This book intends to assemble reviews on the progress in defining and controlling the spatiotemporal organization of key events in immune cell activation. Improved understanding of MIRR-mediated signaling has a number of potential practical applications, from the rational design of drugs and vaccines to the engineering of cells for biotechnological purposes. In Section 1, spatial organization and physiological function of the MIRR family members such as T cell receptor (TCR), B cell receptor (BCR), Fc receptors, natural killer (NK) cell receptors, and platelet glycoprotein VI (GPVI) will be reviewed. Section 2 will focus on current models of MIRR-triggering and highlight modern technologies to visualize cell-cell interaction contacts such as immunological synapse and to measure protein-protein interactions in space in real time. Potential therapeutic strategies targeting the MIRR-mediated transmembrane signal transduction will be shortly reviewed in Section 3. This book will summarize our current knowledge in this field and illustrate how control of the MIRR-triggered signaling could become a potential target of medical intervention, thus bridging basic and clinical immunology.