Chapter 9: IMMUNITY AND DISEASE

9 immunity AND DISEASE Chapter Outline OVERVIEW OF BODY DEFENSES Three lines of defense protect the body We are born with some general defenses and acquire other, specific ones White blood cells and their chemicals are the defenders in immune responses Gender and stress influence the immune system. THE LYMPHATIC SYSTEM The lymph vascular system functions in drainage, delivery, and disposal Lymphoid organs and lymphatic tissues are specialized for body defense barriers to infection INNATE IMMUNITY overview of adaptive defenses Adaptive immunity has four key features Lymphocytes become specialized for different roles in adaptive immunity ANTIBODY-MEDIATED IMMUNITY: DEFENDING AGAINST THREATS OUTSIDE CELLS Antibody-mediated immune responses produce a flood of antibodies There are five classes of antibodies, each with a particular function Cell-Mediated Responses—combating threats inside cells Cytotoxic T cells cause the body to reject transplanted tissue applications of immunology Vaccination stimulates immunity Antibodies provide “borrowed” immunity Monoclonal antibodies are used in research and medicine Immunotherapies reinforce defenses immune system disorders In allergies, harmless substances provoke an immune attack Autoimmune disorders attack “self” Immune responses can be deficient HIV and AIDS HIV is transmitted in body fluids HIV infection begins a fateful struggle Can drugs and vaccines be used to fight HIV? Patterns of infectious disease Pathogens spread in four ways Diseases occur in several patterns There are many public and personal strategies for preventing infection SUMMARY Review questions self-quiz critIcal thinking explore on your own Your future Objectives Describe typical external barriers that organisms present to invading organisms. Explain how the lymphatic system contributes to the body’s defenses. Demonstrate how vertebrates (especially mammals) recognize and discriminate between self and nonself tissues. Distinguish between antibody-mediated and cell-mediated patterns of immune responses. Describe some examples of immune disorders and identify as specifically as you can which line of defense fails in each case. Describe the course of infection for HIV and list some of the potential treatments based on this progression. List the four methods by which infectious diseases are transmitted and give examples for each. Give examples of how knowledge of immune function can be used in a practical way to prevent or treat disease. Key Terms immune system antigen immunity innate immunity adaptive immunity cytokines neutrophils eosinophils basophils mast cells macrophages dendritic cells lymphocytes B and T cells lymphatic system lymph lymph vascular system lymph nodes spleen thymus lysozyme complement system membrane attack complexes inflammation histamine fever MHC markers B cell receptors T cell receptors effector cells memory cells plasma cells antibodies antibody-mediated immune response cytotoxic T cells cell-mediated immune response helper T cells antigen-presenting cell immunoglobulins apoptosis NK cells vaccine active immunity passive immunity monoclonal antibodies immunotherapy interferons multiple sclerosis allergens allergy hay fever anaphylactic shock immunological tolerance autoimmunity rheumatoid arthritis (RA) type 1 diabetes systemic lupus erythematosus (SLE) immunodeficiency severe combined immune deficiency (SCID) acquired immunodeficiency syndrome (AIDS) human immunodeficiency virus (HIV) virulence nosocomial infection epidemic pandemic sporadic disease endemic disease Lecture Outline There are a variety of pathogens that can attack the body. A healthy body is very effective at fighting off infection. Modern medical techniques can help us when the body is overcome. The immune system is responsible for protecting us from infectious agents; the more we learn about this system, the more opportunities we have to improve our health. Overview of Body Defenses Three lines of defense protect the body. Intact skin and mucous membranes are important first-line physical barriers. Innate immunity forms the second line of defense. This is non-specific. Adaptive immunity forms the third line of defense. We have many defenses to protect us from pathogens—those viruses, bacteria, fungi, protozoa, and parasitic worms that cause disease. Antigens on these pathogens identify them as nonself. Most antigens are proteins, lipids, or oligosaccharides. We are born with some general defenses and acquire other, specific ones. “Immunity” is the body’s overall ability to resist and combat anything that is nonself. Innate immunity encompasses preset responses that activate rapidly and in a generalized way to detected damage or invasion. Adaptive immunity responds to specific antigens on specific pathogens; this response takes longer to develop, but the body “remembers” what it sees and responds quicker the next time the same pathogen is