Immunology T1C3

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mobeth89
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65162
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Immunology T1C3
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2011-02-15 23:39:35
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immunology
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Chapter 3
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  1. innate immunity
    • first line of defense; response is quick
    • includes physical, chemical and cellular barriers
    • no immunological memory
    • found in all multicelllar plants and animals
  2. physical barriers
    • skin
    • mucous membranes
  3. chemical barriers
    • acidity of the stomach contents
    • specialized soluble molecules that possess antimicrobial activity
  4. skin
    • epidermis - consists of several tiers of tighly packed epithelial cell (mostly dead) filled with keratin
    • dermis - thicker layer composed of connective tissue, blood vessels, hair follicles, sebaceous glands, sweat glands
  5. protein produced by skin with antimicrobial activity?
    psoriasin (prevents colonization of E. coli)
  6. what are lined with mucous membranes?
    • alimentary tracts
    • trespiratory tracts
    • urinogenital tracts
    • eyes
  7. what washes away the invaders and also contains antibacterial and antiviral substances?
    • saliva
    • tears
    • mucous secretion
  8. some organisms are able to evade the defenses of the mucous membranes
    • influenza virus - attach firmly to the cells in the mucous membrane or respiratory tract
    • gonorrhea producing bacteria - surface projections that bind to the epithelial cells of hte urogenital tract
    • adherence of bacteria to a mucous membrane is mediated by fimbriae or pilli
    • pilli can interact with certain glycoproteins or glycolipids specific to the epithelial cells of the mucous membrane of a particular tissue
  9. the immune system responds to invasion with two critical functions
    • detection (detected by sensors- where the host must deciminate whether it is itself or a nonself aka pathogen)
    • attack (attaked by various mechanisms)
  10. what is most important for innate immunity?
    • PRRs = Pattern Recognition Receptors
    • PAMPs = Pathogen-Associated Molecular Patterns
  11. PRRs
    Pattern Recognition Receptors
    • recognize particular molecular pattern; also present in host
    • membrane-bound toll-like receptors (TLR)
    • each TLR reacts with specific microbial product
  12. PAMPs
    Pathogen-Associated Molecular Patterns
    such patterns are found in pathogens; NOT in the host
  13. Soluble PRR
    • Mannose-binding lectin (MBL)
    • C-reactive protein (CRP)
    • --these soluble mediators are able to activate complement system
    • --when a pathogen bears PAMP recognized by these mediators (MBL or CRP), the complement system will be activated and the pathogen will be targeted
  14. Complement system
    is the collection of proteins that makes a hole in the cell membrane of the targeted microbees and kills the pthogen by lysis; also promotes uptake of microorganisms by phagocytosis
  15. complement system within innate immunity
    the activation cascase of complements can be activated by mannose-binding lectin (MBL) and C-reactive protein (CRP) that recognize PAMPs
  16. complement system within adaptive immunity
    adtibodies bind to specific foreign antigens and activates complement
  17. dendritic cells and macrophages
    contain TLRs which allow them to detect a broad spectrum of pathogens
  18. signals initiated at the TLRs of macrophages stimulate what?
    • phagocyic activity (innate immunity)
    • and the activated macrophages also secrete cytokines (also innate immunity)
  19. what do dendritic cells do?
    internalize antigen, processed, and then present to T cells (adaptive immunity) and also secrete cytokines (innate immunity)
  20. hallmark signs of inflammations:
    • swelling, redness, heat, pain
    • there is an increase in vascular diameter (vasodilation), rise of blood volume in the area, heat, and redden the tissue
    • accumulation of fluid swells the tissue (edema)
  21. what do leucocytes do?
    • come to inflamed region
    • phagocytose
    • release molecular mediators
  22. who are the first to reach the sight of inflammation?
    • neutrophils
    • they must recognize the inflamed endothelium
    • they must adhere strongly (because blood cells are always moving)
  23. the process of leaving blood vessels without damage
    extravasation
  24. 4 steps to leukocye extravasation
    • rolling: attach loosely to the endothelium
    • activation by chemoattractant stimulus
    • arrest and adhesion
    • transendothelial migration
  25. during activation neutrophil receive chemical signals from
    • vascular endothelium
    • (selectin and mucin)
  26. soluble molecules that are produced at the site of infection or injury and act locally:
    • defensins
    • cathelicidins
    • interferons
  27. soluble effectors are produced at distant sites and transported to the target tissues via the bloodstream:
    complement and acute phase proteins
  28. how do antimicrobial peptides generally work?
    • disrupting microbial membranes
    • by inhibiting the synthesis of DNA, RNA and proteins of the invaders
  29. what is an acute protein?
