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Microbes & Disease - Lecture 4

Afronewtzz Microbes & Disease Degree English 89 cards

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  1. 1Describe 3 key points of Adhesion.- Measurable interaction between bacterium and substratum.
    - Initial anchorage to mucosa: without it there is often no colonisation and hence no disease.
    - Reversal requires energy.
  2. 2What is the substratum?A surface with receptors for adhesins.
  3. 3What is an adhesin?A surface molecule capable of binding to a receptor/ a ligand for the receptor.
  4. 4What is a receptor?Something complementary to an adhesin.
  5. 5How many binding sites do receptors and adhesins have?- Receptors have many different binding sites for different adhesins.
    - Adhesins have many different binding sites for a variety of receptors.
  6. 6What is an adhesiotype?An adhesion site of a receptor.
  7. 7What are the 2 different types of adhesion?- Non-specific adhesion
    - Specific adhesion
  8. 8What is non-specific adhesion? What does it normally require to hold together adhesin and receptor?- Precise stereochemical fit not involved.
    - May require forces such as complementary charged pockets/ hydrophobicity.
  9. 9What is specific adhesion? What does it normally require?- A type of adhesion which requires
    stereochemical bonding.
    - Lock and key interaction
    - Hydrogen bonds
    - Ion-ion pairing
    - Hydrophobicitiy
  10. 10What does specific adhesion reflect about the evolution of the bacterium?Its evolutionary success.
  11. 11What is meant by convergent evolution?When independent organisms evolve similar traits as a result of having to adapt to similar environments.
  12. 12How is convergent evolution relevant to adhesion?- When 2 different bacteria/ independent organisms evolve to bind to the same target cell surface molecule despite having a different structure of adhesin and a different effect on the host cell.
  13. 13What are 2 common mechanisms of adhesion?- Hair-like pili
    - Outer membrane proteins
  14. 14What are 2 examples of beta-barrel proteins in the outer membrane surface of N. meningitidis?- Opa
    - Opc
  15. 15What abouts in the beta barrel structures of Opa and Opc outer membrane proteins of N. meningitidis does adhesion occur?In the surface loops whereby antigenic variation can take place
  16. 16What are pili made up of?Pilin (PilE) polymers.
  17. 17Describe why there is a variable domain and a glycosylated site on the pili structures of N. meningitidis' surface.- Sugars are not very good antigens for binding of the immune system.
    - The antigenically variable domain is able to avoid antibody binding of the immune system.
  18. 18What are 3 different types of specific receptors?- Cell-associated molecules i.e. hormone receptors in the plasma membrane of cells.
    - ECM - epithelial cells are embedded here.
    - Molecules free in body fluids - mucas, blood etc.
  19. 19What is defined as a heterotypic receptor?One that binds via lock and key interaction.
  20. 20What is defined as a homotypic receptor?2 identical molecules on 2 identical cells which bind together and make very strong links.
  21. 21Where are homotypic receptors found to be common?In epithelial cells when junctions need to be tight.
  22. 22Give 3 examples of receptors in the body.- Cell to cell adhesion
    - Hormone and cytokine receptors
    - ECM proteins/ serum proteins/ mucins
  23. 23What are 3 examples of cell - cell adhesions?- Transient interactions
    - Stable interactions at junctions
    - Stable interactions between cells and ECM.
  24. 24What are 2 forms of receptor for soluble messengers?- Heterotypic
    - Homotypic
  25. 25Briefly describe the in vitro experiment conducted for evidence of virual induced receptor increase.- Introduce a virus into the cells in vitro.
    - Stimulates inflammatory response.
    - Cytokines recruited.
    - Increase in number of receptors on surface of exposed cells.
    - N. meningitidis uptake is increased as a result of stronger binding to receptors.
  26. 26What is the link between number of receptors and cellular invasion?- Few receptors > lose attachment of bacterium > no invasion.
    - Lots of receptors > stronger binding of bacterium > cellular invasion
  27. 27Define tropism.The inability to infect certain tissues/ host and/ or the preference for some other hosts.
