Pattern Recognition Receptors (PRRs)

Question 1

Innate immune cells detect pathogens via BLANKS

Answer 1

Innate immune cells detect pathogens via interaction of PRRs with “Pathogen Associated Molecular Patterns” (PAMPs)

PAMPs are Molecules or structures that are specific for pathogenic microbes microbes, viruses and fungi and not visible on host cells.

Question 2

PRRs don’t just recognise PAMPs, they also recognise:

Answer 2

Pathogen Associated Molecular Patterns (PAMPs): molecules or structures that are specific for pathogenic microbes, viruses and fungi and not normally visible on host cells.

Damage Associated Molecular Patterns (DAMPs): host cell molecules or structures that are not normally visible to the immune system but which can be released from damaged or dying cells.

Micro-organism Associated Molecular Patterns (MAMPs): molecules or structures that are specific for microbes and viruses and not normally visible on host cells. Overlaps with PAMPs, but includes structures found on commensal microbes

Question 3

PRRs vs T/B Cell Receptors:

Answer 3

PRRs:

• Invariant, germline encoded
• Binding of a specific ligand constant across all cells that express the PRR
• Recognises a broad class of ligands
• Cannot undergo a learned immune response

TCRs/BCRs:

• Sequence diversity due to VDJ recombination during T/B cell development
• Binding of a specific ligand is not constant across all T/B cells
• Highly selective: clonal B/T cells are specific for a very defined antigen
• Memory cells allow for learned immune response: slow initial response but fast response on end infection

Question 4

Classes of PRRs:

Answer 4

Membrane receptors:

• Toll like receptors
• C-type lectin receptors

Cytoplasmic receptors:

• Nod like receptors
• DNA receptors
• RNA receptors (RIG-I, Mda5)

Question 5

Lipopolysaccharide (LPS)

Answer 5

Component of gram negative bacterial cell walls

Precise structure varies between bacterial strains and species

Very potent PAMP

Question 6

Cell responses to PRRs are context dependent

TRUE OR FALSE

Answer 6

TRUE

Most pathogens do not express just one PAMP, allows a tailored immune response to pathogens

Question 7

Dectin-1

Answer 7

• A C-type lectin receptor
• Dectin-1 modifies the TLR response during infection by fungal pathogens
• Dectin-1 modifies the output of TLR stimulation

Question 8

Nod Like Receptors

Answer 8

• Contain central NOD (also called NATCH) domain and Leucine Rich Repeats (LRRs) at the C-terminus (except NLRP10)
• N-terminal region varies – can be divided into 4 subgroups (NLRA, NLRB, NLRC, NLRP)

Question 9

NLRP3 containing inflammasomes

Answer 9

3 components:

NLRP3: sensor for activation. Mutations in NLRP3 result in the auto-inflammatory condition Cryopyrin-associated periodic syndromes (CAPS)

ASC (Apoptosis-associated speck-like protein containing a CARD): Adaptor – allows recruitment of caspase 1 to NLRP3

Csapase 1: made as an inactive pro-enzyme. Contains a cysteine protease domain and a CARD domain

Question 10

DNA Receptors:

Answer 10

Aim2: Acts via ASC to activate caspases 1

cGas – activates Sting to promote type 1 interferon production

Question 11

DNA Receptors:

Answer 11

Aim2: Acts via ASC to activate caspases 1
cGas: Activates Sting to promote type 1 interferon production