Bacterial pathogenesis and immune evasion Flashcards

Question

Host-pathogen interactions - N gonorrhoeae

Answer 1

Fimbriae of Neisseria gonorrhoeae allow the bacterium to adhere to tissues Fimbrae about 2/3 times the size of the bacteria so can easily attach to target Once it has penetrated: it will switch of some of the genes that it needed to adhere to evade the immunity small number of phase variants are the ones that will survive and take over, then will enter cell and express tight adhesins allowing it to survive inside the cell

Answer 2

Commensal gut organism but can become a pathogen, causing: diarrhoea, dysentery, Haemolytic uraemic syndrome (HUS), Urinary tract and kidney infections, Septicaemia, Pneumoniae and meningitis Different strains of E. coli – different repertoire of genes e.g. entero-haemorrhagic E. coli – cause haemolytic uraemic syndrome -> life threatening – they probably have 300 genes different from simple enterotoxigenic E. coli Enteropathogenic Escherichia coli (EPEC) cause the pedestal – it damages the villi, so it can no longer regulate fluid, so get diarrhoea – repair -> acute secretory Enteroinvasive Escherichia coli (EIEC) have mechanisms that allow them to enter by damaging surface – then will express proteins that allows them to survive inside the cell and spread through epithelial layer, dysentery -> blood and puss in faeces due to tissue destruction + shigella like toxin leads to systemic effects on endothelial cells on kidney, haemolytic uraemic syndrome

Answer 3

Pili or fibrillae protruding from the bacterial surface. A - Pili or fibrillar protruding from bacterial surface. These proteinaceous appendages bind to host cell surface molecules, usually carbohydrates, by adhesin proteins located at the distal tip of the pilus/fibrillar organelle. B - Bacterial/epithelial cell interactions mediated by afimbrial adhesin proteins. C - Some bacteria establish intimate associations with eukaryotic cells by intimin proteins, resulting in cytoskeletal rearrangements, host cell signalling, possible internalisation of the bacteria, and in many cases systemic disease. D - Some bacteria secrete their own receptor protein, which is internalised by the target host cell, phosphorylated, and embedded in the eukaryotic cell as a new receptor for tight binding by the bacterium.

Answer 4

1. adhesion to receptors (adhesins/integrins) 2. block phagocytosis (yersinia) 3. membrane disruptions (pore forming toxins) 4. -ve protein synthesis 5. manipulation of lysosomal function (e.g. S typhi) 6. endosomal trafficking 7. manipulation of cytoskeleton

Answer 5

1. influence phagocytosis! (macrophages and PMN's) 2. complement (diff flashcard) - kill cell via leucocidins - staphs - prevent opsonisation via protein A, which binds to the Fc portion of IgG - staphs - block contact via capsules - meningococcus, HibB intracellular pathogens: - promote uptake via C3R, Fc receptors (no ROI) - prepares cell for invasion- class III secretion, Shigella - down regulates P-L fusion - M. tuberculosis - escape P-L to cytoplasm - Listeria - resist oxidative killing via catalase/peroxidase production - blocks MHC, IFN receptors, TNF release

Answer 6

1. Directs phagocytosis via CR3 – no ROI 2. Actin rearrangement - +ve engulfmant 3. Type 3 secretion systems – prepares cell 4. Resists digestion and ROIs, in PLs - SOD, catalase 5. Escape into cytoplasm, e.g. Listeria; Legionella 6. Inhibits PL fusion, maintains early endosome and blocks acidification e. g. mycobacteria 7. Controls antigen presentation - stops CTLs or Pφ activation

Answer 7

Listeria monocytogenes (listeria) is a bacterium that causes an illness called listeriosis.

Answer 8

cell-cell invasion, involves a pore forming toxin called listeriolysin Listeria reorganises actin filaments within the cell – allows it to travel through the cell and from cell to cell

Answer 9

bfp – bundle forming pili – mediate initial attachment Activation of Type 111 secretion systems – secretion of bacterial translocated intimin receptor Tir. Receptor for the adhesion protein, intimin. Cytoskeletal rearrangements – pedestal formation This strain can secrete its own receptor when it comes into contact with the cell. It activates a secretion process, the protein secreted is a receptor which goes into the target cell then becomes expressed on the surface of the target cell, to allow the bacteria to adhere, forms a tight intimin interaction between receptor and the ligand

Answer 10

There are about 8 different ways that bacteria can secrete proteins and into the target cell. This image shows bacteria with loose attachment to cell, it makes a hypodermic needle called a secretory apparatus, that responds to the environment, allows upregulation of some genes to make this bridging structure It then injects proteins or Yops into the cell some which are receptors to be presented, other effector proteins affect the cell in different ways Yop E - actin rearrangement via GTPases, cell rounding, anti-phagocytic YopH - Tyrosine phosphatase, -ve phagocytosis YopT - Actin rearrangement

