ABSTRACT
INTRODUCTION The first decade of this millennium witnessed an explosion in information concerning the mechanisms underlying the host’s immune response to invading microorganisms, as well as during pathological conditions such as autoimmune diseases and cancer. This was largely due to technological advances that include (i) the ability to track specific T cells by using fluorochrome-labeled peptide-major histocompatibility complex (MHC) tetramers and B cells, by using fluorochrome-labeled antigens (Ag); (ii) sophisticated multichromatic (up to 17 colors) and flow cytometric sorting techniques that allow the identification and functional characterization of subpopulations of cells on the basis of the concomitant expression of multiple surface and intracellular molecules (e.g., homing molecules, cytokines); (iii) the availability of an ever-growing number of cytokines, chemokines, and other immunoregulatory molecules produced by recombinant techniques; (iv) gene expression profiling using DNA microarrays that allows simultaneous determination of the expression of thousands of individual genes in response to infection; (v) ‘‘systems biology’’ approaches to predict the magnitude of the immune responses; (vi) the advent of proteomics (i.e., the large-scale analysis of proteins and their interactions); and (vii) engineering of a multitude of single and multiple gene knockout and transgenic animals (and more recently ‘‘conditional knockout’’ and ‘‘knockin’’ mutants). Moreover, the availability of the DNA sequences of entire genomes from an ever-increasing number of eukaryotic and prokaryotic organisms has the potential to identify large numbers of novel target Ag for vaccine development.
