How to repeat a success and control a bad influence.

T he manipulation of adaptive immunity is probably the most successful preventive and therapeutic strategy of modern medicine. Its roots go back to Edward Jenner, who in 1796 induced immunity to smallpox by inoculation with the related cowpox virus. 1 Although the mechanism of action remained completely unknown for more than a century, the concept of vaccination spread rapidly around the world and had an immediate impact on population health. In Sweden, for instance, ≈20 000 people died of smallpox in 1800, just before the introduction of vaccination. Within 20 years, the death rate had fallen to 200! The insightful bishop, Esaias Tegnér, reported to the government that the population in his bishopric was increasing rapidly thanks to " peace, vaccine, and potatoes. " In 1980, the World Health Organization certified that smallpox had been eradicated in the entire world. From Pasteur and onward, the vaccination principle was used to control many other diseases in addition to smallpox. Together with the sanitation of water and foodstuff, it represents the most successful means of disease prevention ever accomplished. Vaccination induces a T-cell response that helps B cells to react against antigen and start to produce high-affinity anti-bodies. The T-cell response also leads to the development of armed effector T cells with the capacity to kill target cells such as infected ones, and to the activation of macrophages to promote inflammation. In this way, the T-cell response initiates both humoral and cellular immunity to the immunogen. The relative importance of these 2 effector arms of adaptive immunity varies between vaccines, but the general principle operates in all vaccination protocols. The immune response elicited by vaccination mimics the one triggered by an invading pathogen. It also resembles the pathological immune responses observed in autoimmune conditions and chronic inflammatory diseases. In these situations, autologous molecules are erroneously recognized as antigens. The ensuing immune response attacks tissues containing these molecules, leading to cell death, tissue destruction, and repair processes. Several immune effector systems contribute to these attacks, including cytotoxic T cells, complement-activating antibodies, phagocytizing macrophages, and other cells. As a potentially dangerous defense system, the immune response is regulated by several sets of inhibitory cells and molecules. Foremost among them, regulatory T cells (Treg) dampen immune responses by inhibiting effector T-cell activity, B-cell and macrophage activation, and inflammatory responses. Several subtypes of Treg have been identified in the CD4 and CD8 T-cell families, with immunosuppressive …