Basic Concepts of Immunology and Neuroimmunology

, and , Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, California

Neurosurg Focus. 2000;9(6) 

In This Article

Neuroimmunology

For many years, the brain has been thought to be an immunologically privileged site, where no immunosur-veillence of lymphocytes occurs. This assumption gained support from the existence of a BBB, which excludes components of the immune system. Additional support of the brain's immunoprivileged nature is its lack of lym-phatic vessels and lymphatic drainage. Moreover, except for astrocytes, there is no constitutive expression of MHC molecules in the cells of the CNS. The most convincing evidence of all is that tissue transplanted from one indi-vidual into the brain of another individual survives for extended periods of time.[4]

Although the CNS does lack a fully developed lym-phatic vasculature, because there is evidence that CNS extracellular fluid drains into the deep cervical lymph nodes,[16] the possibility exists that antigen presentation could occur in the CNS. It has also been shown that, in response to inflammatory reactions, neoplasms, or brain injury, the expression of MHC class I and II molecules can be induced on several cells that reside in the brain; such cells include astrocytes, endothelial cells, microglial cells, pericytes, and choroid plexus epithelia. In recent studies the authors have also shown that an immunological reac-tion occurs in the brain in response to a number of disease processes that affect the CNS and spinal cord. Moreover, extensive migration of lymphocytes into the CNS and ex-pression of MHC molecules on vascular endothelial cells, astrocytes, microglial cells, and pericytes have been ob-served in patients with viral encephalitis, multiple sclero-sis, and allergic encephalomyelitis.[5]

Wekerle, et al.,[17] and Hickey, et al.,[6] have shown that C 14- labeled CD4+ myelin basic protein-specific T-cell lines, when activated either by presentation of specific antigen or by concanavalin A, do migrate to the brain through intact BBB. The first phase of entry occurs with-in 24 hours after injection, and the second phase occurs 96 hours postinjection. It has become evident that CAMs are actively involved in mediating the recruitment of spe-cific lymphocyte subsets into different tissues. Several cell adhesion molecules, such as RANTES, selectins, 4, MCP-1, MIP-1, ICAM-1, ICAM-2, VCAM-1, and LFA-3 are expressed on cerebral endothelial cells. Overexpres-sion of LFA-1, 4, CD44, and CD2 molecules on acti-vated T lymphocytes contributes to adhesion and to their ultimate migration through the BBB (Figure 5).[4]

Figure 5.

Schematic drawing depicting lymphocyte interation with the BBB.

What happens to T cells after they are injected into the brain? In recent studies the authors have suggested that activated cells, when injected into the cannulated CNS, preferentially follow white matter tracts and sometimes are detected in gray matter along the perivascular spaces. The existence of afferent connections from the CNS to the immune system have been supported by investigators who showed that injecting antigen into CNS tissue elicits a systemic immune response.[7] If cells of the immune sys-tem migrate to the brain, do they protect against human tumors? This question requires addressing the use of ad-ditional immune components in developing a vaccine against human brain tumors.

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