Immune System: Phagocytosis and Defensins
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What is the function of cathelicidins in neutrophil granules?

  • To recognize and respond to inflammation
  • To produce adaptive immune responses
  • To kill microbes extracellularly and intracellularly (correct)
  • To store and release microbes in tissues

    • What is the result of arteriolar dilation and dilation of precapillary sphincters?

  • No change in blood flow at the capillary bed
  • Complete stoppage of blood flow at the capillary bed
  • Decreased blood flow at the capillary bed
  • Increased blood flow at the capillary bed (correct)

    • What is the role of phagocytosis in innate immunity?

  • To recognize and respond to inflammation
  • To engulf and destroy microorganisms (correct)
  • To secrete cytokines and chemokines
  • To produce adaptive immune responses

    • What type of cells are macrophages and neutrophils?

    <p>Phagocytic cells</p> Signup and view all the answers

    What is the function of C5a and C3a in acute inflammation?

    <p>They stimulate histamine release</p> Signup and view all the answers

    What is the effect of high concentrations of nitric oxide?

    <p>It destroys both microbes and host cells</p> Signup and view all the answers

    What is the function of pattern recognition receptors (PRRs)?

    <p>To elicit responses to pathogens and damage</p> Signup and view all the answers

    What are the two types of molecular patterns recognized by pattern recognition receptors?

    <p>Pathogen Associated Molecular Patterns (PAMPs) and Danger Associated Molecular Patterns (DAMPs)</p> Signup and view all the answers

    What is vascular congestion characterized by?

    <p>Slower blood flow and increased permeability</p> Signup and view all the answers

    What is the function of Toll-like receptors?

    <p>To recognize pathogens and activate immune responses</p> Signup and view all the answers

    What is the effect of platelet activating factor at low concentrations?

    <p>It leads to vasodilation</p> Signup and view all the answers

    What is the result of increased permeability in acute inflammation?

    <p>Fluid loss from the blood vessels</p> Signup and view all the answers

    What is the role of monocytes in the immune system?

    <p>To differentiate into macrophages and phagocytose pathogens</p> Signup and view all the answers

    What is the function of defensins in the immune system?

    <p>To perform multiple roles, including a chemical barrier</p> Signup and view all the answers

    What is the role of an opsonin in phagocytosis?

    <p>To enhance the effectiveness of phagocytosis by coating the microbe</p> Signup and view all the answers

    Which type of receptor is responsible for recognizing carbohydrate patterns on microbial cell walls?

    <p>Lectin receptors</p> Signup and view all the answers

    What is the outcome of phagocytosis?

    <p>The formation of a phagosome</p> Signup and view all the answers

    What type of receptors bind to opsonins?

    <p>Complement receptors</p> Signup and view all the answers

    What is the role of PI3 kinase in phagocytosis?

    <p>To mediate intracellular signaling events</p> Signup and view all the answers

    What is the function of Fc receptors?

    <p>To recognize the constant region of antibodies</p> Signup and view all the answers

    What is the outcome of the signaling events during phagocytosis?

    <p>The polymerization of actin</p> Signup and view all the answers

    What is the role of collagen-domain receptors in phagocytosis?

    <p>To recognize collectins and ficolin on bacteria</p> Signup and view all the answers

    What is the initial step in the production of prostaglandins and leukotrienes?

    <p>Phospholipase A2 releases arachidonic acid from membrane phospholipids</p> Signup and view all the answers

    What is the primary function of prostaglandins PGE2 and PGD2?

    <p>Vasodilation and increased vascular permeability</p> Signup and view all the answers

    What is the primary function of leukotriene LTB4?

    <p>Chemotaxis and neutrophil chemotaxis</p> Signup and view all the answers

    What is the primary function of lipoxins?

    <p>Decreasing inflammation and vascular permeability</p> Signup and view all the answers

    What is the primary mechanism of increased vascular permeability?

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

    What is the primary site of increased vascular permeability?

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

    What is the primary function of histamine and serotonin in inflammation?

    <p>Vasodilation and increased vascular permeability</p> Signup and view all the answers

    What is transcytosis in the context of inflammation?

