Lecture 5: Pattern Recognition in Innate Immunity

Question 1

Why does the immune system need to be able to recognise ‘self’?

Answer 1

so that it can respond to and resolve issues that may be caused by foreign molecules/entities

Question 2

How does the immune system differentiate from ‘self’?

Answer 2

cells of the innate immune response (such as dendritic cells, macrophages, monocytes, neutrophils and epithelial cells) contain ‘primitive’ pattern recognition receptors

Question 3

What are key features of pattern recognition receptors?

Answer 3

expressed by all cells of a particular type (e.g. macrophages), triggers immediate response, recognises broad classes of pathogens, interacts with a range of molecular structures of a given type, able to discriminate between even closely related molecular structures

Question 4

Why is it important to note that PRRs being expressed by all cells of a particular type is variable?

Answer 4

usually PRRs are all expressed on a given type of cell, however NK cells are an exception as they may have multiple different combinations among individual cells

Question 5

What are PAMPs? What do they enable?

Answer 5

pathogen associated molecular patterns which are highly conserved molecules or molecular patterns in microbes
enable discrimination between self and foreign

Question 6

What are DAMPs? What do they act as?

Answer 6

damage associated molecular patterns which are associated with components of host’s cells released during cell damage or death
they act as a warning sign for the organism to alert it of any damage or infection to its cells

Question 7

What are five events that occur when PAMPs or DAMPs are detected by PRRs?

Answer 7

release of cytokines/chemokines
immune cell recruitment
inflammation
adaptive immunity
tissue repair

Question 8

Do all innate immune cells share the same patterns of receptor expression?

Answer 8

yes

Question 9

Where are PRRs found on/in the cell?

Answer 9

on the cell membrane (extracellular)
in phagosomes/endosomes (intracellular-vesicular)
in the cytosol (intracellular)

Question 10

What type of receptor are TLRs and what do they specifically recognise? What are they always associated with?

Answer 10

germline-encoded receptors that specifically recognise PAMPS

always associated with membranes

Question 11

What does stimulation of TLRs result in?

Answer 11

cytokine and chemokine secretion

Question 12

What does TLR-4 recognise?

Answer 12

bacterial lipopolysaccharide in association with the host accessory proteins MD-2 and CD14, resulting in dimer formation

Question 13

Does TLR-4 act as a monomer or a dimer?

Answer 13

a dimer

Question 14

How does stimulation of TLR4 lead to the release of inflammatory cytokines?

Answer 14

stimulation of TLR4 activates a kinase cascade which activates IKK which becomes phosphorylated and degrades the inhibitor IκB which activates the NFκB transcription factor to start generating the cytokines

Question 15

What is the role of TLR3 in the endosome?

Answer 15

binds to dsRNA and signals via TRIF to induce the transcription factor IRF3 -> drives transcription of type I interferon genes

Question 16

What is the role of IFN-ɑ/β?

Answer 16

inhibits viral protein synthesis + viral assembly
degrades viral DNA
activates other cells of the innate response (e.g. APCs, NK cells)
increases antigen presentation and expression of MHC-I

Question 17

Which receptors detect pathogens in the cytosol?

Answer 17

RIG-I-like receptors (RLRs) detect cytoplasmic viral infection
NOD-like receptors (NLRs) are intracellular sensors of bacterial infection and cellular damage

Question 18

What do RLRs associate with and what do they induce?

Answer 18

associate with mitochondria and induce secretion of inflammatory cytokines and IFN-ɑ/β

Question 19

Where do NOD proteins reside and in what form? How is NFκB activated by NLRs?

Answer 19

in the cytoplasm in an inactive form
binding of bacterial ligands to NOD proteins induces recruitment of RIP2, which activates TAK1, leading to NFκB activation

Question 20

What do NLRs associate with?

Answer 20

additional molecules to form large protein complexes in the cytosol to produce an inflammasome

Question 21

What does the inflammasome complex incorporate and what does this protein do?

Answer 21

pro-caspase-1, which when activates cleaves pro-IL-1β and pro-IL-18 into bioactive IL-1β and IL-18