Lymphocytes and the Nervous System

The immune system maintains the integrity of the human body by recognition and elimination of new antigens coming from outside and inside generated modified substances. The control of immune reactions to infections, tumors and degeneration in the brain is different than in other tissues. The differences in immune control in the brain became clear with the development of transplantology. In 1873 Dutch ophtalmologist van Dooremaal observed prolonged mouse skin graft survival in the dog eye, and later in 1948 Sir Peter Medawar, while trying to explain success of corneal homograft transplantation, performed classic transplantation of skin to the brain and anterior chamber of the eye of nonimmunized or immunized rabbits (previously transplanted with the same donor’s skin sample to the chest). He highlighted two mechanisms involved in the immunologic control in brain: existing systemic immunity to donor’s skin and the status of vasculature. Tissue grafted in the brain or eye survived longer than in any other place in the body without sensitized lymphocyte infiltration via new vessels of the graft. A few more places in the human body obtained definition of “privileged” sites (testis and a placenta) based upon immune tolerance to the graft. Only direct transplantation/injection allows backward introduction of “unknown” antigens. This process in brain parenchyma (not meninges and choroids plexes) is also different than in non-privileged sites due to the absence of endogenous professional antigen-presenting cells capable to trigger immune responses (Hart and Fabre, 1981), and because of the specific properties of non-professional antigen-presenting microglial cells in parenchyma (Matyszak and Perry, 1996; Matyszak, 1998). However, in situ inflammation induced by pathogens or abnormal proteins with complementary peripheral adaptive immune responses will induce brain damage and appearance of tertiary lymphoid structures (Aloisi and Pujol-Borrell, 2006). The role of professional antigen-presenting cells, microglial cells and regulatory T cells in these events will be reviewed in other chapters (4, 9, 18–24, 37, 42, 46).