A short history of time and space in immune discrimination

The destructive effector functions of the immune system pose a problem that has aptly been described as 'horror autotoxicus'. This problem demands a solution that offers an effective self-nonself discrimination mechanism. Unlike all other defence mechanisms, the immune system makes the self-nonself discrimination somatically, and not at the germline level. This discrimination requires a way of separating self from nonself. Two proposals to accomplish this are based on separation in time or in space. In this paper the authors show that separation in time remains the only viable solution. A generally accepted solution to the mechanism of the self-nonself discrimination is overdue as it strongly influences the way in which much of immune regulation is interpreted.