FROM THE FOREHEAD OF ZEUS - THE ONTOGENY OF THE IMMUNE-RESPONSE

Many of the most important developments that result in a fully functio ning vertebrate immune system take place in the developing fetus. From a variety of gene segments there is assembled in B cells a congeries of antibody combining sites, one to a cell, which form the greater par t of the large repertoire of immunological specificities that characte rise the system. This capability is further expanded later by somatic mutations. Just as immunoglobulin isotypes are produced sequentially ( IgM, IgD, IgG, IgE, IgA) as they are read along the chromosome, so doe s the fetus and neonate manifest immunological competence sequentially to different antigens by employing variable region germline genes as they appear along the chromosome. The generation of T cell receptor di versity is accomplished by a similar mechanism of gene segment translo cations. Each stage in the lineage of T and B cells is associated with the appearance of unique combinations of surface molecular markers, w hich in T cells characterise also the specialised functions of differe nt subsets. If the immune system does not spring forth quite fully for med from the evolved vertebrate genome, as Athena did from the forehea d of Zeus, ontogenetic mechanisms have made it very nearly complete.