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Immunology of Brain Endothelium and the Blood-Brain Barrier

  • Chapter
Book cover Physiology and Pharmacology of the Blood-Brain Barrier

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 103))

Abstract

The central nervous system (CNS) is partly shielded from the effector arms of the immune system. For example, a proportion of allogeneic grafts will survive in the CNS, whereas they would be rapidly rejected if implanted into skin. This protection is largely due to functions of the specialised cerebral endothelium, and the critical factors in this respect are:

  1. 1.

    Very low levels of leucocyte migration into normal CNS.

  2. 2.

    Low levels of immunologically important molecules, such as immunoglobulin and complement, in interstitial fluids and cerebrospinal fluid (CSF).

  3. 3.

    Limited access of antigens from the brain to the general immune system.

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Abbreviations

APC:

Antigen presenting cell

CSF:

Cerebrospinal fluid

CNS:

Central Nervous System

CREAE:

Chronic relapsing experimental allergic

EAE:

Experimental allergic encephalomyelitis

ELAM:

Endothelial leucocyte adhesion molecule

ICAM-1:

Intercellular adhesion molecule 1

IFN:

Interferon

IgG:

Immunoglobulin G

IL:

Interleutin

LFA-3:

Lymphocyte functional antigen 3

MBP:

Myelin basic protein

MHC:

Major histocompatibility complex

MS:

Multiple sceerosis

PAF:

Platelet activating factor

SMC:

Smooth muscle cell

SSPE:

Subacute sclerosing Panencephalitis

TNF:

Tumour necrosis factor

VCAM:

Vascular cell adhesion molecule

References

  • Balin BJ, Broadwell RD, Salcman M, El-Kalliny M (1986) Avenues of entry of peripherally administered protein to the CNS in mouse, rat and monkey. J Comp Neurol 251:260–280

    Article  CAS  PubMed  Google Scholar 

  • Bradbury MW, Cserr HF (1985) Drainage of cerebral interstitial fluid and of cerebrospinal fluid into lymphatics. In: Johnston MG (ed) Experimental biology of the lymphatic circulation. Elsevier, London

    Google Scholar 

  • Broadwell RD (1989) Transcytosis of macromolecules through the blood-brain barrier: a cell biological perspective and critical appraisal. Acta Neuropathol (Berl) 79:117–128

    Article  CAS  Google Scholar 

  • Broadwell RD, Balin BJ, Salcman M (1988) Transcytosis of blood-bourne protein through the blood-brain barrier. Proc Natl Acad Sci USA 85:632–636

    Article  CAS  PubMed  Google Scholar 

  • Cannella B, Cross AH, Raine CS (1990) Upregulation and coexpression of adhesion molecules correlating with relapsing autoimmune demyelination in the central nervous system. J Exp Med 172:1521–1531

    Article  CAS  PubMed  Google Scholar 

  • Claudio L, Kress Y, Norton WT, Brosnan CF (1990) Increased vesicular transport and decreased mitochondrial content in blood-brain barrier endothelial cells during experimental autoimmune encephalomyelitis. Am J Pathol 135: 1157–1168

    Google Scholar 

  • Cross AH, Cannella B, Brosnan CF, Raine CS (1990) Homing to central nervous system vasculature by antigen-specific lymphocytes. I. Localization of Relabeled cells during acute, chronic and relapsing experimental allergic encephalomyelitis. Lab Invest 63:162–170

    CAS  PubMed  Google Scholar 

  • Fabry Z, Waldschmidt MM, Moore SA, Hart MN (1990) Antigen presentation by brain micro vessel smooth muscle and endothelium. J Neuroimmunol 28:63–71

    Article  CAS  PubMed  Google Scholar 

  • Fontana A, Fierz W (1985) The endothelium-astocyte immune control system of the brain. Springer Semin Immunopathol 8:57–70

    Article  CAS  PubMed  Google Scholar 

  • Hafler DA, Weiner HL (1987) T cells in multiple sclerosis and inflammatory central nervous system diseases. Immunol Rev 100:307–332

    Article  CAS  PubMed  Google Scholar 

  • Harling-Berg C, Knopf PM, Merriam J, Cserr HF (1989) Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat CSF. J Neuroimmunol 25:185–193

    Article  CAS  PubMed  Google Scholar 

  • Hart MN, Waldschmidt MM, Hanley-Hyde JM, Moore SA, Kemp JD, Schelper RL (1987) Brain microvascular smooth muscle expresses class II antigens. J Immunol 138:2960–2963

    CAS  PubMed  Google Scholar 

  • Hickey WF, Gonatas NK (1984) Suppressor T lymphocytes in the spinal cord of Lewis rats recovered from acute experimental allergic encephalomyelitis. Cell Immunol 85:284–288

    Article  CAS  PubMed  Google Scholar 

  • Ho DD, Rota TR, Hirsch MS (1984) Infection of human endothelial cells by human T-lymphocytotropic virus type I. Proc Natl Acad Sci USA 81:7588–7590

