Name:____________________________ Last four digits of Student ID #:______ PATHOPHYSIOLOGY EXAM 1 Spring 2011 MULTIPLE CHOICE (each correct answer is worth 2pts): PLEASE READ THE ENTIRE QUESTION AND THEN CIRCLE THE LETTER NEXT TO THE ONE BEST ANSWER. 1. The body's nonspecific defenses include: a) skin b) complement system c) Acute Inflammatory Response (AIR) d) all of the above (a, b, and c) e) a and b 2. Which of the following statements is/are TRUE? a) Metaplasia involves the replacement of one mature cell type with another mature cell type that is less differentiated. b) Dysplasia involves a proliferation of mature cells that are abnormal in size, shape, and organization. c) In dysplasia there is uncontrolled cell proliferation. d) all of the above are true statements e) Only a and b are true statements 3. Liquefactive necrosis ______. a) results from the release of hydrolytic enzymes from necrotic cells b) is the type of necrosis that occurs in neural tissue c) results from the release of lactic acid from necrotic cells d) both a and b correctly complete the sentence e) both b and c correctly complete the sentence 4. Which of the following statements is/are TRUE of free radicals? a) Free radicals are molecules which have an unpaired electron in one of their orbitals. b) Superoxide dismutase is an example of a free radical that occurs naturally in macrophages and may be used to kill pathogens. c) Antioxidants convert free radicals to less toxic substances. d) All of the above are true e) Only a and c are true 1 Name:____________________________ Last four digits of Student ID #:______ 5. In an experimental situation, a respiratory virus is injected into a rabbit and the rabbit is allowed to make antibodies for the viral antigen. This rabbit is then exposed to a population of rabbits to allow the pathogen to spread to members of the population. With regard to the population of rabbits, this would be an example of: a) innate immunization b) active immunization c) passive immunization d) natural immunization e) autoimmunization 6. Intracellular deposists of water, lipids, proteins, and/or pigments are examples of: a) infiltrates b) exudates c) chemical injury d) caseous necrosis e) none of the above 7. The protein elements of the membrane attack complex are ______. a) released from mast cells in response to tissue damage b) synthesized by the liver. c) secreted by macrophages that are activately phagocytosing pathogens d) secreted by Tc cells. e) none of the above 8. Which of the following are characteristically found in chronically inflamed tissue? a) epitheliod cells b) fibroblasts c) lymphocytes d) all of the above e) only a and b 9. Coagulative necrosis _______. a) is a combination of caseous and liquefactive necrosis b) is most commonly seen in fatty tissues c) usually results from the release of hydrolytic enzymes that cause proteins to denature giving the necrotic tissue a white color. d) none of the above correctly complete the sentence e) both a and b correctly complete the sentence 2 Name:____________________________ Last four digits of Student ID #:______ 10. Macrophage chemotactic factor is secreted by: a) Mast cells b) Mononcytes c) Neutrophils d) B and T cells e) Eosinophils 11. Steroidal anti-inflammatory drugs (SAIDS), like cortisone, act primarily by ______. a) blocking the action of bradykinin on pain receptors. b) Inhibiting the synthesis of prostaglandins, and thereby releaving pain. c) inhibiting the secretion of interleukin 1 from macrophages, thereby reducing the accumulation of these cells at the site of inflammation and preventing chronic inflammation. d) All of the above e) Only a and c 12. MHC class I protein complexes are expressed ________. a) on all cells in the body with a nucleus b) on macrophages c) on red blood cells d) both b and c 13. Which of the following is/are TRUE of interleukin 1 (IL-1)? a) It is involved in stimulating T helper cells to undergo differentiation and proliferation. b) It is secreted by TH2 cells and is necessary for B cells to respond to antigen exposure. c) It stimulates the liver to produce plasma proteins involved in the coagulation, kinin, and complement systems. d) All of the above are true of IL-1 e) Only a and c are true of IL-1 14. Which of the following is/are TRUE regarding a paper cut? a) This type of wound heals by primary intention. b) This type of wound does not evoke an acute inflammatory response. c) This type of wound heals by secondary intention. d) Both a and b are true e) Both b and c are true 15. NSAIDS, such as aspirin, act by: a) inhibiting the release of histamine b) inhibiting the degranulation of mast cells c) blocking the action of bradykinin