multiple sclerosis and the immune response by terra mcmillan
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multiple sclerosis and the immune response by terra mcmillan

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.

the purpose
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
what is multiple sclerosis
What is Multiple Sclerosis?
  • Autoimmune disease
  • T cell mediated
  • ~250,000 people have MS
  • Women 2:1 ratio with men
common vocabulary
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.
vocabulary cont d
Vocabulary Cont’d
  • PBMC-peripheral blood mononuclear cells
  • MBP-myelin basic protein
  • TCR-T cell receptor
  • CD markers-clusters of differentiation
  • MHC-major histocompatibility complex
materials and methods
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
materials and methods cont d
Materials and Methods Cont’d.
  • 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
materials and methods cont d1
Materials and Methods Cont’d.
  • 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
rationale for figure 1
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
conclusion figure 1
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
rationale figure 2
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
conclusion figure 2
Conclusion-Figure 2.
  • SI’s 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
rationale figure 3
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
ad