presented. White blood cells and their chemicals are the defenders in immune responses. White blood cells are the core of the immune system. Phagocytes release chemicals to activate or initiate further defense responses. Cytokines regulate different aspects of the immune response; interleukins affect inflammation and fever, interferons defend against viruses, and tumor necrosis factor also affects inflammation and stimulates tumor cell death. White blood cells serve a variety of different functions in the immune response: Neutrophils make up two-thirds of all white blood cells and work at the site of inflammation or damage. Eosinophils target pathogens that are too large for the macrophages. Basophils and mast cells produce histamines in response to antigens. Macrophages are the predominant phagocytes that patrol the bloodstream. Dendritic cells signal when antigens are present in skin and body linings. B and T lymphocytes (B and T cells) function in adaptive immunity. Gender and stress influence the immune system. The Lymphatic System The lymphatic system has two key roles: to work with the cardiovascular system to cycle fluids back into the circulation and to circulate lymph from the spleen, lymph nodes, and other lymphoid tissues throughout the body. The lymph vascular system functions in drainage, delivery, and disposal. The lymph vascular system consists of lymph capillaries and other vessels linking it to the cardiovascular system. Water and solutes that drain from the blood vessels collect in the lymphatic vessels and are returned to the blood via these vessels. The lymphatic vessels pick up absorbed fats and deliver them to the blood. Lymphatic vessels also transport foreign material to the lymph nodes for disposal. Lymph capillaries and vessels are structured much like blood capillaries and veins. Lymphoid organs and lymphatic tissues are specialized for body defense. Lymph nodes are located at intervals along the lymph vessels; lymphocytes and macrophages congregate in these nodes, making them key battlefields in fighting off pathogens. The spleen filters blood and serves as a holding station for large numbers of lymphocytes. T cells are produced and become specialized in the thymus. Barriers to Infection The normal microorganisms living on your skin help prevent the growth of unwanted pathogens through competition. Some microorganisms, such as the Lactobacillus species of the vaginal tract in women, lower the pH of their surroundings to prevent growth of other microbes. The mucus coating your lungs contains enzymes such as lysozyme that can attack and destroy many bacteria; cilia can also sweep out pathogens. Chemicals in tears, saliva, and gastric fluid offer similar protection. The natural low pH of urine, as well as its flushing action, helps protect the urinary tract. Innate Immunity Circulating complement proteins can detect pathogens and become activated. Activated complement proteins attract phagocytes, which can destroy the pathogens. Activated complement proteins can also form membrane attack complexes in the pathogen; these are holes that cause the pathogen to disintegrate. Activated complement and cytokines stimulate inflammation, characterized by redness, swelling, warmth, and pain. Tissue irritation causes mast cells to release histamine and cytokines that cause the blood vessels to dilate (tissue redness and warmth) and capillary walls to become leaky (edema). Plasma proteins and phagocytes leave the blood vessels. Plasma proteins contain clotting agents that help wall off the pathogen and promote repair of tissues. Macrophages release cytokines that tell the brain to release prostaglandins, which in turn stimulates fever production; moderate fevers inhibit pathogen growth. Overview of Adaptive Defenses Adaptive immunity has four key features. Adaptive immunity is the body’s third line of defense and has four defining features: Adaptive immunity can distinguish self from nonself. Adaptive immunity is specific; each B and T cell only recognizes one antigen. Adaptive immunity is diverse; B and T cells collectively can recognize more than 2 billion different threats. Adaptive immunity has memory. Lymphocytes become specialized for different roles in adaptive immunity. Both B and T lymphocytes arise in stem cells in the bone marrow. B cells continue to develop within bone marrow. T cells travel to the thymus to finish developing; T cells divide into two populations—helper T cells and cytotoxic (“killer”) T cells. When mature, B and T cells can be found in the lymph nodes, spleen, and other lymphoid tissues where they remain “naive” until they recognize an antigen. Recognition of an antigen results in rapid cell division to produce huge numbers of identical B and T cells that recognize the stimulating antigen. Some of these new cells are effector cells that can immediately destroy pathogens. Others are memory cells, held in reserve for future battles against the same