Skip to main content

Advertisement

SpringerLink
Log in

Basic principles of neuroimmunology

  • Review Article
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

The brain is an immune-privileged organ such that immune cell infiltration is highly regulated and better tolerating the introduction of antigen to reduce risk of harmful inflammation. Thus, the composition and the nature of the immune response is fundamentally different in the brain where avoiding immunopathology is prioritized compared to other peripheral organs. While the principle of immune privilege in the central nervous system (CNS) still holds true, the role of the immune system in the CNS has been revisited over the recent years. This redefining of immune privilege in the brain is a result of the recent re-discovery of the extensive CNS meningeal lymphatic system and the identification of resident T cells in the brain, meningeal layers, and its surrounding cerebrospinal fluid (CSF) in both humans and rodents. While neuro-immune interactions have been classically studied in the context of neuroinflammatory disease, recent works have also elucidated unconventional roles of immune-derived cytokines in neurological function, highlighting the many implications and potential of neuro-immune interactions. As a result, the study of neuro-immune interactions is becoming increasingly important in understanding both CNS homeostasis and disease. Here, we review the anatomically distinct immune compartments within the brain, the known mechanisms of leukocyte trafficking and infiltration into the CNS and unique transcriptional and functional characteristics of CNS-resident immune cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rua R, McGavern DB (2018) Advances in meningeal immunity. Trends Mol Med 24(6):542–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Li Q, Barres BA (2018) Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol 18(4):225–242

    Article  CAS  PubMed  Google Scholar 

  3. Mascagni, and C. Sanctius, 1787 Vasorum lymphaticorum corporis humani historia et ichnographia. Ex typographia Pazzini Carli.

  4. Andres KH et al (1987) Nerve fibres and their terminals of the dura mater encephali of the rat. Anat Embryol (Berl) 175(3):289–301

    Article  CAS  Google Scholar 

  5. Waggener JD, Beggs J (1967) The membranous coverings of neural tissues: an electron microscopy study. J Neuropathol Exp Neurol 26(3):412–426

    Article  CAS  PubMed  Google Scholar 

  6. Louveau A et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523(7560):337–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Aspelund A et al (2015) A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 212(7):991–999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Absinta, M., et al (2017) Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife,  6.

  9. Mundt S et al (2019) The CNS Immune Landscape from the Viewpoint of a T Cell. Trends Neurosci 42(10):667–679

    Article  CAS  PubMed  Google Scholar 

  10. Protasoni M et al (2011) The collagenic architecture of human dura mater. J Neurosurg 114(6):1723–1730

    Article  PubMed  Google Scholar 

  11. Schafflick D et al (2021) Single-cell profiling of CNS border compartment leukocytes reveals that B cells and their progenitors reside in non-diseased meninges. Nat Neurosci 24(9):1225–1234

    Article  CAS  PubMed  Google Scholar 

  12. Korin B et al (2017) High-dimensional, single-cell characterization of the brain’s immune compartment. Nat Neurosci 20(9):1300–1309

    Article  CAS  PubMed  Google Scholar 

  13. Mrdjen D et al (2018) High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease. Immunity 48(2):380-395.e6

    Article  CAS  PubMed  Google Scholar 

  14. Roth TL et al (2014) Transcranial amelioration of inflammation and cell death after brain injury. Nature 505(7482):223–228

    Article  CAS  PubMed  Google Scholar 

  15. Hagan CE, Bolon B, Keene CD (2012) 20 - Nervous system. In: Treuting M, Dintzis SM (eds) Comparative anatomy and histology. Academic Press, San Diego, pp 339–394

    Chapter  Google Scholar 

  16. Iliff JJ (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes including amyloid β. Sci Transl Med 4(147):147ra111

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rasmussen MK, Mestre H, Nedergaard M (2018) The glymphatic pathway in neurological disorders. Lancet Neurol 17(11):1016–1024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Brinker T et al (2014) A new look at cerebrospinal fluid circulation. Fluids Barriers CNS 11:10

    Article  PubMed  PubMed Central  Google Scholar 

  19. McComb JG (1983) Recent research into the nature of cerebrospinal fluid formation and absorption. J Neurosurg 59(3):369–383

    Article  CAS  PubMed  Google Scholar 

  20. Hafler DA et al (1985) In vivo activated T lymphocytes in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. N Engl J Med 312(22):1405–1411

    Article  CAS  PubMed  Google Scholar 

  21. de Graaf MT et al (2011) Central memory CD4+ T cells dominate the normal cerebrospinal fluid. Cytometry B Clin Cytom 80(1):43–50

