A computerized model for the self-non-self discrimination at the level of the T(h) (Th genesis). II. The behavior of the system upon encounter with non-self antigens

Abstract

In the final analysis, the self (S)-non-self (NS) discrimination is regulated by the sufficiency or insufficiency of effector T(h) (eT(h)) specific for the given antigen. We have described a model (Th genesis) for the origin of eT(h) based on an antigen-independent pathway from initial state T(h) (iT(h)) to eT(h), and on obligatory associative recognition of antigen (ARA) by an iT(h) and an eT(h) in order for the iT(h) to be activated. A computer analysis (referred to as Th genesis) was developed to evaluate this model that is extended here to describe the response to NS antigen. Th genesis fills in the missing element of the two-signal or ARA model for the S-NS discrimination, i.e. the origin of the primer eT(h). The conclusions from this analysis are compared with those of the other models for the origin of eT(h).

Fig. 1

The pathway (Th genesis) generating ‘primer’ eT_h in the absence of NS antigen.

Fig. 2

The pathway after the addition of NS antigen.

Fig. 3

The response to an NS antigenic load as a function of time. The NS antigen is added at time step 1000.

Fig. 4

The responses of Th genesis as a function of critical parameters. For default values, see Fig. 3.

Fig. 5

Simulation of the Matzinger ‘space’ model by translation into the Th genesis format.

Fig. 6

Simulating the Zinkernagel `exhaustive differentiation' model.

Fig. 7

The breaking of tolerance by an NS antigen that shares epitopes with S.

Fig. 8

The effect of the removal of NS antigen; simulating the normal response.

Fig. 9

The APC as a determinant of the Mitchison phenomenon. Suppression is dominant (‘positive’) antigen-specific humoral unresponsiveness. Tolerance is recessive (‘negative’) antigenspecific humoral unresponsiveness.