Albert Harris   Unsolved Problems   Biology 446 Autoimmune Diseases in one easy lesson "Go, thou, and do likewise" (Biblical quote) This sheet is meant to be analogous to: "What Watson already knew when he got to Cambridge" 1) When your immune system attacks molecules or cells that are normal parts of your own body, then the result is called an "autoimmune disease". 2) Autoimmune diseases include Multiple Sclerosis, Childhood Diabetes (= type one diabetes), Lupus, Rheumatoid Arthritis, Mumps-induced male sterility and dozens of others. 3) Each of these diseases is caused by having lymphocytes that make protein binding sites that have just the right shape to bind some particular normal molecules of your body. MS results from lymphocytes attacking the myelin sheaths of nerves: Lupus is caused by lymphocytes that make antibodies whose binding sites fit DNA, histones, collagen and many other normal molecules. 4) Tens of millions of Americans suffer (and hundreds of thousands die) from autoimmune diseases. A fundamental cure for any one of these diseases should quickly lead to cures for the others. A student in this class could be the one to discover such a cure, and has as good a chance as Watson did. 5) Instead of finding actual cures, modern medicine is satisfied to treat only the symptoms, by non-specific suppression of the whole immune system (especially with corticosteroids) although this weakens your immune resistance to infectious diseases, and has no chance of actually curing autoimmune diseases. 6) Vertebrate immune systems work by random generation of billions of clones of lymphocytes, each of which makes different-shaped antibody (protein) binding sites or T-cell receptor binding sites. You do NOT inherit genes for these binding sites. What you inherit amounts to a do-it-yourself kit which each lymphocyte uses to create randomly-shaped binding sites. 7) During everyone's embryonic development, as soon as T and B lymphocytes begin to differentiate, every person randomly generates billions of clones of lymphocytes, each of which produces antibodies (or equivalent proteins) with that lymphocytes own special shaped binding site. 8) Everyone develops thousands or millions of anti-self lymphocytes, that will cause autoimmune diseases if these antiself lymphocytes are not inactivated, desensitized, disabled, hit on the head, persuaded to repeat the randomization process for generating binding site DNA sequences, locked up somewhere, or something! 9) This (still unknown!) mechanism for selectively eliminating antiself lymphocytes is called "The Tolerance Mechanism" (or the Self-Tolerance mechanism). 10) Nobody really knows for sure how this self-tolerance mechanism works, except that it acts by weeding out lymphocytes that somehow detect that they are making binding sites that would bind to some "self" protein or other molecule. Many textbooks say, or at least imply, that this selective elimination is by killing the antiself lymphocytes, especially by inducing these lymphocytes to undergo programmed cell death ("Apoptosis"). This may be the true explanation, but I don't know of any good evidence proving it. If you know of such evidence, or find out about such evidence, or can invent one or more experiments that could prove that this explanation is either true or false, then please let me know, and I will buy you lunch.

 

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