  28. 28What leads to tissue/ host tropism?The structural 'lock and key' type interactions/ synergistic nature of adhesins with their host receptors.
  29. 29What is a transgenic mouse?A mouse with an altered gene.
  30. 30What has been found about the adhesins InLA and InLB and their associated receptors Met and E-cadherin in guinea pigs/rabbits, mice and herman gerbils?- InLA binds E-cad in Guinea Pigs/ Rabbits and Gerbils, but NOT Mice.
    - InLB binds Met in Mice and Gerbils, but NOT Guinea Pigs/ Rabbits.
  31. 31What would happen if you were to change the gene in a mouse so that it had an E-cad receptor (Pro 16) for the adhesin InLA (present on L. monocytogenes).The mouse would get very sick since the bacterium can adhere to host cells easily.
  32. 32What adhesins do L. monocytogenes bacteria have to bind to host cells? What are their associated cell surface receptors?- InLA > E-cad
    - InLB > Met
  33. 33Define receptor ligation.When 2 receptors are brought together and fit well (i.e. an adhesin and its associated ligand).
  34. 34What 4 things can happen as a result of receptor ligation?- Cell signalling
    - Host cell response
    - Cytoskeleton activation
    - Internalisation/ invasion
  35. 35After receptor ligation resulting in internalisation/ invasion of bacterium, what 3 things may happen to the microbe?- May survive for a small period of time.
    - May grow/ replicate.
    - May exit for transmission.
  36. 36What is 'active penetration' in terms off Tissue Invasion?- When the microbe breaks through the host's mucas membrane or epithelium.
  37. 37What is 'passive penetration' in terms of Tissue Invasion?When the microbe enters the host via skin lesions, insect bites, wounds, etc.
  38. 38Once bacteria are below the mucas membrane, how do they spread to deeper tissues?Via production of specific products and/ or enzymes that promote spreading.
  39. 39What is the difference between localised and systemic infection?- Localised is when the microbe just stays 'locally' at the site of colonisation.
    - Systemic is when the microbe spreads throughout the body to do further harm.
  40. 40What are 'spreading factors'?- Bacterial enzymes that affect the physical properties of tissue matrices and intercellular spaces.
    - Promoting pathogen spread.
  41. 41Describe the function of the spreading factor, collagenase.- Produced by clostridium.
    - Breaks down collagen, the framework of muscles.
    - Facilitates gas gangrene caused by these organisms.
  42. 42Describe the function of the spreading factor, neuraminidase.- Produced by intestinal pathogens such as Vibrio cholerae and Shagella dysenteriae.
    - Degrades neuraminic acid/ sialic acid - intercellular cement of epithelial cells of the intestinal mucosa.
  43. 43Describe the function of the spreading factor, Hemolysins.- Produced by Staphylococci i.e. alpha-toxin.
    - Produced by Streptococci i.e. streptolysin.
    - Produced by various Clostridia.
    - Channel forming proteins or phospholipases.
    - Destroy red blood cells/ cells via cell lysis.
    - Kills and releases nutrients from the cell.
  44. 44When does microbial growth take place?When pathogen finds an appropriate environment within the host.
  45. 45What 4 elements give the pathogen an idealistic environment to grow?- Correct temp.
    - Correct pH
    - Correct oxygen levels
    - Good supply of nutrients
  46. 46What 3 factors can be in limited supply to pathogens when inside their host?- Soluble nutrients (sugars, amino acids, organic acids etc).
    - Vitamins & growth factors.
    - Trace elements (e.g. Fe)
  47. 47What mechanism has the host adopted to keep Fe away from pathogens?- Production of transferrin (Tf) proteins which bind Fe and keep the trace element away.
  48. 48What can some pathogens do to stop the action of transferrin?- Produce sideophores which can remove the Fe from transferrin.
  49. 49What are the 2 different terms for bacteria which actively grow in blood plasma?- Bacteriemia (presence of viable bacteria in blood).
    - Septicemia (presence of bacteria or their toxins in bloodstream).
