Designing models for the dynamics of T-cell clones antigen presentation and ageing

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The major tasks of the immune system are the protection of the body from undesired external pathogenic attack and the prevention of further and already experienced challenges, which are avoided by the establishment of immunological memory. At the top of the philogenetic tree, the evolution has developed a specific (adaptive) immunity which cooperates with the ancestral innate immunity to control the antigenic insults T-cells are the protagonist of the adaptive immune response in fighting against intracellular infections and in the maintenance of self-tolerance. The T-cell repertoire is characterized by high diversity and size. Moreover, they share and compete each others for resources such as cytokines, MHC-peptide complexes and immunological space. The proteasome machinery plays a crucial role in the maintenance of cell functionality by destroying undesired or unfunctional proteins. Moreover, the proteasome is an important step in the generation of antigenic peptides which, ones mounted on the MHC molecules, are responsible for the activation of T-cell during an immune response. During ageing the immune system undergoes an extended reshaping of the T-cell repertoire, which is now characterized by a different diversity and composition. This phenomenon seems to be a major cause for the increase in the mortality rate for elderly people. In this PHD thesis the study of the T-cells dynamics and their homeostasis has been investigated. In particular we focused on the following questions What is the immunological function of the intracellular protein degradation? And in particular, what is the immunological function of the proteasome? What is the role of the chronic antigenic stimuli on the T-cell dynamics and homeostasis? Can the reshaping of the immune system during ageing influence the survival probability of individuals?