    Article  PubMed  Google Scholar 

  22. Svenningsson A et al (1995) Lymphocyte phenotype and subset distribution in normal cerebrospinal fluid. J Neuroimmunol 63(1):39–46

    Article  CAS  PubMed  Google Scholar 

  23. Kowarik MC et al (2014) Immune cell subtyping in the cerebrospinal fluid of patients with neurological diseases. J Neurol 261(1):130–143

    Article  CAS  PubMed  Google Scholar 

  24. Lepennetier G et al (2019) Cytokine and immune cell profiling in the cerebrospinal fluid of patients with neuro-inflammatory diseases. J Neuroinflammation 16(1):219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gate D et al (2020) Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease. Nature 577(7790):399–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang, et al (2021) Single-cell transcriptome and TCR profiling reveal activated and expanded T cell populations in Parkinson’s disease. Cell Discov. 7(1):52

    Article  Google Scholar 

  27. Ballabh A Braun, Nedergaard M (2004) The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16(1):1–13

    Article  CAS  PubMed  Google Scholar 

  28. Smolders J et al (2018) Tissue-resident memory T cells populate the human brain. Nat Commun 9(1):4593

    Article  PubMed  PubMed Central  Google Scholar 

  29. Pasciuto E et al (2020) Microglia require CD4 T cells to complete the fetal-to-adult transition. Cell 182(3):625-640.e24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lopes Pinheiro MA et al (2016) Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke. Biochim Biophys Acta 1862(3):461–471

    Article  CAS  PubMed  Google Scholar 

  31. Stern JN et al (2014) B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Sci Transl Med 6(248):248ra107

    Article  PubMed  PubMed Central  Google Scholar 

  32. Brioschi S et al (2021) Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders. Science 373(6553)

    Article  Google Scholar 

  33. Unger MS et al (2020) CD8+ T-cells infiltrate Alzheimer’s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice. Brain Behav Immun 89:67–86

    Article  CAS  PubMed  Google Scholar 

  34. Williams G et al (2021) CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson’s disease. Brain 144(7):2047–2059

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gate, D et al. 2021 CD4<sup>+</sup> T cells contribute to neurodegeneration in Lewy body dementia. Science. 0(0): eabf7266.

  36. Bitsch A et al (2000) Acute axonal injury in multiple sclerosis. Correlation demyelination inflamm Brain 123(Pt 6):1174–1183

    Google Scholar 

  37. Prinz M, Priller J (2010) Tickets to the brain: role of CCR2 and CX3CR1 in myeloid cell entry in the CNS. J Neuroimmunol 224(1–2):80–84

    Article  CAS  PubMed  Google Scholar 

  38. Jordão MJC et al (2019) Single cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science 363:6425

    Article  Google Scholar 

  39. Auffray C et al (2007) Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317(5838):666–670

    Article  CAS  PubMed  Google Scholar 

  40. Fife BT et al (2000) CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med 192(6):899–905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Huang D et al (2001) Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J Exp Med 193(6):713–726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Boring L et al (1997) Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J Clin Invest 100(10):2552–2561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Peters W et al (2001) Chemokine receptor 2 serves an early and essential role in resistance to <em>Mycobacterium tuberculosis</em>. Proc Natl Acad Sci 98(14):7958–7963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ajami B et al (2011) Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci 14(9):1142–1149

    Article  CAS  PubMed  Google Scholar 

  45. King IL, Dickendesher TL, Segal BM (2009) Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 113(14):3190–3197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Amorim A et al (2022) IFNγ and GM-CSF control complementary differentiation programs in the monocyte-to-phagocyte transition during neuroinflammation. Nat Immunol 23(2):217–228

    Article  CAS  PubMed  Google Scholar 

  47. Spiljar M et al (2021) Cold exposure protects from neuroinflammation through immunologic reprogramming. Cell Metab 33(11):2231-2246.e8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Herisson F et al (2018) Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration. Nat Neurosci 21(9):1209–1217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cugurra A et al (2021) Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma. Science 373(6553)

    Article  Google Scholar 

  50. Ahn JJ, Abu-Rub M, Miller RH (2021) B Cells in neuroinflammation: new perspectives and mechanistic insights. Cells 10:7

    Article  Google Scholar 

  51. Franciotta D et al (2008) B cells and multiple sclerosis. Lancet Neurol 7(9):852–858

    Article  CAS  PubMed  Google Scholar 

  52. Barr TA et al (2012) B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells. J Exp Med 209(5):1001–1010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Matsushita T et al (2008) Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Investig 118(10):3420–3430