  50. 50What is Iron chelation and its importance in host specificity?- The activity of transferrin/ lactoferrin found in secretory fluids such as milk.
  51. 51What immune response is Iron chelation involved in?Innate
  52. 52What is a siderophore?A molecule which binds and transports iron in microorganisms.
  53. 53What evolutionary feature to Iron do some human-specific microbes have?- Microbes which have the ability to mimic the 'lock and key' interaction of Fe with its associated transferrin protein.
    - They can now bind human transferrin/ lactoferrin.
    - Obtain Fe and grow in this environment.
  54. 54What is an invasin?- Bacterial cell surface molecule that induces a target cell to internalise the microbe.
    - Enables bacteria to invade.
  55. 55What is the link between adhesins and invasins?- Some adhesins are also invasins.
    - Not all invasins are necessarily adhesins.
  56. 56How do invasins initiate phagocytosis?- Interact with host cell receptors or ECM proteins.
    - Triggers local actin cytoskeletal rearrangements within the host cell.
    - Formation of membrane protrusions which engulf + enclose the pathogen in a membrane- bound vacuole.
    - 'Induced endocytosis/ phagocytosis'.
  57. 57What are the 2 distinct uptake strategies initiated, depending on the invasion factor?- Trigger mechanism
    - Zipper mechanism
  58. 58Briefly describe the 'trigger' mechanism. Name a bacterium which utilises this.- Formation of large membrane projections.
    - Membrane ruffling.
    - Type III Secretion system mediated
    - i.e. Salmonella typhimurium
  59. 59Briefly describe the 'zipper' mechanism.- Interaction between invasion proteins and eukaryotic cell receptors.
    - Engulfment/ phagocytosis
  60. 60Name 3 bacteria which utilise the zipper mechanism and describe the specific invasion proteins and receptors used.- Meningococcus = Opa & CEACAM.
    - Listeria = InLA/B & E-cad.
    - Yersinia = InvA/ YadA & Beta integrins.
  61. 61Give 4 examples of bacteria which survive inside the host cell vacuole.- Coxiella burnetti
    - Salmonella enterica
    - Legionella pneumophilia
    - Chlamydia trachomatis
  62. 62Give 6 examples of bacteria which survive inside the host cell's cytoplasm in some form.- Mycobacterium tuberculosis
    - Listeria monocytogenes
    - Shigella flexneri
    - Burkholderia pseudomallei
    - Francisella tularensis
    - Rickettsia
  63. 63What are the 4 main requirements of pathogenic survival inside the vacuole?- Bacteria disrupt the endomembrane system in the cell to acquire otherwise sparse nutrients.
    - Endosome maturation is slowed/ halted to prevent increasing acidity.
    - Changes in bacterial membrane structure to resist the activity of reducing and proteolytic factors in cell.
    - Suppression of expression of MHC Class II molecules in the membranes of endocytic compartments which would otherwise express antigens and conduct an immune response.
  64. 64What are the 7 main requirements of pathogenic survival inside the cytoplasm?- Lyse entry vacuole
    - Ensure nutrients/ essential minerals are plentiful.
    - Ensure pH is near neutral and environment reducing.
    - Antimicrobial peptides may need to be masked.
    - The suppression of signalling cascades for sensing microbe-specific molecules (innate).
    - The suppression of the autophagy pathway (innate).
    - Suppression of proteosomes which degrade antigenic proteins for presentation to immune system.
    - Suppression of MHC Class I molecules which present antigens on the surface of the cell.
  65. 65What is the proteosome?- Protein-degrading mechanism in cytoplasm which degrades proteins tagged with ubiquitine.
  66. 66What is the pH in the following areas of the cell? - Early phagosome - Phagolysosome - Lysosome- Early phagosome = 6.2
    - Phagolysosome = 5.2
    - Lysosome = 4.5
  67. 67What are the 2 major cytoplasmic degradation systems?- Ubiquitine/ proteasome system
    - Autophagy system
  68. 68Describe the Ubiquitine/ proteasome cytoplasmic degradation system.- Target a protein using ubiquitine.
    - Digest the protein into small peptides.
