Immune Surveillance And AutoAntigen Recognition In The Central Nervous System
Aust N Z J Med 1995 Dec;25(6):784-92
Royal Prince Alfred Hospital, Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW
PMID# 8770354; UI# 96366177
The Central Nervous System (CNS) is considered to be a severely disadvantaged site for the elicitation of Immune Responses.
- First, there is no specialised Lymphatic drainage.
- Both Glia and Neuronal Cells normally do not express appreciable levels of Major Histocompatibility Complex molecules.
- The Vasculature of the CNS is, at least in most places, lined by Endothelial Cells that have tight junctions and form a barrier (the Blood-Brain Barrier) against most molecules and cells present in the circulation.
- The cells most important in the initiation of Immune Response, the Leucocyte Dendritic Cell, are not present.
Nevertheless, the existence of Inflammatory Diseases of this tissue, occurring naturally as in Multiple Sclerosis or in animals after Peripheral Immunization with CNS AutoAntigens, indicates that the Immune System can access and recognize Antigens in this site.
How this is achieved has become clearer in recent years and primarily seems to involve extravasation of activated but not resting T-Cells across the Blood-Brain Barrier.
And, recognition of Antigen on Macrophage-like PeriVascular Cells, rather than cells within the CNS Parenchyme such as Astrocytes or Microglia.
The processes involved in Immunological patrolling of the CNS and development of AutoImmune Inflammatory Disease are reviewed.
CNS Antigen Presentation
Hart MN, Fabry Z
Trends NeuroSci 1995 Nov;18(11):475-81
Univ of Wisconsin, Dept of NeuroPathology, Madison 53706, USA
PMID# 8592751; UI# 96145940
Presentation of Antigens for the CNS follows the same general rules as for other tissues.
However, the presence of special CNS cells with Immune Functions plus the Blood-Brain Barrier (BBB) suggests that differences in the way that the Immune System functions in the CNS might help to explain why some AutoImmune Diseases are unique to the CNS.
Irrespective of whether CNS Antigen presentation takes place inside or outside the CNS (or both), the BBB clearly plays a major role in CNS Immune Function.
The BBB governs the quantity and type of Lymphocytes that enter the CNS by way of specific Adhesion-Molecule binding between Lymphocytes and Endothelium and possibly by selecting for Antigen-specific Lymphocytes in Antigen-recognition events.
NeuroEndocrine-Immune Interactions In Homeostasis And AutoImmunity
Smith T, Cuzner ML
Neuropathol Appl NeuroBiol 1994 Oct;20(5):413-22
Institute of Neurology, Multiple Sclerosis Laboratory, Miriam Marks Dept of NeuroChemistry, London, UK
PMID# 7845527; UI# 95148042
Recent experimental evidence confirms the interrelationships between the Central Nervous, NeuroEndocrine and Immune Systems. Indeed, extensive duality exists in the use of NeuroTransmitters, Hormones and Receptors each system displays.
In the present annotation, the effect of Cytokines, soluble mediators of Immune function, on the CNS and NeuroEndocrine Systems is addressed.
And conversely, we discuss the modification of the Immune compartment by the Sympathetic Nervous and NeuroEndocrine Systems, with particular reference to the role of NorAdrenaline and CorticoSterone.
Dysfunction between the systems is considered in the context of AutoImmune conditions, with emphasis on Experimental Allergic EncephaloMyelitis and the contribution of CorticoSterone-driven T-Cell Apoptosis to recovery from the disease.
Finally, we speculate on the relevance of NeuroImmune interactions in the PathoGenesis of Multiple Sclerosis.
Immunology Of Multiple Sclerosis
Williams KC, Ulvestad E, Hickey WF
Clin NeuroSci 1994;2(3-4):229-45
Dartmouth Medical School-DHMC, Dept of Pathology, Lebanon, NH 03756, USA
PMID# 7749893; UI# 95269031
Multiple Sclerosis (MS), a putative AutoImmune Disease of unknown Etiology, is characterized by CNS PeriVascular inflammation, Foci of DeMyelination, and elevated Intrathecal production of OligoClonal IgG's.
T and B-Cells, Macrophages, and Microglia are all implicated in contributing to the initiation and perpetuation of the disease.
In this brief review we discuss the possible role of T-Cells, B-Cells, Macrophages, and Microglia in contributing to the initiation and perpetuation of Inflammation and DeMyelination in MS.
Data from the rodent model of MS, Experimental AutoImmune EncephaloMyelitis (EAE) supporting a Immunological basis for the pathology of MS is noted.
This paper discusses recent data suggesting an interaction of the above-mentioned cells, as well as Serum and CSF proteins including Complement and Anti-Myelin/Oligodendrocyte AntiBodies, in the PathoGenesis of MS and EAE.
Additionally, this review describes each cell type including the clinical and experimental evidence for their contribution to the Immunologically mediated pathology of MS.
Following the description of the role of individual cells, there is consideration of: the possible interaction of cells with the Blood-Brain Barrier (BBB) under normal and pathologic inflammatory conditions; the traffic of cells into the CNS in inflammation; and the role of Antigen presentation within the CNS in the initiation, and perpetuation, of the CNS Immune Response.
Finally, the review suggests a role for T-Cells in the initiation, amplification, and possibly the termination of CNS inflammatory events with particular attention paid to the pattern of T-Cell activation and T-Cell Cytokine production.