Multiple Sclerosis and the Immune Response By: Terra McMillan

1
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.

2
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

3
What is Multiple Sclerosis?

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

4
Basic Physiology of the Nervous System
5
What triggers Multiple Sclerosis?
6
(No Transcript)
7
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.

8
Vocabulary Contd

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

9
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

10
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

11
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

12
Rationale for Figure 1.

• The objective was to test if serum from
  vaccinated patients influenced the proliferation
  of T cells
• PBMC of vaccinated patients were collected at
  various time intervals before and after
  vaccinations
• Samples were irradiated with 3H-thymine

13
Results- Proliferative Responses to T cell
vaccines (y-axis stimulation index)
14
Conclusion-Figure 1.

• All patients showed proliferative responses after
  vaccination, indicating an immune response
• Proliferative responses often increased after the
  second and third vaccinations
• Some clones were more effective than others

15
Rationale-Figure 2.

• Examination of long term proliferative responses
  using stimulation index
• Samples all obtained after the third vaccination
• Same irradiation procedures as for figure 1. were
  used
• PHA blasts were used as the control

16
Results-Long Term Proliferative Cellular
Responses to T-cell Vaccinaation
17
Conclusion-Figure 2.

• SIs gretaer than 2 were observed for all patiens
  at 1 and 2 years after vaccination
• In some patients the response was greater than
  others
• Indicates a memory T cell system within these
  patients

18
Rationale-Figure 3.

• Determining phenotypes of cytokines which
  responded to the vaccine clones
• Short-term cell line cultures were obtained 3
  weeks after vaccination 3
• Results were measured in SI units on the x-axis

19
(No Transcript)