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Weber MS et al (2010) B-cell activation influences T-cell polarization and outcome of anti-CD20 B-cell depletion in central nervous system autoimmunity. Ann Neurol 68(3):369–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Pierson ER, Stromnes IM, Governan JM (2014) B cells promote induction of experimental autoimmune encephalomyelitis by facilitating reactivation of T cells in the central nervous system. J immunol (Baltimore Md 1950) 192(3):929–939

    Article  CAS  Google Scholar 

  56. Duddy M et al (2007) Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J Immunol 178(10):6092–6099

    Article  CAS  PubMed  Google Scholar 

  57. Bar-Or A et al (2010) Abnormal B-cell cytokine responses a trigger of T-cell–mediated disease in MS? Ann Neurol 67(4):452–461

    Article  CAS  PubMed  Google Scholar 

  58. Hafler DA et al (1985) Investigation of in vivo activated T cells in multiple sclerosis and inflammatory central nervous system diseases. Clin Immunol Immunopathol 37(2):163–171

    Article  CAS  PubMed  Google Scholar 

  59. Hafler DA, Weiner HL (1987) In vivo labeling of blood T cells: rapid traffic into cerebrospinal fluid in multiple sclerosis. Ann Neurol 22(1):89–93

    Article  CAS  PubMed  Google Scholar 

  60. Mahad D et al (2006) Modulating CCR2 and CCL2 at the blood-brain barrier: relevance for multiple sclerosis pathogenesis. Brain 129(Pt 1):212–223

    Article  PubMed  Google Scholar 

  61. Balashov KE et al (1999) CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions. Proc Natl Acad Sci U S A 96(12):6873–6878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kivisäkk, et al (2002) T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking. Clin Exp Immunol 129(3):510–8

    Article  Google Scholar 

  63. Reboldi A et al (2009) C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 10(5):514–523

    Article  CAS  PubMed  Google Scholar 

  64. Pappalardo JL et al (2020) Transcriptomic and clonal characterization of T cells in the human central nervous system. Sci Immunol 5:eabb8786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Chofflon M et al (1989) Inflammatory cerebrospinal fluid T cells have activation requirements characteristic of CD4+CD45RA- T cells. Eur J Immunol 19(10):1791–1795

    Article  CAS  PubMed  Google Scholar 

  66. Kivisäkk, et al (2003) Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci U S A 100(14):8389–94

    Article  Google Scholar 

  67. Van Hove H et al (2019) A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nat Neurosci 22(6):1021–1035

    Article  PubMed  Google Scholar 

  68. Ginhoux F et al (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330(6005):841–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Utz SG et al (2020) Early Fate Defines Microglia and Non-parenchymal Brain Macrophage Development. Cell 181(3):557-573.e18

    Article  CAS  PubMed  Google Scholar 

  70. Frost JL, Schafer D (2016) Microglia: architects of the developing nervous system. Trends Cell Biol 26(8):587–597

    Article  PubMed  PubMed Central  Google Scholar 

  71. Schafer D, Stevens B (2015) Microglia function in central nervous system development and plasticity. Cold Spring Harb Perspect Biol 7(10):a020545

    Article  PubMed  PubMed Central  Google Scholar 

  72. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314–1318

    Article  CAS  PubMed  Google Scholar 

  73. Prinz M et al (2011) Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat Neurosci 14(10):1227–1235

    Article  CAS  PubMed  Google Scholar 

  74. Ueno M et al (2013) Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci 16(5):543–551

    Article  CAS  PubMed  Google Scholar 

  75. Arcuri C et al (2019) Parenchymal and non-parenchymal immune cells in the brain: a critical role in regulating CNS functions. Int J Dev Neurosci 77:26–38

    Article  PubMed  Google Scholar 

  76. Marín-Teva JL et al (2004) Microglia promote the death of developing Purkinje cells. Neuron 41(4):535–547

    Article  PubMed  Google Scholar 

  77. Zhan Y et al (2014) Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci 17(3):400–406

    Article  CAS  PubMed  Google Scholar 

  78. Schafer D et al (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74(4):691–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Paolicelli RC et al (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333(6048):1456–1458

    Article  CAS  PubMed  Google Scholar 

  80. Cunningham CL, Martínez-Cerdeño V, Noctor SC (2013) Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J Neurosci 33(10):4216–4233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sierra A et al (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7(4):483–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Frade JM, Barde YA (1998) Microglia-derived nerve growth factor causes cell death in the developing retina. Neuron 20(1):35–41

