Sterile Inflammation Flashcards
What is sterile inflammation?
Inflammation which occurs in the absence of a pathogen or infectious agent
Give examples of different causes of sterile inflammation?
- Protein misfolding (beta amyloids in Alzheimer’s)
- Ischemic heart or brain damage
- Silicosis (inhalation of molecules which phagocytes cannot get rid of hence persistant inflammation leading to tissue damage)
- Cholesterol crystals within arterial walls
Why would it be of interest to target sterile inflammation specificly?
We could target sterile inflammation, which has a huge role in disease production, whilst keeping our defenses against pathogens strong by maintaining infectious inflammation.
Explain why trails that target COX2 and histamine release have failed
These drugs are unable to discriminate between sterile and infectious inflammation - so when used in patients with chronic conditions, their ability to fight infection is impaired
In infectious inflammation, which are the signals which initiate it?
The signals are the antigenic structures on the pathogens called PAMPs (Pathogen-associated molecular patterns).
In sterile inflammation, which are the signals which initiate it?
The signals come from cell death or cell damage. Such as:
- HMGB1 (protein associated with chromatin)
- Prp40 (protein associated with a spliceosome)
- Heat shock proteins
These proteins are degraded following cell damage and their fragments which are exposed are called DAMPs - Damage-Associated Molecular Proteins –> these are the signals for sterile inflammation
What are the receptors for PAMPs?
TLRs
What are the receptors for DAMPs (sterile inflammation)?
Describe their structure
NLRs (Nucleotide binding oligomerization (NOD) like receptors)
Made of 3 domains
- recognition domain (rich in leucine rich repeats)
- NOD domain (for oligomeriation)
- Effector domain (caspase recruitment domain - initiates sterile inflammation through IL1)
