Protection against infection hinges on a close interplay between the innate immune system and the adaptive immune system.
Depending on the type and context of a pathogen, the innate system instructs the adaptive immune system to induce an appropriate
immune response. Here, we hypothesize that the adaptive immune system stores these instructions by changing from a naive to
an appropriate memory phenotype. In a secondary immune reaction, memory lymphocytes adhere to their instructed phenotype.
Because cross-reactions with unrelated Ags can be detrimental, such a qualitative form of memory requires a sufficient degree of
specificity of the adaptive immune system. For example, lymphocytes instructed to clear a particular pathogen may cause autoimmunity
when cross-reacting with ignored self molecules. Alternatively, memory cells may induce an immune response of the
wrong mode when cross-reacting with subsequent pathogens. To maximize the likelihood of responding to a wide variety of
pathogens, it is also required that the immune system be sufficiently cross-reactive. By means of a probabilistic model, we show
that these conflicting requirements are met optimally by a highly specific memory lymphocyte repertoire. This explains why the
lymphocyte system that was built on a preserved functional innate immune system has such a high degree of specificity. Our
analysis suggests that 1) memory lymphocytes should be more specific than naive lymphocytes and 2) species with small lymphocyte
repertoires should be more vulnerable to both infection and autoimmune diseases