Clinical Immunology and Disease Mechanisms
Week 1 HC 1 27-10
Clinical introduction to Multiple Sclerosis + MS and therapy
1. Basics
MS is often not visible
Multiple scars in the central nervous system
Multifocal inflammation in the brain and spinal cord
• White matter (mainly find lesions here)
• Grey matter
Made up of scars in your CNS (brain and spinal cord). Both white and grey matter. Auto-
immune reaction that attacks the myelin sheets
Some facts
• Prevalence 1:1000 in NL
• Starts between 20-40 years, young people disease
• More women get it
• Almost normal life expectancy
Contributing factors
• Vitamin D levels
o Low sun exposure is one of the biggest risk factors of MS
• Diet
o Mediterranean diet is the best diet for MS patients
• Smoking
• Epstein-Barr Virus (EBV)
o All people with MS have EBV, but not all people with EBV have MS
• Ethnicity
• Genes
Anatomy
Grey matter → cell bodies
White matter → axons surrounded by myelin
, • Myelin is necessary to have fast signalling
o Improves conduction
o Oligodendrocytes make the myelin
Pathophysiology
‘chronic inflammatory demyelinating disease of the CNS’
Pathological hallmarks:
• Inflammation
o Blood brain barrier (BBB)
o Immune cells enter the brain
• Demyelination
o Conduction over the axons slows down
• Remyelination
• Gliosis (scarring)
In an active lesion the immune cells travel through the blood vessel and surround it. In a
chronic active lesion, you can see that is being tried to remyelinate, however the myelin
doesn’t really come back. later it will become a scar. The centre of these lesions is fully
demyelinated, and the inflammation is going on in the border.
,Remyelination and scarring
In an chronic active lesion, there is ongoing inflammation at the rim of an lesion, can
also be scaring/gliosis in the lesion, when there is scarring, remyelination is not
possible. There are repeating cycles, of immune cells infiltrating the brain, attacking the
myelin and either fully leaving (active lesions) or leaving behind a scar (chronic active
lesions.
Immune system
• CD4 T cells
• CD8 T cells
• B cells
o Antibodies
• Cytokines
These cells cross the BBB and enter the
CNS
2. Clinical symptoms
The symptoms are linked to the location of a lesion. So every patient has a different
clinical picture.
• Visual problems
o Optic neuritis (lesions on the optic nerve); often one of the first symptoms
▪ Pain behind the eye
▪ Decreased colour vision
▪ Decreased visual acuity, especially central visual
fields
• The center of your vision becomes blurry or
dim because the nerve fibres are affected
o Diplopia (other nerves controlling eye movement or their
coordinating brain stem connections are affected)
▪ Double vision
, ▪ Intranuclear ophthalmoplegia (INO)
• INO left (eyes do not move the same way)
• Lesion in the left fasciculus longitudinal
• Your eyes don’t coordinate together
• Pyramidal symptoms (motor symptoms)
o Paresis
o Spasticity
o Abnormal reflexes
▪ In MS the reflexes are also higher than normal (so not that you
don’t have a reflex anymore)
• Sensory disturbances
o Tingling/painful sensations
o Numbness
o Symptom of Lhermitte
▪ If you have a lesion in your cervical spinal cord, you get a numb
feeling in the rest of you body when you put your head down
▪ Temporary electrical shocking feeling going from the neck down
the spinal cord, sometimes to the arms and legs
• Bladder-/bowel-/sexual problems
o Incontinence
▪ Urine
▪ Faeces
o Urine retention / constipation
o Frequent urinary tract infections
o Sexual problems
• Coordination problems (lesion in the cerebellum)
o Ataxia → you want to move your limbs, but they don’t do what you want
them to do
o Tremor
o Balance
• Cognitive disturbances
o Memory
o Concentration
o Attention
o Difficulties organising
Week 1 HC 1 27-10
Clinical introduction to Multiple Sclerosis + MS and therapy
1. Basics
MS is often not visible
Multiple scars in the central nervous system
Multifocal inflammation in the brain and spinal cord
• White matter (mainly find lesions here)
• Grey matter
Made up of scars in your CNS (brain and spinal cord). Both white and grey matter. Auto-
immune reaction that attacks the myelin sheets
Some facts
• Prevalence 1:1000 in NL
• Starts between 20-40 years, young people disease
• More women get it
• Almost normal life expectancy
Contributing factors
• Vitamin D levels
o Low sun exposure is one of the biggest risk factors of MS
• Diet
o Mediterranean diet is the best diet for MS patients
• Smoking
• Epstein-Barr Virus (EBV)
o All people with MS have EBV, but not all people with EBV have MS
• Ethnicity
• Genes
Anatomy
Grey matter → cell bodies
White matter → axons surrounded by myelin
, • Myelin is necessary to have fast signalling
o Improves conduction
o Oligodendrocytes make the myelin
Pathophysiology
‘chronic inflammatory demyelinating disease of the CNS’
Pathological hallmarks:
• Inflammation
o Blood brain barrier (BBB)
o Immune cells enter the brain
• Demyelination
o Conduction over the axons slows down
• Remyelination
• Gliosis (scarring)
In an active lesion the immune cells travel through the blood vessel and surround it. In a
chronic active lesion, you can see that is being tried to remyelinate, however the myelin
doesn’t really come back. later it will become a scar. The centre of these lesions is fully
demyelinated, and the inflammation is going on in the border.
,Remyelination and scarring
In an chronic active lesion, there is ongoing inflammation at the rim of an lesion, can
also be scaring/gliosis in the lesion, when there is scarring, remyelination is not
possible. There are repeating cycles, of immune cells infiltrating the brain, attacking the
myelin and either fully leaving (active lesions) or leaving behind a scar (chronic active
lesions.
Immune system
• CD4 T cells
• CD8 T cells
• B cells
o Antibodies
• Cytokines
These cells cross the BBB and enter the
CNS
2. Clinical symptoms
The symptoms are linked to the location of a lesion. So every patient has a different
clinical picture.
• Visual problems
o Optic neuritis (lesions on the optic nerve); often one of the first symptoms
▪ Pain behind the eye
▪ Decreased colour vision
▪ Decreased visual acuity, especially central visual
fields
• The center of your vision becomes blurry or
dim because the nerve fibres are affected
o Diplopia (other nerves controlling eye movement or their
coordinating brain stem connections are affected)
▪ Double vision
, ▪ Intranuclear ophthalmoplegia (INO)
• INO left (eyes do not move the same way)
• Lesion in the left fasciculus longitudinal
• Your eyes don’t coordinate together
• Pyramidal symptoms (motor symptoms)
o Paresis
o Spasticity
o Abnormal reflexes
▪ In MS the reflexes are also higher than normal (so not that you
don’t have a reflex anymore)
• Sensory disturbances
o Tingling/painful sensations
o Numbness
o Symptom of Lhermitte
▪ If you have a lesion in your cervical spinal cord, you get a numb
feeling in the rest of you body when you put your head down
▪ Temporary electrical shocking feeling going from the neck down
the spinal cord, sometimes to the arms and legs
• Bladder-/bowel-/sexual problems
o Incontinence
▪ Urine
▪ Faeces
o Urine retention / constipation
o Frequent urinary tract infections
o Sexual problems
• Coordination problems (lesion in the cerebellum)
o Ataxia → you want to move your limbs, but they don’t do what you want
them to do
o Tremor
o Balance
• Cognitive disturbances
o Memory
o Concentration
o Attention
o Difficulties organising
