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Immune- mediated diseases of the Nervous System. Session structure Monday 19 th – lecture Monday pm – SDL – Case: Multiple sclerosis Tuesday 20 th – Case answers. Immune- mediated diseases of the Nervous System. Aim :

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slide1

Immune- mediated diseases of the Nervous System

Session structure

Monday 19th – lecture

Monday pm – SDL – Case: Multiple sclerosis

Tuesday 20th – Case answers

slide2

Immune- mediated diseases of the Nervous System

Aim:

To introduce diseases of the nervous system where autoimmunity contributes to disease pathogenesis

slide3

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
slide4

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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Two types of Immunity

Innate/natural

Adaptive

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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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Multiple Sclerosis

  • Most common crippling neurological disorder of young adults (due to small multifocal patches of demyelination - plaques)
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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
slide19

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
slide21

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
slide26

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?