In last month's issue of Immunology Today, Irun Cohen discussed the inadequacies of the clonal selection paradigm and proposed a cognitive paradigm in which preformed internal images guide and restrict the process of clonal activation. Here he clarifies the nature of these internal images, drawing on concrete examples from the image of infection and the image of self, the immunological homunculus.

Contrary to the expectations of clonal selection, the germ-line effectively encodes a primitive internal image of bacteria, viruses, and the context of inflammation I. These images do not depend on the antigen receptors of lymphocytes. Components of complement can recognize some microorganisms directly, targeting them for phagocytosis or lysis2; natural killer (NK) cells can respond to bacteria3; macrophages and other white blood cells have invariant germ-line receptors for lipopolysaccharides, muramyl dipeptide cell wall elements, and other distinctly bacterial molecules; many different cells recognize viral nucleic acids and the interferons that are elaborated as a consequence of viral infection. This primitive information arms cells with the capacity to recognize and respond to invaders: to secrete cytokines; to migrate, adhere, and penetrate tissues; to engulf bacteria and viruses; to activate enzyme systems and generate toxic molecules and free radicals that can kill invaders 3. The germ-line picture also encodes the organ or site in the body in which invasion has taken place. The patterns of lymphocyte migration, determined by molecules encoded in the germ line, compartmentalize the body 4. Specialized types of monocytes are resident in various tissues-skin, liver, lungs, gut, eye, nervous system-and each type of monocyte processes the information of invasion in specialized ways. The germqine picture of infection and infectious agents developed over evolutionary time as a result of