1. Chander Raman, Ph.D. February 2018
Neuroimmunology
Chander Raman, Ph.D.
February 2018

2. Overview CNS Anatomy Cells of the CNS – Glia
Immune Cell trafficking and lymphatic system
CNS diseases - an immunology focus

3. Overview CNS Anatomy Cells of the CNS – Glia
Immune Cell trafficking and lymphatic system
CNS diseases - an immunology focus

4. CNS versus PNS
CNS - brain and spinal cord, myelin derived from oligodendrocytes
PNS - peripheral nerves myelinated by Schwann cells

5. Myelination differences in CNS versus PNS
One Oligodendrocyte
myelinates many axons
Many Schwann cells
myelinate one axon

6. White Matter versus Gray Matter
Gray matter – nerve cells, cell bodies and vasculature
White matter – fiber tracts myelinated by oligodendrocytes

7. Neurovascular Unit Represents the minimal BBB unit
Composed of the endothelial cell tight junctions, basement membrane, pericytes and astrocyte endfeet
From Zlokovic, Neuron 57:178, 2008

8. The CNS Immune System at Homeostasis
Prinz and Priller, Nat. Neuroscience 20:

9. Overview Cells of the CNS – Glia CNS Anatomy
Immune Cell trafficking and lymphatic system
CNS diseases - an immunology focus

10. GLIA Oligodendrocytes – wrap neurons and synthesize myelin
Astrocytes – Star shaped and wrap most neurosynaptic junctions
Microglia – Mobile, phagocytic

11. Ontogeny of microglia and physiological roles in CNS development, homeostasis, and plasticity.
Salter, M. W. and Stevens Nat. Med. 23: (2017)

12. Microglia and monocytes have distinct cellular origin
Hambardzumyan, D. et al. Nat. Neuroscience 19:20-27 (2016)

13. Microglia states in health and disease
Salter, M. W. and Stevens Nat. Med. 23: (2017)

14. Overview Immune Cell trafficking and lymphatic system CNS Anatomy
Cells of the CNS – Glia
Immune Cell trafficking and lymphatic system
CNS diseases - an immunology focus

15. Reich Lab, NIH/NINDS.

16. Lymphatic drainage of the CNS in humans and in rodents
Engelhardt, B. et al. Nat. Immunol. 18: (2017)

17. Routes of Leukocyte Entry into CNS
Wilson, Weninger and Hunter, J Clin Invest. 2010: 1368–1379

18. Quintana, F. J. J Clin Invest DOI: 10.1172/JCI95769 (2017)
Astrocytes to the rescue! Glia limitans astrocytic endfeet control CNS inflammation
Quintana, F. J. J Clin Invest DOI: /JCI95769 (2017)

19. Leukocyte trafficking across the glia limitans into the parenchyma of the brain
Wilson, Weninger and Hunter, J Clin Invest. 2010: 1368–1379

20. Immune surveillance via the choroid plexus
Wilson, Weninger and Hunter, J Clin Invest. 2010: 1368–1379

22. Astrocytes form borders (glia limitans) that serve as functional barriers at interfaces between non-neural tissue and CNS neural parenchyma along blood vessels, meninges and tissue lesions.
PBM - parenchymal basement membrane
EBM - endothelial basement membrane
SAS - subarachnoid space
Sofroniew, M.V Nat. Rev. Neuroscience 16:249

23. Origin and turnover of tissue macrophages in healthy CNS
pvMΦ - perivascular macrophages
mMΦ - meningeal macrophages
cpMΦ - choroid-plexus macrophages
Prinz, M. et al Nat. Immunol. 18:

24. The localization and genetic signature of CNS macrophages
pvMΦ - perivascular macrophages
mMΦ - meningeal macrophages
cpMΦ - choroid-plexus macrophages
Prinz, M. et al Nat. Immunol. 18:

25. QA – quisqualate KA - kainate
Kelin, R.S. et al. Nat. Immunol. 18: (2017)

26. Overview CNS diseases - an immunology focus CNS Anatomy
Cells of the CNS – Glia
Immune Cell trafficking and lymphatic system
CNS diseases - an immunology focus

27. Peripheral immune cells in the CNS immune system during disease.
Prinz and Priller, Nat. Neuroscience 20:

28. Potential mechanisms of neurological sequelae subsequent to bacterial and fungal meningoencephalitis.
Kelin, R.S. et al. Nat. Immunol. 18: (2017)

29. Stress-associated changes in neuroimmune function.
Wohleb et al. Nat. Rev. Neuroscience 17:497 (2016)

30. Microglia–neuron interactions in the naive, homeostatic brain and in the stressed or depressed brain.
P2X7 - P2X purinoceptor 7
RAGE - receptor for advanced glycation end products
Wohleb et al. Nat. Rev. Neuroscience 17:497 (2016)

31. Immune system dysregulation inside the CNS in early multiple sclerosis
Dendrou, C. et al. Nat. Rev. Immunol. 15:545 (2015)

32. Immune system dysregulation inside the CNS in late multiple sclerosis
Dendrou, C. et al. Nat. Rev. Immunol. 15:545 (2015)

33. Neuroinflammation after traumatic brain injury
Simon, D. W. et al Nat. Rev. Neurology 13: (2017)