Which infection processes are enforced by host defences but evaded by bacterial evasion mechanisms?
Attachment to host cells
Proliferation
Invasion of host tissues
Toxin-induced damage to host cells
Host defence + Bacterial evasion mechanism: Attachment to host cells
Host defence: Blockage of attachment by IgA antibodies
Bacterial evasion mechanisms:
Secretion of proteases that cleaves sIgA (Haemophilus influenca)
Antigenic variation in attachment structures (pili of N. gonorrhoeae)
Host defences + Bacterial evasion mechanism: Proliferation
Proliferation:
Host defence
Bacterial evasion mechanisms
Phagocytosis
Production of surface structures that inhibit phagocytic cells (capsules, coats)
mechanisms for surviving within phagocytic cells (Salmonella)
Induction of apoptosis in macrophages
Complement-mediated lysis and localised inflammatory response
Resistence of gram-positive bacteria to complement-mediated lysis
Prevent insertion of membrane-attack complex by long side chain in cell wall LPS (some Gram-negative bacteria)
nutrient starvation (iron)
Secreation of siderophore
transport of host Fe-chelating proteins across the outer membrane
Host defences + Bacterial evasion mechanism: Invasion of host tissues
Host defence: Ab-mediated agglutination
Bacterial evasion mechanism: Secreation of elastase that inactivates C3a and C5a
Host defences + Bacterial evasion mechanism: Toxin-induced damage to host cells
Host defence: Neutralisation of toxin by antibody
Bacterial evasion mechanism: Secretion of hyaluronidase, which enhaces bacterial invasiveness
Describe how B. pertussis limits its removal via mucus
Produces Tracheal cytotoxin (TCT) —> inhibits mucus removal
Toxin is actually a particular fragment that is released from cell wall during growth
List the 3 classes of AMPs and their mode of action
3 classes of Antimicrobial peptides:
defensins
cathelicidins
thrombocidins
Modes of action:
Barrel stave
Carpet-like
Toroidal pore
Provide 4 examples of how bacterial pathogens limit AMP action
1) Modification of membrane charge (Salmonella enterica)
2) Direct destruction of peptides (Staphylococcus areus)
3) Efflux pump -> removal of AMPs from bacteria (Yersinia)
4) Bacterial biofilms -> resistance to AMPs
Describe how bacterial pathogens avoid the activity of sIgA
2 ways of evading IgA:
1) Bacteria produce various glycosilidases
sIgA is heavily glycosylated
cleavage of sugars make antibody sensitive to proteases
2) IgA1 proteases produced by several bacteria
for example Haemophilus influenzae
cleave IgA1 H chain near chain region
Describe some of the strategies used by bacteria to avoid phagocytosis (Evasion, DNAse NETs, capsules, toxins)
Toxin release:
organism releases a toxin that kill the phagocyte
Many of the toxins are lethal when injected in large amounts, but under physiological concentrations it only lyses phagocytes
Opsonization prevention:
organism produces a protein which prevents interaction between opsonizing antibody and phagocyte
Evasion:
Engagement with defined surface recptors
Modification of signal transduction pathways
Controlling the fate of the endosome
Survial under hostile vonditions
Escape from the phagosome
Replication in phagocytes
DNAse NETs:
activity of neutrophil extracellular traps (NETs) can be significantly reduced by DNAse
—> degrades DNA backbone and enables liberation of bacteria from NETs
Capsules:
organism possesses a capsule which prevents contact with the phagocytes
usually acidic polysaccharides
Briefly describe how superantigens disrupt efficient T cell-mediated clearance
superantigens (SA) -> potent exotoxins
What are the methods used by bacteria to avoid complement-mediated killing (direct and in-direct methods)
Describe how bacterial pathogens employ molecular mimicry to avoid immune clearance and list some examples
Molecular mimicry:
Bacteria possess antigenic determinants that are very similar or identical to normal host cell components
occurs in a wide variety of bacteria
may be the initiating step in autoimmune diseases
Examples:
Briefly describe what is meant by the term antigenic (phase) variation
provide an example of a bacterial pathogen that employs this to avoid anti-infection responses
Antigenic phase variation:
mechanism by which bacteria alters its surface proteins in order to avoid host immune response
bacteria will change a variety of cell surface molecules that can be determined by specific antibodies
Example:
N. gonorrhoeae can produce over a million different antigenically distict pili
Provide examples of methods that bacterial pathogens use to modulate host inflammatory responses
Bacteria can “hijack” host signaling pathways to inhibit inflammation
suppress cellular activation and increase bacterial survival
N. meningitidis ligate the ITIM-containing CEACAM1 with TLR2 on epithelial cells (???)
inhibits co-engaged TLR2 signalling and cytokine release
Describe how poor recognition, desensitisation of immune responses, and inhibition of secondary immune signals may also faciliate pathogen survival
Poor recognition:
not usually absolute, but rather slow or weak response
sufficient to allow pathogen to prosper
Desensitization of response:
Due to presence of large amount of antigen or antigen / antibody complexes
lack of second signal can lead to non-responsive state by T-cells
Inhibition of the second signal:
T cell responses are only generated if activation through T cell receptor and through the second signal
Lack of second signal as above
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