PMC

Patient and physician factors leading to ill-timed pregnancy and medication adherence.

In these simulations, killing activity against cancer stem cells was increased (ImmunoTHx2CSC intens = 53). This increase leads to stable tumor control with elimination of cancer stem cells. Remaining tumor cells can successfully be eliminated by subsequent cytotoxic therapy (MTC THx intens = 0.9, MTC THx time = 3000) (A). Additional increase in the activity of “Killer Cells” against mature tumor cells and transit amplifying cells (ImmunoTHx2MTC intens = ImmunoTHx2CTAC intens = 53) lead to paradox increase in tumor cell number (B). Under these conditions, cytotoxic therapy (MTC THx intens = 0.9, MTC THx time = 3000) cannot eradicate tumor cells. Similar effects were observed after ill-timed cytotoxic therapy (MTC THx intens = CTAC THx intens = 0.9; MTC THx time = CTAC THx time = 1000) against MTC and CTAC (C). In both cases, increasing the number of “Killer Cells” (ImmunoTHx1 time = 1000; ImmunoTHX1 intens = 3.5e+010) restored tumor control (D: ImmunoTHx2MTC intens = ImmunoTHx2CTAC intens = 53; E: CTAC THx intens = MTC THx intens = 0.9; CTAC THx time = MTC THx time = 1000). The time scale for all simulations in this figure is 4000 days.

T cell differentiation. Top: APC [i.e., dendritic cell (DC)] recognition of a spectrum of pathogens through various pathogen-associated molecular pattern receptors results in cytokine release from the APC. Along with TCR engagement, milieu cytokines initiate (top middle) differentiation to one of a variety T cell subsets programmed by transcription factors to specifically respond to the spectrum of the instigating pathogen [pathogen and T helper (Th) subset color coordinated]. Upon differentiation, T cells themselves produce cytokines, which feed back into the cellular milieu, amplifying and balancing the immune response to promote specific pathogen clearance (bottom middle) and host survival. Finally, sustained, ill-timed, or otherwise exaggerated T cell immune responses from any of the T cell subsets results in a range of immunopathologies from autoimmunity to allergy and cancer (bottom). IFN, interferon; TGF-β, transforming growth factor-β; Gz, granzyme.

(A–D) Example trial trajectories and behavioral metrics for high/low opponent sensitivity and high/low advantageous timing. For each panel, the black line at the bottom shows a trajectory of the puck’s horizontal and vertical position on a given trial, with the puck moving rightward as the trial progresses. The orange line in the middle denotes that the same trial’s opponent sensitivity. The green line at top represents the expected value (i.e. probability of winning), conditional on making the final direction change at that time point; optimal behavior involves moving when this metric is at its maximum. The solid gray line vertically spanning all three subplots indicates the timing of the final change in direction actually taken by the participant, whereas the dotted gray line at the top subplot denotes when the participant should have made the final change in direction. The shaded gray region provides a measure of advantageous timing or the difference in time between when the participant should have switched vs when they actually switched. Low advantageous timing means there is a large difference between these times (i.e. the final direction change for that trial was ill-timed; see right column) and high advantageous timing means there is a small difference (i.e. the final direction change for the trial was well-timed; see left column).