d) all of the above e) None of the above 3 Name:____________________________ Last four digits of Student ID #:______ MATCHING: (each correct answer is worth 2pts): From the list below (a-e), select the word that best matches the numbered item and place the letter next to the numbered item. Some of the words in the list may not be used, and some may be used more than once. a) IgA b) IgD c) IgE d) IgG e) IgM __D__ 16. Comprise 80% of the free antibodies in the blood plasma . __C__ 17. Antibodies that cause mast cells to degranulate when they bind antigen. __A__ 18. Antibodies found in external body secretions. __E__ 19. These antibodies are known to be responsible for the primary response of B cells 4 Name:____________________________ Last four digits of Student ID #:______ TRUE/FALSE. Circle T if the statement is true. Circle F if the statement is false. For false statements you must cross out the word or words that make the statement false and replace them with a word or words to make a true statement. You may not add additional words to the sentence to make it true without crossing out words. You may not cross out the entire statement in constructing a true statement. (Each is worth 2 point) east Example: T F The sun rises in the west. B or TH-----------------or----------------------I T F 20. Cytotoxic T cells are activated by binding to MHC class II- antigen protein complexes. macrophages chemotactic factor T F 21. Actively phagocytosing neutrophils secrete leukotrienes. T F 22. Dysplasia involves a proliferation of mature cells that are abnormal in size, shape, and organization. T F 23. A keloid scar is the result of over production of collagen by fibroblasts. liquefactive T F 24. Caseous necrosis is a combination of coagulative necrosis and fat necrosis. T F 25. During the AIR, the overall affect of histamine is vasodilation. DROP 26. Actively phagocytosing macrophages secrete growth factors that stimulate wound contracture. 5 Name:____________________________ Last four digits of Student ID #:______ ESSAY/SHORT ANSWER QUESTIONS: 27. Define the following terms: (Each is worth 2 points) Edema: Tissue swelling due to the accumulation of extracellular fluid. Epithelialization: The re-establishment of the epithelial cell covering over deeper tissues that occurs duing wound healing. Bradykinin: The chemical agent that is the end result of the kinin plasma protein system, acts to stimulate pain receptors and prolongs the effects of histamine released by mast cells. Granuloma: A collagen enclosed mass of chronically inflamed tissue that contains giant macrophages, fibroblasts, and lymphocytes. Ischemia: Insufficient blood flow to tissues that may result in hypoxia and tissue damage including cell death. 6 Name:____________________________ Last four digits of Student ID #:______ 28. Compare and contrast wet gangrene, dry gangrene, and gas gangrene. (Worth 6 points) Gangrene result from the necrosis of large groups of cells or tissues. There are three types of gangrene , wet gangrene, dry gangrene, and gas gangrene. In wet gangrenous tissue liquefactive necrosis occurs, in which the necrotic cells release hydrolytic enzymes that digest the surrounding tissues. It results from the interruption of the venous blood flow out of the necrotic tissue. Wet gangrenous tissue appears moist, black in color, and typically has a bad odor as a result of bacterial infection. In dry gangrene the tissue undergoes coagulative necrosis, in which the necrotic cells release lactic acid that denatures the proteins being released from the lysing cells. It is caused by the interruption of arterial blood flow to the tissue. Dry gangrenous tissue appears dark brown or black in color and is very dry. Gas gangrene results from invasion of necrotic tissue by one of the strains of the anaerobic Clostridium bacteria. This bacteria produces enzymes that destroy connective tissues and cell membranes producing hydrogen sulfide gas that bubbles out of the necrotic tissue. 7 Name:____________________________ Last four digits of Student ID #:______ 29. Three types of hyperplasia were discussed in lecture (this does not include atypical hyperplasia). Describe and give an example of each type of hyperplasia. (worth 6 points) The three types of hyperplasia are compensatory, hormonal, and pathologic. In compensatory hyperplasia, cell proliferation occurs in response to repeated damage or removal tissue. An example of compensatory hyperplasia is the formation of callus on the hands or feet in response to normal wear and tear of daily work activities. Hormonal hyperplasia is cell proliferation in response to stimulation by a hormone. An example is the normal proliferation of the endometrium that occurs in the uterus as a result of the monthly estrogen cycle. Pathologic hyperplasia is abnormal cell proliferation caused by excessive hormonal stimulation. An example is seen if there is oversecretion of estrogen. The oversecretion of estrogen causes excessive hyperplasia of the endometrium, which results in excessive bleeding during menses. 