Flashcards
Microbes & Disease - Lecture 4
Cards in this deck (89)
- 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. - 2What is the substratum?A surface with receptors for adhesins.
- 3What is an adhesin?A surface molecule capable of binding to a receptor/ a ligand for the receptor.
- 4What is a receptor?Something complementary to an adhesin.
- 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. - 6What is an adhesiotype?An adhesion site of a receptor.
- 7What are the 2 different types of adhesion?- Non-specific adhesion
- Specific adhesion - 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. - 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 - 10What does specific adhesion reflect about the evolution of the bacterium?Its evolutionary success.
- 11What is meant by convergent evolution?When independent organisms evolve similar traits as a result of having to adapt to similar environments.
- 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.
- 13What are 2 common mechanisms of adhesion?- Hair-like pili
- Outer membrane proteins - 14What are 2 examples of beta-barrel proteins in the outer membrane surface of N. meningitidis?- Opa
- Opc - 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
- 16What are pili made up of?Pilin (PilE) polymers.
- 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. - 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. - 19What is defined as a heterotypic receptor?One that binds via lock and key interaction.
- 20What is defined as a homotypic receptor?2 identical molecules on 2 identical cells which bind together and make very strong links.
- 21Where are homotypic receptors found to be common?In epithelial cells when junctions need to be tight.
- 22Give 3 examples of receptors in the body.- Cell to cell adhesion
- Hormone and cytokine receptors
- ECM proteins/ serum proteins/ mucins - 23What are 3 examples of cell - cell adhesions?- Transient interactions
- Stable interactions at junctions
- Stable interactions between cells and ECM. - 24What are 2 forms of receptor for soluble messengers?- Heterotypic
- Homotypic - 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. - 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 - 27Define tropism.The inability to infect certain tissues/ host and/ or the preference for some other hosts.
- 28What leads to tissue/ host tropism?The structural 'lock and key' type interactions/ synergistic nature of adhesins with their host receptors.
- 29What is a transgenic mouse?A mouse with an altered gene.
- 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. - 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.
- 32What adhesins do L. monocytogenes bacteria have to bind to host cells? What are their associated cell surface receptors?- InLA > E-cad
- InLB > Met - 33Define receptor ligation.When 2 receptors are brought together and fit well (i.e. an adhesin and its associated ligand).
- 34What 4 things can happen as a result of receptor ligation?- Cell signalling
- Host cell response
- Cytoskeleton activation
- Internalisation/ invasion - 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. - 36What is 'active penetration' in terms off Tissue Invasion?- When the microbe breaks through the host's mucas membrane or epithelium.
- 37What is 'passive penetration' in terms of Tissue Invasion?When the microbe enters the host via skin lesions, insect bites, wounds, etc.
- 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.
- 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. - 40What are 'spreading factors'?- Bacterial enzymes that affect the physical properties of tissue matrices and intercellular spaces.
- Promoting pathogen spread. - 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. - 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. - 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. - 44When does microbial growth take place?When pathogen finds an appropriate environment within the host.
- 45What 4 elements give the pathogen an idealistic environment to grow?- Correct temp.
- Correct pH
- Correct oxygen levels
- Good supply of nutrients - 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) - 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.
- 48What can some pathogens do to stop the action of transferrin?- Produce sideophores which can remove the Fe from transferrin.
- 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). - 50What is Iron chelation and its importance in host specificity?- The activity of transferrin/ lactoferrin found in secretory fluids such as milk.
- 51What immune response is Iron chelation involved in?Innate
- 52What is a siderophore?A molecule which binds and transports iron in microorganisms.
- 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. - 54What is an invasin?- Bacterial cell surface molecule that induces a target cell to internalise the microbe.
- Enables bacteria to invade. - 55What is the link between adhesins and invasins?- Some adhesins are also invasins.
- Not all invasins are necessarily adhesins. - 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'. - 57What are the 2 distinct uptake strategies initiated, depending on the invasion factor?- Trigger mechanism
- Zipper mechanism - 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 - 59Briefly describe the 'zipper' mechanism.- Interaction between invasion proteins and eukaryotic cell receptors.
- Engulfment/ phagocytosis - 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. - 61Give 4 examples of bacteria which survive inside the host cell vacuole.- Coxiella burnetti
- Salmonella enterica
- Legionella pneumophilia
- Chlamydia trachomatis - 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 - 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. - 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. - 65What is the proteosome?- Protein-degrading mechanism in cytoplasm which degrades proteins tagged with ubiquitine.
- 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 - 67What are the 2 major cytoplasmic degradation systems?- Ubiquitine/ proteasome system
- Autophagy system - 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. - 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. - 70What is the main difference between the Ubqiuitine/ proteasome degradation system and the autophagy degradation system?- U/P = Selective digestion
- Autophagy = Bulk digestion - 71What does Autophagy often affect the fate of?Intracytoplasmic bacteria
- 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. - 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. - 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. - 75Give the names of 4 different effector proteins secreted by Coxiella into the cytoplasm of host by T4SS.- CBU
- Cpe
- Cae
- Ank - 76Define cytolysis.Destructive and sequential rupture of the vacuole and cell membranes.
- 77Give 2 examples of microorganisms which can cause cytolysis using proteases.- P. falciparum
- Chlamydia spp. - 78Give an example of a microorganisms which can cause cytolysis using pore-forming proteins.Leishmania spp.
- 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. - 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. - 81Give an example of a bacterium which utilises Actin-based protrusion to escape from host cell.L. monocytogenes
- 82State 2 ways that cells can carry out induced cell death.- Apoptosis
- Pyroptosis - 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. - 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. - 85What is essential for certain species' survival ?That a way of transmission between hosts is established.
- 86What are 3 infectious agents which have been specialised for tranmission of pathogens?- Coughing/ Sneezing
- Diarrhea
- Vomit - 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.
- 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. - 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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