threat; memory cells are what make you “immune” to various pathogens. B cells and T cells respond to pathogens in different ways. B cells produce antibodies (proteins) and are responsible for antibody-mediated immune response. T cells directly attack invaders; their response is called cell-mediated immune response. Proteins called MHC markers label body cells as “self.” All body cells have MHC markers (from Major Histocompatibility Complex genes) to identify them as self. T cells have additional receptors that see MHC in context with antigen and respond. T cells and B cells can only “see” antigens that have been processed by an antigen-presenting cell (APC). Macrophages, dendritic cells, and B cells can all present antigen. The antigen is ingested and digested; then its fragments are linked with MHC markers and displayed on the cell’s surface as antigen-MHC complexes. Helper T cells see the antigen-MHC complex, release cytokines, and trigger repeated rounds of division to produce the large numbers of activated B and T cells. Specialization of activated cells into effector or memory cells also occurs. Antibody-Mediated Immunity: Defending Against Threats Outside Cells Antibody-mediated immune responses produce a flood of antibodies. An effector B cell is called a plasma cell; it can flood the bloodstream with antibodies. An antibody has a Y-shaped protein structure; antigens are bound by the two “arms” of the antibody. Prior to activation, B cells serve as antigen-presenting cells. Antibodies on the B cell surface bind antigens, internalize them, process them, and then display antigen-MHC complexes. Helper T cells see the antigen-MHC complex and bind; binding causes the cells to exchange signals. The T cell disengages, but the B cell is now activated; when it recognizes unbound antigen, the B cell will divide into plasma cells and memory cells. Plasma cells can release up to 2,000 antibodies per minute into the bloodstream; these antibodies “flag” invaders for destruction by phagocytes and complement. There are five classes of antibodies, each with a particular function. Collectively, antibodies are referred to as immunoglobulins, or Igs. The five different classes of Igs are the protein products of gene shuffling that takes place as the B cells mature: IgM antibodies cluster into a structure with 10 binding sites, making them more efficient at binding clumped targets; IgM is the first antibody produced in a response. IgD is the most common antibody bound to naive B cells; it may help activate T cells. IgG antibodies neutralize toxins, turn on complement, are long lasting, can cross the placenta, and are found in mother’s milk. IgA antibodies are present in secretions of exocrine glands (tears, saliva, and breast milk) and in the mucus of the respiratory, digestive, and reproductive tracts. IgE antibodies are involved in allergic reactions; they bind to basophils and mast cells where they act as traps for antigen, causing the release of histamine. Cell-Mediated Responses: Combating Threats Inside Cells Cell-mediated responses fight those pathogens (viruses, bacteria, and some fungi and protozoans) that can enter cells to avoid antibody defenses; cell-mediated responses also fight abnormal body cells such as cancer cells. APCs present antigen to T cells, similar to their role in antibody-mediated immunity. Helper T cells can be stimulated this way to divide into effector and memory cells. Effector helper T cells or APCs directly can stimulate cytotoxic T cells to divide. Cytotoxic T cells rapidly multiply and release molecules that can “touch-kill” infected and abnormal body cells. Cytotoxic T cells also secrete chemicals that stimulate apoptosis—the programmed cell death of the infected cell. Helper T cells can also stimulate NK cells; they will attack any cell that has too few or altered MHC, any cells that have been tagged by antibodies, and cells showing “stress markers” as indicators of infection or cancer. Cytotoxic T cells cause the body to reject transplanted tissue. During organ transplants, donor tissues must be matched to a recipient to ensure that the MHC markers do not differ enough to stimulate rejection by cytotoxic T cells. Donor and recipient usually must share at least 75% of their MHC markers for the transplant to succeed; close relatives make the best donors because of this. Recipients usually also take drugs to suppress the immune system to prevent rejection; often they will also take antibiotics to ward off potential infections. Tissues of the eye and testicles do not stimulate rejection; instead, cells of these tissues secrete signals that cause lymphocytes to undergo apoptosis, thus preventing the lymphocytes from attacking. Applications of Immunology Vaccination stimulates immunity. Immunization increases immunity against specific diseases. In active immunization, a vaccine is given by injection or is taken orally. The first dose of vaccine elicits a