CTE2 - bacteriology Flashcards
(20 cards)
PRRs and effects
- TLRs –> MyD88 (NfkB) TRIF (IFN)
- Complemenet receptors (CR3) –> co-stimulation/phagocytosis
- Scavenger –> phagocytosis
- Formyl peptide receptor –> chemoattraction
- NK cell recptors (KIRs) –> NK activation
- C-type lectin receptors –> Th17(dectin-fungi) phagocytosis (mannose receptor)
- soluble lectin receptors –> complement activation and opsonisation
koch’s postulates
- microbe must be present during disease
- must be isolated and grown pure in culture
- when cultured microorganism is applied to other organism it must get disease
- must be isolated from inoculated and now diseased host and be identical to step 2
tolerance by exclusion (intestine)
- Firm mucus layer and AMPs, sIgA prevent access to epithelial cells
- Commensals can further strengthen these barriers
- Anti-inflammatory properties of commensal metabolites (SCFAs)
- PAMP-modifications: commensal lipidA less toxic
- Damage requirement: PAMP in combination with DAMP activate Inflammasome
- Compartmentalization of PRRs:
-TLR4-expression only on IECs in crypts
-TLR5 on basolateral side of IECs- NLR in cytosol
tolerance by constraint
- Certain commensals can block NfkB pathway via two main mechanisms:
o Promoting the nuclear export of NF-kB through PPAR-g signalling
o Inhibiting the polyubiquitination of IkB, or preventing IkB phosphorylation
Salmonellae and Lactobacillus (prevent ubiquitin)
Yersinia spp. (prevent phosphorylation)
NFkB pathway
- PAMP - TLR
- MyD88
- activation the IkB–kinase complex (IkK)
- Phosphorylation of IkB (the inhibitor of transcription factor NF-kB).
- IkB is then polyubiquitinated and subsequently degraded by a proteasome
- Releasing the transcription factor NF-kB for nuclear localization where it mediates pro-inflammatory gene expression.
phagocytosis
- In the process of phagocytosis, the cell takes up microbes via (complement, scavenger, Fc, lectin) receptors on its plasma membrane. pH=7.4
- The microbe is then present inside the cell in a phagosome. pH=5.5-6.5
- The phagosome then fuses with a lysosome (pH=4.5) and becomes a phagolysosome. pH=5
- Inside the phagolysosome microbes are killed by ROS, NO and lysosomal enzymes. pH=5
evasion of phagocytosis
- prevention of acidification of phagolysosome
- encapsulation
- Capsular polysaccharides are poor immunogens
- Capsular can consist of hyaluronic acid mimicking human connective tissue
- Capsules are slippery -> hard to grab by phagocyte
- Capsule protects destruction within phagolysosome - biofilm
- resistance to lysosomal enzymes
- inhibition phagosome/lysosome fusion
complement
Alternative pathway
- spontaneous lysis of C3
Classical pathway
- C1q binds to IgM, IgG, pentraxins (CRP)
Lectin pathway
- MBL binding to mannose or
- Ficolin binding to lipoteichoic acid
evasion of complement
- encapsulation and biofilm
- long O-antigen (LPS)
- cleavage of C5a –> inhibit chemotaxis
humoral effects on bacteria
- neutralisation
- opsonisation and phagocytosis
- complement activation
- ADCC
evasion of Abs
- encapsulation and biofilm
- proteases
- antigenic masking
- antigenic variation
- intracellular growth
- binding Fc region of Abs
M cells as invasion mode
- M cells express many receptors, which are more accessible due to the decreased amount of mucus and Paneth cells around the M cells.
o β1-integrin –> Yesinia spp.
o β1-integrin –> MAP which forms a fibronectin bridge - E-cadherin and hepatocyte growth factor receptor (MET).
o Listeria monocytogenesattaches to E-cadherin and MET –> intracellular actin recruitment and infection
vibro cholerae
- Vibrio cholerae secretes a Zn2+-dependent metalloproteinase, called haemagglutinin protease (Hap) –> mucinolytic
o Vibrio cholerae also produces the toxin zonula occludens toxin (ZOT), which interacts with occludin and ZO1 tight junction disruption
clostridium
- Clostridium perfringens secretes enterotoxin, which acts on the tight junction protein claudin.
giardia lablia
- Giardia lamblia is a protozoan that is able to degrade the mucus layer.
o It can also reorganize cytoskeletal F-actin filaments and disrupt ZO1, which increases permeability.
goblet cells as invasion mode
- L. monocytogenes can enter the epithelium via goblet cells when they have secreted their mucus.
o When the goblet cells have secreted their mucus, the host receptor E-cadherin will become accessible. - L. monocytogenes can bind to E-cadherin, after which it is internalized into the epithelium via transcytosis and excreted again via exocytosis
AMP evasion
- S. typhimurium has the ability to change the anionic charge of its own lipid A.
o It does this using phase variation.
o Its goal is to reduce the negative charge by adding amino acid groups that are positively charged through aminoarabinose. - This is beneficial for the bacterium since normally the negative charge attracts positive/cationic antimicrobial peptides (CAMPs
salmonella virulence
- Can evade activity of cationic AMPs by altering
the anionic character of the cell surface - Use fimbriae to bind to M-cells
- T3SS injects effector molecules into cells
- Effector molecules facilitate uptake and
intracellular survival (video) - Remain in endocytic vacuoles
shigella virulence
Uptake by M-cells
* Effector molecules facilitate uptake (membrane ruffling)
* Endocytosed by M cells -> transcytosed toward pocket -> uptake by resident macrophages
* Shigellae lyse the phagocytic vacuole and replicate in the host cell cytoplasm
* Massive inflammatory cell death of macrophages
* Subsequent released bacterial cells enter enterocytes from basolateral side –> T3SS
* Bacteria released from vacuole and replication in cytoplasm
* Shigella proliferation induces actin polymerization at one pole of the bacterium, providing the propulsive force required for intracellular movement (thus immune evasion)
superantigens in S.aureus and S. pyogenes
- Superantigens are a type of exotoxin that are able to activate T cells by binding both to the TCR and MHCII on an APC, without needed an antigen to do this –> cytokine storm
o Toxin shock syndrome toxin S. aureus
o Staphylococcus enterotoxins and erythrogenic toxin A and C S. pyogenes
