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Flashcards

Macrophages

Eleanor Smith Immunology and Microbiology FHS Part I English 41 cards

Cards in this deck (41)

  1. 1Monocyte cluster of differentiationCD14
  2. 2Macrophage cluster of differentiationCD68
  3. 3Macrophage function in tissue maintenanceTissue homeostasis via scavenger receptors
    Tissue remodelling e.g. in development
    Trophic functions e.g. in bone marrow
    Apoptotic cell clearance
    Tissue repair e.g. in wound repair
  4. 4Macrophage function in immune regulationKey cell type in acute and chronic inflammation
    Production of cytokines and growth factors
    Antigen presentation (professional APC)
  5. 5Macrophage function in pathogen controlSentinel cells - initiate acute inflammation
    Pathogen phagocytosis
    Pathogen killing via reactive oxygen and nitrogen
  6. 6Embryonic origin-derived macrophagesKupffer cell (liver)
    Marginal zone macrophages (kidneys)
    Red pulp macrophages (kidneys)
    Microglia (brain)
    Peritoneal macrophage (stomach)
    Alveolar macrophage (lungs)
  7. 7Adult Ly6C^(hi) monocyte-derived macrophagesOsteoclasts (bone and joints)
    Mammary gland macrophages (breast)
    Muscularis gut macrophage (intestines)
    Intestinal lamina propia macrophage (intestines)
  8. 8Macrophage populationsLess flexible programming - determined during ontogeny
    Specific transcription factors and epigenetic modifications = direct lineage commitment
  9. 9Macrophage activation phenotypesFlexible programming - driven by microenvironmental signals
    Cytokines, transcription factors and epigenetic changes modulate phenotypic and functional plasticity
  10. 10Different macrophage typesM0
    M1
    M2
    Myeloid-derived dendritic cells (mDCs)
    Tumour Associated Macrophages (TAMs)
    Myeloid-derived suppressor cells (MDSCs)
  11. 11Acute phase reactantsInflammation markers that increase or decrease in the patient's serum during times of acute tissue injury or inflammation
    - Mannose binding lectin (MBL)
    - C-reactive protein (CRP)
  12. 12Intracellular recognition systemsProtein kinase PKR (dsRNA activated)
    2' - 5' oligoadenylate synthase (OAS)
    NOD, RIG and some TLR proteins
  13. 13Macrophage cell surface receptorsMacrophage mannose receptor (MMR)
    Macrophage scavenger receptor (SR-AI and SR-AII)
    Macrophage scavenger receptor MARCO
    Dectin-1 (beta-glucan receptor)
    Toll-like receptors (TLRs)
  14. 14LectinsProteins that recognise specific sugar residues
  15. 15Scavenger receptorsFamily of 8 classes of receptor (A-H)
    SR-AI
    CD36
    dSR-CI
    CD68
    LOX-1
    SREC
    SR-PSOX
    FEEL-1
  16. 16Almost all scavenger receptors detectE. coli
    S. aureus
  17. 17Lectin receptorsC-type (MMR)
    C-type lectin-like (betaGR-Dectin-1)
    Sialic acid (Sialoadhesin)
    Others (MAC-2)
  18. 18Cell wall of Candida albicans (yeast)Mannoprotein (30-40%)
    beta-glucan (50-60%)
    beta-glucan-chitin (0.5-3%)
    Plasma membrane
  19. 19YeastMicroscopic fungi
  20. 20Candida albicansMost prevalent fungus in humans
    Normal part of commensal
    Opportunistically causes thrush
  21. 21Dectin-1 receptorMajor macrophage receptor for beta-glucan
    Classic non-opsonic receptor
    Uptake of fungal beta-glucan stimulates macrophage TNF-alpha secretion
    Expressed by most macrophage populations and some dendritic cells
  22. 22Activation of the TLRsActivate the transcription factor NF-kB via homologous protein kinases (Pelle and IRAK)
  23. 23TLR1:TLR2 heterodimerRecognises:
    Lipopeptides from bacteria
    GPI from parasites
    Found on:
    Monocytes, dendritic cells, eosinophils, basophils, mast cells
    Cellular location:
    Plasma membrane
  24. 24TLR2:TLR6 heterodimerLigands:
    Lipoteichoic acid on GP bacteria
