Spatio-temporal aspects of bovine paratuberculosis. 1. A. Following uptake of MAP, macrophages will be subverted within 12–24 h into immune suppressed niche environments for bacterial replication. B. Bacterial replication will be limited by the natural lifespan of the macrophage (21–42 days), and/or reaching bursting capacity due to space limitations of harboring dividing MAP bacteria. (1 CFU infection with bacterial replication time of 40 h. will lead to accumulation of 300–500 MAP in 35–42 days). 2. Immature dendritic cells (DC) which have taken up MAP/antigen migrate to the draining mesenteric lymph node. Maturation to professional antigen presenting DC occurs during transit, barring interference by live MAP. 3. In the mesenteric lymph nodes DC will become stationary in the T cell zone to be interrogated by migrating T cells. Antigen specific recognition leads to the induction of effector T cells and clonal expansion, obtain addressins for targeted migration to the intestine and migrate out of the lymph node into the venous circulation over the course of days. 4. The activated and memory T cells will recirculate randomly through the organs and may remain in the circulation for prolonged periods of time (days) depending on their route of migration and additional signals. 5. Passing through arterio-venous capillary beds in the intestine effector T cells may migrate from the circulation into the lamina propria based on their homing receptors. This process may be random when pro-inflammatory chemokine signals are lacking but highly targeted when these signals are present and efficiently directing T cell migration. In the lamina propria these T cells may encounter MAP infected macrophages and start antigen specific effector functions such as IFN-γ production and induction of apoptosis in infected cells. However if the infected macrophage has been transformed to an immunosuppressive state T cell recognition will likely be hampered as will subsequent effector mechanisms.