Answer 11

• ‘injects’ effectors into host cell: MOLECULAR SYRINGES • examples: Salmonella gut epithelium invasion modification macrophage phagosome Yersinia inhibition neutrophil and macrophage function Shigella macrophage invasion and escape from phagosome cell-to-cell spread E. coli EHEC and EPEC adhesion to gut epithelium Legionella inhibition phagolysosomal fusion

Answer 12

2. complement - failure to trigger - LPS/capsules - downregulation of binding - coating with non-fixing with IgA - block MAC - C5a proteases

Answer 13

``` induces inflammatory response promotes chemotaxis ↑ phagocytosis by opsonisation ↑vascular permeability mast cell degranualtion lysis of cell membranes ```

Answer 14

look at table

Answer 15

part of complement pathway Mannose-binding lectin - an acute phase protein Binds MBL-associated serine protease (MASP)

Answer 16

Bacterial polysaccharide capsules: -poor activators -long side chains (O antigens) fix C3b - prevent access to membrane -capsules rich in sialic acid promote interaction with H and I factors and thus promotes MAC dissociation - eg Group B Streps, Neisseria meningitidis, E.coli K1 - outer layer of G-ve bacteria can rapidly shed C5b-C9 MAC - C3a and C5a proteases - coat self with non-complement fixing IgA e.g. The M-protein of S. pyogenes binds factor H of the complement pathway and this leads to the degradation of the opsonin C3b by factor I and the formation of C3 convertase

Answer 17

inhalation into the lung colonises by the nasopharynx due to adhesion molecules, produces secretory IgA proteases during colonisation so they can invade further after post-viral damage - viral infection will damage structure of epithelial cells. switches on genes for pneumolysin, a toxin that damages pneumocyte membranes - destroys defensive barriers allowing bacteria to replicate there escapes phagocytosis via capsules Inflammatory process driven by teichoic acids pneumonia - bacteraemia - meningitis and septicaemia

Answer 18

look at table

Answer 19

successive expression of alternative forms of an antigen - in a specific clone or its progeny Phase variation - ON/OFF of an antigen at low frequency - occurs: during course of infection in an individual host or during spread of microbe through a community

Answer 20

immune evasion and pathogenesis

Answer 21

- genetically stable and alternative forms of antigens in a population of microbes e.g. serotypes of Strep.pneumoniae

Answer 22

- surface components interact with host cell - components vary at high frequency in a population of bacteria - variation to avoid immune response

Answer 23

affects cell surface components: capsule, pilus, opa, outer and inner membrane All of these structures can undergo either: 1. Phase variation i.e. an ON-OFF switch (capsule, Opa’s) 2. Antigenic variation e.g. pilins (or both phase and antigenic)

Answer 24

Intra-genomic recombination e.g. N.gonorrhoeae Pillins

Answer 25

Bacterial toxin production - tightly controlled Regulatory elements - sensitive to environmental signals found in host ``` 1. Diphtheria toxin - totally repressed by adequate Iron. Limiting iron (i.e. in blood) - toxin de-repressed = expressed ``` 2. Cholera toxin and related virulence factors (adhesins) - controlled by environmental osmolarity and temperature 3. B. pertussis, induction of different virulence components – staggered attachment factors are produced initially to establish the infection, toxins are synthesized and released later to counter the host defences and promote bacterial survival.

Answer 26

INNATE: - C3a and C5A proteases - opsonisation (binding) inhibition - complement activation inhibition - survival inside macrophages ADAPTIVE - antigen presentation inhibition - blockage of cell cycle progression - apoptosis inhibition - superantigens and appropriate immune activation - Ig binding proteins (protein A) - sIgA proteases host mimicry - M protein Phase and antigenic variation

Answer 27

pili - adherence to mucosal surfaces non-fimbrial adhesins - tight binding to cells sIgA proteases - prevent trapping in mucin siderophores - iron acquisition capsules - prevent phagocytosis and block complement altered LPS - serum resistance, no MAC Ca5 peptidases - downregulation of complement signalling surface protein variation - evade immunity toxic proteins/enzymes - kill PMN's, damage tissues

Answer 28

Signalling – TLRs, PRRs and PAMPs 1. Inter- and intra – cellular communications in eukaryotic cells - signalling -receptors and signal transduction e.g. G-proteins ion channels second messengers e.g. cAMP actin, microtubules 2. Bacterial signalling - 2 component signal transduction systems Quorum sensing Cytokine mimics 3. Bacterial reception of host signals adaptation through gene expression

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Bacterial pathogenesis and immune evasion Flashcards

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