As Pasteur famously said, “chance favours only the prepared mind”, and many immunologists have been richly rewarded for discoveries that were happy accidents. However, history tends to forget the less well-prepared, would-be pioneers, who did not initially grasp the full implications of their work. An example of the latter is the little-known story of Milan Hašek and his unknowing 'discovery' of immunological tolerance 50 years ago. This tale of politics and personal endeavour is told on page 591 by Hašek's one time Ph.D. student Juraj Ivanyi. He tells us how those credited with the discovery of tolerance recognized the importance of Hašek's experiments and recalls how Hašek later developed a keen interest in immunology.

Other articles in this issue cover some of the hottest and most controversial topics in immunology today. Carlos Ardavin gets to grips with the complex issues surrounding dendritic-cell origins and functional diversity. Chris Rudd and Helga Schneider untangle the signalling pathways of the co-stimulatory receptors CD28, ICOS and CTLA4. Carlos Martínez-A and colleagues discuss how pathogens can use lipid rafts — membrane microdomains that have an essential role in lymphocyte signalling — to their own ends. Warren Strober and Gerd Bouma bring together the latest immunological and genetic insights into inflammatory bowel disease. They discuss how the recently identified susceptibility gene NOD2 might contribute to the disease process. Min Li-Weber and Peter Krammer describe the transcriptional regulation of the IL4 gene, which is an important target for the therapy of atopic disease. Finally, Richard Ransohoff and colleagues trace the probable routes used by leukocytes to enter the central nervous system, both during normal immune surveillance and in inflammatory disease.