Polly Matzinger - Pattern Recognition and A Tissue-driven Immune System

Pattern Recognition and A Tissue-driven Immune System

Recently, Seong and Matzinger have suggested that the "patterns" that the immune system recognizes on bacteria are not as different from the alarm signals released by damaged cells as one might have thought. They suggested that, because life evolved in water, the hydrophobic portions (Hyppos) of molecules are normally hidden in the internal parts of molecules or other structures (like membranes) and that the sudden exposure of a Hyppo is a sure sign that some injury or damage has occurred. They suggested that these are the most ancient alarm signals, that they are recognized by evolutionarily ancient systems of repair and remodeling, and that the modern immune system piggy-backed on this ancient system. Thus bacteria and other organisms may have very similar alarm systems. They describe these ancient signals as Danger-associated molecular patterns, or DAMPs.

In a recent article in Nature Immunology, Matzinger makes a case for what she now views as the most important implication of the Danger Model: that the tissues of the body are a large part of what drive immune response. She argues that immunologists have had overly simplistic and schematic ideas about immune response because of the limits of their assays, and that organs are likely to induce immune responses that are best-suited to defending the organ from the damage of microbes but also from the damage of the immune system itself. She also asserts that the relationship of the immune system to commensal bacteria remains poorly understood but is likely to be important.

Matzinger argues that the idea of DAMPs may explain why Toll-like receptors seem to respond both to external and endogenous signals (while acknowledging controversy over this issue). By emphasizing her theory that the tissues drive the nature of the immune response (i.e., the "what type" rather than the "whether" of immune response), Matzinger describes a dynamic immune system with complex webs of signalling, rather than an immune system that can be explained by a simple and easily reducible set of molecular signals that initiate response, or by a small set of cells (e.g., "regulatory" T-cells) which shut it down.