Immunology
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	Summary questions for Final review
	Study Guide III: "The good, the bad, & the ugly" Material covered will be from 11/9 through 12/9.  Steps to success: Begin using this study guide 11/9 [11/16 is probably more realistic], not the weekend before the exam! Review Vocabulary List 5 and List 6. READ For sample exam questions, see case outside D234. Review self-quiz 8. READ again.  Study exercises and questions: 1. Summarize the immune response to tumor cells. Which is more effective, a humoral response or a cell mediated response? Support your answer. 2. What is hypersensitivity? What parts of the immune response lead to hypersensitivity? What are the Gel and Coombs types? For each type of hypersensitivity, list the cells and chemicals involved, give examples of antigens involved, and give a brief description of the response. What is anaphylaxis? How can it be controlled? Give four examples of diseases associated with hypersensitivity? Describe their key characteristics. Why are autoimmune diseases considered to be hypersensitivity diseases? What understanding regarding immune function can be gained by studying hypersensitivity? 3. What does "immunodeficiency" mean? What is the difference between primary and secondary immunodeficiency? What parts of the immune system are involved in immunodeficiency when they are lacking or dysfunctional? Give one example each of primary immunodeficiencies involving T cells, B cells, phagocytes, and C'. Describe cause, symptoms, and prognosis or outcome. What understanding regarding immune function can be gained by studying immunodeficiency? Summarize how HIV causes immunodeficiency. Why is this infection different from most viral infections? 4. For transplants to be accepted, a patient is given immunosuppressants, which induce a therapeutic immunodeficiency. Why is this necessary? What are the risks of using immunosuppressive drugs? 5. What is "passive immunity"? What are two examples of natural passive immunity? When would therapeutic passive immunization be used? Give some examples. 6. What is "immunization" or "vaccination"? How does this type of "active immunization" differ from passive immunization? Give two examples of vaccines and why they are used? Give an example for each of the following: whole-cell vaccine, sub-unit vaccine, recombinant vaccine. What is a toxoid? How is it prepared? What is the difference between "killed" and "attenuated" viral vaccines? How can passive immunity interfere with active immunization? Give two examples to illustrate. Give two examples of antibody production for research, commercial, or diagnostic applications. Include target antigen, means of antibody production, and applied use. 7. Make a summary diagram of the evolution of immune system and responses. At what point and in which animals did the various cells develop? Do analogous cells exist in other phyla which arose from different lineages? Follow the diversification of the Ig supergene family through evolution. Describe two unique structures, cells, or chemicals involved in immune responses NOT found in mammals. 8. Regarding "Optional topics": Diagram, chart and summarize as you have done all semester. Generate questions related to the topics and share them with your group members and study buddies.   [top of page] Summary Questions for Final Review 1. Another adaptive transfer game: Mice of H-2 (a/a) strain [homozygous strain at MHC] were sublethally irradiated [All mature lymphocytes were killed; stem cells were unaffected.] In addition, they were thymectomized just prior to irradiation. After six weeks, the mice were divided into three groups and immunized with specific antigens as shown below. Which group(s) was/were able to mount a humoral response? [If "none", say so.] Why? Group 1: ragweed pollen Group 2: killed Salmonella bacteria Group 3: DNP (hapten)- BSA conjugate Another batch of these mice were divided into three groups and given thymus transplants from fetal mice of other strains as follows: Group 4: thymus from H-2 (a/b) strain Group 5: thymus from H-2 (b/b) strain Group 6: thymus from H-2 (b/c) strain Are any of these groups able to mount a cell mediated response to tumor antigens? If so, which ones(s)? Are any able to mount a humoral response to tumor antigens? If so, which one(s)? For the groups in 'b' which did not respond, state what else needs to be done to fully reconstitute the mice to immunocompetence. Be specific. Some group 6 mice [from 13-b above] were fully reconstituted and shown to have both cell mediated and humoral responses. Skin grafts from sibling mice [H-2 a/a] which were not irradiated or thymectomized were transplanted to the backs of the group 6 mice. Will the grafts be accepted or rejected? Why? 2. Some elderly people living in a residential home were part of an experiment on stress and NK cell activity. One group served as a control and did nothing differently in their daily activities. A second group participated in more interactive activities, including craft projects and field trips to museums and concerts. A third group were taught active coping skills and relaxation techniques. At the end of the study, it was found that the third group showed improved NK cell activity. The second group showed no change from that at the beginning of the study or from the control group. However, both the second and third groups reported subjectively feeling better about themselves and about things in general. The control group reported no change in attitude. Describe a probable mechanism for the effect seen in the third group. Include the source and mediators involved, as well as the target(s) for the mediators. Both the second and third groups reported improved outlook, yet only the third group improved their NK activity. What is a probable explanation for this difference? What would be another type of indicator system which could be used to study the effects of stress? How would you construct your study? [Be brief.] 3. Under normal circumstances, humans do not make antibodies to self-components, e.g., red blood cell antigens. What are three possible explanations for this type of self-tolerance? Following a penetrating injury to one eye, a 30 year-old patient was found to have antibodies to retinal antigens. These antibodies were causing major complications in the healing of the eye. This patient had no prior history of autoimmune disease. Would antibodies to retinal antigens normally be found? Why (not)? Why did this patient develop antibodies to the retinal antigens? 