The immune system undergoes profound age-related changes, collectively termed immunosenescence. This process affects various cell types including hematopoietic stem cells (HSCs), lymphoid progenitor cells in the bone marrow and in the thymus, the thymus itself, mature lymphocytes in peripheral blood and secondary lymphatic organs and also elements of the innate immune system. These immunological changes contribute to elevated susceptibility to infectious diseases, to more severe symptoms, prolonged duration and poorer prognosis of infections and to decreased protective effects of vaccinations. Reactivation of Varicella-Zoster virus leading to herpes zoster is observed by far more frequently in elderly compared to young adults. Infections with influenza virus are associated with more severe symptoms in elderly patients and with an increased risk for secondary complications. Additionally, risks for many other infections are increased in elderly people. As the elderly population is particularly susceptible to infection and vulnerable in case of disease, vaccination is of special importance. Unfortunately, the efficacy of various vaccines, e.g., influenza, hepatitis A and hepatitis B, is lower in elderly people. New strategies are needed to improve vaccination and to develop vaccines that specifically target and stimulate the aged immune system.
Hematopoietic Stem Cells and Lymphoid Progenitor Cells
All circulating blood cells of an adult individual including immature lymphocytes are generated in the bone marrow. Both liver and spleen can also be recruited as sites for haematopoiesis in case of increased need for newly generated blood cells or if the bone marrow is injured. All blood cells originate from a common stem cell (HSC) and become committed to develop along particular lineages. The first step of differentiation leads to the separation of myeloid and lymphoid progenitors. Myeloid progenitors further differentiate to become erythrocytes, platelets, basophils, eosinophils, neutrophils, monocytes, macrophages, mast cells, or dendritic cells (DC). Lymphoid progenitors give rise to B lymphocytes, T lymphocytes, and natural killer (NK) cells (Figure 3-1A). Maturation of B cells, which includes rearrangement and expression of immunoglobulin genes as well as selection for cells with functional immunoglobulins and against self-reactive B cells, takes place in the bone marrow. Mature B cells then enter the circulation and lymphoid organs where they encounter their specific antigens. T lymphocytes leave the bone marrow in an immature state and migrate to the thymus where maturation with somatic recombination and expression of the T cell receptor (TCR) genes occur. Additionally, positive selection for functional TCRs and negative selection against self-reactive T cells take place in the thymus. Like B cells, mature T cells finally migrate to lymphoid organs and are also found in the blood stream (Figure 3-1B).
Hematopoiesis and maturation of lymphoid cells. (A) Schematic representation of hematopoiesis. Hematopoietic stem cells differentiate into lymphoid and myeloid progenitors that give ...