Infection may be caused by…
viruses, bacteria, fungi, and parasites
What are the 4 main types of infection?
- meningitis (caused by diff viruses, bacteria, or parasites)
- encephalitis (caused by viruses)
- abscesses (caused by bacteria)
- spongiform encephalopathies (caused by prions)
What are the 3 ways that CNS infections can alter brain function?
- Acidosis
- Hypoxia
- Destruction of neurons
Most infections do not result from the passage of pathogens across the BBB.
A. true
B. false
B. false
Intraneural pathways are the least common route to the CNS, but which viruses do use this route?
- rabies virus - use peripheral sensory nerves
- herpes virus - uses trigeminal nerve
What is Edema and what are the subtypes?
Edema = increased intracranial pressure, compression of the brain, and restricted air flow
- vasogenic edema - swelling by BBB alterations
- cytotoxic edema - swelling by toxic substances
Most viral infections are controlled by the innate immune system.
A. true
B. false
A. true
What is hematogenous spread?
-a way in which viruses can gain access to the CNS through blood - by infecting an immune cell that carries the virus to the CNS or by crossing the blood capillaries (as a free virus)
What is transneuronal spread?
-a way in which viruses can gain access to the CNS within neurons
What are 3 tools for clearance?
-cytotoxic T cells, antibodies, and cytokines
What is Encephalitis?
- an inflammation of the brain, often as a result of a complication from a usual viral infection
- common cause: Herpes simplex virus (HSV1 and HSV2)
- clinical syndrome: fever, confusion, behavioural change, olfactory and gustatory hallucinations
- can cause: confusion, epileptic seizures
- w/o viral therapy, mortality rate is ~70%
What are the features of Herpes simplex virus?
- transneuronal spread, trigeminal nerve (cranial nerve V)
- after initial infection, virus remains latent in the trigeminal ganglion, from which it can spread to the skin or the brain meninges. From meninges –> rest of the brain
What can be seen in Herpes encephalitis?
- mutations in TLR3 (TLR3 deficiency)
- high allelic heterogeneity and recurrence risk
- typically is seen in previously healthy patients
What is a rare cause of encephalitis?
HIV or rabies virus
What is the Trojan horse hypothesis in reference to?
A. Herpes encephalitis
B. HIV encephalitis
C. Rabies encephalitis
D. CNS edema
B. HIV encephalitis
What is the Trojan horse hypothesis?
An hypothesis that HIV-1 enters the brain in HIV encephalitis via the migration of monocytes which differentiate into perivascular macrophage.
How does HIV-1 enter the brain in HIV encephalitis?
- Trojan horse hypothesis - via migration of monocytes
- the passage of infected CD4+ T cells into the brain
- the direct entrance of the virus via tight junctions
- via the transcytosis phenomenon
What are the symptoms of Rabies encephalitis?
Odd behaviours, muscle spasms, drooling, convulsions, pain, hydrophobia
What is the typical cycle of a rabies infection in humans?
- RV binds to nerve/muscle cells via nicotinic ACh receptors (can remain here up to several months)
- RV can replicate in muscle cells at the site of the bite
- RV moves along the nerve axons to the CNS through retrograde axonal transport and transsynaptic spread
- RV spreads from the post-synaptic site to the pre-synaptic site via receptor mediated endocytosis
- brain infection leads to encephalitis and neural degeneration. During this time virus can spread from CNS via neurons to skin, eye, and salivary glands
How does rabies virus evade the immune response?
- RV inhibits alterations in BBB during infection
- RV kills T cells
- RV enters CNS without triggering apoptosis of infected neurons
- RV evade immune clearance and cause lethal infection
What is Progressive multifocal leukoencephalopathy (PML) and where can it be seen?
- can be seen in AIDs patients as a consequence of immunosuppressive treatment
- PML alters B cell functions
- it prevents the entry of T and B cells into organs by blocking binding to adhesion integrins
- it alters T and B cell functions
What are symptoms of Meningitis?
- back/neck stiffness, pain, fever, sudden onset, headache
- in meninges
What is Meningitis?
- an inflammation of the meninges
- usually caused by an infection (bacterial/viral)
What are features of viral meningitis?
- aseptic
- the less severe form of meningitis, usually resolves without a specific treatment
- most are caused by enteroviruses
- best prevention method is to prevent spread
