Becoming a Danger to One’s Self

Damage-Associated Molecular Patterns (DAMPs) are endogenous molecules that are typically found within cells but become exposed or released into the extracellular environment following cellular damage, stress, or injury. These molecules are recognized by the immune system as signals of cell damage or danger. Here are some examples of DAMPs:

1. HMGB1 (High Mobility Group Box 1):
   • Source: A nuclear protein that can be released from cells during necrosis, apoptosis, or cellular stress.
   • Function: HMGB1 acts as a DAMP when outside the cell, signaling danger and promoting inflammation.
2. ATP (Adenosine Triphosphate):
   • Source: Normally found inside cells as an energy carrier.
   • Function: Released into the extracellular space during cell damage, ATP acts as a DAMP and can trigger inflammation and immune responses.
3. Heat-Shock Proteins (HSPs):
   • Source: Intracellular proteins that play a role in cellular stress responses.
   • Function: Certain HSPs, when released or exposed on the cell surface, can act as DAMPs, signaling cellular stress and eliciting immune responses.
4. Uric Acid:
   • Source: Normally present in cells as a metabolic byproduct.
   • Function: Released during cell injury, necrosis, or inflammation, uric acid can act as a DAMP, contributing to the inflammatory response.
5. S100 Proteins:
   • Source: A family of calcium-binding proteins.
   • Function: Some S100 proteins are released from damaged or stressed cells and act as DAMPs, contributing to inflammatory responses.
6. DNA and RNA Fragments:
   • Source: Nucleic acids normally found within cells.
   • Function: Fragments of DNA and RNA released during cell damage or death can act as DAMPs, triggering immune responses.
7. Mitochondrial Components:
   • Source: Mitochondria contain various molecules that can be released during cellular stress or damage.
   • Function: Mitochondrial DAMPs, such as mitochondrial DNA or formyl peptides, can activate immune responses when released into the extracellular space.

Detection in Normal Cells: These DAMPs are typically not detected in normal, healthy cells because they are sequestered within the cell’s intracellular compartments. Normal physiological conditions involve a tightly regulated internal environment where cellular components remain contained within the cell membranes. DAMPs become exposed or released under conditions of cellular stress, damage, or pathological events, triggering the immune system to respond to these signals of danger.

The immune system is designed to recognize and respond to signals of danger or abnormality. When cells are healthy and functioning normally, DAMPs remain hidden within cells, and the immune system does not mount an unnecessary response against them. It is only under conditions of cellular stress or damage that DAMPs become apparent and contribute to immune activation.

Next Topic: Diversity of PRRs and the Types of PAMPs They Detect

Source: ChatGPT response prompted and edited by Joel Graff.

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