CNS Cells
Astrocytes
Functions
1) Physical Support
2) BBB
3) NT metabolism
4) Neurotrophic support
5) Modulate neuronal synaptic transmission
Labeled by
GFAP
Structure
Forms/Maintains BBB Basement membrane
Neuronal support
Provides growth factors
Synapto/neurogenesis
NT metabolsim
Absorbs and breakdown glutamtae
Recovery
Glial Scar formation
Regulation
Activation:
IL1B, IL-6, TNF-a, IFN-y
TLRs, ATPRs, Glut
Effects
Positive:
Walls off damaged area
- prevent further neurodegen.
BBB recovery
Negative:
Prevent axonal regrowth
Prevent neurogenesis
Astrocyte KO
Axonal regrowth
Increased neurodegeneration
Increased leukocyte trafficking
Astrocyte-Microglia reg.
Microglial activation: leads to
Incr. IL1B, IL6, IL10 --> bind to astrocyte receptor and activate astrocyte
Astrocyte deactivation leads to:
Decr. IL1B, IL6 ; incr TGF-B
TGF-B binds to microglia to deactivate
Astrocyte-Microglia interaction/regulation
Microglia
Antigen presentation?
No MHC II
Labeling
CX3CR1, CSF1R, CD45 low, P2XRs, Iba+, CD11b, MHC II
Antigen Presentation
MHC Class II
Roles
(Surveying Microglia)
BBB formation and maintainence
Immune surveillance
Structural support
Neuronal and oligo support
Immune sensor
At CVOs, surveys immune cells
Neuronal support
Synaptic pruning
Monitor synapses
Roles (Activated microglia)
Cytokine production
Complement system activation
Reactive mediators (NO)
Cytokines
Pro-inflame:
IL1B, IL-6, TNF-a
Anti-inflame:
IL-10, TGF-B
MHC-II
TLR2/TLR4 (innate immunity)
Cytokine/chemokine receptors
Complement receptors
Activated and deactivated microglia
M1 macrophage/microglia
Classical activation
Roles
Pro-inflammatory (Th1 response)
Cytokines: IL1B, TNF-a, IL6
Non classical activation
M2 macrophage/microglia
3 different subtypes
M2a macrophage/microglia
Alternative activation
Function: Tissue Repair
M2b macrophage/microglia
Inflammatory and homeostatic
M2c macrophage/microglia
Classical deactivation
Function: anti-inflammatory
Signals
Signals: Arginase
Signals
IL1B, IL10
Signals
IL-10, IL-4, SOCS
Perivascular Macrophages
Definition
Peripheral macrophages in the CNS perivascular with CNS function
Roles
Similar to microglia
Has MHC II receptor (APC)
Neurons
Functions
Brain signaling
Immune regulation
MHC I presentation
Immune regulation
Regulate T-cell entry into CNS via Fas-L (Fas-L kills T-cells)
Immune regulation
Contact inhibition of microglia
- Via CD200/CD22
Deactivate microglia via release of fractalkine onto glial CX3CR1
Secrete IFN-y and Substance P to increase glial response
Activate microglia via cell death which release glutamate, laminin
Oligodendrocytes
Labeling
MBP, NG2 (progenitors)
Functions:
Oligos Map
1) Axonal Myelination
2) Re-myelination during repair
Negative regulation of OGs
TNF-a, NO
Endothelial Cells
Labeling
Glut-1, CD31, Ly6C, IL-1R, COX2
Functions
Barrier to brain - tight junctions
Nutrient transport - Glut-1
Adhesion of leukocytes
Cytokine receptors and transport
Adhesion
Integrins
Selectins
Together help with extravasation/diapedesis of leukocytes into brain
Astrocyte-Microglia-Neuron interaction/regulation
New Note
New Note
Labeling
CD116, CD45, MHCII, TLR's, CX3CR1
Antigen presentation
Antigen Presentation