    Article  CAS  PubMed  Google Scholar 

  • Hughes CCW, Male DK, Lantos PL (1988) Adhesion of lymphocytes to cerebral microvascular cells: effects of interferon-y, tumour necrosis factor and interleukin-1. Immunology 64:677–682

    CAS  PubMed  Google Scholar 

  • Kelero de Rosbo N, Bernard CC, Simmons RD, Carnegie PR (1985) Con-commitant detection of changes in myelin basic protein and permeability of blood spinal cord barrier in experimental allergic encephalomyelitis by immunoblotting. J Neuroimmunol 9:349

    Article  Google Scholar 

  • Lawrence JM, Morris RJ, Wilson DJ, Raisman G (1990) Mechanisms of allograft rejection in the rat brain. Neuroscience 37:431–462

    Article  CAS  PubMed  Google Scholar 

  • Leibowitz S, Hughes RAC (1983) Immunology of the nervous system Arnold, London

    Google Scholar 

  • Lossinsky AS, Badmajew V, Robson JA, Moretz RC, Wisniewski HM (1989) Sites of egress of inflammatory cells and horse radish peroxidase transport across the blood brain barrier in a murine model of chronic relapsing experimental allergic encephalomyelitis. Acta Neuropathol (Berl) 78:359–371

    Article  CAS  Google Scholar 

  • Male DK, Pryce G (1988a) Kinetics of MHC gene expression and mRNA synthesis in brain endothelium. Immunology 63:37–42

    CAS  PubMed  Google Scholar 

  • Male DK, Pryce G (1988b) Synergy between interferons and monokines in MHC induction on brain endothelium. Immunol Lett 17:267–272

    Article  CAS  PubMed  Google Scholar 

  • Male DK, Pryce G (1988c) Induction of la molecules on brain endothelium is related to susceptibility to experimental allergic encephalomelitis. J Neuroimmunol 21:87–90

    Article  Google Scholar 

  • Male DK, Pryce G, Hughes CCW (1987) Antigen presentation in brain: MHC induction on brain endothelium and astrocytes compared. Immunology 60: 453–459

    CAS  PubMed  Google Scholar 

  • Male DK, Pryce G, Hughes CCW, Lantos PL (1990a) Lymphocyte migration into brain modelled in vitro: control by lymphocyte activation, cytokines and antigen. Cell Immunol 127:1–11

    Article  CAS  PubMed  Google Scholar 

  • Male DK, Pryce G, Rahman J (1990b) Comparison of the immunological properties of rat cerebral and aortic endothelium. J Neuroimmunol 30:161–168

    Article  CAS  PubMed  Google Scholar 

  • Massa PT, Ter Meulen V, Fontana A (1987) Hyperinducibility of la on astrocytes correlates with strain-specific susceptibility to experimental allergic encephalomyelitis. Proc Natl Acad Sci USA 84:4219–4223

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto Y, Naoyuki H, Tanaka R, Fujiwara M (1986) Immunochemical analysis of the rat central nervous system during experimental allergic encephalomyelitis with special reference to la-positive cells with dendritic morphology. J Immunol 136:3668–3676

    CAS  PubMed  Google Scholar 

  • McCarron RM, Kempsi O, Spatz M, McFarlin DE (1985) Presentation of myelin basic protein by murine cerebral vascular endothelial cells. J Immunol 134:3100–3103

    CAS  PubMed  Google Scholar 

  • Pardridge WM, Yang J, Buciak J, Tourtellotte WW (1989) Human brain microvascular DR antigen. J Neurosci Res 23:337–341

    Article  CAS  PubMed  Google Scholar 

  • Pryce G, Male DK, Sedgwich J (1989) Antigen presentation in brain: brain endothelial cells are poor stimulators of T cell proliferation. Immunol 66:207

    CAS  Google Scholar 

  • Pryce G, Male DK, Sarkar C (1991) Control of lymphocyte migration into brain: selective interaction of lymphocyte subpopulations with brain endothelium. Immunology (in press)

    Google Scholar 

  • Raine CS, Cannella B, Duijvestijn AM, Cross AH (1990) Homing to central nervous system vasculature by antigen-specific lymphocytes. II. Lymphocyte /endothelial cell adhesion during the intial stages of autoimmune demyelination. Lab Invest 63:476–489

    CAS  PubMed  Google Scholar 

  • Risau W, Engelhardt B, Wekerle H (1990) Immune function of the blood brain barrier: incomplete presentation of protein (auto-) antigens by rat brain microvascular endothelium in vitro. J Cell Biol 110:1757–1766

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez M, Pierce ML, Howie EA (1987) Immune response gene products on glial and endothelial cells in virus-induced demyelination. J Immunol 138:3438–3442

    CAS  PubMed  Google Scholar 

  • Rose LM, Petersen R, Mehra R, Alvord EC (1988) Endothelial cell la increases before inflammatory cell infiltration in EAE induced in long-tailed macaques. Ann NY Acad Sci 540:315–318