4. As a young physician interested in immunology, you have a brilliant idea. One common type of leukemia is a cancer of the lymphocyte. Why not irradiate these leukemia patients with a dose of X rays sufficient to destroy all their lymphocytes (i.e., normal and leukemic cells) and then give them an adoptive transfer of spleen cells form another individual? The host's immune system is destroyed, hence the cancer should be cured. An older colleague finds your proposal highly amusing. Give two reasons why and discuss. Your colleague suggests that a better alternative would be to remove some of the patient's bone marrow before whole-body irradiation and treat the stem cells in vitro to remove the leukemic cells, and then return the bone marrow to the patient following the irradiation. Describe one way in which leukemia cells could be removed in vitro. What are the possible limitations of your method? 5. Upon examining Z cells isolated from Horta, the cells were shown to be defense cells. It was found that they reproduced primarily in response to an autocrine signal. In other words, Z cells produced a stimulating factor and also expressed receptors for the stimulating factor. When cultured in vitro, they only produced the stimulating factor if physically disturbed or if toxins were added. Describe the advantages of this reproductive system for Z cells in vivo. What are some of the possible disadvantages? 6. If a kidney patient could choose between an HLA haplo-identical sibling (only one HLA haplotype matched) or a parent as a possible donor, who will you recommend? Why? 7. An 81 year old woman was admitted to the hospital with wheezing and difficulty breathing. The attending physician noted that the symptoms were similar to asthma, and prescribed corticosteroid treatment. There was some initial improvement; but after five days, she was having increased difficulty. A sputum sample was cultured and examined microscopically. The cultures were positive for an excessive amount of a species of bacteria seen in normal flora. In addition, some parasitic worms were noted in the sputum. These were identified as being of a species rarely seen in the U.S., yet common in South America. In reviewing her history, it was noted that she had lived in Peru until she was 27 years old. Other than occasional colds, she reported no respiratory problems during her time in Peru or since she moved to California. There was no prior history of her current symptoms. What is the primary cause of this woman's respiratory problems? What is your rationale? Was the use of corticosteroids a good idea? Why (not)? Is it possible that she was infected with the worms for over 50 years? Why (not)? 8. You've just spent two months and $10,000 purifying a unique enzyme from a rare strain of yeast which yields a high quality product important to the food industry. To become marketable, you need to develop a high yield cost effective method of purification. Affinity chromatography using antibodies specific for the enzyme might be the perfect approach. You've agreed to a challenge from a colleague to produce the best antibody for the job. [The stakes: the loser pays for a week in Hawaii for the winner.] Day 1: You arrive in the lab to find your competition has helped herself to 800 mg of your precious enzyme. You only have 100 mg left. You decide on a three-dose immunization schedule over six weeks using 1 mg per dose. You also decide to use an oil based adjuvant and to inject subcutaneously. Your competitor is giving away no information just yet.  Seven weeks later: At this time you discover that your competitor used a two-dose immunization schedule at a four-week interval and injected intravenously. She used 400 mg per dose, therefore she has a rabbit worth nearly $9000, but no enzyme left for testing the antisera. [It is a good thing the rabbit is alive and well.] With some of your remaining enzyme, you both test your rabbits for antibody titer, major isotype, and relative affinity. You have test bleeds taken 6 days after the second and third immunizations. Your competitor has test bleeds taken 6 days, 14 days, and 21 days after the second immunization. Who won? Describe why, including information on relative titer, isotype, and relative affinity of the antibodies produced. 10. When the nerve endings at neuromuscular junctions release acetylcholine [ACH], muscles are stimulated to contract. ACH binds to acetylcholine-receptors [AChR] on muscle cell membranes, which depolarize the membranes and initiate contractions. A group of clinical researchers injected rats with 1.1 to 350 picomoles of purified electric eel AChR protein suspended on complete Freund's adjuvant. This immunization elicited a set of physical symptoms that included weight loss, generalized muscle weakness, a characteristic hunched posture with chin and elbows off the floor, and jerky movements of the head and forelimbs when attempting ambulation. The animals were graded, as shown in the table, on the following simple scale: 0, no definite weakness; +, weak grip with fatigability; ++, hunched posture with head down and movements uncoordinated; +++, severe generalized weakness, no grip, tremulous, moribund. Can you explain all the symptoms [including weight loss] by a single underlying cause? What further studies could you do on the sera of these rats to test your explanation? The adjuvant was absolutely required to induce the clinical syndrome. What is a reasonable explanation for this? Thymectomized rats do not develop this syndrome. What model would you propose to explain the results of AChR immunization? What autoimmune disease does this set of experiments model? Patients with this disease show a reduced number of AChR in biopsied neuromuscular junctions. Give an explanation as to why the receptor number is reduced. What type of therapy would be beneficial? Why?   Dose [picomoles] Number of animals with the syndrome Maximum severity 350.0 110.0 55.0 35.0 11.0 3.5 1.1 0 Totala Earlyb Latec 21/23 21 15 10/10 9 9 2/2 2 2 8/9 6 6 6/11 5 4 7/9 6 4 0/10 0 0 0/10 0 0 + ++ +++ 2 2 17 0 2 8 0 1 1 1 1 6 3 2 1 2 5 0 0 0 0 0 0 0 a Number with syndrome/number injected b Rats were observed up to 80 days. Early: before day 16; late: generally after day 20. c See text of question [From V.A. Lennon, et al, 1975, J. Exp. Med. 141:1365.] [top of page]
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 Updated 8/27/04 by thatcher@sonoma.edu