Blood is the pipeline of the immune system. Transcriptional profiling in the blood consists of measuring RNA abundance in circulating nucleated cells. Changes in transcript abundance can result from exposure to host or pathogen-derived immunogenic factors (for example, pathogen-derived molecular patterns activating specialized pattern recognition receptors expressed at the surface of leukocytes) and/or changes in relative cellular composition (for example, influx of immature neutrophils occurring in response to bacterial infection). The main blood leukocyte populations circulating in the blood are represented in this figure. Each cell type has a specialized function. Eosinophils, basophils and neutrophils are innate immune effectors playing a key role in defense against pathogens. T lymphocytes are the mediators of the adaptive cellular immune response. Antibody producing B lymphocytes (plasma cells) are key effectors of the humoral immune response. Monocytes, dendritic cells and B lymphocytes present antigens to T lymphocytes and play a central role in the development of the adaptive immune response. Blood leukocytes can be exposed in the circulation to factors released systemically from tissues where pathogenic processes take place. In addition, leukocytes will cross the endothelial barrier to reach local sites of inflammation. Dendritic cells exposed to inflammatory factors in tissues will be transported via the lymphatic system and reach lymph nodes via the afferent lymphatic vessels. These dendritic cells will encounter naïve T cells that are transported to the lymph node via high endothelial venules. 'Educated' T cells will then exit the lymph node via efferent lymph vessels that collect in the thoracic lymph duct, which in turn connects to the subclavian vein, at which point these T cells rejoin the blood circulation.