    Article  CAS  Google Scholar 

  • Sedgwick J, Hughes CCW, Male DK, MacPhee I AM, Ter Meulen V (1990) Antigen-specific damage to brain vascular endothelial cells mediated by encephalitogenic and non-encephalitogenic CD4+ T cell lines in vitro. J Immunol 145:2474–2481

    CAS  PubMed  Google Scholar 

  • Simmons RD, Willenborg DO (1991) Direct injection of cytokines into the spinal cord causes autoimmune encephalitis-like inflammation. J Neurol Sci (in press)

    Google Scholar 

  • Sobel RA, Colvin RB (1985) The immunopathology of experimental allergic encephalomyelitis (EAE). Differential in situ expression of strain 13 la on endothelial and inflammatory cells of (strain 2 × 13) Fl guinea pigs with EAE. J Immunol 132:2382–2401

    Google Scholar 

  • Sobel RA, Blanchette BW, Bahn AK, Colvin RB (1984) The immunopathology of experimental allergic encephalomyelitis. II. Endothelial cell la increases prior to inflammatory cell infiltration. J Immunol 132:2402–2407

    CAS  PubMed  Google Scholar 

  • Sobel RA, Mitchell ME, Fondren G (1990) Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am J Pathol 136:1309

    CAS  PubMed  Google Scholar 

  • Tanaka M, McCarron RM (1990) The inhibitory effect of tumour necrosis factor and interleukin-1 on la induction by interferon-gamma on endothelial cells from murine central nervous system micro vessels. J Neuroimmunol 27:209–215

    Article  CAS  PubMed  Google Scholar 

  • Traugott U (1989) Detailed analysis of early immunopathologic events during lesion formation in acute experimental allergic encephalomyelitis. Cell Immunol 119:114–129

    Article  CAS  PubMed  Google Scholar 

  • Traugott U, Scheinberg LC, Raine CS (1985) On the presence of la-positive endothelial cells and astrocytes in multiple sclerosis lesions and its relevance to antigen presentation. J Neuroimmunol 8:1–14.

    Article  CAS  PubMed  Google Scholar 

  • Tretter J, Steinman L (1984) Homing of Lyt2+ and Lyt2– T cell subsets and B lymphocytes to the CNS of mice with acute experimental allergic encephalomyelitis. J Immunol 132:2919–2923

    Google Scholar 

  • Tsukada N, Tanaka Y, Yanagisawa N (1989) Autoantibodies to brain endothelial cells in the sera of patients with human T-lymphocytotropic virus type I associated myeolpathy and other demyelinating disorders. J Neurol Sci 90:33–42

    Article  CAS  Google Scholar 

  • Vass K, Lassmann H, Wisniewski HM, Iqbal K (1984) Ultracytochemical distribution of myelin basic protein after injection in the CSF. Evidence fro transport through the blood brain barrier and binding to the luminal surface of cerebral vessels. J Neurol Sci 63:423–433

    Article  CAS  Google Scholar 

  • Vass K, Lassmann H, Wekerle H, Wisniewski HM (1986) The distribution of la antigens in the lesions of rat acute experimental allergic encephalomyelitis. Acta Neuropathol (Berl) 70:149–160

    Article  CAS  Google Scholar 

  • Vorbrodt AW, Dobrogowska DH, Lossinsky AS, Wisniewski HM (1990) Changes in the distribution of anionic sites in brain micro-blood vessels with and without amyloid deposits in scrapie-infected mice. Acta Neuropathol (Berl) 79:353–363

    Article  Google Scholar 

  • Widner H, Moller G, Johansson BB (1988) Immune response in deep cervical lymph nodes and spleen after antigen deposition in different intra-cerebral sites. Scand J Immunol 28:563–571

    Article  CAS  PubMed  Google Scholar 

  • Wilcox CE, Healey DG, Baker D, Willoughby DA, Turk JL (1989) Presentation of myelin basic protein by normal guinea pig brain endothelial cells and its relevance to experimental allergic encephalomyelitis. Immunology 67:435–440

    CAS  PubMed  Google Scholar 

  • Wisniewski HM, Brown HR, Thormar H (1983) Pathogenesis of viral encephalitis: demonstration of viral antigens in the brain endothelium. Acta Neuropathol (Berl) 60:107

    Article  CAS  Google Scholar 

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Authors
  1. D. K. Male
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Editors and Affiliations

  1. Physiology Group Biomedical Sciences Division King’s College London, University of London, Strand, WC2R 2LS, London, Great Britain

    Michael W. B. Bradbury M.A., D.M. (Oxon)

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© 1992 Springer-Verlag Berlin Heidelberg

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Male, D.K. (1992). Immunology of Brain Endothelium and the Blood-Brain Barrier. In: Bradbury, M.W.B. (eds) Physiology and Pharmacology of the Blood-Brain Barrier. Handbook of Experimental Pharmacology, vol 103. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76894-1_16

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  • DOI: https://doi.org/10.1007/978-3-642-76894-1_16

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-76896-5

  • Online ISBN: 978-3-642-76894-1

  • eBook Packages: Springer Book Archive

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