    • a groups of serum proteins that increase in concentration in response to inflammation (some complements, MBL, interferons)
    • LIVER is one of the most important sites
  30. Actue phase response (APR)
    the increase of acute phase protein after infection (innate immune system)
  31. what are major signals for the induction of APR?
    Cytokines (TNF-alpha, IL-1, and IL-6)
  32. receptors to detect infection
    • TLR
    • MBL and CRP (soluble PRR, bind to microial surfaces, promoting phagocytosis, making the invader ready for complement-mediated lysis)
    • Lypopolysaccharide-binding protein (LBP - recognizes and signals a response to lipopolysaccharide)
    • Nucleotide-binding oligomerization domain (NOD - cytosolic, two members NOD1 and NOD2, recognize products derived from bacterial peptidoglycans
    • Scavenger receptors (present in the macrophages and many types of dendritic cells, involved in binding and internalization of gram-positive and gram-negative bacteria, phagocytose apoptic host cells)
  33. Toll-like receptors (TLR)
    membrane-spanning proteins, share a common structual element called leucine-rich repeats or LRR in the extracellular region
  34. LLR is the extracellular ligand-binding region of the:
    TLR
  35. the intracellular domain of TLR is know as
    TIR (I= IL-1) which has 3 highly conserved domain (boxes 1,2,3)
  36. several TLR operate as
    • dimmers
    • monomers
    • or partners yet to be discovered! O_o
  37. viruses, bacteria, fungi, and some protozoa can be detected by
    a complete set of TLRs
  38. Lipolysaccharide (LPS)
    found in the cell walls of gram-negative bacteria
  39. 4 cell types of innate immunity
    • Neutrophils - in blood
    • Macrophages - in tissues
    • NK cells - in blood
    • Dendritic cells - in lymph
  40. functions of neutrophils
    • 1st to migrate from the blood to the sites of infection
    • phagocytosis
    • TLRs and other pattern recognition receptors are present on their surfaces (TLR2 detects peptidoglycans; TLR4 detects LPS)
    • able to attack by both oxidative and nonoxidative
    • able to express high levels of inducible nitric oxide synthetase (iNOS)
  41. Macrophage functions
    • phagocytic activity, increased ability to kill ingested microbes, secrete mediators of inflammation
    • express high levels of class II MHC molecules
    • promote acute phase response
    • secrete cytokines and complement proteins
    • produce both ROS and RNS
    • express high levels of iNOS
  42. NK cells
    • provide 1st line of defense against many viral infection
    • able to produce cytokines (INF-gamma and TNF-alpha)
  43. Dendritic cell function
    • recognize pathogens
    • mature DCs expressed both MHC class I and MHC class II molecules
    • capable of generating reactive oxygen species and nitric oxide
    • capable to produce antimicrobial peptides
    • phagocytic activity
  44. signal transduction
    transmission of the signal to the inside of the cell
  45. signal transduction in innate innumity:
    • signal: a microbial product
    • receptor: a PRR on a leukocyte
    • signal transduction: by the interactions of specific intracelluar molecules
    • the effector mechanism: the action that takes place as a consequence of the signal
    • result: the clearance of the invading organism
  46. ubiquity of innate immunity
    a system of immunity protects all multicellular organisms from microbial infection and exploitation
  47. antheroclerosis
    progressive accumulation of lipids and fibrous elemments in the arteries
  48. it is necesary to identify inflammatory markers as predictors of
    cardiovascular events
  49. markers of infammation are
    • IL-6
    • TNF-alpha
    • the actue phase response protein CRP
  50. traditional markers of cardiovascular events are
    • cholesterol
    • LDL
    • HDL
  51. what happens in the initial stages of antherosclerosis?
    monocytes attached to the arterial walls migrate through endothelial cells and differentiate into macrophage
  52. what do scavenger receptors on the macrophages do?
    bind lipoprotein particles, internalize them, accumuating lipid droplets and assuming a "foamy" appearance
  53. proteolytic enzymes, ROS and cytokines are all secreted by
    foamy macrophages
  54. what do proteolytic enzymes do?
    degrade the local extracellular matrix which undergoes some remodeling during repair process
  55. how do cytokines and ROS intensify inflammation?
    they accumulate more cells and lipids into the newly forming plaque; as a result the artery is narrowed and more susceptible to blackage
  56. myocardial infraction
    blocked arteries in the heart
  57. inflammatory marker CRP is
    • an agent of innate immunity
    • a mediator of inflammation is also associated with high risk of coronary heart disease
  58. what are statins?
    drugs that are able to inhibit cholesterol biosynthesis as well as inflammation
  59. statins also reduce
    CRP

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