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Whole Blood Assay with Dual Co-Stimulation for Antigen-Specific Analysis of Host Immunity to Fungal and Viral Pathogens

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The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity.

Michael T Lotze¹, Herbert J Zeh, Anna Rubartelli

¹Department of Surgery, G.27A Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. lotzemt@upmc.edu

Immunological Reviews

|November 6, 2007

Summary

Damage- or pathogen-associated molecular patterns (DAMPs, PAMPs) are crucial for immunity but can cause chronic inflammation if not cleared. Oxidative mechanisms are key to eradicating these molecules and preventing disease.

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Area of Science:

Molecular Biology
Immunology
Cell Biology

Background:

Pathogen and damage responses in organisms involve complex molecular mechanisms for resistance and healing.
Damage- or pathogen-associated molecular patterns (DAMPs, PAMPs) have intracellular and extracellular roles.
Abnormal extracellular persistence of DAMPs/PAMPs is linked to inflammation, wound healing, and clinical disorders.

Purpose of the Study:

To explore the molecular mechanisms underlying pathogen resistance and wound healing.
To investigate the role of DAMPs/PAMPs in inflammation and disease.
To hypothesize the role of oxidative mechanisms in clearing DAMPs/PAMPs and preventing chronic inflammation.

Main Methods:

Review of molecular mechanisms in plant and animal immunity.
Analysis of DAMP/PAMP recognition by host receptors (e.g., Toll-like receptors, NOD-like receptors).
Speculative analysis of oxidative destruction versus extracellular persistence of DAMPs/PAMPs.

Main Results:

DAMPs/PAMPs are recognized by various host receptors, initiating inflammatory cascades.
Extracellular DAMPs/PAMPs can contribute to inflammation and disease.
Oxidative mechanisms, particularly by myeloid cells, are proposed as crucial for DAMP/PAMP eradication.

Conclusions:

The balance between DAMP/PAMP sensing and clearance is critical for health.
Chronic inflammation may arise from the persistence of DAMPs/PAMPs in reducing extracellular environments.
Targeting oxidative mechanisms could offer therapeutic strategies for chronic inflammatory conditions.