Microbial triggers to innate immunity

Question 1

How do bacteria hang on?

Answer 1

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

Question 2

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

Answer 2

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

Question 3

What causes scalded skin syndrome?

Answer 3

S. aureus has an exfoliative toxin that cleaves desmosomes

Question 4

What happens following host recognition of a pathogen?

Answer 4

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

Question 5

What does the recognition of pathogen actually lead to?

Answer 5

Transcriptional changes that lead to the production of cytokines

Question 6

Why is there inflammation during infection?

Answer 6

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

Question 7

What toll-like receptor detects lipoproteins from various bacteria?

Answer 7

TLR2 which is always in a heterodimer with TLR1 or TLR6

Question 8

What does TLR 4 detect?

Answer 8

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

Question 9

What does TLR5 detect?

Answer 9

Flagellin- feature of some Gram-negative bacteria

Question 10

What does activation of TLRs lead to?

Answer 10

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

Question 11

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

Answer 11

NOD and various TLRs

Question 12

Give the triggers for the following receptors:
TLR2/TLR1
TLR2/TLR6
TLR4
TLR5
NOD
TLR9

Answer 12

TLR2/TLR1- Lipoproteins
TLR2/TLR6- Mycoplasmal lipoproteins
TLR4- LPS
TLR5- Flagellin
NOD- Peptidoglycan
TLR9- Bacterial DNA

Question 13

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

Answer 13

Loads of neutrophils- responsible for characteristic stiff neck of meningitis

Question 14

How are Gram-negative bacteria cleared?

Answer 14

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

Question 15

What is very important in dealing with meningococcal infection?

Answer 15

Complement

Question 16

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

Answer 16

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

Question 17

What components of Gram Positive bacteria trigger the immune system?

Answer 17

Peptidoglycan (through TLR2 or NOD)

Lipoteichoic acid

Question 18

How are Gram-positive bacteria cleared?

Answer 18

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

Question 19

What is the general relationship between pathogens and PRRs?

Answer 19

Pathogens trigger multiple PRRs because they have multiple PAMPs

Question 20

What does streptococcus pneumonia trigger?

Answer 20

TLR2- Lipoproteins
TLR4- Pneumolysin
TLR9- Bacterial DNA

Question 21

What does legionella trigger?

Answer 21

TLR4- Lipopolysaccharide
TLR5- Flagellin
TLR9- Bacterial DNA

Question 22

What does herpes virus trigger?

Answer 22

TLR9- DNA
TLR3- dsRNA
TLR2- Viral protein

Question 23

What does influenza trigger?

Answer 23

TLR7/8 ssRNA

TLR3 dsRNA

Question 24

What TLRs do viruses trigger?

Answer 24

Intracellular

Question 25

How does staphylococcus aureus cause toxic shock?

Answer 25

Production of a superantigen (toxic shock syndrome toxin-1) | Streptococcus pyogenes also causes this

Question 26

What happens normally to antigens?

Answer 26

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

Question 27

How do superantigens work?

Answer 27

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

Question 28

What defense system is there against toxic shock syndrome?

Answer 28

Antibodies

Question 29

How does streptococcus pyogenes evade the immune system?

Answer 29

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

Question 30

How does staphylococcus aureus evade the immune system?

Answer 30

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

Question 31

How does Neisseria meningitides evade the immune system?

Answer 31

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

Question 32

What does mecA gene do?

Answer 32

Confers resistance to beta-lactams

Question 33

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

Answer 33

In hospitals

Question 34

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

Answer 34

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

Question 35

How does PVL exist?

Answer 35

It forms a heptamer that has a pore

Question 36

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

Answer 36

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