BBB & infection

Question 1

How to pathogens invade the CNS

Answer 1

Transcellular invasion:
Pathogens bind host cells & invade through cell
Can be passive or active
Examples:
Bacterial: streptococci, Listeria sp.
Fungal: candida (yeast), cryptococcus

Paracellular invasion:
Tight junctions must dramatically change or new routes open
Increased pinocytic activity leading to trans-endothelial channels formation or tight junction function can be broken
Examples:
Viral: Nipah virus
Bacterial: Borrelia burgodorferi

Intracellular within leucocytes:
Requires primary infection
Will spread where virus migrates to
May be hidden from antibodies once established
Examples:
Viral: HIV, canine distemper

Question 2

What are features of the blood brain barrier

Answer 2

Endothelial cells form tight barrier between blood & CNS tissue

Tight junctions stop paracellular flux

Pinocytosis allows transfer of material from blood to brain

P-glycoprotein pumps actively eject undesired substances

Question 3

Describe canine distemper virus

Answer 3

Highly infectious disease

Spread through urine, close contact or aerosols

Causes generalised infection in many organ systems as receptors are common on many cells

Causes encephalitis (swelling of brain) due to virus infection of neurons & inflammatory response

Spreads to tonsils & bronchial lymph nodes

Viral replication leads to leukopenia

Diagnosed using lateral flow test detecting CDV antigen or PCR

Question 4

Describe listeriosis

Answer 4

Gram positive rod

Facultative anaerobe

Common in cattle but zoonotic – can affect pregnant women, newborns & adults with weakened immune systems

Causes sepsis & meningitis

Move from nerve cell to nerve cell

Clinical signs:

Dullness, circling, tilting head & facial paralysis

Treated with antibiotics

Question 5

Describe rabies

Answer 5

Enveloped RNA virus

Transmitted by biting carnivores (present in saliva)

Causes encephalitis

Fatal

Process:
1. Virus replicates in muscle
2. Viruses reaches sensory/motor nerve ends
3. Binds to acetylcholine receptors
4. Virus enters nerves
5. Virus delivered to CNS
6. Virus reaches limbic system of brain & replicates
7. Spread continues

Question 6

Outline role of clostridia toxins in neurological disease

Answer 6

Gram positive rod that forms endospores

Anaerobe

Toxins are proteins that are activated by proteolytic cleavage

Tetanus:
Stops inhibitory transmitter binding at synapse –> continuous stimulation
Creates muscular spasms –> spastic paralysis

Botulism:
Passes into nerve terminal & inhibits release of acetylcholine
Causes paralysis