2_Immune Priv, Lymphatics, BBB

Immune Privilege, Lymphatics, BBB

Definition

Immune Privilege - areas of the body that can sustain the presence of antigens w/o eliciting an inflammatory response

Experiment

Skin graft:

1) Put graft in skin

- rejected from skin (immune response)

2) put in CNS

- tolerated in CNS (no immune rxn.)

3) put in CNS after put in skin

- rejection of graft in CNS due to rxn in skin

Proved two things....

Result:

Immune Privilege is confined to CNS parenchyma

- Not all areas of CNS are privileged (e.g. CVOs, choroid plexus, ventricles, meninges)

Result:

Proved that immune privileged is monitored and dynamically regulated

- Determined from difference between experiment 2 & 3

BBB definition

Barrier protecting brain from pathogens and other harmful molecules

Example

Neutrophil recruitment:

In SC:

- Recruits wherever necessary

In Brain:

- Confined to Perivascular Space (VRS)

Make up:

Endothelial Cells

Basement membrane

Glia limitans

Astrocytes/Microglia

Some effects of BBB:

Prevent peripheral immune cells from reaching brain

Prevent inflammatory molecules from reaching brain

Circumventricular Organs

Regions of brain that lack the BBB (not immune privileged)

E.g. Area Postrema

Importance

In these areas, there is a humoral sampling (i.e. sampling of immune cells) and direct contact with inflammatory mediators)

- Important for periphery-CNS communication

(afferent signaling)

Importance

Contain resident CNS immune cells: astrocytes & microglia and low levels of T/B-cells

Lymphatic Drainage

Drainage of fluid waste from the body back to the heart

Cerebral Spinal Fluid (CSF)

Made by ependymal cells in choroid plexus

Flows into subarachnoid space

Immune cells exist in CSF

Interstitial Fluid: (ISF)

Made by endothelial cells

Bathes the brain parenchyma

Immune cells not in ISF since it bathes the brain and that could be dangerous (inflammatory)

Drainage Path 1:

Olfactory bulb --> Nasal Lymphatics --> Cervical Lymph Nodes

10% CSF in humans

Drainage Path 2:

Subarachnoid Space --> Arachnoid Villi --> Venous Blood

90% CSF in humans

Drainage Path:

Basement membrane of capillary and arterial walls --> pass over VRS --> base of skull --> cervical lymph nodes

CELLS CANNOT LEAVE THROUGH THIS PATH

What about immune cells in CSF?

Immune cells cannot use these paths to get out

Immune lymphatic system

Lymph vessels exist within the meninges to drain out immune cells and macromolecules

Proof

Peripheral Immune Cells (T, B, dendritic) are regularly present within lymphatic vessels, which proves that this drainage system is how immune cells are trafficked out of the CNS

Immune privilege

The endothelial cells in these lymphatic vessels may be immune privileged to withstand possible immune inflammation from CNS antigens