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S and P- POI > Microbial triggers to innate immunity > Flashcards

Microbial triggers to innate immunity Flashcards

1
Q

How do bacteria hang on?

A

Non-specific electrostatic interactions
Tethering via projections or pili
Attachment via special receptors on human cell surfaces (fibronectin binding proteins)
Internalisation into epithelial cell

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2
Q

What does the penetration of epithelial barriers/endothelial barriers consist of?

A 
Artificial penetration (breach of epithelium)
Entry into and through the cell
Transit in between cell layers
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3
Q

What causes scalded skin syndrome?

A

S. aureus has an exfoliative toxin that cleaves desmosomes

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4
Q

What happens following host recognition of a pathogen?

A

There are danger signals and release of chemokines, cytokines and the complement kills Gram negatives

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5
Q

What does the recognition of pathogen actually lead to?

A

Transcriptional changes that lead to the production of cytokines

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6
Q

Why is there inflammation during infection?

A

Nitric oxide is released which leads to relaxation of blood vessels and characteristic features of inflammation- redness and swelling

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7
Q

What toll-like receptor detects lipoproteins from various bacteria?

A

TLR2 which is always in a heterodimer with TLR1 or TLR6

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8
Q

What does TLR 4 detect?

A

Endotoxins (LPS)- important for detection of gram-negative bacterial infections

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9
Q

What does TLR5 detect?

A

Flagellin- feature of some Gram-negative bacteria

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10
Q

What does activation of TLRs lead to?

A

Signalling inside the cell and transcriptional changes which causes release of inflammatory mediators and recruitment of innate immune response and clearance of bacteria

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11
Q

What are the pattern recognition receptors (PRRs) found inside the cells?

A

NOD and various TLRs

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12
Q 
Give the triggers for the following receptors:
TLR2/TLR1
TLR2/TLR6
TLR4
TLR5
NOD
TLR9
A 
TLR2/TLR1- Lipoproteins
TLR2/TLR6- Mycoplasmal lipoproteins
TLR4- LPS
TLR5- Flagellin
NOD- Peptidoglycan
TLR9- Bacterial DNA
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13
Q

What will be found in the CSF of someone with bacterial meningitis?

A

Loads of neutrophils- responsible for characteristic stiff neck of meningitis

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14
Q

How are Gram-negative bacteria cleared?

A

Antibodies can opsonise the bacterium prior to phagocytosis
Complement can also opsonise bacteria
Chemotaxis of neutrophils (complex mediated- C5a)
Membrane attack complex (MAC) which results from complement activation can lyse certain Gram-negative bacteria

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15
Q

What is very important in dealing with meningococcal infection?

A

Complement

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16
Q

What is ineffective against Gram Positive bacteria and what is the result of this?

A

Complement can’t lyse Gram-positive bacteria, they don’t have lipopolysaccharide and this means that they must be phagocytosed

17
Q

What components of Gram Positive bacteria trigger the immune system?

A

Peptidoglycan (through TLR2 or NOD)

Lipoteichoic acid

18
Q

How are Gram-positive bacteria cleared?

A 
Specific antibody opsonising
Complement opsonising
Chemotaxis of neutrophils
Clearance by phagocytosis and then killing 
(Complement is insufficient on its own)
19
Q

What is the general relationship between pathogens and PRRs?

A

Pathogens trigger multiple PRRs because they have multiple PAMPs

20
Q

What does streptococcus pneumonia trigger?

A

TLR2- Lipoproteins
TLR4- Pneumolysin
TLR9- Bacterial DNA

21
Q

What does legionella trigger?

A

TLR4- Lipopolysaccharide
TLR5- Flagellin
TLR9- Bacterial DNA

22
Q

What does herpes virus trigger?

A

TLR9- DNA
TLR3- dsRNA
TLR2- Viral protein

23
Q

What does influenza trigger?

A

TLR7/8 ssRNA

TLR3 dsRNA

24
Q

What TLRs do viruses trigger?

A

Intracellular

25
Q

How does staphylococcus aureus cause toxic shock?

A

Production of a superantigen (toxic shock syndrome toxin-1)

Streptococcus pyogenes also causes this

26
Q

What happens normally to antigens?

A

They are taken up by antigen presenting cells, processed and presented on MHC class II to T cells (specific to that antigen)- antigenic peptides are loaded on MHC groove

27
Q

How do superantigens work?

A

They trigger a much more powerful immune response, they deceive the immune system because they can bind to MHC class II outside of antigen binding groove. Around 20% of T cells will see super antigen stuck onto MHC class II and will think it is their peptide so will proliferate massively and there is massive production of cytokines- toxic shock syndrome

28
Q

What defense system is there against toxic shock syndrome?

A

Antibodies

29
Q

How does streptococcus pyogenes evade the immune system?

A

Anti-neutrophil strategies e.g. streptolysin
Anti-opsonisation strategies e.g. complement binding
Toxins that interfere with immune response e.g. superantigens

30
Q

How does staphylococcus aureus evade the immune system?

A

Anti-neutrophil strategies e.g. panton valentine leukocidin
Anti-opsonisation strategies e.g. Ig binding proteins
Toxins that interfere with immune responses e.g. superantigens

31
Q

How does Neisseria meningitides evade the immune system?

A

Anti-complement/Anti-MAC strategies e.g. capsule

32
Q

What does mecA gene do?

A

Confers resistance to beta-lactams

33
Q

Where do bacteria resistant to beta-lactams tend to be found?

A

In hospitals

34
Q

What have clones of the resistant bacteria in the community been found to have?

A

Similar anti-biotic resistance element (mecA) but also they’ve acquired a phage that encodes a bacterial roxin called panton valentine leukocidin (PVL)

35
Q

How does PVL exist?

A

It forms a heptamer that has a pore

36
Q

What does the heptameric pore do at low and high concentrations?

A

Low- makes human neutrophils apoptose
High- Makes human neutrophils lyse
PVL producing staphylococci causes very nasty infections associated with abscesses that can’t be cleared by the patients

S and P- POI (7 decks)

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