Vaccination in Old Age

With increasing age the immune system undergoes characteristic changes, termed immunosenescence. Cells of the innate immune system – such as neutrophilic granulocytes, monocytes, macrophages and dendritic cells – show decreased migration, signaling, phagocytosis and antimicrobial activity. As a consequence, the first line of defence against infections is impaired and pathogens are less efficiently eliminated. Another important task of the innate immune cells is antigen processing and presentation. After phagocytosis pathogen-derived proteins are fragmented into peptides, which are then loaded onto MHC (major histocompatibility complex) proteins and presented on the cell surface. These complexes are recognized by T cells and induce their activation. Antigen processing and presentation is impaired in old age leading to a diminished activation of T cells. The output of naïve T and B cells is decreased, whereas antigen-experienced and particularly highly differentiated lymphocytes accumulate. As a consequence, the repertoire and diversity of the adaptive immune system is diminished. Cellular functions of T cells, such as signaling after antigenic stimulation, proliferation and cytokine production are impaired limiting T cell responses. In addition, somatic hypermutation and class switch, which take place in B cells to optimize antibody production, are diminished in older age. T cell help is required for these processes and the age-related impairments we observe are caused by intrinsic defects of the B cells as well as by suboptimal T cell help. Overall, these age-related changes of the immune system contribute to increased incidence and severity of infections in old age. Infectious diseases are frequently associated with long-term sequelae such as impairments in activities of daily living, onset of frailty, or the loss of independence. In view of demographic changes leading to a dramatic increase of old and very old individuals, this represents a serious challenge for public health systems. The prevention of infectious diseases is therefore an important measure to ensure healthy aging and improve the quality of life.