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

Basic physiology of the nervous system

Basic Physiology of the Nervous System

What triggers multiple sclerosis

What triggers Multiple Sclerosis?

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

Results proliferative responses to t cell vaccines y axis stimulation index

Results- Proliferative Responses to T cell vaccines (y-axis= stimulation index)

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

Results long term proliferative cellular responses to t cell vaccinaation

Results-Long Term Proliferative Cellular Responses to T-cell Vaccinaation

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

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