    <p>Transcellular transport of plasma components into the interstitial space</p> Signup and view all the answers

    What is the first step in the emigration and activation of leukocytes?

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

    What is required for a leukocyte to form stable adhesion bonds?

    <p>Chemokines presented on endothelial cells</p> Signup and view all the answers

    What is the result of a chemokine presented on an endothelial cell stimulating a leukocyte?

    <p>Increased affinity of leukocyte integrin for its ligand</p> Signup and view all the answers

    What is the role of endothelial cells in the activation of leukocytes?

    <p>Presenting chemokines to stimulate activation</p> Signup and view all the answers

    What is the result of a leukocyte forming stable adhesion bonds with an endothelial cell?

    <p>Migration of the leukocyte through the vessel wall</p> Signup and view all the answers

    What is the purpose of rolling in the emigration and activation of leukocytes?

    <p>Formation and dissociation of adhesion bonds between leukocytes and endothelial cells</p> Signup and view all the answers

    What is the primary function of lysozyme in innate immunity?

    <p>To break apart the peptidoglycan wall of bacterial cells</p> Signup and view all the answers

    What is the characteristic of defensins that allows them to act as a chemical barrier?

    <p>They are secreted by epithelial cells in mucosal surfaces</p> Signup and view all the answers

    What is the role of innate immunity in the host's defense against infection?

    <p>To discriminate between host cells and pathogens</p> Signup and view all the answers

    What is the outcome when innate defenses are overwhelmed or bypassed?

    <p>An adaptive immune response is required</p> Signup and view all the answers

    What is the function of pattern recognition receptors (PRRs) in innate immunity?

    <p>To recognize and bind to pathogens</p> Signup and view all the answers

    What is the characteristic of Toll-like receptors that allows them to play a key role in innate immunity?

    <p>They recognize and bind to pathogens</p> Signup and view all the answers

    What is the primary function of acute inflammation in the host's defense against infection?

    <p>To eliminate the pathogen from the host</p> Signup and view all the answers

    What is the characteristic of antimicrobial peptides that allows them to be effective against a wide range of pathogens?

    <p>They have multiple antimicrobial effects</p> Signup and view all the answers

    Which molecule is a potent vasodilator at low concentrations but can destroy both microbes and host cells at high concentrations?

    <p>Nitric oxide</p> Signup and view all the answers

    What is the result of increased blood flow at the capillary bed due to arteriolar dilation and dilation of precapillary sphincters?

    <p>Vascular congestion</p> Signup and view all the answers

    What is the function of C5a and C3a in the context of acute inflammation?

    <p>Stimulating histamine release</p> Signup and view all the answers

    What is the role of lysosomes in phagocytosis?

    <p>To break down and digest phagocytosed pathogens</p> Signup and view all the answers

    What is the outcome of vasodilation and fluid loss in acute inflammation?

    <p>Vascular congestion</p> Signup and view all the answers

    What type of signaling molecules are interferons?

    <p>Autocrine and paracrine</p> Signup and view all the answers

    What is the role of macrophages in the production of nitric oxide?

    <p>Producing nitric oxide at high concentrations</p> Signup and view all the answers

    What is the consequence of a MyD88 deficiency?

    <p>Suffer frequent and severe bacterial infections and antiviral responses generally unaffected</p> Signup and view all the answers

    What is the effect of platelet activating factor at low concentrations?

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

    What do Nod-like receptors detect?

    <p>Products derived from the intracellular degradation of phagocytosed pathogens</p> Signup and view all the answers

    What is the function of Toll-like receptors?

    <p>To elicit responses such as phagocytosis and cytokine secretion</p> Signup and view all the answers

    What is the role of cytokines secreted in response to Toll-like receptors?

    <p>To influence the differentiation of a wide variety of cells</p> Signup and view all the answers

    What is the function of pattern recognition receptors?

    <p>To recognize pathogen-associated molecular patterns</p> Signup and view all the answers

    What is the primary function of cytokines?

    <p>To mediate the activity of cells, including leukocytes</p> Signup and view all the answers

    What is the characteristic of CXC chemokines?