8 Name:____________________________ Last four digits of Student ID #:______ 30. Answer one (A or B) of the following: (3 extra credit points if you answer both questions completely correct, no partial extra credit will be given. If you answer both A and B, circle the letter of the question you want used as your primary answer.) A) Name and describe the three phases of wound healing. Include in your essay the terms: fibroblast, macrophage, growth factors, angiogenesis, collagen, granulation tissue, epithelialization, myofibroblast, wound contraction. (Worth 6 points) Or B) Describe the main events that lead to cell death following hypoxic injury to a cell, indicating particularly which of the events are reversible and which are irreversible. (Worth 6 points). A) During the AIR, the most important cells with regard to wound healing are the macrophages. At the site of tissue damage the macrophages secrete growth factors that stimulate epithelial cell division, angiogenesis, and fibroblast chemotactic factor. The fibroblast chemotactic factor attracts fibroblasts to the site of tissue damage. These fibroblasts play the key role in the subsequent two phases of wound healing. During the reconstructive phase, fibroblasts secrete collagen that forms a framework that replaces lost tissue. The fibroblasts and collagen together form what is called granulation tissue or scar tissue. The angiogenesis that was initiated during the AIR results in capillaries growing into the scar tissue giving it a pinkish color. As the reconstructive phase progresses some of the fibroblasts differentiate into myofibroblasts that have the ability to contract, much like muscle cells. The contraction of the myofibroblast results in wound contracture in which the edges of the wound are pulled together. Also during this phase, epithelialization occurs in which the epithelial cells at the margins of the wound divide and spread under the blood clot that covers the surface of the wound, re-establishing the epithelial lining and sealing the deeper tissues from the environment. During the maturation phase, the scar tissue that was formed during the reconstructive phase is remodeled giving it increased tensile strength. The capillaries that were established during the reconstructive phase degenerate leaving an avasuclar scar tissue. B) Cell death from hypoxia results from two causes: Anaerobic metabolism---> increased lactic acid---> pH decreases-lysosomal swelling and damage to membrane---> release of hydrolytic enzymes----> Death Anaerobic metabolism--->decreased ATP production--->decreased function and eventual failure of Na+/K+ and Na+/Ca++ pumps--->Disruption of ionic gradients for Na+ and Ca++--->Na+ and Ca++ buildup inside cell disrupting osmotic gradient--- 9 Name:____________________________ Last four digits of Student ID #:______ >Water enters cell down osmotic gradient causing swelling--->swelling of cell membrane disrupts normal selective permeability of the membrane further disrupting normal gradients and allowing cell proteins and enzymes to leak out-->mitochondrial swelling and swelling of endoplasmic reticulum which causes ribosomes to fall off, causes disruption of normal respiration and protein synthesis--> Death 10 Name:____________________________ Last four digits of Student ID #:______ 31. Starting with degranulation of mast cells, describe the acute inflammatory response to tissue damage. In your essay you must correctly use the terms: mast cells, NCF, ECF-A, MCF, histamine, leukotrienes, macrophages, neutrophils, interleukin-1, plasma protein systems, bradykinin, membrane attack complex (Worth 12 pts) The acute inflammatory response is triggered by tissue damage resulting in the release of histamine from mast cells in the tissue, this is referred to as degranulation of the mast cells. The released histamine causes vasodilation increasing blood flow to the tissue causing it to become red and increasing the temperature of the tissue. Histamine also increases the permeability of the capillaries in the inflammed tissue allowing plasma and blood cells to leak into the tissue. The leakeage of plasma causes the tissue to swell (edema). In addition to the release of histamine, additional chemical signals are released from mast cells, these include the leukotrienes, prostaglandins, neutrophil