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Modern cellular and molecular studies have made great progress in characterizing the mechanisms that control immune responses. Now it is time to broaden the present views to accommodate evidence from epitope-specific and other immunoregulatory systems, which were well studied some years ago and are still highly relevant to contemporary work.
Mutations have been the driving force behind some of the most important discoveries in immunology, and the growing speed with which they can be found has impelled the use of random mutagenesis to create new immunological phenotypes in mice. Here we describe how phenotypes are created, detected and ascribed to genetic change.
Conditional gene targeting based on excision or inversion of loxP-flanked DNA segments by Cre recombinase is a powerful technology for the analysis of gene function, but unexpected expression patterns of cre transgenes, variability of recombination efficiency depending on the target gene and potential toxicity of Cre recombinase represent serious challenges for the experimenter.
There is general appreciation that 'genetic background effects' can profoundly affect the immune phenotypes of congenic, transgenic and knockout mice. We suggest that attributing phenotypes to genetic background effects is outmoded and that new databases containing single-nucleotide polymorphisms obtained with a group of inbred mouse strains can be used to define the flanking DNA of nearly all mouse genes.
Investigations of immune recognition in nonmammalian species provide new insights into the evolution of immunity and the inner workings of the mammalian immune system. Very diverse mechanisms are used by different multicellular organisms to recognize and cope with the rapidly evolving microbial world.
Innate immunity has come to the forefront in immunology, aided by the discovery of antifungal defense in drosophila. Here Jules Hoffmann recounts his team's pioneering work on insect immunity.
Blimp-1 is a transcription factor that affects the expression of hundreds of genes in lymphocytes. Recent work confirmed its role in the maturation of B cells into immunoglobulin-secreting plasmablasts, as well as in the control of T cell homeostasis and tolerance. What follows is a short history of how Blimp-1 was discovered.
Discovering the transcription factors that direct lineage commitment in the T helper cell was a formidable task. Laurie Glimcher describes how she and Susanne Szabo hunted down T-bet, a transcription factor that is a 'master regulator' of commitment to the T helper type 1 lineage.
Understanding how transcription factors direct lymphocyte lineage determination requires appreciation of the myriad ways in which they interact with and influence other cellular processes.