    <p>They are angiogenic and attract neutrophils</p> Signup and view all the answers

    What is the primary function of chemokines?

    <p>To induce the movement of leukocytes along a concentration gradient</p> Signup and view all the answers

    What is the role of CC chemokines?

    <p>They act on a wide variety of leukocytes</p> Signup and view all the answers

    What is the result of chemokines binding to cell-surface receptors?

    <p>Induction of leukocyte movement along a concentration gradient</p> Signup and view all the answers

    What is the function of cytokines in regards to stem cells?

    <p>To increase the production of stem cells</p> Signup and view all the answers

    What is the function of histamine in the emigration and activation of leukocytes?

    <p>Increasing the expression of selectin on endothelial cells</p> Signup and view all the answers

    What is the role of ICAM in the emigration and activation of leukocytes?

    <p>Mediating the tight adhesion of leukocytes to the endothelium</p> Signup and view all the answers

    What is the effect of TNF and IL1 on endothelial cells?

    <p>Increasing the expression of ICAM</p> Signup and view all the answers

    What is the role of chemokines in the emigration and activation of leukocytes?

    <p>Guiding leukocytes to the site of inflammation</p> Signup and view all the answers

    What is the purpose of the stable adhesion stage in the emigration and activation of leukocytes?

    <p>Forming tight adhesion bonds between leukocytes and endothelial cells</p> Signup and view all the answers

    What is the role of integrins in the emigration and activation of leukocytes?

    <p>Mediating the tight adhesion of leukocytes to the endothelium</p> Signup and view all the answers

    What is the effect of chemotactic agents on leukocytes?

    <p>Guiding them to the site of inflammation</p> Signup and view all the answers

    What is the significance of the concentration gradient of chemotactic agents?

    <p>It guides leukocytes to the site of inflammation</p> Signup and view all the answers

    Study Notes

    Cathelicidins and Defensins

    • Cathelicidins are stored in neutrophil granules and can be released within tissues in response to inflammation
    • They can kill microbes extracellularly when released when neutrophils die during inflammation
    • They can also kill microbes intracellularly after a cell (e.g. neutrophil) phagocytoses a pathogen

    Phagocytosis and Phagocytes

    • Phagocytosis is a key role in innate immunity as they can recognize, ingest, and destroy many pathogens without aid of an adaptive immune response
    • Phagocytosis can also occur after an antibody has bound to an antigen – the antibody can act as a “signal” that triggers efficient phagocytosis
    • Macrophages and neutrophils are the major phagocytes in the body

    Phagocytic Cells

    • Monocytes and macrophages: pro-monocytes (BM) → monocyte (blood) → macrophage/macrophage-like cells (tissues)
    • Long-lived cells resident within the tissues
    • Neutrophils: derived from hematopoietic precursors in the BM, non-dividing, short-lived cell type in blood (dominant WBC)

    Pattern Recognition

    • Evolutionarily conserved mechanism for recognizing common, conserved ‘signs’ of microbial infection, physiological stress, or other damage
    • Recognition is immediate, does not require prior recognition, and activates several arms of the innate (and adaptive) immune response
    • Responses are elicited via the engagement of Pattern Recognition Receptors (PRRs) found on phagocytes, in response to:
      • Pathogen Associated Molecular Patterns (PAMPs)
      • Danger Associated Molecular Patterns (DAMPs)

    Pattern Recognition Receptors

    • Examples of PRRs:
      • Toll-like receptors
      • Nod-like receptors
      • Lectins
    • Elicit responses such as:
      • Phagocytosis
      • Cytokine secretion

    Phagocytosis – the Process

      1. A pattern-recognition-receptor (PRR) binds to a microbe or bit of debris, OR an opsonin created by another cell binds to the microbe
      1. The microbe is engulfed – the PRR receptors signal the cell membrane to approach, coat, and then surround the sites where the receptor is bound
    • 3 & 4. The phagosome is formed, mediated by intracellular signaling events and actin polymerization