primary immune response; a second dose (“booster”) elicits a secondary, and more long-lasting, response. Vaccines are made from killed or very weak pathogens, inactivated forms of toxins, or transgenic (genetically engineered) viruses. Antibodies provide “borrowed” immunity. Passive immunization involves injecting antibodies into already infected individuals. Vaccines are not risk free. Monoclonal antibodies are used in research and medicine. Monoclonal antibodies are antibodies made by cells cloned from a single antibody-producing B cell; they are generally produced using genetically altered bacteria or sometimes plants. Monoclonal antibodies are being used commercially in home pregnancy tests, screening for prostate cancer, and other uses. Immunotherapies reinforce defenses. Immunotherapy alters the body’s own immune mechanisms to enhance defense against infections and cancer. Cytokines can be used to activate B and T cells to fight cancer. Monoclonal antibodies can be used to bind to proteins on cancer cells to draw NK cells to the tumor. Other monoclonal antibodies are bound to toxins to make immunotoxins; these substances bind to cancer cells, enter them, and prevent growth. These are being tested as treatment for HIV. Gamma interferon, produced by T cells, stimulates NK cells and boosts activity of macrophages; it is currently being used to treat hepatitis C. Beta interferon is being used to treat multiple sclerosis. Immune System Disorders In allergies, harmless substances provoke an immune attack. An allergy is an immune response to a normally harmless substance, called an allergen. Allergens include: pollen, some foods and drugs, dust mites, fungal spores, insect venom, and certain ingredients in cosmetics. Allergens trigger mild to severe inflammation of various tissues. A variety of causes, from genetic to stress, lead to allergies. Exposure to an allergen triggers production of IgE antibodies, which cause the release of histamines and prostaglandins from mast cells. Histamines and prostaglandins fuel inflammation. Hay fever manifests as stuffed sinuses, a drippy nose, and sneezing. In a few individuals, explosive inflammatory responses trigger life-threatening anaphylactic shock in which air passages constrict and fluid rushes out of the capillaries. Serious allergies, such as peanut allergies and wasp and bee venom allergies, can trigger anaphylactic shock. Rapid injections of the hormone epinephrine can prevent shock and save lives. Antihistamines are often used to relieve the short-term symptoms of allergies; desensitization can be used to “train” the body not to see allergens. Autoimmune disorders attack “self.” In an autoimmune response, lymphocytes turn against the body’s own cells. Examples of autoimmune diseases include the following: Rheumatoid arthritis, an inflammation of the joints caused by immune attack against collagen and antibodies in the joints; inflammation, complement, and faulty repair mechanisms contribute to the damage. Type 1 diabetes is a type of diabetes mellitus, caused when the immune system attacks and destroys the insulin-secreting cells of the pancreas, impairing glucose absorption from the blood. Systemic lupus erythematosus causes patients to develop antibodies to their own DNA and other “self” components. Autoimmune diseases tend to be more frequent in women than in men. Immune responses can be deficient. Immunodeficiency is used to describe the state when a person’s immune system is weakened or lacking; under these conditions the body is vulnerable and infections that would normally not be serious become life threatening. In severe combined immune deficiency (SCID) both B and T cells are in low numbers; infants born with SCID usually die early in life. In acquired immune deficiency syndrome (AIDS), the HIV virus attacks the body’s macrophages and helper T cells, crippling the immune response. HIV and AIDS Definitions of the well-known acronyms. AIDS – acquired immune deficiency syndrome. A group of diseases characterized by an infection with HIV. Other characteristics include depressed immune system and one or more indicator diseases. HIV – human immunodeficiency virus. No way to rid the body of this virus. Estimated over 38 million worldwide are infected. HIV is transmitted in body fluids. Blood and semen are most common. Sexual contact is most common delivery method. Anything that damages mucous linings increases chances of infection. The virus is not transmitted in food, air, water, insect bites, by casual contact, or in urine. Half those infected are women. Some from IV drug use. Most from sexual contact with infected men. HIV infection begins a fateful struggle. HIV is a retrovirus. The enzyme reverse transcriptase is used to read the RNA and create DNA that encodes for the viral proteins. This virus targets cells with a specific MHC receptor—the CD4+ receptor; often helper-T cells. Infected cells cease to do the jobs for which