A virus infects an epithelial cell, multiplies, and soon spreads to a few hundred cells in the vicinity. At the same time, a paper cut to a finger a meter away is infiltrated by bacteria. These attacks happen every day to us or those around us, usually without complications. How do the cells of the immune system respond to these insults quickly and efficiently?
The cellular immune response is performed by a collection of cells, consisting of leukocytes (also known as white blood cells) that circulate between the blood and lymphatic systems. Some of these cells, such as neutrophils and mono-cytes, kill foreign or infected cells directly or when tagged with antibodies produced elsewhere in the immune system. Others, such as lymphocytes, are more specific, requiring a perfect match between cell-surface receptors and antigens on the interrogated cell before killing commences. But how do these cells, which circulate through the bloodstream, find the tissue where injury or invasion has occurred?
The answer is a sophisticated combination of fluid dynamics and adhesion molecules that bring the leukocytes to the endothelial wall in the area of insult, slow their motion, and finally arrest them. The specificity of the response comes from a signaling cascade that starts in the infected or damaged cells and propagates through "sentinel" mast cells. Cytokines produced by these cells diffuse to nearby endothelial cells. The end effect is an upregulation of the required adhesion molecules on the endothelium. These adhesion molecules collect the leukocytes.
Although the cellular components of the inflammatory response were identified 100 years ago, most of our understanding of the biophysics of this process has come from research performed in the past 20 years. This research has relied on carefully designed analytical tools and computational methods to characterize blood rheology and adhesive mechanisms responsible for leukocyte infiltration. In this article, each of the critical steps in leukocyte trafficking is discussed in light of the analytical methods that have contributed to their understanding.
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