Recognition strategies in the innate immune system of ancestral chordates

Many components of the innate immune system in vertebrates can be reliably traced to urochordates and successful strategies for the detection and elimination of pathogens are present at that level of animal evolution, but the issue of where and how the adaptive immune system emerged is still obscure. There is a paucity of evidence for a gradual transition from the innate immune system of invertebrates to the recombinatorial immune system of higher vertebrates. None of the classical elements of MHC based transplantation immunity (MHC, TCR) or humoral immunity (Ig) have been found in urochordates or Agnathans. Nevertheless there is abundant evidence for adaptive immune responses in the agnathans. This remarkable paradox raises a number of questions. How do these ancestral chordates discriminate between the constituents of the external world and the constituents of "self"? Are these strategies universal within the animal kingdom and among chordates, or are different strategies used by representatives of the different taxonomic groups? The current state of our knowledge indicates that the immune system of lower chordates is very different from that of cartilaginous fishes. Pure homology hunting for vertebrate-specific immuno-relevant molecules in invertebrates is therefore of limited value. A more promising approach may involve unbiased functional screening methods. To understand better the evolution of adaptive immune systems, more comparative data from jawless vertebrates (lamprey or hagfish) and a representative of Acrania (e.g. Amphioxus) are clearly needed. (C) 2004 Elsevier Ltd. All rights reserved.