Chemical Mediators of Inflammation Quiz
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Questions and Answers

Which of the following statements does NOT accurately describe the chemical mediators of inflammation?

  • They are responsible for mediating oxidative damage in the affected tissues.
  • They function through direct enzymatic activity.
  • They contribute to the inflammatory response through receptor-ligand interactions.
  • They are generally characterized by a long half-life, allowing for sustained inflammatory responses. (correct)

    • Which of the following is NOT a known stimulator of the release of vasoactive amines?

  • Binding of IgE-antigen complexes.
  • The release of leukotrienes by mast cells. (correct)
  • Fragments of C3a and C5a.
  • Direct physical or chemical injury.

    • Which of the following is a primary mechanism by which chemical mediators of inflammation contribute to pain?

  • Direct activation of nociceptors by the mediators. (correct)
  • Suppression of the inflammatory cascade, eliminating pain-inducing factors.
  • Induction of tissue damage, leading to secondary nociception.
  • Inhibition of the production of prostaglandins, reducing pain signaling.

    • Which of the following plasma protease systems is NOT directly involved in the inflammatory response?

    <p>Fibrinolytic system (C)</p> Signup and view all the answers

    Which of the following statements accurately describes the role of prostaglandins in the inflammatory response?

    <p>They contribute to vasodilation, fever, and pain responses during inflammation. (B)</p> Signup and view all the answers

    Which of the following systems are activated by Hageman factor (factor XIIa)?

    <p>Kinin system, clotting system, and complement system (D)</p> Signup and view all the answers

    What are the two molecules that are considered anaphylatoxins, causing histamine release from mast cells?

    <p>C3a and C5a (A)</p> Signup and view all the answers

    What is the primary function of the complement system's membrane attack complex (MAC, C5b-9)?

    <p>To lyse cells by disrupting their cell membrane integrity. (B)</p> Signup and view all the answers

    Which of the following correctly describes the role of bradykinin in the kinin system?

    <p>Bradykinin is a potent vasodilator that increases vascular permeability and causes pain. (C)</p> Signup and view all the answers

    What is the primary function of plasmin in the coagulation system?

    <p>To break down fibrin clots and generate fibrin-split products. (C)</p> Signup and view all the answers

    Which of the following are NOT known to activate Hageman factor?

    <p>Complementary proteins (A)</p> Signup and view all the answers

    Which of the following accurately describes the function of thrombin in the coagulation system?

    <p>Thrombin converts fibrinogen to fibrin, a key step in clot formation. (B)</p> Signup and view all the answers

    What are the main consequences of activating Hageman factor?

    <p>Activation of the coagulation, fibrinolytic, and kinin systems, leading to inflammation and coagulation. (D)</p> Signup and view all the answers

    Which cytokine is primarily associated with eosinophils?

    <p>IL-5 (D)</p> Signup and view all the answers

    What is one of the primary effects of nitric oxide (NO) in the body?

    <p>Acts as a physical mediator of vascular tone (D)</p> Signup and view all the answers

    Which type of cells are primarily affected by oxygen-derived free radicals?

    <p>Endothelial cells (A)</p> Signup and view all the answers

    Which antioxidant is responsible for detoxifying peroxides in the body?

    <p>Glutathione peroxidase (A)</p> Signup and view all the answers

    What role does transforming growth factor β play in the body?

    <p>Is primarily involved in tissue regeneration and repair (C)</p> Signup and view all the answers

    What is primarily indicated as a potent chemotactic agent among leukotrienes?

    <p>Leukotriene B4 (D)</p> Signup and view all the answers

    Which enzyme pathway produces thromboxane A2, known for aggregating platelets and causing vasoconstriction?

    <p>Cyclooxygenase pathway (D)</p> Signup and view all the answers

    Which cytokines are classified as 'master cytokines' due to their similar actions and origin?

    <p>IL-1 and TNF (B)</p> Signup and view all the answers

    What role does prostacyclin (PGI2) primarily play in vascular health?

    <p>Inhibits platelet aggregation and causes vasodilation (D)</p> Signup and view all the answers

    Which of the following is a characteristic of leukotrienes C4, D4, and E4?

    <p>They are effective in increasing vascular permeability in venules. (D)</p> Signup and view all the answers

    What is the primary effect of the platelet activating factor?

    <p>Aggregates platelets and causes bronchoconstriction (D)</p> Signup and view all the answers

    What is the main mechanism through which corticosteroids exert their anti-inflammatory effects?

    <p>Suppress phospholipase activity (B)</p> Signup and view all the answers

    Which of the following statements is true regarding the lipoxygenase pathway?

    <p>It is primarily responsible for synthesizing leukotrienes. (A)</p> Signup and view all the answers

    Flashcards

    Complement system

    A group of plasma proteins that help fight infections and promote inflammation.

    Chemotaxis

    The movement of cells toward chemical signals, often during inflammation.

    C3a and C5a

    Anaphylatoxins that increase inflammation by releasing histamine and attracting immune cells.

