Danger Theory
Polly Matzinger's revolutionary framework that transformed our understanding of how the immune system decides when to respond
Traditional Model
"Attack what's foreign"
Self vs Non-Self
MHC-restricted recognition
Binary discrimination paradigm
Danger Theory
"Respond to danger signals"
Context-dependent activation
DAMP-mediated activation
Tissue damage recognition
Understanding the Paradigm Shift
Polly Matzinger's Danger Theory revolutionized immunology by proposing that the immune system responds to danger signals rather than simply distinguishing "self" from "non-self."
Traditional Model
The immune system recognizes and attacks "foreign" invaders based on molecular patterns.
Think of it like a security guard checking IDs at a building entrance.
Based on MHC recognition and self/non-self discrimination paradigms.
Danger Theory
The immune system responds to danger signals from damaged tissue.
Like a fire alarm that responds to smoke, not just strangers.
DAMPs (Damage-Associated Molecular Patterns) provide contextual activation signals.
Clinical Impact
Better explains autoimmune diseases and transplant rejection.
Helps doctors understand why treatments work or fail.
Informs immunotherapy design and tolerance induction protocols.
Traditional vs Danger Model
3D Cell Visualization
See how cells send danger signals when they're damaged
Healthy Cell
A healthy cell keeps its danger signals inside, like keeping the alarm system off when everything is safe.
Healthy cells maintain membrane integrity and do not release DAMPs, preventing unnecessary immune activation.
Damaged Cell
When a cell is damaged, it releases danger signals like a fire alarm, calling for help from the immune system.
Damaged cells release DAMPs (Damage-Associated Molecular Patterns) that activate dendritic cells and initiate immune responses.