Topic 3: Innate Immunity II Flashcards
What is PRR
pattern recognition receptors (host)
What is PAMP
pathogen associated molecular patterns (microbe)
What happens when PAMP and PRR are combined?
causes activation of immune responses which can be through stimulation of phagocytosis and release of cytokines
What are some examples of PAMPS
- bacterial lipopolysaccharide - present on many bacteria
- glycoproteins - bacterial glycoproteins have terminal mannose residues (our cells can respond to mannose), mammalian ones have terminal sialic acid or N-acetylgalactosamine
- double-stranded RNA - common to many viruses
- unmethylated CpG DNA - common to bacteria, while humans have methylated C+G
What are PRR characteristics?
- detect non-self structures
- ubiquitous, either as a circulating molecule or through expression on innate immune cells
- rapidly triggers potent antimicrobial responses
What are toll-like receptors?
- are PRRs for PAMPs
- have leucine rich repeats on the exterior domain which is connected to a TIR domain which can lead to phagocytosis
Where are TLRs located?
- some are anchored in the cell membrane while others are within endosomes
What are TLR 1 and 2
- located in the cell membrane and respond for bacterial parasites
- heterodiamers
What are TLR 2 and 6
- located in the cell membrane and respond to gram positive bacteria and fungi
-heterodiamers
What are TLR 4
- located in the cell membrane and respond to gram-negative bacteria
- homodiamers
What are TLR 5?
- located in the cell membrane and respond to flagellated bacteria
- mono/homodiamers
What is TLR 3?
- located in the endosome and respond to viral dsRNA
- monomers
What is TLR 7?
- located in the endosome and respond to ssRNA
- monomers
What is TLR8?
- located in the endosome and respond to viral ssRNA
- monomers
What is TLR9?
- located in the endosome and respond to bacterial DNA elements
- monomers
How can PRRs differ in structure and function
- some PRRs are phagocytic receptors while others are not but can stimulate the activation of immune cells
What are advantages of having pattern recognition receptors?
- pathogens can change rapidly, since there are so many pathogens you want multiple PRRs to recognize them
- patterns are disadvantages by having small genomes and at least some conserved (low variation) components: these are targets of PRRs
- they surveil for intact PAMPs, degraded PAMPs and PAMPs that are never outside of the cell
What are the three molecules that enter the nucleus and bind to DNA
- Nf-kB
- AP-1
- IRF3
What is the goal of Nf-kB in the nucleus
goal is to express new types of gene expressions through Nf-kB
What are the functions of RIG-like receptors?
- have signalling pathways similar to TLRs
- can amplify TLR signalling
- Phosphorylates IkB and IRF-3 so that Nf-kB and IRF-3 can enter the nucleus
What are the results of PRR signalling?
- production of type I interferon (IFN-I). IFN-I augments innate and adaptive immunity
- production of various pro-inflammatory cytokines
- induces many other immune response genes
What is the importance of PRR Innate Immune Signalling
- Speed: TLR signalling is on within minutes of detecting microbial PAMP. Initial activation of adaptive immune responses requires days
- Economy: a small number of TLR can detect large numbers of different pathogens
- Amplification: localized detection of microbes can result in activation of large, systemic responses
Why are there so many types of redundancy in pattern recongition?
- overcome attempts by microbes to evade PRRs
- having multiple PRRs that can detect common features of the same microbe enhances chance of microbe getting detected
- cross-talk in signalling pathways induced by different PRRs allows for better control over the type of response