    Acute Inflammation

    • Steps of Acute Inflammation: A. Alteration of vascular caliber - vasodilation B. Enhancement of vascular permeability
    • Vasodilation and fluid loss (due to increased permeability) lead to slower blood flow, known as vascular congestion
    • This helps with margination of leukocytes

    Prostaglandins and Leukotrienes

    • Prostaglandins and leukotrienes are produced when PLA2 generates arachidonic acid from membrane phospholipids
    • Different types of cyclooxygenases produce different types of prostaglandins from arachidonic acid
    • Important prostaglandins – PGE2, PGD2, and PGI2 cause vasodilation and increase vascular permeability, important acute inflammatory mediators
    • Lipoxins are generated from arachidonic acid by 12-lipoxygenase – they decrease inflammation

    Vascular Permeability

    • Increased vascular permeability is due to contraction of endothelial cells
    • Occurs mainly in venules, often short-lived
    • Endothelial damage can also cause increased permeability

    Leukocyte Migration

    • Steps: a. Margination – leukocytes migrate towards vessel wall b. Rolling – formation & dissociation of adhesion bonds between leukocytes and endothelial cells
    • Activation by chemokines presented on endothelial cells is required before the leukocyte can form stable adhesion bonds

    Innate Immunity

    • Innate immune defenses exist in all individuals and act within minutes to hours after encountering an infectious agent.
    • Innate immunity discriminates effectively between host cells and pathogens.

    Barriers

    • Chemical barriers:
      • Lysozyme: present in secretions (mucus, tears, milk, saliva), breaks apart the peptidoglycan wall of bacterial cell walls through hydrolysis.
      • Defensins: small, heterogeneous, cationic peptides that kill Gram-negative and Gram-positive bacteria, some enveloped viruses, and fungi through multiple antimicrobial effects (destabilizing membranes, proteolytic degradation of bacterial proteins, inhibiting viral binding and entry, and inhibiting virus particle assembly).

    Pattern Recognition Receptors

    • Examples of pattern recognition receptors (PRRs):
      • Lectins
      • Toll-like receptors (TLRs)
      • Nod-like receptors
    • PRRs elicit responses such as phagocytosis and cytokine secretion.

    Toll-Like Receptors

    • TLRs are a family of 10 cell membrane receptors with variable specificity for a range of pathogens.
    • Ligands can include LPS, dsRNA, ssRNA, DNA, and flagellin.
    • Cytokines secreted in response to TLRs include inflammatory cytokines (IL-1b, IL-6, CXCL8, IL-12, TNFa) and interferons (IFNa, IFNb, IFNl).

    Nod-Like Receptors

    • Nod-like receptors are intracellular receptors that detect products derived from the intracellular degradation of phagocytosed pathogens and recognize damage-associated molecular patterns (DAMPs) associated with cellular stress.
    • They activate the expression of inflammatory cytokines.

    Acute Inflammation

    • Steps of acute inflammation:
      1. Alteration of vascular caliber - vasodilation
      2. Increased permeability and fluid loss
      3. Emigration and activation of leukocytes
      4. Chemotaxis of leukocytes to sites of injury or infection

    Leukocyte Migration

    • Leukocyte migration involves:
      1. Rolling: selectin expression by endothelial cells
      2. Tight adhesion: ICAM expression by endothelial cells and integrin affinity
      3. Diapedesis/transmigration: leukocyte migration through the endothelium
      4. Chemotaxis: migration to sites of injury or infection in response to chemotactic agents (leukotriene B4, bacterial products, activated complement, and chemokines)

    Chemokines

    • Chemokines are structurally-related cytokines that:
      • Bind to cell-surface receptors (usually leukocytes)
      • Induce movement of leukocytes along the chemokine concentration gradient
      • Mediate adhesion of leukocytes for the purposes of differentiation, inflammation, and migration
    • There are two major chemokine families: CXC and CC.

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    This quiz covers the role of defensins and cathelicidins in the immune system, including their storage in neutrophil granules and release during inflammation, as well as their ability to kill microbes both extracellularly and intracellularly. It also touches on phagocytosis and phagocytes as a first line of defense.

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