Pathogen Induced Tolerance

Using a dynamic model we study the adaptive immune response to a sequence of two infections. As expected, memory cells generated by the first (primary) infection generate rapid response when the secondary infection is identical (homologous). When the secondary infection is different (heterologous), the memory cells have a positive effect or no effect at all. In exceptional instances in nature the primary infection generates vulnerability to a heterologous infection. This model predicts “Original Antigenic Sin”, but shows that average effector affinity is not an accurate measure of the quality of an immune response, and does not on its own provide a mechanism for vulnerability. In this paper we propose and mathematically study a novel mechanism “Pathogen Induced Tolerance” (PIT), where antigen from the primary infection takes part in the immune system tolerance mechanisms, prohibiting the creation of new naive cells specific for the secondary response. The action of this mechanism coincides with Original Antigenic Sin but is not caused by it. We discuss the model in the context of the dengue virus and show that PIT is better suited to describe observed phenomena than the proposed Antibody Dependant Enhancement (ADE). ∗Electronic address: [email protected] †Electronic address: [email protected]