    Zymosan on yeast
    Found on:
    Monocytes, dendritic cells, eosinophils, basophils, mast cells
    Cellular location:
    Plasma membrane
  25. 25TLR3Ligands:
    dsRNA on viruses
    Found on:
    Natural killer cells
    Cellular location:
    Endosomes
  26. 26TLR4:TLR4 homodimerLigand:
    Lipopolysaccharide on GN bacteria
    Found on:
    Macrophages, dendritic cells, mast cells and eosinophils
    Cellular location:
    Plasma membrane
  27. 27TLR5Ligand:
    Flagellin on motile bacteria
    Found on:
    Intestinal epithelium
    Cellular location:
    Plasma membrane
  28. 28TLR7Ligand:
    ssRNA on viruses (e.g. HIV)
    Found on:
    Plasmacytoid dendritic cells, NK cells, eosinophils, B cells
    Cellular location:
    Endosome
  29. 29TLR8Ligand:
    ssRNA on viruses (e.g. influenza)
    Found on:
    Natural killer cells
    Cellular location:
    Endosomes
  30. 30TLR9Ligand:
    Unmethylated CpG-rich DNA on bacteria and viruses (e.g. herpes)
    Found on:
    Plasmacytoid dendritic cells, B cells, eosinophils, basophils
    Cellular location:
    Endosomes
  31. 31TLR10 homodimer and heterodimers with TLR1 and TLR2Ligand:
    unknown
    Found on:
    Plasmacytoid dendritic cells, B cells, eosinophils, basophils
    Cellular location:
    Unknown
  32. 32LPS recognition and signallingLPS transport in the plasma is mediated by the protein LBP. LBP transfers LPS to the macrophage CD14 receptor. CD14 facilitates TLR4 recognition of LPS. This requires a small protein bound to TLR4 - MD-2. TLR4 signalling inside macrophages involves the proteins Myd88 and IRAK-4. LPS treatment of macrophages stimulates the secretion of TNF-alpha, IL-1, IL-6, IL-10 and inflammatory mediators inc. chemokines
  33. 33TLR2 recognises many PAMPsMediate responses to LPS when over-expressed
    S. aureus peptidoglycan and lipoproteins
    GPI anchors from Trypanosoma cruzi
    Lipoarabinomannan from M. tuberculosis
    Zymosan from yeast cell walls
  34. 34TLR2 recognises even more PAMPs by...Dimerising with TLR1 (lipopeptides) and TLR6 (lipoteichoic acid)
  35. 35Effects of IL-6Causes fever and induces acute-phase protein production by hepatocytes
  36. 36Effects of IL-12Activates natural killer cells
  37. 37Effects of TNF-alphaActivates vascular endothelium and increases vascular permeability, which leads to an increased entry of complement components and cells to tissue, and increased fluid drainage to lymph nodes. Systemically it causes fever, mobilisation of metabolites and shock
  38. 38IL-1betaActivates vascular endothelium, activates lymphocytes, causes local tissue destruction and increases the access of effector cells. Systemically it causes a fever and the production of IL-6
  39. 39CXCL8Chemotactic factor recruits neutrophils and basophils to the site of infection
  40. 40Nucleotide-binding domain leucine-rich repeat containing receptors (NLRs)NLRP are a central component of the inflammasome, a molecular assembly that regulates IL-1 secretion in response to bacterial toxins and particulates
  41. 41How TLR4 activation leads to cytokine secretionA complex of TLR4, MD-2, CD14 and LPS assemble on the macrophage surface
    MyD88 binds TLR4 and activates IRAK4 to phosphorylate TRAF6, which leads to the phosphorylation and activation of IKK
    IKK phosphorylates IkB, causing its degradation and release of NFkB
    NFkB enters the nucleus and activates the genes of inflammatory cytokines which are synthesised in the cytoplasm and secreted by the ER

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FHS Part I Immunology and Microbiology (Innate Immunity) Flashcards on Macrophages, created by Eleanor Smith on 19/12/2019.
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Eleanor Smith
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