Immuno: Phagocytosis, Inflammation Flashcards Preview

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Flashcards in Immuno: Phagocytosis, Inflammation Deck (22)
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1

describe PAMPs (pathogen associated molecular patterns)

  • essential to microbial survival and metabolism which makes them relatively invariant and evolutionary stable
  • examples:
    • peptidoglycan found in bacterial cell walls
    • flagellin, a protein found in bacterial flagella
    • LPS from the outer membrane of gram-negative bacteria
    • lipopeptides, molecules expressed by most bacteria
    • nucleic acids such as viral ds RNA

2

which toll like receptors (TLRs) are associated with viruses?

TLR 3, 7, 8, 9

3

describe opsonization

  • addition of an opsonin, to ensure cell is readily identified, and more efficiently taken by phagocytes (enhance phagocytosis)
  • phagocytes have specific receptors for this mechanism:
    • CR1 - complement receptor for C3b fragment (complement cascade)
    • Fc receptors for Fc region of immunoglobulins (antibodies)

4

describe the opsonins

  • antibodies: opsonize the antigen
    • Fc region of antibody binds to phagocytic cell receptors
    • phagocytic cells do not have Fc receptors for IgM but IgM activates complement to do the opsonization
    • main opsonin: IgG
  • complement molecules: opsonize the antigen
    • opsonized antigen binds to CR1 receptor on the phagocyte
    • main opsonins: C3b, C4b and C1q
  • circulating proteins (secreted pattern recognition receptors): pentraxins, ficolins, collectins (Mannose-binding lectin, MBL) 

5

describe the mechanism of phagocytic recognition, engulfment and killing

  • chemotaxis and ingestion: phagocytes migrate and recognize PAMPs that drive initiation and perpetuation of the inflammatory response
  • phagolysosome formation: lysosome fused with phagosome (death ~30 min)
  • destruction and elimination
    • oxygen-dependent system (respiratory burst)
    • liberation of lactic acid, lysozyme and nitric oxide

6

describe oxygen-independent phagocytic killing

  • lysozyme: split peptidoglycan
  • lactoferrin and reactive nitrogen intermediates: deprive pathogens of iron
  • proteolytic enzymes: degrade dead microbes
  • defensins, cathepsin G and cationic proteins: damage microbial membrane

7

describe oxygen-dependent degradation (oxidative burst)

  • NADPH oxidase produces superoxide which recombines with other molecules to produce reactive free radicals
  • the superoxide reacts with NO forming peroxynitrate
  • myeloperoxidase uses the derived H2O2 to produce hypochlorite (antimicrobial)
  • to combat infxns, immune cells use NADPH oxidase
  • absence of NADPH oxidase will prevent the formation of ROS and resulti n chronic granulomatous disease (CGD)

8

describe lab tests for CGD

  • the nitroblue-tetrazolium (NBT) test 
  • the higher the blue socre, the better the cell is at producing ROS
  • in CGD, the test will be negative

9

describe Chediak-Higashi syndrome

  • autosomal recessive disorder that arises from a mutation of a lysosomal trafficking regulator protein
  • the disease is characterized by large lysosome vesicles in phagocytes with poor killing action leading to:
    • susceptibility to infxns
    • abnormalities in nuclear structure of leukocyte
    • anemias
    • hepatomegaly
    • Dohle bodies (cytoplasmic inclusions in neutrophils)
  • clinical presentation: albinism, neutropenia, periodontal disease, recurrent infxns

10

describe the steps of the inflammatory response

  • injury/immediate rxns:
    • injury/damage causes release of chemical mediators, cytokines, histamine
    • attracts leukocytes to the site of injury
  • vascular reactions:
    • histamine causes vasodilation, increased vessel permeability (redness and heat)
    • delivers leukocytes, fluid and clotting factors to the site of injury
  • edema and pus formation:
    • edema (swelling) helps contain the infxns and attract neutrophils
    • debris and WBCs form pus
    • bradykinin stimulates pain receptors 

11

summarize the mediators of acute inflammation

12

describe the cell adhesion molecules (CAMs)

  • selectins
    • glycoproteins
    • bind to carbohydrates
    • expressed on leukocytes and endothelial cells
  • mucins
    • proteins
    • present CHO ligands to selectins
    • present on endothelial cells and neutrophils
  • integrins
    • proteins; heterodimers
    • expressed on leukocytes
    • bind to Ig superfamily molecules
  • ICAMs
    • Ig CAMs
    • expressed on endothelial cells
    • bind to integrins

13

describe the 4 steps of leukocyte extravasation

  • rolling
    • mediated by binding of selectins (endothelium) to mucin-like CAMs (leukocyte)
  • activation
    • chemokine binding induces conformational change in integrins (leukocyte)
  • arrest/adhesion
    • integrins now capable of binding Ig-superfamily CAMS (endothelium)
  • transendothelial migration
    • migration through tight junctions of inflamed endothelium

14

describe leukocyte adhesion defect (LAD)

  • patients with LAD1 have an inherited defect that causes a deficiency of the B-2 integrin subunit (CD18)
    • this subunit is involved in the formation fo the B-2 integrins by dimerization with different CD11 subunits
  • the main function of these proteins is to allow neutrophiles to make their way out of the blood stream by adhering to the different ligand ICAM-1
  • in LAD1 patients, neutrophils cannot extravasate and fight against bacteria in tissues

15

describe the Kinin system (mediator of inflammation)

  • Hagman factor (XII) activation leads to bradykinin formation 
    • increased vasodilation, permeability, pain and smooth muscle contraction

16

describe the clotting system (mediator of inflammation)

  • Hagman factor activation leads to increased thrombin and clot formation that stops bleeding
  • forms a fibrinous meshwork at an injured or inflamed site
    • prevents the spread of infxn and keeps microbes at the site of inflammatory cell activity
    • provides a framework for repair and healing
    • main substance: fibrin

17

describe the fibrinolytic system (mediator of inflammation)

  • Hagman factor activation leads to plasmin activation
  • Plasmin breaks down clots and activates complement

18

describe the complement system (mediator of inflammation)

  • anaphylatoxins activate mast cells, which increase permeability

19

describe the early events of the inflammatory process

  • acute inflammation
    • increased E-selectin and P-selectin on endothelium
      • due to thrombin, histamine, IL-1, TNFa
    • attachment of circulating neutrophils
    • transendothelial migration
  • infiltration of neutrophils
    • chemotaxis
      • IL-8, leukotriene B4, C5a, fibrinopeptides act as chemokines
  • phagocytosis
    • increased Fc receptor expression, complement receptors, stimulation of cytotoxic compounds (free radicals)

20

describe the localized events of the inflammatory process

  • vasodilation
    • bradykinin
  • vascular permeability
    • bradykinin, fibrin breakdown, histamine
  • neutrophils release chemokines
    • chemoattractant for macrophages
    • macrophages arrive 5-6 hours after inflammation begins
  • activated tissue macrophages
    • secrete IL-1, IL-6, TNFa

21

describe the systemic acute phase response of the inflammatory process

  • mediated by IL-1, IL-6, TNFa
    • act on hypothalamus: fever
    • act on liver: increase acute phase proteins
    • act on bone marrow: increase leukocytosis
  • increased acute phase proteins
    • C-reactive protein, fibrinogen, haptoglobin, amyloid, ceruloplasmin
    • activates complement
  • increase leukocytosis
  • left shift, increase in immature cells (bands)

22

describe the chronic inflammatory response

  • inflammation lasting 2 weeks or longer
  • often related to an unsuccessful acute inflammatory response
  • IFNγ and TNFa play a major role