers

    How are plasma-derived mediators primarily activated?

    <p>By enzymatic cleavage</p> Signup and view all the answers

    What role does the mediator TNF play in inflammation?

    <p>It stimulates the production of another cytokine IL1.</p> Signup and view all the answers

    Which of the following statements about the short-lived nature of most mediators is true?

    <p>They rapidly decay or are inhibited to control inflammation.</p> Signup and view all the answers

    What is a primary function of vasoactive amines like histamine during inflammation?

    <p>To enhance vascular permeability and blood flow.</p> Signup and view all the answers

    Which statement about the action of primary mediators is correct?

    <p>One mediator can stimulate the release of other mediators.</p> Signup and view all the answers

    What is the role of complement activation products in inflammation?

    <p>They stimulate the release of histamine from mast cells.</p> Signup and view all the answers

    What triggers the activation of phospholipase A2?

    <p>Increase in cytoplasmic Ca2+ levels and activation of kinases</p> Signup and view all the answers

    Which enzyme is responsible for generating prostaglandins?

    <p>Cyclooxygenase</p> Signup and view all the answers

    Which statement about COX2 is true?

    <p>COX2 is induced by inflammatory stimuli.</p> Signup and view all the answers

    What is the primary function of prostacyclin (PGI2)?

    <p>Vasodilation and inhibiting platelet aggregation</p> Signup and view all the answers

    Which eicosanoid is primarily produced by platelets?

    <p>Thromboxane A2 (TxA2)</p> Signup and view all the answers

    Which of the following is NOT involved in mediating inflammation?

    <p>Phospholipase B</p> Signup and view all the answers

    Which prostaglandin is considered to be important in inflammatory reactions?

    <p>All of the above</p> Signup and view all the answers

    What distinguishes COX1 from COX2?

    <p>COX1 is always present in tissues, while COX2 is induced by inflammatory stimuli.</p> Signup and view all the answers

    What is the main role of PGD2 in inflammation?

    <p>Causing vasodilation and increasing venule permeability</p> Signup and view all the answers

    Which type of leukotriene is primarily responsible for causing bronchospasm?

    <p>LTC4</p> Signup and view all the answers

    How do lipoxins differ from prostaglandins and leukotrienes?

    <p>They suppress inflammation</p> Signup and view all the answers

    What is the function of LTB4 in the inflammation response?

    <p>Acting as a chemotactic agent for neutrophils</p> Signup and view all the answers

    Which of the following statements is true regarding leukotrienes?

    <p>They play a significant role in bronchospasm and increased vascular permeability</p> Signup and view all the answers

    What triggers the production of leukotrienes in leukocytes and mast cells?

    <p>Arachidonic acid metabolism by lipoxygenase</p> Signup and view all the answers

    Which enzyme is primarily responsible for leukotriene synthesis in neutrophils?

    <p>5-lipoxygenase</p> Signup and view all the answers

    What effect does PGF2a have in the body?

    <p>It stimulates contraction of uterine and bronchial smooth muscle.</p> Signup and view all the answers

    Study Notes

    Mediators of Inflammation

    • Mediators of inflammation are substances that initiate and regulate inflammatory reactions.
    •  They are either secreted by cells or generated from plasma proteins.
    •  Cell-derived mediators are stored in intracellular granules and released by exocytosis or synthesized de novo.
    •  Plasma-derived mediators are produced in the liver and are present in the circulation as inactive precursors that are activated by proteolytic cleavages.
    •  Active mediators are produced in response to stimuli such as microbial products and substances from necrotic cells.
    • Most mediators are short-lived and are inactivated by enzymes or scavenged.
    •  One mediator can stimulate the release of other mediators, creating a cascade of effects.

