Lecture: Infection and Immunity
Date: Friday 15th March
Time: 1pm – 2pm
Meningitis: Breaching the Blood- CSF Barrier
There is a video on Moodle discussing the basics of CSF infections for a recap.
Meningitis is the inflammation of the protective membranes covering the brain and spinal
cord. It can be a bacterial, viral, fungal, or parasitic. It can cause a build-up of fluid around
the brain and spinal cord. There can be other problems such as cancer, certain drugs etc
that. Can cause meningitis. It is life threatening and needs immediate treatment. Today we
are looking at bacterial and fungal meningitis.
Bacterial
This is the most common form; it is the infection within the meninges. Bacteria can become
blood born, they generally can’t transverse the blood brain barrier. Some bacteria can
overcome mechanism to break through these barriers. Unfortunately, drugs cannot reach
past the barrier, therefore after this treatment is unlikely.
Example: Neisseria Meningitidis (NM)
These can cause systemic infections, life threatening meningitis and septicaemia. Younger
individuals can have ongoing problems such as impaired hearing or amputation of certain
limbs.
NM is a bacterial meningitis; it is gram negative diplococcus with an antigenic polysaccharide
capsule. The polysaccharide capsule can undergo genetic changes to make it more slippery.
20% of us are carrying NM up our nose or back of the throat, it is when it leaves these sites
that it causes disease. In some circumstances it can enter the blood and causes septicaemia,
crossing the Blood Brain Barrier and enters the meningitis.
Virulence factors:
- Attachment via pili – these are long structures from the membrane of the cell with a
receptor on the ends to bind to human cells.
- Capsules to make bacteria slippery.
- Endotoxin (lipopolysaccharide) causing an immune disruption.
- IgA protease destroys IgA immune response.
-
Transmission is through person to person through droplets; therefore, outbreaks are likely to
happen in crowded places.
Diagnosis:
Put glass over skin of rash on patient, if you can see the rash all the way through it means
you have meningitis. They are a medical emergency, if left untreated it is fatal.
1
, Incubation period: 1-3 days.
Symptoms:
- Sore throat
- Rash – this is the main giveaway for children under 5 years.
- Headache
- Dizziness
- Neck stiffness
- Photophobia
Diagnosis clinically:
Take CSF samples for white blood cell counts CSF/ Serum glucose ratio or CSF and blood
cultures for septicaemia.
Some of these processes take a while so in some cases it is better to treat it immediately.
Treatment is more productive than waiting for clinical tests, you can treat it with antibiotic
therapy. It needs to be bactericidal therapy. Some use chloramphenicol or ceftriaxone.
Fungal Meningitis
Breaching of blood CSF barrier. Fungal infections can lead to meningitis, anyone can get this,
but it is rare. It is normally transferred to those with immunodeficiency, HIV infections,
weakened immune system or people with cancer.
Premature babies: these can get candida species rapidly in the blood which can spread to
the brain.
Example: Cryptococcus Neoformans (CN)
Encapsulated yeast, opportunistic pathogen. The primary site is the lungs, once in the lungs
it can get into the blood and travel to the brain. It is often seen in patients that have aids.
Transmission itself comes from birds such as pigeons, once you have this there is a unique
mechanism that allows the yeast to get into the CNS and cause cryptococcal meningitis.
House series 2: part 1 and 2.
Crossing the blood brain barrier.
1) Phagocytosis mediated – shown in diagram 1. This is phagocytosed and white blood
cell moves across the blood into the brain leading to the transmission of the
organism into the brain.
2) Lateral transfer – white blood cell lines the blood stream, which is infected by the
toxin, transferring to into the endothelial cell and transmit to the brain.
3) Transcellular route- these pass into the endothelial cells and straight through. This is
initiated by receptor-ligand interaction.
Capsular polysaccharides:
2
Date: Friday 15th March
Time: 1pm – 2pm
Meningitis: Breaching the Blood- CSF Barrier
There is a video on Moodle discussing the basics of CSF infections for a recap.
Meningitis is the inflammation of the protective membranes covering the brain and spinal
cord. It can be a bacterial, viral, fungal, or parasitic. It can cause a build-up of fluid around
the brain and spinal cord. There can be other problems such as cancer, certain drugs etc
that. Can cause meningitis. It is life threatening and needs immediate treatment. Today we
are looking at bacterial and fungal meningitis.
Bacterial
This is the most common form; it is the infection within the meninges. Bacteria can become
blood born, they generally can’t transverse the blood brain barrier. Some bacteria can
overcome mechanism to break through these barriers. Unfortunately, drugs cannot reach
past the barrier, therefore after this treatment is unlikely.
Example: Neisseria Meningitidis (NM)
These can cause systemic infections, life threatening meningitis and septicaemia. Younger
individuals can have ongoing problems such as impaired hearing or amputation of certain
limbs.
NM is a bacterial meningitis; it is gram negative diplococcus with an antigenic polysaccharide
capsule. The polysaccharide capsule can undergo genetic changes to make it more slippery.
20% of us are carrying NM up our nose or back of the throat, it is when it leaves these sites
that it causes disease. In some circumstances it can enter the blood and causes septicaemia,
crossing the Blood Brain Barrier and enters the meningitis.
Virulence factors:
- Attachment via pili – these are long structures from the membrane of the cell with a
receptor on the ends to bind to human cells.
- Capsules to make bacteria slippery.
- Endotoxin (lipopolysaccharide) causing an immune disruption.
- IgA protease destroys IgA immune response.
-
Transmission is through person to person through droplets; therefore, outbreaks are likely to
happen in crowded places.
Diagnosis:
Put glass over skin of rash on patient, if you can see the rash all the way through it means
you have meningitis. They are a medical emergency, if left untreated it is fatal.
1
, Incubation period: 1-3 days.
Symptoms:
- Sore throat
- Rash – this is the main giveaway for children under 5 years.
- Headache
- Dizziness
- Neck stiffness
- Photophobia
Diagnosis clinically:
Take CSF samples for white blood cell counts CSF/ Serum glucose ratio or CSF and blood
cultures for septicaemia.
Some of these processes take a while so in some cases it is better to treat it immediately.
Treatment is more productive than waiting for clinical tests, you can treat it with antibiotic
therapy. It needs to be bactericidal therapy. Some use chloramphenicol or ceftriaxone.
Fungal Meningitis
Breaching of blood CSF barrier. Fungal infections can lead to meningitis, anyone can get this,
but it is rare. It is normally transferred to those with immunodeficiency, HIV infections,
weakened immune system or people with cancer.
Premature babies: these can get candida species rapidly in the blood which can spread to
the brain.
Example: Cryptococcus Neoformans (CN)
Encapsulated yeast, opportunistic pathogen. The primary site is the lungs, once in the lungs
it can get into the blood and travel to the brain. It is often seen in patients that have aids.
Transmission itself comes from birds such as pigeons, once you have this there is a unique
mechanism that allows the yeast to get into the CNS and cause cryptococcal meningitis.
House series 2: part 1 and 2.
Crossing the blood brain barrier.
1) Phagocytosis mediated – shown in diagram 1. This is phagocytosed and white blood
cell moves across the blood into the brain leading to the transmission of the
organism into the brain.
2) Lateral transfer – white blood cell lines the blood stream, which is infected by the
toxin, transferring to into the endothelial cell and transmit to the brain.
3) Transcellular route- these pass into the endothelial cells and straight through. This is
initiated by receptor-ligand interaction.
Capsular polysaccharides:
2
