Multiple Sclerosis and the Immune Response By: Terra McMillan

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Multiple Sclerosis and the Immune ResponseBy
Terra McMillan

• Hermans, Guy, Ulrike Denzer, Ansgar Lohse, Jef
  Raus, and Piet Stinissen. 1999. Cellular and
  Humoral Immune Responses Against Autoreactive T
  cells in Multiple Sclerosis Patients After T cell
  Vaccination. Journal of Autoimmunity 13, 233-246.

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The Purpose

• Study the safety, immune responses and clinical
  effects of T cell vaccination in 49 multiple
  sclerosis patients.
• Gain insight on the mechanisms of autoreactive T
  cells

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Basic Physiology of the Nervous System
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What is Multiple Sclerosis?

• Autoimmune disease
• T cell mediated
• 250,000 people have MS
• Women 21 ratio with men

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What triggers Multiple Sclerosis?
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Common Vocabulary

• Antigen-A substance that cause the production of
  specific antibodies and combine with those
  antibodies.
• Antibodies-Protein produced by the body to
  specifically react with a foreign substance
• EAE- experimental autoimmune encephalomyelitis
• Cytokines-Protein released in response to an
  antigen which influences other cells.

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Vocabulary Contd

• PBMC-peripheral blood mononuclear cells
• MBP-myelin basic protein
• TCR-T cell receptor
• CD markers-clusters of differentiation
• MHC-major histocompatibility complex

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Materials and Methods

• MBP reactive T cells were isolated from the
  peripheral blood and cloned
• T cell clones was analyzed for TCR,
  rearrangements, and CDR3 sequence
• Inactivation by irradiation
• 49 MS patients were injected subcutaneously with
  10x106 cells for T cell vaccination
• 3 immunizations were performed at 2-month
  intervals

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Materials and Methods Contd.

• Mononuclear cells isolated from blood samples and
  irradiated with T cell vaccine
• Incubated for 4 days
• Purified, label with radioactivity, and stored at
  20oC for cytokine analysis
• Results recorded in Stimulation Indexes (SI)
• Net production of cytokine

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Materials and Methods Contd.

• Patient serum Ig was bound to vaccine T cells
  using flow cytometry
• Results were used in immunoblotting
• Also patient serum was used to determine the
  proliferation of T cells

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Results- Proliferative Responses to T cell
vaccines
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Results- Stimulation Index
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Results-Phenotypic profile of short-term cell
lines
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Results Contd.
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Results Contd.