It seems that the structurally and physiologically very diverse Sia with their complicated structure were superior to other acidic sugars found on cell surfaces, e.g. sulfated or phosphorylated monosaccharides, thus stimulating the evolution to higher animals. Sia may have been much better suited for distinct cell contacts regulating tissue differentiation. They probably contributed to a better immune system, not only with regard to innate defense mechanisms but mainly by providing a high adaptability of the immune system. This may have augmented the chances of animals to survive the constant fight against continuously changing environmental antigens and may have contributed to a more independent life by better adaptation to or conquest of
new biotopes. Evidence is brought forward that siglecs and other mammalian Sia-recognizing receptors co-evolved with Sia and in this way created a very versatile system of cell contacts which was superior to those already in existence. Since siglecs are mainly found on cells of the immune system and CD22 as the best studied example
seems to be involved in the regulation of the interaction between B and T lymphocytes, Sia, along with other carbohydrate residues, made the more vulnerable higher
animals fitter in the battle against microorganisms. Comparable to the ‘‘Red Queen’’ in ‘‘Alice in Wonderland’’ (Varki, 1997), new carbohydrate structures had constantly to be developed in order to combat bacteria and viruses, which, as outlined above, start infection by binding to cell surface carbohydrates. A flexible immune system had to be adapted to the evolution of new glycan structures, and to accept them as ‘‘self’’. This is occasionally ‘‘mis’’-used by some microorganisms by successfully creating a molecular mimicry on their surface, thus evading the host immune system. For example, lipopolysaccharides of Campylobacter jejuni are sialylated in the peripheral part, thus giving them a structure resembling gangliosides, which are not recognized by the human immune system (Gilbert et al., 2000).