they are designed and spend all their time making the virus. First symptoms are flu-like. Adaptive immune response results in antibodies that fight and can be detected in the blood when tested. Eventually the immune system loses the fight, the number of healthy helper-T cells drops, and the individual has a difficult time fighting of other infections. Can drugs and vaccines be used to help fight HIV? Protease inhibitors block the enzyme needed to assemble new virus particles. Most effective is a drug “cocktail” of several drugs combined. Making an HIV vaccine is tricky because the virus mutates so quickly. Several trials are underway. The best defense is currently education about how to avoid acquiring the virus. Patterns of Infectious Disease Pathogens are measured by their virulence. Different pathogens have different abilities to make a human ill. Virulence is determined by three factors: How fast the pathogen can infect tissues. How much damage the pathogen causes. Which tissues the pathogen infects. Pathogens spread in four ways. Direct contact involves body fluids. Indirect contact involves touching inanimate (non-living) objects. Inhaling airborne pathogens is the most common method of transmission. Contact with a vector that carries the pathogen to a new home. The vector is often a critical part of the lifecycle of the pathogen. Common vectors include mosquitoes, flies, ticks, and fleas. Conditions in hospitals can result in nosocomial infections. Diseases occur in several patterns. An epidemic is widespread in greater numbers than expected. Pandemic diseases are spread worldwide. Sporadic diseases are irregularly occurring in few people. Endemic diseases are continually present in a population. There are many public and personal strategies for preventing infection. Prevention is always the best strategy. Hand washing tops the list. Public methods include vaccines, testing blood supplies, treating food products, and education. Suggestions for Presenting the Material The understanding of defense against foreign organisms by the human body is complicated by the fact that so many mechanisms and factors are operating at the same time. One approach is to compare the textbook author’s “lines of defense” to the military defense of a country. There are many analogies such as “general barriers” (moats were once a very useful 1st line of defense) and as is burning a city (think of General Sherman). Missiles are very specific, fairly accurate, and may be used to describe acquired immunity. Using animations from the text or toys as models will help students visualize the process of immune stimulation; interlocking toys often work well for this exercise. Students sometimes have difficulty distinguishing “antibody” from “antigen.” This may help: antigen is short for ANTIbody GENerator. The topics of immunization and immune diseases are always of interest to students and should be given sufficient time to allow for student discussion. When discussing disease transmission it works best to select diseases students are familiar with or which are common to the area or age group. Classroom and Laboratory Enrichment While being careful to not exploit any individual, the suffering and death of a victim of AIDS (or a similar disease) will serve as an attention-getter for this topic. Ryan White’s story gripped the nation in the 1980s. Magic Johnson’s story is another that would be useful to share. Tracking down the cause of an annoying allergy can involve some real detective work. Survey the class for such an experience, and ask for a brief oral report if the person is willing to share his/her experience. Many students will be familiar with allergic reactions resulting in itching. Use examples of short-term reactions (like to mosquito bites) and delayed reaction (like poison ivy) and relate these to the adaptive defenses involved. Compare labels of over-the-counter treatments to determine which medicine works best for each type of reaction. Are insect bodies filth carriers? Attempt to answer this by letting different insects including a cockroach, house fly, and cricket crawl over the surface of an agar-filled Petri dish. Investigate the relative cleanliness of a dog’s mouth. Classroom Discussion Ideas Do you think medical advances or the immune system are more responsible for the low rate of death by infection seen today? Where does our term “vaccination” derive its meaning? Was it first used as a medical term as it now is? Every year a small number of children die from diseases that develop as a result of vaccines received to protect them. It seems to be an inherent hazard associated with mass preventative inoculation. Is it worth the risk? Can you debate both sides of the issue? Thomas Malthus proposed three “grim reapers” that would restrain human population growth. One of these was “pestilence,” or disease. How effective is disease as a population-limiting factor in the developed countries