חישה תוך-תאית ודלקת

Intracellular Sensing

• Cytoplasmic NOD proteins are inactive in the cytoplasm, but become active when bacterial ligands bind to them.
• Binding of bacterial ligands to NOD proteins triggers a chain reaction, recruiting RIPK2.
• This activation leads to the activation of TAK1, which results in NF-κB activation.
• NOD proteins detect intracellular bacteria through muramyl dipeptide or IE-DAP.

Inflammasomes

• Inflammasomes are protein complexes that initiate inflammation.
• They are composed of three main proteins, including an NLRP protein.
• The NLRP protein's LRR domain is crucial for pathogen recognition, without this inflammasome won't form.
• The other components are ASC and proCaspase-1.
• ProCaspase-1 is an inactive, long protein, which needs to be cleaved to release the active part.
• The inflammasome's function is to cleave proCaspase-1 when it detects a foreign microbe.
• It can also be activated by tissue damage, not just by recognizing microbes.
• This is a positive feedback loop, the inflammasome's mechanisms, along with TLRs and other mechanisms trigger a desired response.

Other Cytoplasmic Receptors

• Additional cytoplasmic receptors exist, such as RIG-1 and MDA-5, which recognize uncapped RNA.
• Binding to uncapped RNA triggers a cascade, involving adaptor proteins and ultimately activating NF-κB.
• This mechanism prevents viruses from replicating within cells.
• These methods all activate adaptor proteins, leading to NF-κB activation.