Immune mediated diseases of the Nervous System

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Immune- mediated diseases of the Nervous System
Session structure Monday 19th lecture Monday pm
SDL Case Multiple sclerosis Tuesday 20th
Case answers
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Immune- mediated diseases of the Nervous System
Aim To introduce diseases of the nervous
system where autoimmunity contributes to disease
pathogenesis
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Immune- mediated diseases of the Nervous System

• Objectives
• By the end of the session you should be able to
• describe the immune system components in the
  normal CNS
• describe the diagnostic criteria for MS, the
  clinical and laboratory features of MS, the
  potential mechanisms of pathogenesis and
  treatment.
• describe how the pathogenesis of MS differs from
  Guillain-Barre syndrome and myasthenia gravis

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Immune- mediated diseases of the Nervous System

• Objectives for lecture
• By the end of the lecture session you should be
  able to
• describe the immune system components in the
  normal CNS
• describe the basic features of MS
• describe the basic features and pathogenesis of
  Guillain-Barre syndrome and compare with the
  pathogenesis of myasthenia gravis

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Revision of the immune system
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Two types of Immunity
Innate/natural
Adaptive
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Acute inflammation
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Adaptive Immunity Two kinds of lymphocytes T
and B
T lymphocytes T helper cells (CD4)
Tcytotoxic cells (CD8)
B lymphocytes
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Cell mediated Immunity
Th
Help macrophages to get rid of intracellular
microbes
Kill virus infected cells
Tc
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B lymphocytes make antibodies
With T helper cells
Plasma cells in tissues
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What happens in the CNS regarding immune cells?
Normally the brain is shielded from the immune
system limit inflammation attributed to

• Low lymphocyte trafficking
• lack of conventional lymphatic drainage from
  brain
• low level of MHC molecules by neurons and glia
• absence of dendritic cells, or other cells
  capable of activating resting T cells
• the blood-brain barrier , which restricts the
  movement of immunologically important molecules
  into the brain parenchyma

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Immunological cells and main components of a
healthy CNS
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Multiple Sclerosis

• Most common crippling neurological disorder
  of young adults (due to small multifocal patches
  of demyelination - plaques)

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Magnetic resonance imaging (MRI) showing typical
lesions
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Electrophoresis of CSF in MS
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Guillain-Barre syndrome

• Guillain-Barre syndrome is an inflammatory
  peripheral neuropathy
• Guillain-Barre syndrome is often preceded by a
  viral-like illness cause unknown but myelin and
  nerve axons destroyed
• GBS carries significant mortality risk

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Events triggering Guillain-Barre syndrome

• viral-like illness in 60-70
• immunisation in 5
• pregnancy
• surgical procedure
• lymphoma

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• Immunological features
• Mononuclear cell infiltration of affected
  peripheral nerves
• Antibodies to myelin components
• Peripheral T cell activation

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• Pathogenesis of GBS
• Antibodies to components of Schwann cell myelin
  P2 protein and galactocerebroside, also other
  lipids (ganglioside LM1 50 of patients
  increased antibodies)
• Complement components increased

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Putative mechanism of immune pathogenesis in
Guillain-Barre syndrome
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Myasthenia Gravis

• disorder of neuromuscular transmission
  characterised by abnormal fatigability of
  skeletal muscle ranging from transient double
  vision to life-threatening respiratory paralysis
• prevalence is 5-9 per 100,000 and the
  incidence 2-4 per million
• all ages and and races can be affected
• 12 of babies born to myasthenic mothers due
  to transfer of maternal antibodies

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Mechanisms of pathogenesis
Primary abnormality is a decrease in functional
acetyl choline receptors at the post-synaptic
muscle membrane This leads to reduction of
muscle endplate potential which is often
insufficient to trigger a muscle action
potential Pathogenesis mediated by
autoantibodies to ACR
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Immune- mediated diseases of the Nervous System

• Objectives for lecture
• By the end of the lecture session you should be
  able to
• describe the immune system components in the
  normal CNS
• describe the basic features of MS
• describe the basic features and pathogenesis of
  Guillain-Barre syndrome and compare with the
  pathogenesis of myasthenia gravis

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Multiple Sclerosis Case (1) 35 yr old female
presented with loss of vision in her left eye.
She had had attacks of insomnia and had lost
weight during the last year and felt tired and
depressed. She had remembered an episode of
tingling sensation in her left leg 3 years
previously, lasted for some weeks and then
disappeared.
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Multiple Sclerosis Case (2) On examination vital
signs were normal. Neurological examination
revealed partial loss of vision in her left eye,
and ophthalmoscopy revealed inflamed optic nerve.
Both legs were hyper-reflexic with increased
muscle tone.
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Multiple Sclerosis Case (3) Laboratory
tests Examinastion of CSF by lumbar puncture
showed 7 cells/ml, normal protein conc. (0.43
g/l) but increased IgG conc. (0.12g/l). An MRI
scan revealed multiple foci of demyelination in
both cerebral lobes as well as the left optic
nerve.
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Multiple Sclerosis Case (4) In this case the
presence of a long history, relapsing remitting
symptoms, evidence for involvement of multiple
parts of the nervous system, plus the CSF and
imaging findings strongly suggest a diagnosis of
MS
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• Case Study Questions
• How does MS present?
• What are the key clinical features and laboratory
  tests that aid in diagnosis?
• What are the mechanisms of pathogenesis leading
  to the symptoms seen?
• What are the current treatments and how are they
  thought to work?