Maximal frustration as an immunological principle

Abstract

A fundamental problem in immunology is that of understanding how the immune system selects promptly which cells to kill without harming the body. This problem poses an apparent paradox. Strong reactivity against pathogens seems incompatible with perfect tolerance towards self. We propose a different view on cellular reactivity to overcome this paradox: effector functions should be seen as the outcome of cellular decisions which can be in conflict with other cells' decisions. We argue that if cellular systems are frustrated, then extensive cross-reactivity among the elements in the system can decrease the reactivity of the system as a whole and induce perfect tolerance. Using numerical and mathematical analyses, we discuss two simple models that perform optimal pathogenic detection with no autoimmunity if cells are maximally frustrated. This study strongly suggests that a principle of maximal frustration could be used to build artificial immune systems. It would be interesting to test this principle in the real adaptive immune system.

Can the Immune System Perform a t-Test?

“…Positive selection would homogenize the dynamics associating to all cells conjugation lifetime distributions with close normalization factors. This allows measuring conjugation lifetimes by measuring the rate of conjugations of a given duration [49] (see Fig 2a). …”

“…In [49] it was shown that conjugation lifetimes are inversely proportional to the probability of destabilizing a conjugate and consequently are related to how cells prioritize interactions. In a stationary regime it was derived that conjugation lifetimes τ ij can be calculated according to: …”

“…Estimating the stationary frequencies can be difficult because APCs can present diverse information and also because their dynamical equations involve numerous feedbacks [49]. Therefore finding stationary frequencies demands self-consistent solutions which can only be found numerically.…”

“…In [49] it was proposed that this organization could be established by the negative selection education mechanisms in the adaptive immune system. During education APCs present self-ligands.…”

Intrusion Detection in Circular Frustrated Systems: An Eminently Parallel Processing Algorithm

“…The cellular frustration framework (CFF) is a new approach capable of performing single intrusion detections in large populations of very diverse agents [1]. A classical approach in the literature consists in defining a set of detectors where each one surveys a sub-domain of the space of patterns that characterize non-self agents.…”