ICS week 3 Flashcards
what are the types of PRRs?
- soluble
- cell associated
what do PRRs respond to?
pathogens and associated pathogen associated molecular patterns (PAMPs)
how do soluble PRRs respond to PAMPs?
- direct attack of microorganism by soluble PRR molecules
- enhancement of phagocytosis of PRR-bound PAMPs
- proteolytic cascade resulting in lysis of microorganism
how do cell associated PRRs respond to PAMPs?
- phagocytosis of PAMP and associated microorganism
- activation of immune cell encountering PAMP
- release of inflammatory mediators to amplify response
what are DAMPs? what are they released by?
- danger associated molecular patterns
- necrotic cells
- apoptotic cells typically don’t release DAMPs
what is the response to severe injury?
- production of DAMPs
- uncontrolled cell death (necrosis)
- release of DAMPs
- processing of DAMPs by soluble and cell-associated PRRs
- immune response
what is the response to physiological stimuli or mild injury?
- DAMPs produced
- regulated cell death (apoptosis)
- DAMPs remain hidden in the cell
- recognition and phagocytosis of apoptotic cell by macrophage
- immune system remains quiscent
how is recognition of nonself entities achieved by the immune system?
array of pattern recognition receptors and proteins that have evolved to detect components of infectious agents that are not usually present in the body
what are PAMPs?
- pathogen-associated molecular proteins
- components of infectious agents that are normally present in the body
- not normally in the body, but is a common feature of many frequently encountered pathogens
what are some examples of PAMPs?
- carbohydrates not normally exposed in vertebrates
- proteins only found in bacteria e.g. flagellin
- double-stranded RNA that is typical of RNA viruses
what soluble (humoral) pattern recognition molecules are bound to the infectious agents? what does this lead to?
- complement
- mannose-binding lectin
- C reactive protein
- lysozyme
leads to killing through destruction of microbial cell wall constituents and breaching of the plasma membrane due to protein actions
what does engagement of infectious agents with cell associated pattern recognition receptors lead to?
- can lead to phagocytosis followed by its destruction within phagocytic vesicles
- leads to activation of signal transduction pathways that culminate in the release of soluble messenger proteins (cytokines, chemokines etc) that mobilise components of the immune system
what do several PRRs bind to?
- several are lectin-like
- bind multivalently with considerable specificity to exposed microbial surface sugars with their characteristic rigid three-dimensional geometric configurations
what do PRRs often not bind to?
array of galactose or sialic acid groups that are commonly the penultimate/ultimate sugars on surface polysaccharides
other than sugars, what else can PRRs bind to?
- detect nucleic acids derived from bacterial and viral genomes by virtue of modifications not found within vertebrate nucleic acids or conformations not normally found in the cytoplasm
what are families of PRRs?
TLRs, CTLRs, NLRs, RLRs and scavenger receptors
how many PRRs could be expressed by a phagocyte at a given time?
in excess of 50 distinct PRRs
what are TLRs?
toll like receptors
how did TLRs get their name?
- similarity to the Toll receptor in the fruit fly (Drosophila)
what is the function of TLRs?
- triggers an intracellular cascade generating the expression of antimicrobial peptides in response to microbial infection
- series of cell surface TLRs acting as sensors for extracellular infections have been identified
what are cell surface TLRs activated by?
microbial elements e.g.:
- peptidoglycan
- lipoproteins
- mycobacterial
- lipoarabinomannan
- yeast zymosan
- flagellin
- other pathogen derived ligands
what are examples of TLRs that are not displayed on the cell surface? where are they located?
some are responsive to intracellular viral RNA and unmethylated bacterial DNA
- e.g. TLR3 and TLR 7/8/9
- are located in endosomes and become engaged when encountered with phagocytosed material
what does engagement of TLRs with their respective ligaments lead to?
drives activation of nuclear factor kB (NFkB) adn members of the interferon-regulated factor (IRF) family of transcription factors
- depends on specific TLR
where are TLRs located?
within the plasma membrane or endosomal membrane compartments