Abstract: The immune system defends us from pathogens. But what is an antigen? Does each lymphocyte really know the complete ensemble of all the molecules of our body? Is there, instead, a systemic cooperation among these  cells resembling neurons in the brain? Is the immune system able to "think"? And, even more interesting, what is self? Is there a sharp separation between self and not-self?
From the pioneering papers by Jerne, Varela and Couthino, the idea of a network of B-clones interacting by exchanging antibodies was formulated as an hypothetical way for explaining tolerance toward self proteins by mature peripheral B-cells (beyond clonal deletion and receptor editing during the ontogenesis). However, despite anti-antibodies are commonly encountered,  evidence in favor of an extensive network is still lacking and even worse, always sharper experiments (e.g. the works by Goodnow) highlighted strong evidence of a phenomenon called "anergy": the latter shifts the responsibility of this lacking of attack by B-cells self-directed to a lacking of signalling by helpers cells (the second key needed for B-cell activation beyond the primary antigenic target, self or not-self): In a nutshell, B-cells need two activation signals, the former being the target (antigen) the latter being a "consensus" by the helpers. Helpers do not allow this consensus and the resulting B-cell with only one signal undergoes into a regime of "anergy". But how can helpers recognize those B-cells self-directed? The problem seems only shifted...  Coupled to a large introduction to theoretical immunology and its formalization through statistical mechanics, we try to revise this discussion within a thermodynamical framework by using the tools of disordered systems.