versus the underdeveloped countries? If there are so many infectious people as patients in hospitals, why are doctors and nurses not continuously ill? There are alarming reports of widespread resistance of pathogens to antibiotics. Speculate on the significance of this to the general public and to healthcare workers specifically. One growing source of organs for transplantation comes from “living donation” rather than from cadavers. Altruism is generally cited when the gift is between family members, but some advocate allowing individuals to sell their organs to strangers. The need for organs is constantly growing, so should a free market approach to organ procurement be considered? What could be the immunological risks of such a free market? Although they may not occur in your region of the world, there are many diseases such as malaria and Chagas disease that have a significant impact on the economy of a region. Discuss ways to help reduce the impact that occurs from the loss of healthy workers. Term Paper Topics, Library Activities, and Special Projects Controversy still surrounds the polio vaccines of Salk and Sabin. Explore the details of how each of these vaccines is made and used. Include the advantages and disadvantages of each. Research on the cause and treatment of AIDS has been rapid and continues to progress. Report on the latest strategies. Use Scientific American, October 1988 issue, for background material, the August 1998 issue, and the January 2010 issue of the same magazine for an update. What does the most recent literature of 2012 have to say? Although vaccines are available throughout the world for the prevention of measles, diphtheria, and polio, there are about 20 other infectious diseases for which vaccines could be developed. However, there seems to be little incentive on the part of pharmaceutical companies to do so. Report on the reasons why this is so. Smallpox has been conquered by effective vaccination programs; polio came close to eradication, but control efforts are slipping. Prepare a report on the development of the vaccine for either of these diseases; be sure to include the chronology of events leading up to the marketing of the vaccine. Discuss where the world stands today in terms of polio eradication. Several infectious diseases are considered potential bioterrorism weapons. Investigate which ones are highest on these lists, how they might be used, and what is being (or can be) done to prevent it. Report on the difficulties and successes in the development of a vaccine for malaria. Gene therapy is currently being used to cure children of SCID. However, some “successes” have now been linked to the development of cancer in these children. Report on the current status of this therapy and the evidence linking gene therapy to cancer. Videos, Animations, and Websites VIDEOS Films for the Humanities and Sciences Our Immune System http://ffh.films.com/id/7927/Our_Immune_System.htm Films for the Humanities and Sciences The Human Immune Systems: The Fighting Edge (immunodeficiency) http://ffh.films.com/id/2279/The_Human_Immune_System_The_Fighting_Edge.htm Films for the Humanities and Sciences HIV and Me: A Global Exploration with Stephen Fry. http://ffh.films.com/id/15939/HIV_and_Me_A_Global_Exploration_with_Stephen_Fry.htm ADAM – Immune Response An overview of the immune system http://www.pennmedicine.org/encyclopedia/em_DisplayAnimation.aspx?gcid=000073&ptid=17 ANIMATIONS PBS NOVA – Making Vaccines Interactive animation on making vaccines. http://www.pbs.org/wgbh/nova/body/making-vaccines.html NobelPrize.org – Immune Response Interactive animation on the immune system http://www.nobelprize.org/educational/medicine/immuneresponses/game/index.html#/plot1 WEBSITES University of Hartford Complete study of the immune system with an introduction, the fluid systems, innate immunity and adaptive or acquired immunity. http://uhaweb.hartford.edu/bugl/immune.htm Cells Alive! – Immunology A number of specific types of incidents that may illicit an immune response are used to help understand the complexity of the topic. http://www.cellsalive.com/toc_immun.htm Possible Responses to Review Questions The “sting” of the jellyfish causes inflammation accompanied by the visible signs of redness, swelling, warmth, and pain. The sting causes damage that is a signal for the inflammation process to begin. Mast cells in the tissue release histamine, triggering vasodilation (redness and warmth) and capillary permeability. Water, plasma proteins, and cells leak out of the capillaries causing swelling (edema) and pain. Clotting factors may wall off the area while factors in the blood attempt to neutralize the toxin from the jellyfish. Neutrophils are the first white blood cells to respond in inflammation responses; while macrophages are also phagocytes, they arrive later and are also involved in antigen presentation. Cytotoxic T cells respond to specific antigens and kill