BIOL243 - L8

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  • Created by: Katherine
  • Created on: 05-04-17 17:03
What are phagocytes?
The cells that protect the body by ingesting (phagocytosisn) harmful foreign particles, bacteria, and dead or dying cells.
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What types of cells are phagoctes?
Neutrophils, monocytes, macrophages, dendritic cells and mast cells.
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When are phagocytes important?
Crucial in fighting infections, as well as in maintaining healthy tissues by removing dead and dying cells that have reached the end of their lifespan.
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What is a good analogy in nature?
Amoebae
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Where do we find phagocytes?
In medical biofilms and in the environment (e.g. heterotrophic protozoa).
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How do you resist phagocytosis?
Defence virulence factors, offensive virulence factors, negative cell signals, antigenic variation.
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How do defensive virulence factors resist phagocytes?
They are in a biofilm, covered in a matrix and can be encapsulated
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How do offensive virulence factors resist phagocytosis?
Production of leukocidins, cytotoxins that kill white blood cells (phagocytes) so they actively fight off the invaded
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How do negatvie cell signals resist phagocytosis?
Interkingdom quorum sensing - it will switch on the virulence
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How does antigenic variation resist phagocytosis?
White cells rely on recognising the protein of the walls of the protein - if your pathogen is changing constantly then it's hard to keep up and track it down. White cells find them hard to fight off
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How do defence cells phagotose bacteria?
Phagosome fuses with acidosome - pH decreases from neutral to acidic. Acidic phagosome then fuses with lysosomes (-lysozyme, acid phosphatases, hydrogen peroxide, proteases. Toxic substances contained within a membrane.
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How does bacteria avoid digestion?
Escape (they leave the food vaculoe and divide in the host cytoplasm), tolerance (they survive the digestive process and emerge unharmed) or avoidance (do not divide by are egested unharmed, divide in the food vacuole then burst the host cell).
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What happens when bacteria enter the phagosome?
Bacteria go into a shock response. They produce stress proteins (SPs).
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What do SPs?
Begin to repair the cell (Molecular chaperonin). They correct folding of polypeptide and re-fold incorrectly folded proteins.
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What are the types of chaperonin genes?
Chaperone DnaJ and DnaK.
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What are sigma factors?
Proteins that bind to the promoter and allow rna polymerase to start gene expression
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When are most folding mistakes made
When there is high stress in a cell
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During stress what becomes distracted?
DnaK. Less goes into control of sigma32 - it's not degraded at the same rate. You get more transcription of the heat shock proteins. More Dna K and J are produced.
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DnaK and DnaJ bind to...
The protein to repair it.
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Is shock protein production irreversible?
No
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Egested bacteria may still be in the stress response and therefore may have...
Increased resistance to antimicrobials
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You get increased virulence with this.
.
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Cells not burst are in close assocaiteion in the...
food vacuole (they're pushed together) - it is a hotspot for genetic exchange.
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How do bacteria avoid phagocytosis?
Interferences with the biochemistry of digestion, inhibits lysosomal fusion with the phagosome, prevents digestive enzyme activity, production of a protease that disrupts the host superoxide anion generation, some species do not divide but sit on vac
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In order to avoid phagocytosis, some bacteria divide in the food vacuole, what does this result in?
If they divide rapidly, then there will be more cells than there is volume, causing the macrophage to burst.
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What is an example of a bacterium that avoids phagocytosis by causing the cell to burst?
Legionella pneumophila
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What are the features of legionella pneumophila?
Main virulence system is the dot/Icm IV type secretion system. Secretes macromolecules into host cells. Prevents lysosomal fusion. If this has passed - can resist oxidative attack by producing a protease. Divides and lyses the cell
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What does the legionella pneumophila protease do?
It disrupts the host suerpoxide anion generation.
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Why is it difficult to isolate L.pneumophila alone?
It is the trojan horse of the microbial world. It can survive in amoebic cysts ( it is a parasite) and is protected from environmental conditons.
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How do L.pneumophila escape?
They lyse the encoding food vacuole membrane and escape into the cytoplasm where they proliferate. They eventually burst the host cell.
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What is Pseudomonas aeruginosa?
It is an opportunistic pathogen
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What are the key features of P.aeruginosa?
Gram -ve, rod shaped. Catalase +ve, oxidase +ve. Does not ferment lactose (MacConkey test = colourless). Facultative anaerobe. Can grow t 43'C. 1 polar flagellum. Simple nutrient needs. Does the enter doudoroff pathway (Glycolysis). Chemoorganohetero
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What are P.aeruginosa's adhesins?
Single polar flagellum, fimbrae, pili, capsule and excessive slime production.
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What are P.aeruginosa's invasins? (spreading factors)
Elastase (lyses collagen and fibronectin), Alkaline protease (lyses fibrin), Pyocyanin (inhibits cilia, disrupts epithelial cells, instigates an inflammatory response in phagocytosis).
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What are P.aeruginosa' toxins?
Endotoxins - these are the lipopolysaccharides present in the outer membrane of gram -ve cell walls.
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What are the Exotoxins present in P.aeruginosa?
Cytotoxin, AB toxin, Superantigen
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What are the cytotoxins in P.aeruginosa?
Leukacidin (a pore forming toxin) kill leukocidins. Haemolysin (lyses erythrocytes by forming pores in phospholipid bilyates. Others lyse erythrocyte by hydrolyzing phospholipids in bilayer. Phospholipase C, Lecithinase
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What do Phospholipase C do?
Enzyme attack of phospholipid in membrane of eukaryotic cells.
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What do Lecithase do?
Degrades Lecithin.
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What type of secretion system do P.aeruginosa have?
Type 3 secretion system that injects effectors directly into the cytoplasm of eukaryotic cells
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What are the Superantigens present in P.aeruginosa?
Exoenzyme S.
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What is Exoenzyme S?
An extra cellular ADP ribosyltransferase of P.aeruginosa. Requires type III secretion apparatus for export of exoenzyme S and potentially other co-ordinately regulated proteins. Exoenzyme S is capable of transferring ADP ribose to various proteins.
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What do superantigens (SAgs) do?
They cause non specific activation of T cells and masssive cyotkine realease.
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What is released into the blood in high levels due to mass T cell activation from SAg binding?
TNF-a = severe and life threatening symptoms.
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What does P.aeruginosa's A-B toxin do?
Acts like the diphtheria toxin. It inhibits elongation factor 2. It does do by ADP ribosylation of EF2. This then causes the elongation of polpeptides to cease.
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List of virulence in P.aeruginosa'
39 mins L8
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