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The model was then used to simulate time courses of wild-type infections and
infections in which either host or pathogen nodes are perturbed. Despite the
asynchronicity, the model results in a conserved activation pattern of key nodes,
indicating three phases in the wild-type infections (Fig. 4.8). These phases
correspond to the activation of innate immune responses, followed by the
generation of Th2 related responses and then Th1 related responses. The
clearance of bacteria was always associated with the generation of Th1 related
responses, as observed experimentally. The model reproduces the early clearance
of bacteria deficient in virulence factors such as the type III secretion system and
the persistence of bacteria in hosts deficient in B cells and T0 cells. The model
prediction that adoptive transfer of antibodies can clear
B. bronchiseptica
but not
B. pertussis
was also validated. Next, the model was used to simulate secondary
infections by the same and different pathogen. The novel model prediction that
the secondary invasion of the same pathogen in the third phase can be cleared
faster was experimentally tested and validated. The model also indicates that Th1
related cytokines and antibodies are the most important factors controlling the
bacterial numbers.
B. bronchiseptica
B.pertussis
Fig. 4.8. Activation pattern indicating the activity of the immune components at each time-step in.
The two panels correspond to the two bacterial strains modeled. Colored squares represent the ON
state of the given node, while white boxes mean the OFF state of the node. The white box in the
lower right corner of each pattern represents the clearance of bacteria on the last time-step. The
figure is adapted from (Thakar
et al
. 2007).
