CNS

Dura mater

Outer, tough fibrous layer providing physical protection

Arachnoid mater

Middle, web-like structure that helps contain CSF

Pia mater

Inner, delicate layer adhering to brain surface; highly vascularized

Provides buoyant force to brain
Protects from mechanical injury
Regulates intracranial pressure
Clears CNS metabolites

What is the function of cerebrospinal fluid (CSF)?

Neurons

Conduct electrical impulses

Oligodendrocytes

Form myelin sheaths

Astrocytes

Regulate blood-brain barrier and ion balance

Microglia

CNS-resident macrophages

Meningitis

Inflammation of meninges, symptoms include fever, headache, photophobia, stiff neck

Encephalitis

Inflammation of brain parenchyma, symptoms include altered mental status, seizures, focal deficits

rhombencephalitis

brainstem encephalitis

ataxia, cranial nerve deficits, tremors, respiratory abnormalities, shock

what are the symptoms of rhombencephalitis

Presence of BBB restricts immune cell access
Lacks conventional lymphatic drainage
Antigens in CNS do not typically provoke systemic immune responses

Why is the CNS considered an immune-privileged site?

Transcellular

Via receptors on endothelial cells

Paracellular

Between tight junctions of endothelial cells

Trojan horse

Within infected immune cells (e.g., TB, HIV)

Retrograde axonal transport

E.g., Rabies, HSV

Lytic

Pathogen replication causes cell destruction

Transendothelial

Receptor-mediated entry through CSF barrier

Rabies

Retrograde axonal transport example

gp120 binds CCR5/CXCR4 → tight junction degradation

HIV entry mechanism

Binds CD155 on motor neurons

Poliovirus entry mechanism

Detects Cryptococcus neoformans via its polysaccharide capsule
Appears as a clear halo around the yeast cell

What is the significance of India Ink stain in CSF?

It is invasive and only indicated for diagnostic or therapeutic purposes

Why is lumbar puncture not used for screening?

pressure measurement
drug administration

How is lumbar puncture used for therapeutic purposes?

It is isolated by the blood-brain barrier
Lacks conventional lymphatic drainage
Antigens injected into CNS parenchyma do not typically elicit adaptive immune responses

Why is the CNS historically considered an “immune-privileged” site?

CSF acts as a functional lymphatic equivalent
Immune cells like microglia, macrophages, and dendritic cells exist in the choroid plexus, meninges, and perivascular space

What recent findings challenge the idea of CNS immune privilege?

Increase in immunocompromised populations (e.g., HIV, transplant patients)
Rise of reemerging and opportunistic neurotropic pathogens

Why are CNS infections increasingly recognized as a public health burden?

Autoimmune conditions such as autoimmune encephalitis (e.g., anti-NMDAR)
Persistent neurological damage even after pathogen clearance

What is the consequence of post-CNS infection immune dysregulation?