Review for the third hour exam, part two

37) What is the name of the particular kind of differentiated cells that synthesize antibodies?

38) Suggest why it's necessary that the great majority of lymphocytes undergo apoptosis.
(Hint: Remember the randomness of the VDJ recombination of lymphocyte DNA.

39) Which of the following is closest to the true reason that people don't normally make antibodies against their bodies' own antigens?

    a) Because every molecule in the body is labeled with special molecules that are special for them, and which lymphocytes recognize as "self", in the sense of avoiding attacks or binding to any molecule with that "self" label ?

    b) Genetic linkage prevents anybody who inherits the gene for the A antigen from also inheriting the gene for antibodies that bind to the A antigen, and likewise for every combination of antigens and antibodies?

    c) Transcription of RNA is selectively inhibited for any antibody whose binding site would fit any of a person's own antigens?

    d) Because some mechanism weeds out those V, D and J regions of DNA that would code for antibodies that would fit any of that person's own antigens?

    e) Some mechanism selectively kills, inactivates or sequesters all B and T lymphocytes whose combinations of V, D and J regions of DNA actually do code for antibodies (or T-cell receptors) that actually do fit any of that person's own antigens?

    f) When antibodies bind to antigens that are present in large enough amounts, then those antibodies are quickly filtered out of the blood.)?

    g) Some other mechanism? Put it in your own words.

40) You should be able to write a few sentences about each of the following:
    autoimmune disease
    immune tolerance

41) Explain the errors in the following misleading statements:

    Autoimmune diseases result from failure of lymphocytes to distinguish between "self" and "non-self" histocompatibility antigens.

    Autoimmune diseases are caused by excess strength of the immune system.

42) Which of the following are already known? (And briefly explain the known mechanism). Also tell which of the following are not known.

    a) How does the immune system produce genes for antibodies that fit (="recognize"="selectively bind to") molecules of your own body?
    Hint: Explain VDJ recombination.

    b) Does your immune system ever contain genes for antibodies that selectively bind ("recognize") molecules that neither you nor any of your ancestors have ever encountered?

    c) How does the immune system (or any system) "recognize" something that it hasn't encountered before?

43) If a B lymphocyte's antibody binding sites fit a certain molecule, then based on what criterion does the lymphocyte "recognize" whether the bound molecule is "self" or "non-self"??

    a) If the molecule had been self, then that lymphocyte would have been weeded out = induced to die) during embryonic development. Therefore if a lymphocyte still exists, then whatever antigen it binds to must be non-self?

    b) All your cells have the equivalent of identification badges, and if a lymphocyte's badge matches the badge of another cells, then the latter must be "self"?

44) If immune tolerance really did work by means of matching badges, then by what means would you treat, or try to treat, autoimmune diseases?

45) People who have type A blood somehow avoid making antibodies whose binding sites fit the type A blood group antigen. If they did make such antibodies, that would cause a very severe autoimmune disease. How do their lymphocytes avoid making antibodies with that specificity?

46) Tens of thousands of people become autoimmune to the special kind of myelin made by oligodendrocyte cells inside the central nervous system. (Many more than become autoimmune to any other differentiated cell type).
Absolutely nobody develops autoimmunity to Schwann cell myelin!
Can you invent some possible reasons for these facts? Why do you think each occurs?

47) Explain why the following would be a possibility:
Perhaps oligodendrocytes differentiate later during embryonic development than Schwann cells. (After the process of weeding out lymphocytes whose randomly-generated binding sites fit "anti-self" binding sites?)
Suggest and support a hypothetical explanation.

48) All cells of the body contain all the enzymes and signalling proteins needed to cause the cell to digest itself from the inside out (apoptosis). Why should cancer researchers be trying to cause apoptosis in all cells that have any cancerous properties, as opposed to trying to inhibit DNA synthesis and mitosis in fast-growing cells

49) How could you use apoptosis (in general terms) as part of a cure for autoimmune diseases or cancer?

50) People who have either type A or type AB blood would quickly die if any of their lymphocytes secreted antibodies whose binding sites have the right shape to fit and bind to the type A "blood group substance". In contrast, people with either type B blood or type O blood do have lymphocytes that secrete anti-A antibodies.
What mechanism causes this difference? Do people who inherit the genes for anti-A antibodies somehow not inherit genes for type A blood?
Hint: definitely NOT; It's closer to the opposite of that.

51) Is it true that immune self-tolerance (not making antibodies that bind to any of your own molecules) is caused by lymphocytes being able to distinguish between self and non-self molecules.
Hint: NO

52) Actually, lymphocytes whose binding sites fit molecules present in the embryo are selectively eliminated (probably induced to self-destruct, by apoptosis.) Does this selective elimination process (whatever it is) sometimes fail to occur?
Hint: What causes autoimmune diseases?

53) What is the function of the random DNA splicing that is part of the normal development of the differentiation of both B lymphocytes and T lymphocytes?

54) What would be the result if a lymphocyte failed to undergo this random DNA splicing?

55) What would happen if this DNA splicing occurred too late during the differentiation of a lymphocyte? ("Too late" means after the time when self-destruction is stimulated to occur in those lymphocytes whose binding sites fit normal molecules of your body).

56) What could happen if the normal self-destruction mechanism failed to detect certain molecules?

57) What are some possible reasons why this self destruction might fail to occur? What if a "self" molecule were "hidden" in the myelin of the central nervous system, perhaps tightly wrapped by other molecules?

58) Can lymphocyte binding sites have shapes that fit the binding sites of antibodies made by different binding sites?
Hint: Yes, they certainly can. Monoclonal antibodies have been made whose binding sites fit the binding sites of other antibodies.

59) Why are lymphomas the only kind of cancer that can be cured using monoclonal antibodies that selectively fit only the cancer cells?
Hint: Remember that each lymphocyte, including each cancerous lymphocyte, makes lots and lots of binding sites that all have the same shape as each other.

60) Why is this method of curing cancer not profitable enough to be used to save people's lives? How could the same basic method (Binding sites that fit binding sites) also be used to cure multiple sclerosis? Why would this method be much more profitable as a cure for autoimmune diseases than it is as a cure for lymphocyte cancers?

61) Researchers have discovered that cleavage-stage mouse embryos can merge with rat embryos at the same stage, and develop into animals in which some parts consist of mouse cells and other parts are rat cells. Why do the immune systems of these "chimeric" animals not produce an autoimmune attack on any parts of their body?

Suppose that you grafted mouse tissue into a rat-mouse chimera, would the graft be rejected by the chimera's immune system? Explain why or why not.

What if you grafted tissue from such a rat-mouse chimera into an adult mouse, would that graft be rejected by the mouse's immune system?