Danger model

The danger model of the immune system proposes that it differentiates between components that are capable of causing damage, rather that distinguishing between self and non-self.

History of immunologic models

The first major immunologic model was the Self/Non-self Model proposed by

Matzinger's work emphasizes that bodily tissues are the drivers of immunity, providing alarm signals on the location and extent of damage to minimize collateral damage.[9]^[10] The adaptive immune system relies on the innate immune system using its antigen-presenting cells to activate B and T lymphocytes for specific antibodies, exemplified by low dendritic cell counts resulting in common variable immunodeficiency (CVID).^[11] For example, gut cells secrete transforming growth factor beta (TGF-β) during bacterial invasions to stimulate B cell production of Immunoglobulin A (IgA).^[12] Similarly, 30-40% of the liver's T cells are Type I Natural Killer T (NTK) cells, providing Interleukin 4 (IL-4) for an organ-specific response of driving naïve CD4+ T cells to become Type 2 Helper T cells, as opposed to Type 1.^[13][14]

Damage-associated molecular pattern (DAMP) model

Whereas the danger model proposes non-silent cell death releasing intracellular contents and/or expressing unique signalling proteins to stimulate an immune response, the damage-associated molecular pattern (DAMP) model theorizes that the immune system responds to exposed hydrophobic regions of biological molecules. In 2004, Seung-Yong Seong and Matzinger argued that as cellular damage causes denaturing and protein misfolding, exposed hydrophobic regions aggregate into clumps for improved binding to immune receptors.^[15]

Pattern Recognition Receptors (PRRs)

Pattern Recognition Receptors (PRRs) are a family of surface receptors on antigen-presenting cells that includes