Guest Lecture: Infectious Diseases Flashcards
How do infections directly damage the nervous system?
They produce toxins and steal nutrients
How do infections indirectly damage the nervous system?
They trigger an overactive immune response
What can microglia and infiltrating immune cells do?
- proliferate (multiply)
- Release signals to other cells
- Phagocytose pathogens
- Release toxic products
- Restrict nutrient availability
- Trigger cell death
For myelitis, where is the inflammation?
The spinal cord
For encephalitis, where is the inflammation?
The Brain
For Meningitis, where is the inflammation?
In the meninges
For Endophthalmitis, where is the inflammation?
In the Eye
Organisms which consume nutrients from a living host, at the host’s expense.
- Can cause irreversible damage before symptoms
- Non-specific symptoms, like headaches
Parasites
Disease burden: about 250 million cases and 700,000 deaths globally per year
* Plasmodium parasites (protozoa (single-celled))
* Transmitted by bite from infected mosquito
Neurological effects: seizures, coma
Malaria
Severe form of malaria spreads to
the brain
Cerebral malaria
How to treat Malaria?
- Malaria vaccine
- Antimalarial drugs
- CDC: up to 40 million
people in US could be
infected - Mostly asymptomatic
because immune system can
prevent illness - Anti-parasitic medications
for severe disease,
immunocompromised - Exposure to oocytes (eggs)
- Eating undercooked meat
- Exposure to cat feces
- Increases excitatory neurotransmission in CNS
Neurological effects: seizures, mood disorders
Toxoplasmosis
- Reduced glutamate re-uptake
by astrocytes -> more
excitation - GABA used as carbon
source -> less inhibition
Toxoplasmosis
- Single-celled, prokaryotic
microorganisms - General concerns:
- Ubiquitous (can be found all over
the place) - Spread of antibiotic resistance
Bacteria
How do antibiotics kill bacteria?
They inhibit some vital cellular
process
How do bacteria become
antibiotic resistant?
Decrease import, increase export,
alter target of antibiotic, enzymes
to inactivate
How does methicillin kill bacteria?
- Penicillin-binding proteins (PBPs) are necessary to form their protective cell wall
- Methicillin enters bacteria and
Inhibits PBPs
infection of the fluid within the eye
* Causes
- intraocular surgery
- traumatic injury
- systemic infection
* Can quickly lead to irreversible
vision loss
- Retinal degeneration, detachment
Endophthalmitis
- Damage the retina directly
- Degrade proteins (proteases)
- Lyse retinal cells (pore-forming
toxins) - Combat immune response
- Bind to immune cell receptors to
prevent recognition - Inhibit inflammatory signaling
- Lyse immune cells after phagocytosis
Staphylococcus aureus toxins
Treatments for Endophthalmitis
- Antibiotics: vancomycin
- Extreme case: enucleation (removal
of eye)
- Eukaryotic microorganisms
- General concerns:
- Newly infectious species
- Resistance to anti-fungal
medications
Fungi
- DNA or RNA surrounded by
protein coat - Typically considered non-living
since on their own they can’t: - Grow
- Reproduce
- Create proteins
- Make/use their own energy
- General concerns
- Evade detection by immune system
- Hard to develop antiviral drugs
-> Lack cellular processes to target
-> Diversity of structures
Viruses
Neurotropic viruses:
preferentially target the nervous
system
* CDC: causes ~59,000
deaths per year worldwide
* Caused by bite/scratch from
infected animal
Rabies
Treatment for Rabies
Rabies vaccine
* Once symptoms are present,
there are no effective treatments
* >99% mortality rate
- Infected muscle -> neuromuscular junction -> nervous system
- Virus endocytosed by presynaptic neuron, trafficked to soma by dynein (retrograde transport)
- Flu-like symptoms progress to
cognitive dysfunction - Mild: confusion, anxiety
- Severe: hallucinations, hydrophobia, insomnia
Rabies
2015-2016, Brazil: hundreds of
babies born with microcephaly
- Cause
* Bite from infected mosquito
* Sexually transmitted
* Transmitted to fetus during
pregnancy
Zika Virus
Guide migration of new neurons
during development
Radial glia
What happens when Zika infects fetal brain?
- Impaired cell division
- Cells destroyed by virus,
apoptosis, immune system
- Mainly in young children
- Poor hand washing
- Contaminated food/water
- Mainly in anterior horn motor
neurons (can spread to
posterior horn, brain stem,
thalamus) - Viral replication within motor
neurons leads to cell death - Paralysis, including of breathing
muscles
Poliomyelitis
Treatment for poliomyelitis
- Polio vaccine
- No cure
- Ventilator
- Chronic inflammation and
neurodegeneration - Demyelinating disease of CNS
- Autoimmune disease: immune
system targets myelin - Muscle weakness, vision
impairment
Multiple Sclerosis (MS)
Treatment for Epstein-barr virus
Clinical trials for vaccines
- Most abundant protein in the nervous system
- Normal function: several cellular
processes including protection from stress - General concerns
- No cure or treatments
-> Difficult to target (non-living)
-> Difficult to physically destroy - Can progress rapidly and is always fatal
- No cure or treatments
Prions
_________ fold abnormally -> cause
others to as well -> form toxic
aggregates within tissue ->
neurodegeneration
* Widespread symptoms
(dementia, personality change)
Prions
- Neural
- Glial
Progenitor cells