    C5b-9 complex

    Membrane attack complex that lyses cells and triggers inflammation processes.

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    Bradykinin

    A vasoactive nonapeptide that causes vasodilation and increases permeability.

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    Hageman factor (Factor XII)

    A protein that initiates clotting and inflammatory responses upon activation.

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    Clotting system

    System of plasma proteins that forms blood clots to prevent bleeding.

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    Fibrinolysis

    Process of breaking down fibrin clots, important for tissue repair.

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    Chemical Mediators of Inflammation

    Messengers that contribute to the inflammatory response by acting on cells and blood vessels.

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    Vasodilation

    Widening of blood vessels, often mediated by prostaglandins and nitric oxide during inflammation.

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    Vasoactive Amines

    Substances like histamine and serotonin that increase vascular permeability during inflammation.

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    Cytokines

    Proteins, such as IL-1 and IL-6, that help in signaling to amplify the inflammatory response.

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    Plasma Proteases

    Enzymes involved in the kinin system which are highly vasoactive in inflammation.

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    IL-5

    A cytokine that stimulates eosinophil production.

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    Nitric Oxide (NO)

    A signaling molecule that mediates vascular tone and has various effects in the body.

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    Growth Factors

    Proteins that stimulate cell growth, differentiation, and regeneration.

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    Oxygen-Derived Free Radicals

    Reactive molecules that can damage cells and tissues, causing inflammation.

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    Antioxidants

    Substances that protect against free radical damage.

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    Arachidonic Acid

    A 20-carbon polyunsaturated fatty acid involved in inflammation.

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    Cyclooxygenase Pathway

    Pathway involving COX-1 and COX-2 that produces thromboxane and prostacyclin.

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    Thromboxane A2

    A product of the cyclooxygenase pathway that aggregates platelets and causes vasoconstriction.

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    Prostacyclin (PGI2)

    Inhibits platelet aggregation and causes vasodilation, opposite of thromboxane A2.

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    Lipoxygenase Pathway

    Pathway producing leukotrienes involved in inflammation and allergic reactions.

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    Leukotriene B4

    A potent chemotactic agent that attracts white blood cells to inflammation sites.

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    IL-1 and TNF

    Major cytokines produced by monocytes and macrophages that modulate inflammation.

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    Study Notes

    Chemical Mediators of Inflammation

    • Chemical mediators are messengers that affect blood vessels, immune cells, and other cells, contributing to the inflammatory response. They are essentially anything that participates in the inflammatory process
    • Exogenous mediators include endotoxins.
    • Endogenous mediators include plasma proteins, leukocytes, endothelial cells, and fibroblasts.

    Cellular Mediators and Sources

    • Preformed mediators are contained within secretory granules of cells.
    • Newly synthesized mediators are produced by cells.
    • Examples of mediators include histamine, serotonin, lysosomal enzymes, prostaglandins, leukotrienes, platelet-activating factors, activated oxygen species, nitric oxide, and cytokines.
    • The source of these mediators varies, including mast cells, basophils, platelets, neutrophils, macrophages, all leukocytes, platelets, endothelial cells, and macrophages.

    Mechanism of Action of Mediators

    • Mediators primarily act through receptor-ligand interactions.
    • Direct enzymatic activities are a second mechanism of action.
    • Mediate oxidative damage is a third mechanism of action.

    Network of Interacting Chemicals

    • Interacting chemical mediators lead to redundancy.
    • This redundancy ensures the inflammatory response is maintained and amplified.
    • Molecules have short half-lives and can be harmful.

    Vasodilation and Increased Vascular Permeability

    • Vasodilation involves the widening of blood vessels, influenced by mediators like prostaglandins and nitric oxide
    • Increased vascular permeability leads to increased passage of fluids and proteins into tissues, facilitated by mediators such as vasoactive amines (histamine and serotonin), C3a and C5a, bradykinin, leukotrienes and PAF
    • Chemotactic leukocyte activation draws immune cells to the affected area.

    Fever, Pain, and Tissue Damage

    • Inflammatory mediators like IL-1, IL-6, TNF, and prostaglandins trigger fever.
    • Prostaglandins and bradykinin cause pain.
    • Neutrophil and macrophage products, lysosomal enzymes, and oxygen metabolites, including NO, cause tissue damage.

    Vasoactive Amines (Histamine and Serotonin)

    • Histamine and serotonin, as vasoactive amines, lead to increased vascular permeability.
    • They are primary mediators in immediate phases of increased permeability and promote contraction of smooth muscles.
    • They also promote the release of exotoxins.
    • Rodent mast cells are a source of serotonin.

    Releasing Stimulators

    • Direct physical or chemical injury activates mediators.
    • The binding of IgE-Ag complexes can trigger mediators.

    Fragments of Complement Proteins

    • C3a and C5a fragments (anaphylatoxins) lead to histamine release from mast cells.
    • Release of lysosomal enzymes is observed in inflammatory cells.
    • C5a activates the lipoxygenase pathway. C5a also attracts inflammatory cells and increases the attachment of leukocytes.

