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Ramunas M. Vabulas, Max-Planck-Institut für Biochemie, Martinsried, Germany,
Hermann Wagner, Institut für Med. Mikrobiologie, Immunologie u. Hygiene, Technische Universität München, München, Germany
The basic concept of the immune system postulates an ability to discriminate between self and non-self and to free the organism from the latter. Two major contributions advanced the comprehension of the cellular basis of self- versus non-self-discrimination. The first was the hypothesis regarding the expansion of antigen-recognising clones on encounter with a respective antigen, which allowed antigenic specificities of the resulting immune reactions to be explained. The co-stimulatory signal hypothesis represented another essential advancement. It postulated the necessity of a second, antigen-independent signal for lymphocyte activation. Its nature was put into an elegant metaphor of the ‘immunologist's dirty little secret’ , referring to substances of microbial origin that should be present concomitant with an antigen to prime an immune response to it.
Of a number of host receptors participating in detection of microbial constituents , Toll-like receptors (TLRs) currently represent the most interesting group. Their importance is assumed from the prominent cell activating capacity which they display after engagement with their cognate ligands. The name originates from the Drosophila homologue Toll, which was discovered as a part of the dorsoventral patterning cascade during the developmental larva stage of the fruit fly, and this seminal study established an additional, anti-microbial function for Toll in adult flies . It demonstrated that mutants of the genes in the cassette between the Toll ligand Spätzle down to the IκB homologue Cactus showed a compromised inducibility of the anti-fungal peptide drosomycin upon fungal challenge and consequently succumbed to the infection.
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