A modular framework for multiscale, multicellular, spatiotemporal modeling of acute primary viral infection and immune response in epithelial tissues and its application to drug therapy timing and effectiveness
Fig 1
Schematic of the innate and adaptive immune response during primary acute viral infection.
Exposure to the virus occurs at time 0 and extracellular viral load begins to rise (shaded green curve). Initial innate immune responses include phagocytosis of virus by neutrophils and macrophages, Type I interferon-induced antiviral resistance (IFN) (dark blue) and killing of infected cells by Natural Killer (NK) cells and other cell types (red). The black vertical dashed line denotes the transition between innate and adaptive immune responses. The adaptive immune response is triggered both by cytokine signaling to the lymph nodes and the migration of antigen-presenting cells from the tissue to the lymph nodes (not shown). In the later phases of infection, innate immune responses continue, but additional adaptive immune components come into play, including virus-specific cytotoxic T-cells (light blue) kill infected cells directly and also kill nearby cells through a variety of mechanisms. The orange vertical dashed line denotes the onset of the humoral adaptive immune response. B-cells produce virus-specific antibodies (orange line) which bind and inactivate virus directly and also allow its clearance and clearance of infected cells by other cell types. Tissue damage (shaded purple curve) accumulates due to cell death from direct responses to virus and from immune-cell killing by contact-mediated, diffusible factor-mediated and bystander-mediated mechanisms and eventually dissipates as cells proliferate to repair the damage (Adapted from [50,51]). The specific time course of all components varies among viruses, host tissues and host species, but the general sequence of events and immune response components are generally preserved.