Healthy Subjects Primary and Secondary Immune Response to a Generic Antigen

There are several ways in which normal immune response to a generic antigen can be simulated using our model. For instance one can inhibit the production of IL-4 in the model, thus "knocking-out" IL-4 activity [60]. Another possibility is to force Th cells to be of class 1 only (i.e., ^ = 1 ). Here we mimic a healthy subject by using the first method, that is, we set things so that no IL-4 can be released by Th2 cells. The consequence is a bias towards the Th1 response, i.e., a normal immune response.

The drug administration protocol consists of a first injection at initiation (time zero) and a burst injection at day 40. The drug dose for both injections is calculated so that in one TOm3 the concentration is 2000 ng/mL (recall paragraph 12.4). Results suggest that the model system reproduces a classical primary and secondary Th1-type, response (Figure 12.3, panels a, b, and c). In panel (a) we see simulation of the blood levels profiles of the interleukins IFN-7, IL-4, and IL-12. Note that the first increase in all three interleukins is only marginal, occurring 14 days following the first drug challenge. In contrast, the second drug challenge generates a much more significant response in all the simulated interleukins. The level of T-GF is also different during the first and the second response, but the difference from the hypersensitive case (next paragraph) emerges only at the second injection. Panel (b) shows the level of immunoglobulins produced by plasma cells where the IgM type are eventually overtaken by IgG during the second response. Finally, the system

Figure 12.3

Immune response in healthy subjects (or IL-4 knockout mice [60]). Allergenic drug injections are scheduled to be at initiation and in day 40. No histamine is released, because mast cells are not sensitised (not shown) given that no IgEs are secreted (panel (b)). The immune response is of the Th1-type (panel (c)) since IL-4 is absent (panel (a)).

Figure 12.3

Immune response in healthy subjects (or IL-4 knockout mice [60]). Allergenic drug injections are scheduled to be at initiation and in day 40. No histamine is released, because mast cells are not sensitised (not shown) given that no IgEs are secreted (panel (b)). The immune response is of the Th1-type (panel (c)) since IL-4 is absent (panel (a)).

develops immune memory of the Th1-type for the specific antigen (panel (c)). In summary, using our CA tool we retrieve

• the production of antigen-specific IgG antibody (Figure 12.3, panel (b));

• the production of IFN-7 by type 1 Th cells (Figure 12.3, panel (a)); and

• a moderate degree of proliferation of helper cells (Figure 12.3, panel (c)).

Note that in our "healthy subject" model no IgEs are produced (panel (b)) and therefore mast cells do not get sensitised (panel (a)) and no histamine is released (for simplicity we assumed that the basic level of histamine secretion is null).

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