infected cells; natural killer cells are innate responders that also kill cells, but do not require specific antigen stimulation. Effector cells “effect” an outcome—plasma cells secrete antibodies and cytotoxic T cells kill cells. Memory cells “remember” the primary response and are activated upon secondary exposure; they stimulate a quicker immune response, including more memory. Antigens are parts of molecules that are not “self.” In the body, antigens are recognized by antibodies, produced by B cells, and removed by them. Innate immunity is a second line of defense that uses general reactions to limit invasion or tissue damage; the responses are essentially non-specific. Adaptive immunity specifically responds to identified antigens in a particular way, through the generation of B cells, antibodies, and T cells geared toward removing the antigen. An allergy is a response to an allergen, an otherwise benign antigen in the environment; allergies are thus stimulated by something outside the body. Autoimmune responses are internal; they are self-directed immune responses that damage tissues without antigen being present. Basically the immune cells fail to recognize “self” and attack its own body tissue. Possible Responses to Critical Thinking Questions The cardiovascular system and lymphatic system are intimately linked; what flows through one system will sooner or later end up in the other. Gum disease is a usually long-term infection, difficult to get rid of and heal. Inflammatory mediators are thus going to be present in the body for long periods of time. Since lymph ultimately makes it into the blood, and since all blood passes through the heart, it is not difficult to see that the heart could end up being exposed not only to bacteria from the gums, but at a minimum to at least a low level of inflammatory mediators. Over time both will stimulate inflammation in the heart itself and this ultimately can create problems in heart function, perhaps severe enough to cause a heart attack. We know that the antigens from foreign invaders are displayed on the surface of memory cells to be recognized by other members of the “defense team.” If a mutated form of the virus invades the body, the memory cells from the prior invasion(s) will not recognize it. New cells must be produced that will recognize this new form of the virus. When transplanting organs, physicians always face the problem of rejection by the recipient’s immune system. The usual procedure is to give drugs that reduce the recipient’s rejection by compromising the immune system’s response. Of course, this reduction also makes the recipient more susceptible to opportunistic infections that surround us every day. Any advances that would allow the acceptance of foreign tissue without causing reduction in immune response would be welcomed. Elena did not develop chicken pox when exposed to her infected children because her body retained memory cells (lymphocytes) that recognized the antigen and mounted a defensive action so quickly and effectively that she did not even realize it was occurring. Today Edward Jenner’s experiment would not be permitted because it represents a violation of protocols for safe human experimentation established following the Nazi trials at Nuremberg after World War II. One part of the Nuremberg Code, as it is called, is called informed consent, where individuals participating in experiments must be made aware of the risks they incur. Another part of the code, however, deals with the concept of risk itself. It is not permitted to directly test any vaccine on humans unless it has first been shown to be safe in animals and through other experiments. Furthermore, children are viewed as a “special case” in terms of human experimentation; drugs and vaccines are routinely tested on healthy adult volunteers well before they are ever tested on children. Possible Responses to Explore on Your Own Questions The requirement for TB varies widely from state-to-state and to some degree will depend on the relative number of immigrants from certain countries known to carry high rates of TB infection. TB essentially exists in two forms in the population: active TB, which involves symptoms and which can be passed on, and inactive TB, where the bacterium is present in the lungs but dormant. Active cases need to be treated, but there is some question as to whether inactive cases need to be. Treatment is long, expensive, and often unpleasant. Some forms of TB are also resistant to standard therapies. Public health authorities believe it is important to trace TB cases because of the problem of resistance, the communicability of the disease, and the threat to those of immunocompromised status, particularly AIDS patients. 120 Chapter Nine Immunity and Disease 93 120 Chapter Nine Immunity and Disease 119 120 Chapter Nine Immunity and Disease 119 120 Chapter Nine Immunity and Disease 119 120 Chapter Nine Immunity and Disease 119