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The recent explosion of information in innate immune pathways for recognition, effect or responses, and genetic regulation has given impetus to investigations into analogous pathways in the human immune response, which in turn has produced attendant insights into both normal physiology and immunopathology. This volume presents a compendium of methods and protocols for the investigation of human innate immunity with application to the study of normal immune function, immunosenescence, autoimmunity and infectious diseases. Among the topics covered are quantitative flow cytometry for Toll-like receptor expression and function; multidimensional single cell mass cytometry (CyTOF) in complex immune interactions and tumor immunity; imaging techniques such as Imagestream high resolution microscopy coupled to flow cytometry, immune cell infiltration of organotypic, biomimetic organs; high-throughput single cell secretion profiling; multiplexed transcriptomic profiling; microsatellite and microRNA methodologies, RNA interference; and the latest bioinformatics and biostatistical methodologies, including in-depth statistical modeling, genetic mapping, and systems approaches.