Danger model

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

[5][6] When injured or stressed, tissues typically undergo non-silent types of cell death, such as necrosis or pyroptosis, releasing danger signals like DNA, RNA, heat shock proteins (Hsps), hyaluronic acid, serum amyloid A protein, ATP, uric acid, and cytokines like interferon-α, interleukin-1β, and CD40L for detection by dendritic cells.

[4][6][7] In comparison, neoplastic tumors do not induce significant immune responses because controlled apoptosis degrades most danger signals, preventing the detection and destruction of malignant cells.

[13][14] 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.

Function of T helper cells: Antigen-presenting cells ( APCs ) present antigens on their Class II MHC molecules ( MHC2 ). Helper T cells recognize these by expressing the CD4 co-receptor . The activation of a resting helper T cell causes it to release cytokines and other signals (green arrows) that stimulate the activity of macrophages , killer T cells , and B cells , the last of which produces antibodies . The proliferation of Helper T cells stimulates B cells and macrophages.