GoConqr hat ein neues Design! Sag uns, wie es dir gefällt.

Kostenlos registrieren

Karteikarten

Innate Immunity I

Marissa Alvarez Immunology Graduate Englisch 60 Karten

Innate Immunity I

Karten in diesem Stapel (60)

  1. 1Innate Immunity Mechanisms1) Mechanical Barriers
    2) Soluble Mediators
    3) Cellular Defense Mechanisms
  2. 2Innate Immunity Mechanisms Mechanical Barriers/surface secretion:skin, acidic pH in stomach, cilia
  3. 3Innate Immunity Mechanisms Soluble MediatorsLysozymes, basic proteins, complement, cytokines
  4. 4Innate Immunity Mechanisms Cellular Defense Mechanismsnatural killer (NK) cells, neutrophils (PMNs), macrophages, mast cells, basophils, eosinophils
  5. 5Compare and contrast: Innate and Adaptive immunityInnate immunity: not as specific, more broad
    -coded germ line (the genes code for what is made - no change)
    -nonclonal: identical receptors on ALL cells
    Adaptive immunity: more specific, more diversity (somatic gene rearrangements)
    -clonal: clones of lymphocytes w/distinct specificities express different receptors
    Both:
    distinguish between self and non-self peptides
    -have similar effector mechanisms for killing pathogens    Compare and contrast: Innate and Adaptive immunity
  6. 6Inflammationan innate response that involves response that involves cellular & physiological elements
    Can be:
    1) Localized: Infection or wounding can trigger:
    Capillary vasodilation – redness (erythrema)
    Capillary vasopermeation – swelling (edema)
    Cellular influx
    2) ‘Vasoactive molecules’ (pro-inflammatory) released by white blood cells (WBC)
    3) Systemic - Infection ONLY
    Fever
    Increase in WBC
    Changes in serum proteins (e.g., Acute
    phase proteins)
    Diagnostic for infection
    **Excessive inflammation causes immunopathogies
    -->Critical to the start of the immune response, but if you cannot turn it off then it becomes pathogenic
  7. 7Buildup of ImmunityBuildup of Immunity
  8. 8The Acute Phase Response Black Bile & Medieval BleedingSystemic inflammatory response
    Fever, Changes in “Acute Phase Proteins”
    e.g., CRP, Complement proteins, plasminogen, fibrinogen, etc.
    Fibrinogen causes RBCs to stick together to form a Rouleaux (“Ru-Lo”)
    = “Black bile”
    Fast sedimentation rate (indicates some kind of septic response)
    Was bled to cure illness    The Acute Phase Response Black Bile & Medieval Bleeding
  9. 9"Danger Signals" activate innate cells“Danger signals” = PAMPs
    “Pathogen-associated molecular patterns”
    -Molecules of pathogens or wounding
    -General structure/widespread occurrence
    -Conserved in evolution
  10. 10PAMPS bind to Receptors called PRRs “Pattern Recognition Receptor”“Pattern Recognition Receptor” (PRRs):
    Toll-like receptors (TLR)
    NOD-like receptors (NLR)
    RIG-like receptors (RLR)
    Caspase Recruitment Domain (CARD)-containing proteins
    **Very important to DC (dendritic cell) activation
    -Upregulates major histocompatibility complex (MHC) (HLA) expression
    -Allows T-cell activation
  11. 11Some Danger Signals IncludeViral dsRNA
    Viral ssRNA
    Bacterial LPS, flagellin, pili
    Bacteral and fungal cell wall components
    Microbial polysaccharides
    Reactive oxygen molecules:
    H202, OH-, O2-
    Certain cellular molecules
  12. 12TLR4 (Toll-like Receptor 4) recognizes:EXTRACELLULAR
    things like LPS (can recognize conserved areas of pathogens)
  13. 13Location of pathogen-associated molecular patterns (PAMPs)NLR (nod-like) and RLR's (rig-like receptors) are intracellular
    TLR's (toll-like receptors) are extracellular    Location of pathogen-associated molecular patterns (PAMPs)
  14. 14TLR (toll-like receptor) Ligands-Contain leucine-rich repeats
    -Toll/IL-1 receptor (TIR) homology domain in their cytoplasmic tails    TLR (toll-like receptor) Ligands
  15. 15TL4 recognizesLPS
  16. 16TLR5 recognizesbacterial flagellin
  17. 17TLR3 recognizesdsRNA
  18. 18TLR7 & TLR8 recognizessRNA
