On Recognizing ‘Shades‐of‐Gray’ (Self–Nonself Discrimination) or ‘Colour’ (Integrity Model) by The Immune System

Abstract

The aim is to discuss Cohn's T-cell receptor (TCR) Tritope model of recognition, propose a novel suggestion for prior-to-positive selection of thymocytes contributing to inherent major histocompatibility complex (MHC) reactivity of a T-cell repertoire and clarify the Integrity model about the function of the immune system. If we compare the perception of light with the recognition of nonself, we could imagine that the opacity might be a measure of docking interaction between specific receptors for antigen on T or B cells (TCR / peptide-MHC or BCR / antigen). From this viewpoint, the self-nonself discrimination (S-NS) metaphor would be perception of black (self) versus white (nonself). However, whereas detection of shades-of-gray suffices to describe S-NS discrimination principle, colour vision of the antigenic world portrays best the Integrity model. In concert with recognition of opacity, the Integrity model proposes detection of at least three colours (signals): red (harmful), blue (useful) and yellow (the rest, including homoeostatic ones). As a result, recognition of nonself is transferred into communication within self while deciding on type of the immune response. Hence, the S-NS discrimination model seems to be an oversimplification, because it fails to see colours and consequently lacks the need for suppressor/regulatory function. Similarly, the Danger model stops short of detecting being useful signals that confer immune asylum to helpful micro-organisms like commensals. I suggest that the immune system's repertoire for recognition, in general, has evolved by a novel drive called 'natural integrity' alongside natural selection, thus facilitating communication between cells of the immune system.

Theories about the Function of the Immune System

“…In contrast to the "Danger" model, the "Integrity" model (Dembic) [14][15][16][17] stipulates that any exogenous stress has to be recognized in the context of endogenous stress. In other words, dendritic cells would be activated (and matured) only if they receive at least two such signals (endogenous + exogenous) (Figure 9-3), whereas, in the Danger model, either of them would suffice for DC activation (i.e., for kick-starting the immune response).…”

Antitumor Drugs and Their Targets

“…The cancer immunosurveillance hypothesis has proposed that the immune system checks the integrity of an organism by innate and adaptive immune responses. The immune system contributes to homeostasis by protecting the body and tissues, overseeing the development and balancing the growth and maintenance of organs and tissues [225,226]. In Figure 3 Tregs: Cancer can activate or induce suppressor T cells (Tregs) that suppress antitumor T, B and NK immunosurveillance cells [230].…”

“…In Figure 3 Tregs: Cancer can activate or induce suppressor T cells (Tregs) that suppress antitumor T, B and NK immunosurveillance cells [230]. The development of regulatory T cells in the thymus and periphery of the immune system [226] is known, and their role was suggested to be of paramount importance for the immunosurveillance of cancer [225].…”

Challenging The Tritope Model of T cell Receptor Structure–Function Relationships with Classical Data on ‘Super’ and ‘Allo‐MHC’ Antigens

“…In appreciation of Dembic's probing analysis of the Tritope Model [34] It certainly is a tribute to a structure-function model when a colleague takes the time to write a detailed analysis that places the model in the much broader context of immune responsiveness. Dembic has dealt with aspects that I did not discuss, so I have decided to limit my comments in an Addendum to what he views as weaknesses of logic and contradictory interpretations of data.…”