    - Peptides get transported into the lumen of the ER.
    - Here they bind to MHC Class I complexes.
    - Traffiked to the surface of the cell for antigenic presentation.
  69. 69Briefly describe the Autophagy cytoplasmic degradation system.- Membrane forms around organelles of the cell.
    - Creates an autophagosome which fuses with the lysosome > autolysosome.
    - Leads to degradation of the membranes of the organelle.s & the breakdown of its contents.
  70. 70What is the main difference between the Ubqiuitine/ proteasome degradation system and the autophagy degradation system?- U/P = Selective digestion
    - Autophagy = Bulk digestion
  71. 71What does Autophagy often affect the fate of?Intracytoplasmic bacteria
  72. 72Describe how Coxiella burnetti might survive in a vacuole. List any pHs.- T4SS injects virulence effector into host cell.
    - Coxiella is injested into host cell via endocytosis (pH 5.4).
    - Nascent coxiella cell vacuole fuses with autophagosome.
    - Maturing CCV fuses with lysosome > autophagolysosome (pH 5).
    - Coxiella multiply inside vacuole/ vacuole growth (pH 4.5).
    - Vacuole bursts and bacteria take over the cell.
  73. 73What is the purpose of the Type IV SS when a bacteria is living within the host cell inside a vacuole?- Secrete effector proteins into the host cell.
    - Divert host cellular processes.
  74. 74Give an example of a bacterium which utilises T4SS in its vacuole, and give 2 functions.- Coxiella burnetti
    - Coxiella cell vacuole stability
    - Coxiella cell vacuole fusogenicity with other cell organelles.
  75. 75Give the names of 4 different effector proteins secreted by Coxiella into the cytoplasm of host by T4SS.- CBU
    - Cpe
    - Cae
    - Ank
  76. 76Define cytolysis.Destructive and sequential rupture of the vacuole and cell membranes.
  77. 77Give 2 examples of microorganisms which can cause cytolysis using proteases.- P. falciparum
    - Chlamydia spp.
  78. 78Give an example of a microorganisms which can cause cytolysis using pore-forming proteins.Leishmania spp.
  79. 79What is the unique cytolytic mechanism utilised by the bacterium T. gondii ?Can avoid degradation and escape from a newly formed phagosome by rapidly invading into a secondary, tight-
    fitting vacuole.
  80. 80What is actin-based protrusion?- Single bacterium uses force generated by actin polymerisation to protrude from the cell membrane.
    - Force engulfment into a neighbouring cell.
  81. 81Give an example of a bacterium which utilises Actin-based protrusion to escape from host cell.L. monocytogenes
  82. 82State 2 ways that cells can carry out induced cell death.- Apoptosis
    - Pyroptosis
  83. 83What is apoptosis? What is significant about this during infection with a bacterium?Programmed cell death.
    Immunologically silent - the infected cell is removed without causing disturbance to neighbouring tissue.
  84. 84What is pyroptosis? What is significant about this during infection with a bacterium?- Programmed cell death
    - Pro-inflammatory - Immune cells recognise cell induced death and draw to site of infection, causing inflammatory response.
    - Bacterial cells can abuse this to escape and invade neighbouring cells.
  85. 85What is essential for certain species' survival ?That a way of transmission between hosts is established.
  86. 86What are 3 infectious agents which have been specialised for tranmission of pathogens?- Coughing/ Sneezing
    - Diarrhea
    - Vomit
  87. 87Why are coughing/ sneezing symptoms a great survival advantage of some pathogens?Much more likely to be ejected from one host and carried to another.
  88. 88Give an example of a bacteria which utilises diarrhea as an effective transmission method - briefly describe why it is so effective..- Cholera
    - 'Rice water stools' > Contain a very high concentration of bacteria.
    - Transmission likely since extremely violent and watery.
  89. 89Give an example of a bacterium which has toxins which induce vomiting.- Staph. aureus has emetic properties.
    - Effective since the vomit contains a high conc. of bacteria and can land on people/ surfaces.

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Bacterial adhesion to and invasion of host tissues/ cell.
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