Block A - Pathogen Recognition Flashcards
(44 cards)
What are the 3R’s (3 marks)
-recognition
-reaction
-resolution
Are PAMPs and PRRs part of the adaptive or innate immune system?
Innate immune system
By which process do antigen-specific receptors acquire their uniqueness
gene segment recombination
What’s the role of Mucins?
prevents adhesion to the epithelium by microorganisms
What’s the role of Lysozymes?
attacks peptidoglycan in bacterial cell wall
What’s the role of Defensins?
disrupts cell membranes of bacteria and fungi via pore formation
What’s the role of Cathelicidins?
disrupts cell membrane of a wide range of microorganisms
What’s the role of Histatins?
active against pathogenic fungi
What’s the role of RegIII family?
contain C-type lectins, which target peptidoglycans which promote pore formation
What’s IL-1R’s role in the inflammatory response
binds to the cytokine IL-1
What’s TLR’s role in the inflammatory response
recognizes pathogen-associated molecular patterns (PAMPs)
Both TLRs and IL-1R possess a _______
conserved intracellular signalling domain (TIR domain)
Name the purpose of the TIR domain and the proteins it recruits/activates
-TIR domain is critical for activating signalling pathways in innate immune receptors
-activates signalling cascades such as MAPK and NFkB
-recruits adaptor proteins such as MyD88
Where in the cell are TLRs usually found
in the extracellular structure of the cell
How do 2 TLRs become a heterodimer?
2 different proteins, such as TLR-1 and TLR-2 bring their Toll-IL-1 receptor (TIR) domains together to initiate cell signalling
How does a TLR form a homodimer?
2 of the same proteins, such as 2 TLR-4 proteins recognise LPS and after exposure to LPS, binds to both TLR’s stabilising them together
Describe the process of the MyD88 dependant pathway in relation to TLR4 after LPS binding to MD-2 has occurred. (3 marks)
-TLR binds to the TIR domain.
-which contains the adaptor protein TIRAP which activates MyD88, forming an active TLR4/MyD88 complex
-this activates NF-kB which leads to the production of pro-inflammatory cytokines like IL-6
Describe the process of the TRIF dependant pathway in relation to TLR4 after LPS binding to MD-2 has occurred. (3 marks)
-the adaptor proteins TRIF and TRAM are recruited which activates TRAF3
-which activates TBK1
-which phosphorylates IRF3
-IRF3 induces the expression of genes that encode interferons (type 1)
What are the 4 key outcomes of TLR4 signalling?
-pro-inflammatory cytokines
-type 1 interferons
-activation of MAPK pathways which contribute to inflammation, cell survival and apoptosis
-antimicrobial defence
What purpose do Nod like receptors have?
they are intracellular sensors of bacterial invasion and cellular damage
Whats the name of the domain for NLRs
CARD domain (caspase recruitment domain)
Describe the inflammasome and its activation?
-multi-protein complex that detects harmful stimuli and triggers inflammation via activation of caspase-1 which activates inflammatory cytokines like IL-1B and IL-18
-PAMPs and DAMPs are detected by sensor proteins like NLRP3
-sensor proteins interact with ASC, which has a domain that binds to caspase-1
-pyrin domains are structurally related to CARD and TIR domains
What are the potential consequences of the inflammasome?
recently been linked to the pathogenesis of several inflammatory diseases
Describe what 3 molecules help activate the NLRP3 inflammasome?
NLRP3, ASC and pro-caspase