    Vasoactive Amines: Histamine and Serotonin

    •  Histamine is a vasoactive amine stored in mast cells, basophils, and platelets.
    •  It is released by degranulation triggered by various stimuli:
      • Physical injury
      • Antibody binding to mast cells
      • Complement products (anaphylatoxins)
      • Neuropeptides
      • Cytokines
    •  It causes dilation of arterioles and increases venule permeability, leading to edema.
    •  Its vascular effects are mediated by binding to H1 receptors.
    •  Histamine also causes contraction of some smooth muscles.
    •  Serotonin is a vasoactive mediator present in platelets, neuroendocrine cells, and mast cells in rodents (but not humans).
    •  It is mainly a neurotransmitter in the gastrointestinal tract.
    •  Its vasoconstrictor function in inflammation is unclear.

    Arachidonic Acid Metabolites

    •  Prostaglandins and leukotrienes are lipid mediators produced from arachidonic acid (AA) present in membrane phospholipids.
    •  AA is a 20-carbon polyunsaturated fatty acid released from membrane phospholipids by phospholipase A2.
    •  Eicosanoids (AA-derived mediators) are synthesized by two major enzyme classes:
      • Cyclooxygenases (COX)
      • Lipoxygenases
    •  They bind to G-protein coupled receptors on various cell types and mediate virtually every step of inflammation.

    Prostaglandins

    •  Prostaglandins are produced by mast cells, macrophages, endothelial cells, and other cell types.
    •  They are involved in the vascular and systemic reactions of inflammation.
    •  COX1 is constitutively expressed and serves a homeostatic function in various tissues.
    •  COX2 is induced by inflammatory stimuli and generates prostaglandins involved in inflammatory reactions.
    •  Prostaglandins are classified into series based on their structure (e.g., PGD, PGE, PGF, PGG, PGH).
    •  The most important ones in inflammation:
      • PGE2
      • PGD2
      • PGF2a
      • PGI2 (prostacyclin)
      • TxA2 (thromboxane A2)
    •  Each prostaglandin is derived by the action of a specific enzyme on an intermediate in the pathway.
    •  TxA2 is a potent platelet aggregator and vasoconstrictor.
    •  Prostacyclin (PGI2) is a vasodilator, inhibitor of platelet aggregation, and potentiates the permeability-increasing and chemotactic effects of other mediators.
    •  A thromboxane-prostacyclin imbalance has been implicated in thrombosis.
    •  PGD2 and PGE2 cause vasodilation and increase postcapillary venule permeability, contributing to edema.
    •  PGF2a stimulates smooth muscle contraction and small arteriole constriction.
    •  PGD2 is a chemoattractant for neutrophils.
    •  Prostaglandins are involved in the pathogenesis of pain and fever in inflammation.

    Leukotrienes

    •  Leukotrienes are produced by leukocytes and mast cells by the action of lipoxygenases.
    •  5-lipoxygenase is the predominant form in neutrophils.
    •  It converts AA to 5-hydroxyeicosatetraenoic acid, a chemoattractant for neutrophils.
    •  LTB4 is a potent chemotactic agent and activator of neutrophils, promoting aggregation, adhesion, ROS generation, and lysosomal enzyme release.
    •  Cysteinyl-containing leukotrienes (LTC4, LTD4, LTE4) cause intense vasoconstriction, bronchospasm, and increased venule permeability.
    •  They are more potent than histamine in increasing vascular permeability and causing bronchospasm.

    Lipoxins

    •  Lipoxins are also generated from AA by the lipoxygenase pathway.
    •  Unlike prostaglandins and leukotrienes, lipoxins suppress inflammation.
    •  They inhibit neutrophil chemotaxis and adhesion to endothelium.
    •  Their biosynthesis requires two cell populations: leukocytes (neutrophils) produce intermediates, and platelets convert them into lipoxins.

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    Description

    This quiz explores the various mediators of inflammation, including both cell-derived and plasma-derived substances. It covers how these mediators function, their activation, and their roles in inflammatory responses, with a focus on vasoactive amines like histamine and serotonin.

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