    Plasma Proteases (Kinin, Complement, Clotting Systems)

    • The kinin, complement, and clotting systems are interrelated within this category.

    ###Complement System

    • Plasma proteins act against microbial agents within the complement system.
      • Products of activated complement include vascular permeability, chemotaxis, opsonization, and lysis.
    • There are two main pathways: classical and alternative, with a common pathway that follows.
    • Activation components like C3a and C5a and components like C5b-9 generate the membrane attack complex.
    • The components of the complement system lead to cell lysis and stimulate arachidonic acid metabolism, resulting in oxidative metabolites.

    Kinin System

    • The kinin system is activated by Hageman factor (XIIa).
    • The system results in the release of bradykinin, a potent vasodilator from plasma.
    • Bradykinin triggers increased vascular permeability, smooth muscle contraction, pain, and the arachidonic acid cascade.

    Clotting System

    • Plasma proteins in the clotting system can be activated by Hageman factor.
    • Thrombin converts fibrinogen to fibrin.
    • The resulting fibrinopeptides increase vascular permeability and act as chemoattractants for leukocytes.

    Hageman Factor (Factor XII)

    • Factor XII is a part of the intrinsic coagulation cascade.
    • It is activated by negatively charged surfaces, platelets, and proteases from inflammatory cells.

    Causes of Activation (general)

    • Coagulation system.
    • Activation of the fibrinolytic system.
    • The result is bradykinin production & complement activation.
    • An amplification system is provided.

    Important Note (general)

    • Activated Hageman factor initiates the clotting, fibrinolytic, and kinin systems.
    • The resulting products (kallikrein, factor XIIa, and plasmin, particularly kallikrein) activate Hageman factors via feedback, leading to significant amplification of the initial stimulus.

    Arachidonic Acid Metabolites

    • These are important in biologic and pathologic processes, including inflammation
    • Arachidonic acid is a 20-carbon polyunsaturated fatty acid that is derived from dietary sources or conversion of linoleic acid.
    • It's released through the activation of cellular phospholipases from various stimuli.
    • Mediators such as prostaglandins, thromboxanes, and leukotrienes are derived through cyclooxygenase (COX) and lipoxygenase pathways.

    Cyclooxygenase Pathway

    • The COX enzymes (COX-1, COX-2) are required.
    • Thromboxane A2 causes platelet aggregation and vasoconstriction.
    • Prostacyclin (PGI2) inhibits platelet aggregation and leads to vasodilation through endothelial cells.
    • Diverse prostaglandins (PGE2, PGF2, PGD2) affect vascular tone and permeability.

    Lipoxygenase Pathway

    • Leukotrienes (LTB4, LTC4, LTD4, LTE4) are produced through the lipoxygenase pathway.
    • Leukotrienes are potent chemoattractants and vasoconstrictors, increasing vascular permeability, mainly in venules up to 1000 times more potent than histamine.

    Platelet Activating Factor

    • Aggregation of platelets and the release of mediators is a key function.
    • Bronchoconstriction and vasoconstriction are common effects.
    • Increased vascular permeability and leukocyte adhesion/chemotaxis follow.

    Cytokines

    • Transmitters for cell communication, mediating cell function.
    • Primarily produced by activated macrophages and lymphocytes. Examples include IL-1, IL-8, and TNF.

    IL-1 and TNF

    • These are "master cytokines" originating from monocytes, macrophages, in similar function to endothelium and acute phase proteins in fibroblasts.

    Other Cytokines

    • IL-5 (eosinophils), IL-6 (B and T cells), IL-8 (neutrophils) are other cytokines

    Growth Factors

    • Platelet-derived growth factor (PDGF), transforming growth factor β (TGFβ), and various chemokines are growth factors that promote regeneration and repair, affecting leukocytes and mesenchymal cells.

    Nitric Oxide (NO)

    • NO is a mediator derived from L-arginine by enzymes and multiple factors.
    • It acts as a physical mediator of vascular tone, a signaling molecule in the brain, and inhibiting mast cell-initiated inflammation. It also participates in host defense.
    • Reduces platelet aggregation and adhesion.

    Lysosomal Constituents

    • Neutrophils and monocytes/macrophages contain enzymes and proteins in granules.
    • Cationic proteins within granules lead to increased vascular permeability.
    • Neutral proteases degrade the extracellular matrix (ECM).

    Oxygen-Derived Free Radicals

    • These radicals cause endothelial damage.
    • They inhibit protease activity, leading to protein destruction.
    • Damage to various cells also occurs
    • Antioxidants like ceruloplasmin, transferrin, superoxide dismutase, catalase, and glutathione peroxidase counteract free radicals.

    Summary of Mediators of Acute Inflammation

    • A table summarizing mediators, sources, vascular leakage, chemotaxis, and other effects.

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