Questions for class discussion regarding multiple sclerosis

2) Which of these are possible explanations of autoimmune diseases?
   a) Mutation in a lymphocyte changing the amino-acid sequence of its antibody.
   b) If embryonic lymphocytes never contact a brain myelin protein in development.
   c) If VJD recombination is delayed and occurs after embryonic development.
   d) If a somatic mutation occurs in the gene that codes for a myelin protein.
   e) If a myelin protein can fold into several different shapes, changing with age.

3) If Multiple Sclerosis patients produce anti-myelin B-lymphocytes and also anti-myelin T-lymphocytes that both bind selectively to exactly the same protein:
   a) The binding sites of antibodies must be produced by splicing the same DNA as occurs in T-lymphocytes, in the creation of T-cell receptors (same splicing in T-cells as in B cells).
   b) MS results from lack of contact between a brain myelin protein and all embryonic lymphocytes.
   c) There must be some kind of conversion of B-lymphocytes into T-lymphocytes, or the reverse.
   d) Failure of the weeding-out process must have occurred in both B and T lymphocytes.
   e) Some reason different from any of the above?

4) Which of the drugs now being used to treat MS is most specific, in the sense of doing the least harm to patients, relative to the amount of improvement in the symptoms of MS?

5) Which of the drugs now being used to treat MS is least specific?

6) Which of the anti-MS drugs has the best chance of being improved enough to be an actual cure?

7) Which of the anti-MS drugs has the least chance of being improved enough to be an actual cure?

8) Do any of these drugs have absolutely zero chance of being improved enough to become cures?

9) If you had a pure source of the myelin protein that gets attacked in MS, how could you use this protein either to treat MS patients, to make drugs or vaccines for treating MS, or for use in experiments or other tests of theories about MS?

10) Figure out how to use "genetic knockouts", "interference RNA", Clustered Regularly Interspaced Short Palindromic Repeats, or other molecular biological methods as the basis for improving treatment of Multiple Sclerosis.

11) Imagining that you could somehow ask a series of yes or no questions about MS to an all-knowing source, figure out exactly what questions you would ask? You can't ask: "What is a cure?"; but you can ask: "Does the abnormality start after, or before, DNA splicing?" etc.

12) Please arrange the following processes in the order in which they need to occur.
   a) Irreversible commitment of which cells of the body will become lymphocytes.
   b) Decision which lymphocytes will become B lymphocytes versus which will become T lymphocytes.
   c) Random splicing of certain parts of the DNA to create genes for binding sites.
   d) Transcription of the genes for antibodies and T-cell receptors.
   e) Translation of these genes to create the amino acid sequences of these immune binding sites.
   f) Contact of early differentiating lymphocytes with as many as possible different normal proteins.
   g) Self destruction or permanent inactivation of all B and T lymphocytes whose binding sites fit any normal body molecules
   h) Reversal of the preceding response, such that binding of lymphocytes to molecules that are not part of the body causes them to grow, divide, and produce lots of binding sites.
   i) Development of properties by which "self" molecules can be distinguished from non-self molecules.

13) In order to cure Multiple Sclerosis, which of the following do you need to accomplish? A) Identify the exact "self" molecule that gets attacked by the immune system.
   B) Sequence all genes which have consistently different (abnormal) sequences in MS victims.
   C) Reactivate the normal "weeding-out" mechanism that eliminates anti-self lymphocytes.
   D) Make antibodies that bind and selectively kill all anti-myelin lymphocytes.
   E) Cause anti-myelin lymphocytes either to lose their differentiated state, or to re-differentiate into some other cell type, such as macrophages. F) Kill any lymphocytes that penetrate into the brain.
   G) Cause brain nerves to replace their oligodendrocytes with Schwann cells.
   H) Cause oligodendrocytes to make the kinds of myelin proteins normally used by Schwann cells.
   I) Kill or inactivate all lymphocytes that bind to oligodendrocytes, and/or to proteins isolated from oligodendrocytes.
   J) Synthesize a poison shaped like the myelin protein that gets attacked in people with MS.
   K) Implant surgical sponges covered with molecules shaped like the proteins that get attacked in MS.
   L) Synthesize a vaccine that stimulates T-lymphocytes to attack and kill any other lymphocyte that attacks oligodendrocyte myelin.
   M) Invent some other ways that a cure might work.