Immunological Memory, from Thucydides to Burnet and Beyond

Abstract

Immunological memory has been observed since ancient times because those who recovered from an epidemic (infectious) disease usually did not contract it a second time. For centuries, fanciful hypotheses were put forward on the origin of this acquired refractoriness to specific diseases, which mainly imagined the depletion in the host of some factor that normally allowed the production of the pathologies. In 1890, the antibody was discovered, and the problem became twofold. On the one hand, as the result of an infectious or antigenic stimulus in the body, how could specific antibodies appear, and how were antibodies made? On the other hand, what does immunological memory depend on, that is, how is the specific trace of the encounter with the infectious challenge or an antigen preserved? Immunochemical research demonstrated the intrinsic or spontaneous diversity of antibodies. The specificity of recognition is not absolute or exclusive to one antibody but rather the result of a multiplicity of partial recognitions by antibodies with different affinities for the antigenic determinant(s). Furthermore, a comparison of successive immune responses showed that a second stimulus with the same antigen elicits faster and more chemically effective antibodies. At that point, diversity could be imagined and then established to pre-exist, i.e. it became the condition that allowed the immune response to be thought of as adaptive. In the meantime, each specific antibody was synthesised by differentiated cells undergoing clonal expansion. Therefore, the functional logic of immunological memory was based on the formation of B or T cells, which spontaneously express on their surfaces receptors with predefined specificity and undergo clonal expansion following the encounter with the antigen. Selected antibodies made by plasma cells can remain in circulation for some time. Some B and T cells evolve into memory cells ready to be activated in case of a further stimulus from the same antigen. Explaining the functional logic of immunological memory has inspired one of the most successful neurobiological models of how the brain works as a selective system, Gerald Edelman's theory of neural Darwinism.