chemotactic factor (NCF), and eosinophil chemotactic factor (ECF-A). Leukotrienes have similar affects as histamine in that they cause vasodilation and increased capillary permeability. Leukotrienes also act as a chemotactic agent for neutrophils and eosinophils, drawing these cells to the site of inflammation. The neutrophils are the first phagocytic cells to arrive at the site of inflammation. They begin the initial attack on invading pathogens and also begin cleaning up cellular debris. Eosinophils release chemical agents, such as histaminase, that control the acute inflammatory response, preventing an over-response. Eosinophils are also the main defense against parasites that my attempt to gain access to the body through the damaged tissue. The leakage of plasma proteins into the inflammed tissue activates the plasma protein systems, which include the kinin system, complement system, and the clotting system. The kinin system is a casacade that lead to the synthesis of bradykinin. Bradykinin acts along with prostaglandins to stimulate pain receptors, it also has similar effects to histamine except that it is longer lasting and so may be responsible for prolonging the inflammatory response. The complement system is responsible for producing membrane attack complex that inserts pores into the cell membrane of invading pathogens causing them to swell and eventually burst. Some of the intermediates of the complement cascade also have chemotactic properties that attract neutrophils to the site of inflammation. The clotting system produces a network of fibrin fibers that prevent blood loss, and also serve to keep pathogens and the cells that fight the pathogens localized to the site of inflammation. The neutrophils that begin the initial phagocytosis of invading pathogens release macrophage attracting factor (MCF) that draws macrophages to the site. The macrophages are large, long lived phagocytositic cells capable of phagocytosing thousands of pathogens before they die. Actively phagocytosing macrophages release Interleukin-1 (IL-1), which has systemic inflammatory effects. Systemically, IL-1 acts on the hypothalamus to reset the body's temperature center resulting in fever. It also stimulates the liver to synthesize and release plasma proteins. It also stimulates the maturation and release of neutrophils from the bone marrow. In severe inflammation, the increased levels 11 Name:____________________________ Last four digits of Student ID #:______ of IL-1 can lead to the release of premature neutrophils, called band cells. The presence of band cells in the blood is indicative of a severe inflammation somewhere in the body. 12 Name:____________________________ Last four digits of Student ID #:______ 32. Discuss the roles and interactions of each of the following in the immune response to a bacterial infection: macrophages, IL-1, IL-2, IL4, B cells, cytotoxic T cells, helper T cells, TH1 and TH2 cells, IgM and IgG, MHC class I and class II antigen-protein complexes, CD4, CD8. (Worth 8 points) Macrophages are the primary antigen presenting cells. After phagocytosing and digesting pathogen, the macrophages complex antigens from the pathogen with MHC class 1 and 2 proteins and express them on their cell membrane. The MHC class 2 protein-antigen complexes are responsible for activating mature helper T cells. The helper T cells bind to the MHC class 2-antigen complex with their T cell receptor. The CD4 protein helps the T helper cell to bind by binding to the MHC class 2 protein. The macrophage also releases IL-1, which stimulates the helper T cell to respond to the binding of antigen by differentiating and proliferating into activated helper T cells and memory helper T cells. The activated helper T cells release IL-2, which stimulates them to differentiate and proliferate into TH1 and TH2 cells. The TH1 cells release IL-2, which stimulates mature cytotoxic T cells to proliferate and differentiate into plasma cytotoxic T cells and memory cytotoxic T cells. In order to respond to the IL-2, the cytotoxic T cell must first have been presented with antigen by cells expressing MHC class 1-antigen complex. The CD8 protein helps the cytotoxic T cell bind to antigen by binding to the MHC class 1 proteins. The plasma cytotoxic T cells attack infected cells, releasing toxins that kill the infected cell. The TH2 cells secrete IL-4 that stimulates B cells that have been activated by binding antigen with IgM expressed on their cell surface, to proliferate and differentiate into plasma B cells and memory B cells. The plasma B cells secrete IgG that fights the invading pathogen. 13
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