Summary Innate and Adaptive Immune System Overview

TOLL-LIKE RECEPTORS (TLRs)
• LOCATION: PLASMA MEMBRANE AND ENDOSOME
• 10 TLRs in mammals— each recognizes a different set of
molecules.
• 1st recognized receptor in Drosophila
• Induces activation of transcription factors
- NF-KB (Nuclear Factor Kappa B):
- (1) synthesis and secretion of cytokines;
- (2) expression of adhesion molecules;
- (3) both leads to recruitment and activation
of leukocytes to the site of inflammation
- IRFs (Interferon Regulatory Factors): for
production of antiviral cytokines and Type I IFN
• “Loss of function” mutation: problems with antiviral and
antimicrobial functions of transcription factors




NOD-LIKE RECEPTORS (NLRs)
• LOCATION: CYTOSOL
• Recognizes:
- Necrotic cell products (uric acid and ATP)
- Ion disturbances (K+ loss)
- Microbial products
• Signals inflammasome




INFLAMMASOME
• LOCATION: CYTOSOL
• Cytosolic multiprotein complex
• Components:
- NLRP3: activates the inactive caspase-1
- Adapter
- Caspase-1: cleave precursor of IL-1
• IL-1: induces fever and further leukocyte recruitment
• NLR-Inflammasome Pathway
- Periodic Fever Syndrome/ Autoinflammatory Syndrome
• Not autoimmune; unregulated production of IL-1
• Causes: “Gain of function” (NLR mutation) and
“Loss of function” (Inflammasome mutation)
• Management: IL-1 antagonist
- Gout
- Obesity associated with T2DM and atherosclerosis