0000000000286129
AUTHOR
Adriano Barra
Anergy in self-directed B lymphocytes from a statistical mechanics perspective
The ability of the adaptive immune system to discriminate between self and non-self mainly stems from the ontogenic clonal-deletion of lymphocytes expressing strong binding affinity with self-peptides. However, some self-directed lymphocytes may evade selection and still be harmless due to a mechanism called clonal anergy. As for B lymphocytes, two major explanations for anergy developed over three decades: according to "Varela theory", it stems from a proper orchestration of the whole B-repertoire, in such a way that self-reactive clones, due to intensive interactions and feed-back from other clones, display more inertia to mount a response. On the other hand, according to the `two-signal …
A Hebbian approach to complex-network generation
Through a redefinition of patterns in an Hopfield-like model, we introduce and develop an approach to model discrete systems made up of many, interacting components with inner degrees of freedom. Our approach clarifies the intrinsic connection between the kind of interactions among components and the emergent topology describing the system itself; also, it allows to effectively address the statistical mechanics on the resulting networks. Indeed, a wide class of analytically treatable, weighted random graphs with a tunable level of correlation can be recovered and controlled. We especially focus on the case of imitative couplings among components endowed with similar patterns (i.e. attribute…
Retrieving infinite numbers of patterns in a spin-glass model of immune networks
The similarity between neural and immune networks has been known for decades, but so far we did not understand the mechanism that allows the immune system, unlike associative neural networks, to recall and execute a large number of memorized defense strategies {\em in parallel}. The explanation turns out to lie in the network topology. Neurons interact typically with a large number of other neurons, whereas interactions among lymphocytes in immune networks are very specific, and described by graphs with finite connectivity. In this paper we use replica techniques to solve a statistical mechanical immune network model with `coordinator branches' (T-cells) and `effector branches' (B-cells), a…
Immune networks: Multi-tasking capabilities at medium load
Associative network models featuring multi-tasking properties have been introduced recently and studied in the low load regime, where the number $P$ of simultaneously retrievable patterns scales with the number $N$ of nodes as $P\sim \log N$. In addition to their relevance in artificial intelligence, these models are increasingly important in immunology, where stored patterns represent strategies to fight pathogens and nodes represent lymphocyte clones. They allow us to understand the crucial ability of the immune system to respond simultaneously to multiple distinct antigen invasions. Here we develop further the statistical mechanical analysis of such systems, by studying the medium load r…
Collective behaviours: from biochemical kinetics to electronic circuits
In this work we aim to highlight a close analogy between cooperative behaviors in chemical kinetics and cybernetics; this is realized by using a common language for their description, that is mean-field statistical mechanics. First, we perform a one-to-one mapping between paradigmatic behaviors in chemical kinetics (i.e., non-cooperative, cooperative, ultra-sensitive, anti-cooperative) and in mean-field statistical mechanics (i.e., paramagnetic, high and low temperature ferromagnetic, anti-ferromagnetic). Interestingly, the statistical mechanics approach allows a unified, broad theory for all scenarios and, in particular, Michaelis-Menten, Hill and Adair equations are consistently recovered…
Can persistent Epstein-Barr virus infection induce Chronic Fatigue Syndrome as a Pavlov reflex of the immune response?
Chronic Fatigue Syndrome is a protracted illness condition (lasting even years) appearing with strong flu symptoms and systemic defiances by the immune system. Here, by means of statistical mechanics techniques, we study the most widely accepted picture for its genesis, namely a persistent acute mononucleosis infection, and we show how such infection may drive the immune system toward an out-of-equilibrium metastable state displaying chronic activation of both humoral and cellular responses (a state of full inflammation without a direct "causes-effect" reason). By exploiting a bridge with a neural scenario, we mirror killer lymphocytes $T_K$ and $B$ cells to neurons and helper lymphocytes $…
Organization and evolution of synthetic idiotypic networks
We introduce a class of weighted graphs whose properties are meant to mimic the topological features of idiotypic networks, namely the interaction networks involving the B-core of the immune system. Each node is endowed with a bit-string representing the idiotypic specificity of the corresponding B cell and a proper distance between any couple of bit-strings provides the coupling strength between the two nodes. We show that a biased distribution of the entries in bit-strings can yield fringes in the (weighted) degree distribution, small-worlds features, and scaling laws, in agreement with experimental findings. We also investigate the role of ageing, thought of as a progressive increase in …
Immune networks: multitasking capabilities near saturation
Pattern-diluted associative networks were introduced recently as models for the immune system, with nodes representing T-lymphocytes and stored patterns representing signalling protocols between T- and B-lymphocytes. It was shown earlier that in the regime of extreme pattern dilution, a system with $N_T$ T-lymphocytes can manage a number $N_B!=!\order(N_T^\delta)$ of B-lymphocytes simultaneously, with $\delta!<!1$. Here we study this model in the extensive load regime $N_B!=!\alpha N_T$, with also a high degree of pattern dilution, in agreement with immunological findings. We use graph theory and statistical mechanical analysis based on replica methods to show that in the finite-connectivit…
Multitasking associative networks.
We introduce a bipartite, diluted and frustrated, network as a sparse restricted Boltzman machine and we show its thermodynamical equivalence to an associative working memory able to retrieve multiple patterns in parallel without falling into spurious states typical of classical neural networks. We focus on systems processing in parallel a finite (up to logarithmic growth in the volume) amount of patterns, mirroring the low-level storage of standard Amit-Gutfreund-Sompolinsky theory. Results obtained trough statistical mechanics, signal-to-noise technique and Monte Carlo simulations are overall in perfect agreement and carry interesting biological insights. Indeed, these associative network…