How does the immune system distinguish self from nonself?

One of the cornerstones of modern immunology is the ability of the adaptive immune system of lymphocytes to discriminate between self and nonself. Yet lymphocytes frequently make this distiction very poorly, as seen for instance by the ability to mount an adaptive immune response to self-tissues. In this brief essay on the ability to distinguish self from nonself, we will consider one model to explain how the immune system in its broader sense, including both adaptive and innate immunity, makes these distinctions reliably most of the time.