  19. 19TLR9 recognizesCpG DNA
    short interspersed DNA sequences that deviate significantly from the average genomic pattern by being GC-rich, CpG-rich, and predominantly non-methylated
  20. 20TLR Signaling Two Core signaling proteins:MyD88 and TRIFTLR Signaling Two Core signaling proteins:
  21. 21MyD88 and TRIF (core TLR signaling proteins)Lead to acute inflammation and stimulation of adaptive immune responses
    -downstream mediators of the TLR's
    -activate BOTH (not smart enough to to do one or the other in innate immunity)
  22. 22TLRs in the pathogenesis of Human DiseaseCDs: surface markers on cells (allow to distinguish)
    *Know the 5 Genetic mutations    TLRs in the pathogenesis of Human Disease
  23. 23TLR4: D299G Mutation Results indecreased response to inhaled LPS
  24. 24NEMO Mutation: (several polymorphisms) results inincreased bacterial and viral infections
  25. 25IkBa: S321 Mutation results inimpaired T cell memory
  26. 26IRAK4: stop codons 287, 293 Mutation results inincreased gram-positive infections
  27. 27CARDs (Caspase Recruitment Domain- containing proteins) in human disease: CARD9 deficiency mutationReduced DC (dendritic cell) activation of specific T cell subsets
    -Leads to increased susceptibility of Candida albicans    CARDs (Caspase Recruitment Domain- containing proteins) in human disease: CARD9 deficiency mutation
  28. 28Cytokines**COMMUNICATION network for cells (recruited to different sites of infection)
    -Small soluble proteins
    -Important for development and immune system maturation/function
    *specific functions!!
  29. 29The cytokines of innate immunity:IL10
    TNF
    TNF1alpha and TNF1beta
  30. 30Cytokine IL10anti-inflammatory
    (targets macrophages and dendritic cells)
  31. 31Cytokine TNFpro-inflammatory
    (many targets-neutrophils, endothelia, etc.)
  32. 32Cytokines TNF1alpha and TNF2betaVIRAL response
    (targets every cell because anybody could be infected by a virus)
  33. 33Chemokines and Chemokine ReceptorsLow molecular weight proteins
    Highly conserved secondary structure
    Two types: CC or CXC
    REGULATE:
    1) Inflammation
    2) Leukocyte trafficking (indicates where the lymphocyte should go in the lymph node)
    3) Immune cell differentiation
  34. 34Chemokine Subfamily: HIV Co-receptors Main receptor?CCR5 and CXCR4
    (main receptor = CDR4)
  35. 35What is complement? Four principles of complement activation1) Lysis of the target cell
    2) Opsonization (deposit proteins that enhance uptake of the bacteria)
    3) Activation of inflammatory response
    4) Clearance of Immune Complexes    What is complement? Four principles of complement activation
  36. 36Complement involves a “proteolytic activation cascade”Complement involves a “proteolytic activation cascade”
  37. 37What are the 3 pathways of initiation? Classical (antibody required) Alternative (innate) Lectin (innate)1) Classical (antibody required)
    -- initiated by Ab bound to AG (antibody:antigen complexes)
    2) Alternative (innate)
    -- does not involve Ab binding
    3) Lectin (innate)
    -- activated by mannose-binding lectin
  38. 38All three pathways of complement converge at?C3 Convertase
  39. 39C3 Convertase can split into:C3a and 5a
    and C3b
  40. 40C3a and C5aanaphylatoxins
    INFLAMMATORY
    recruit phagocytes
  41. 41C3bOPSONIZATION
    (deposit proteins that enhance uptake of the bacteria)
    AND can split into C5b-C9
  42. 42C5b, C6, C7, C8, and C9 or C5b-C9forms the "MAC" (Membrane Attack Complex) complex
    -lysis of pathogens and cells by forming pores
  43. 43The Classical Pathway involves 3 Stages Stage 1:Initiation begins with C1 binding
    to Ab bound to Ag (antigen:antibody complex)
    Bind to Fc part of Ab
    (antigen binds to Fc part of Ab)    The Classical Pathway involves 3 Stages Stage 1:
  44. 44The Classical Pathway involves 3 Stages Stage 2:Activated C1 triggers activation of C4 and then C2
    -- to form C3 Convertase