    Article  CAS  PubMed  Google Scholar 

  83. Battista D et al (2006) Neurogenic niche modulation by activated microglia: transforming growth factor beta increases neurogenesis in the adult dentate gyrus. Eur J Neurosci 23(1):83–93

    Article  PubMed  Google Scholar 

  84. Dong Y, Yong VW (2019) When encephalitogenic T cells collaborate with microglia in multiple sclerosis. Nat Rev Neurol 15(12):704–717

    Article  PubMed  Google Scholar 

  85. Goldmann T et al (2016) Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat Immunol 17(7):797–805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Anthony IC, Crawford DH, Bell JE (2003) B lymphocytes in the normal brain: contrasts with HIV-associated lymphoid infiltrates and lymphomas. Brain 126(Pt 5):1058–1067

    Article  CAS  PubMed  Google Scholar 

  87. Berer K et al (2011) Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479(7374):538–541

    Article  CAS  PubMed  Google Scholar 

  88. Fitzpatrick Z et al (2020) Gut-educated IgA plasma cells defend the meningeal venous sinuses. Nature 587(7834):472–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Pröbstel AK et al (2020) Gut microbiota-specific IgA(+) B cells traffic to the CNS in active multiple sclerosis. Sci Immunol 5(53)

    Article  Google Scholar 

  90. Rattazzi L et al (2013) CD4+ but not CD8+ T cells revert the impaired emotional behavior of immunocompromised RAG-1-deficient mice. Transl Psychiatry 3(7):e280–e280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Fan K-Q et al (2019) Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior. Cell 179(4):864-879.e19

    Article  CAS  PubMed  Google Scholar 

  92. Yonk LJ et al (1990) CD4+ helper T cell depression in autism. Immunol Lett 25(4):341–345

    Article  CAS  PubMed  Google Scholar 

  93. Marazziti D et al (1999) Immunological alterations in adult obsessive-compulsive disorder. Biol Psychiat 46(6):810–814

    Article  CAS  PubMed  Google Scholar 

  94. Miyajima M et al (2017) Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior. Nat Immunol 18(12):1342–1352

    Article  CAS  PubMed  Google Scholar 

  95. Derecki NC et al (2010) Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med 207(5):1067–1080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Filiano AJ et al (2016) Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour. Nature 535(7612):425–429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Alves de Lima K et al (2020) Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons. Nat Immunol 21(11):1421–1429

    Article  CAS  PubMed  Google Scholar 

  98. Ribeiro M et al (2019) Meningeal γδ T cell-derived IL-17 controls synaptic plasticity and short term memory. Sci Immunol 4(40)

    Article  Google Scholar 

  99. Clark IC et al (2021) Barcoded viral tracing of single-cell interactions in central nervous system inflammation. Science 372(6540):eabf1230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by grants to D. A. H. from the National Institutes of Health (NIH) (U19 AI089992, R25 NS079193, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, and R01 CA227473); the National Multiple Sclerosis Society (NMSS) (CA 1061-A-18 and RG-1802–30153); the Nancy Taylor Foundation for Chronic Diseases, and Erase MS, by grants to. A. W. from the NIH (K08 AI128745, and R01 AI162645); the Pew Charitable Trusts; and the Richard and Susan Smith Family Foundation, and by grants to T. Y. from the NIH (5T32 AI 007019–46).

Author information

Authors and Affiliations

  1. Department of Immunobiology, Yale School of Medicine, New Haven, CT, 06520, USA

    Tomomi M. Yoshida, Andrew Wang & David A. Hafler

  2. Department of Internal Medicine (Rheumatology), Yale School of Medicine, CT, 06520, New Haven, USA

    Tomomi M. Yoshida & Andrew Wang

  3. Department of Neurology, Yale School of Medicine, New Haven, CT, 06520, USA

    Tomomi M. Yoshida & David A. Hafler

Authors
  1. Tomomi M. Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David A. Hafler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David A. Hafler.

Ethics declarations

Conflict of interest

D. A. H. has received research funding from Bristol-Myers Squibb, Novartis, Sanofi, and Genentech. He has been a consultant for Bayer Pharmaceuticals, Bristol Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme. Further information regarding funding is available on https://openpaymentsdata.cms.gov/physician/166753/general-payments

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is a contribution to the special issue on: Neuroimmune Interactions in Health and Disease - Guest Editors: David Hafler & Lauren Sansing

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoshida, T.M., Wang, A. & Hafler, D.A. Basic principles of neuroimmunology. Semin Immunopathol 44, 685–695 (2022). https://doi.org/10.1007/s00281-022-00951-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-022-00951-7

Search

Navigation