    **Activation of C3 is an important AMPLIFICATION step
    -C3 convertase C3b (for opsonization)
  45. 45The Classical Pathway involves 3 Stages Stage 3:C3 Convertase also activates:
    anaphylatoxins – C3a & C5a
    C5a is the MOST potent and dominant anaphylatoxin
  46. 46What do C5a and C3a do?1) increase vascular permeability
    -allowing increased fluid leakage and inflammatory runs
    -also increases migration of PMNs from blood to tissue and vice versa    What do C5a and C3a do?
  47. 47C5b triggers formation of the Membrane Attack ComplexC5b triggers formation
    -C5b678 = center and C9 surrounds it to form the MAC (membrane attack complex)
    -pore lyses target cells    C5b triggers formation of the Membrane Attack Complex
  48. 48MAC (Membrane attack complex) is MOST effective against:Gram-negative bateria
    Enveloped Viruses
  49. 49The Alternative pathwayC3 spontaneously turns over C3a and C3b
    -Pathogens and Immune complexes
    --Binding to other protein "factors"
    creates alternative C3 and C5 Covertases
    leading to MAC formation
    *Factor D, Factor B, Properdin
  50. 50Alternative Pathway *Factor D, Factor B, Properdin*Alternative Pathway *Factor D, Factor B, Properdin*
  51. 51The Lectin Pathway (MB Lectin)*Mannose Binding Lectin*
    -binds to bacterial glycoproteins
    -Creates C1-like activator (activating C4, C2 --> C3 convertase)
  52. 52Complement RegualtionNegative regulatory step of complement: prevents you from getting affected by complement "attack"
  53. 53Complement Regulation (1) liability of? (2) Sialic acid inactivates? (3) Regulatory proteins?1) Lability of protein fragments
    -rapid, spontaneous inactivation
    2) Sialic acid in glycoproteins
    inactivates C3b on body cells
    3) Regulatory proteins
    e.g., C1 inhibitor
    Consequence of problems w/regulation of complement: Hereditary Angiodema    Complement Regulation (1) liability of? (2) Sialic acid inactivates? (3) Regulatory proteins?
  54. 54Complement receptors mediate other functions: -- immune complex clearing -- chemotaxis -- opsonizationComplement receptors mediate other functions: -- immune complex clearing -- chemotaxis -- opsonization
  55. 55How does C3b cause opsonization by phagocytic cells?Roles for both Fc (binds IgG) and Complement receptors
    C3b is primary opsonin binds to CR1 receptor
    Coating of viruses blocks
    receptors and enhances opsonization    How does C3b cause opsonization by phagocytic cells?
  56. 56RBCs and CR1 play major role in immune complex clearanceImmune complexes generate C3b
    -- via classical or alternative pathways
    Transport to spleen & liver
    for Phagocytosis
    Deficiencies in complement-mediated
    immune-complex clearing are major cause of Systemic Lupus Erythromatosus (SLE) (C2 deficiency)    RBCs and CR1 play major role in immune complex clearance
  57. 57Complement and MedicineTargeted biologics
    Eculizumab
    (1) Humanize monoclonal
    binds to complement component C5, inhibiting its cleavage and preventing activation of the lytic pathway
    --Approved to treat paroxysmal nocturnal hemoglobinuria (PNH)
    ---Acquired complement deficiency – lack regulatory proteins
    BLACK BOX WARNING: Increased risk of N. meningitidis infection
  58. 58BUILDUP OF IMMUNITYBUILDUP OF IMMUNITY
  59. 59Macrophage Killing Mechanisms(1) External: Mediator secretion
    (2) Internal: requires phagocytosis
    Receptor mediated, or not
    Antibody Fc receptors, PRR, etc.
    (3) O2 dependent: “respiratory burst” O2 Independent: Enzymes (TNF)    Macrophage Killing Mechanisms
  60. 60Neutrophil (PMNs) Mechanisms(1) Rapid responders FIRST responders!
    (2) Degranulation & phagocytosis
    (3) Extracellular Traps:
    Chromatin & antimicrobial enzymes (non-inflammatory, explodes and forms web to inhibit growth of bacteria)

Informationen

Beschreibung
Immunology UNC MED 2017
Erstellt von
Marissa Alvarez
Aufrufe
32
Bewertung

Feedback

Worum geht es?

Wie gefällt dir das neue Design?

Dein Eindruck