346 ✦ CHAPTER SEVENTEEN C hapter 5 presents a rather frightening list of harmful organisms that surround us in our environment. For- tunately, most of us survive contact with these invaders Finally, an individual’s condition, or predisposition, to infection is also important. Disease organisms are around us all the time. Why does a person only occasion- and even become more resistant to disease in the process. ally get a cold, flu, or other infection? Part of the answer The job of protecting us from these harmful agents be- lies in the person’s condition, as influenced by general longs in part to certain blood cells and to the lymphatic physical and emotional health, nutrition, living habits, system, which together make up our immune system. and age. The immune system is part of our general body de- Checkpoint 17-1 What are some factors that influence the oc- fenses against disease. Some of these defenses are non- currence of infection? specific; that is, they are effective against any harmful agent that enters the body. Other defenses are referred to as specific; that is, they act only against a certain agent and no others. ◗ Nonspecific Defenses The features that protect the body against disease are usu- ally considered as successive “lines of defense,” beginning ◗ Why Do Infections Occur? with the relatively simple or outer barriers and proceed- Although the body is constantly exposed to pathogenic ing through progressively more complicated responses invasion, many conditions determine whether an infec- until the ultimate defense mechanism—immunity—is tion will actually occur. Pathogens have a decided prefer- reached. ence for certain body tissues and must have access to these tissues. Some viruses attack only nervous tissue. Chemical and Mechanical Barriers The poliovirus, for example, may be inhaled or swallowed Part of the first line of defense against invaders is the skin, in large numbers and therefore may come into direct con- which serves as a mechanical barrier as long as it remains tact with the mucous membranes lining the respiratory intact. A serious danger to burn victims, for example, is and digestive tracts, yet it causes no apparent disorder of the risk of infection as a result of skin destruction. these tissues. In contrast, the viruses that cause influenza The mucous membranes that line the passageways and the common cold do attack these mucous mem- leading into the body also act as barriers, trapping foreign branes. HIV, the virus that causes AIDS, attacks a certain material in their sticky secretions. The cilia in membranes type of T cell (lymphocyte), which has surface receptors in the upper respiratory tract help to sweep impurities for the virus. out of the body. The portal of entry is an important condition influ- Body secretions, such as tears, perspiration, and encing the occurrence of infection. The respiratory tract saliva, wash away microorganisms and may contain acids, is a common entrance route for pathogens. Other impor- enzymes, or other chemicals that destroy invaders. Diges- tant avenues of entry include the digestive system and the tive juices destroy many ingested bacteria and their tox- tubes that open into the urinary and reproductive sys- ins. tems. Any break in the skin or in a mucous membrane al- Certain reflexes aid in the removal of pathogens. lows organisms such as staphylococci easy access to Sneezing and coughing, for instance, tend to remove for- deeper tissues and may lead to infection, whereas unbro- eign matter, including microorganisms, from the upper ken skin or mucous membranes are usually not affected. respiratory tract. Vomiting and diarrhea are ways in The virulence (VIR-u-lens) of an organism, or the or- which toxins and bacteria may be expelled. ganism’s power to overcome its host’s defenses, is another important factor. Virulence has two aspects: one may be Checkpoint 17-2 What tissues constitute the first line of de- thought of as “aggressiveness,” or invasive power; the fense against the invasion of pathogens? other is the organism’s ability to produce toxins (poi- sons) that damage the body. Different organisms vary in Phagocytosis virulence. The virulence of a specific organism also can change; the influenza virus, for example, can be more Phagocytosis is part of the second line of defense against dangerous in some years than in others. Organisms may invaders. In the process of phagocytosis, white blood cells gain virulence as they pass from one infected host to an- take in and destroy waste and foreign material (see Fig. other. 13-6 in Chapter 13). Neutrophils and macrophages are The dose (number) of pathogens that invade the body the main phagocytic white blood cells. Neutrophils are a also is a determining factor in whether or not an infection type of granular leukocyte. Macrophages are derived from develops. Even if the virulence of a particular organism monocytes, a type of agranular leukocyte. Both types of happens to be low, infection may occur if a large number cells travel in the blood to infection sites. Some of the enter the body. macrophages remain fixed in the tissues, for example, in BODY DEFENSES, IMMUNITY, AND VACCINES ✦ 347 the skin, liver, lungs, lymphoid tissue, and bone marrow, enlarged and tender, a sign that they are performing their to fight infection and remove debris. protective function by working overtime to produce phagocytic cells that “clean” the lymph flowing through Natural Killer Cells them. The natural killer (NK) cell is a type of lymphocyte dif- ferent from those active in specific immunity, which are Fever described later. NK cells can recognize body cells with ab- An increase in body temperature above the normal range normal membranes, such as tumor cells and cells infected can be a sign that body defenses are at work. When with virus, and, as their name indicates, can destroy them phagocytes are exposed to infecting organisms, they re- on contact. NK cells are found in the lymph nodes, lease substances that raise body temperature. Fever spleen, bone marrow, and blood. They destroy abnormal boosts the immune system in several ways. It stimulates cells by secreting a protein that breaks down the cell phagocytes, increases metabolism, and decreases certain membrane, but the way in which they find their targets is organisms’ ability to multiply. not yet completely understood. A common misperception is that fever is a dangerous symptom that should always be eliminated. Control of Inflammation fever in itself does little to alter the course of an illness. Healthcare workers, however, should always be alert to Inflammation is the body’s effort to get rid of anything fever development as a possible sign of a serious disorder that irritates it or, if this is not possible, to limit the harm- and should recognize that an increased metabolic rate ful effects of the irritant. Inflammation can occur as a may have adverse effects on the hearts of weak patients. result of any irritant, not only microorganisms. Friction, fire, chemicals, x-rays, and cuts or blows all can be clas- sified as irritants. If irritation is caused by pathogenic in- Interferon vasion, the resulting inflammation is termed an infection. Certain cells infected with a virus release a substance that With the entrance of pathogens and their subsequent prevents nearby cells from producing more virus. This multiplication, a whole series of defensive processes be- substance was first found in cells infected with influenza gins. This inflammatory reaction is accompanied by four virus, and it was called interferon because it “interferes” classic symptoms: heat, redness, swelling, and pain, as de- with multiplication and spread of the virus. Interferon is 17 scribed below. now known to be a group of substances. Each is abbrevi- When tissues are injured, histamine (HIS-tah-mene) ated IFN with a Greek letter, alpha ( ), beta ( ), or and other substances are released from the damaged cells, gamma ( ) to indicate the category of interferon and ad- causing the small blood vessels to dilate (widen). More ditional letters or numbers to indicate more specific blood then flows into the area, resulting in heat, redness, types, such as 2a or 1b. and swelling. Pure interferons are now available in adequate quan- With the increased blood flow come a vast number of tities for treatment because they are produced by genetic leukocytes. Then a new phenomenon occurs: the walls of engineering in microorganisms. They are used to treat the tiny blood vessels become “coarsened” in texture (as certain viral infections, such as hepatitis. Interferons are does a piece of cloth when it is stretched). Blood flow also of interest because they act nonspecifically on cells of slows down, and the leukocytes move through these al- the immune system. They have been used with varying tered walls and into the tissue, where they can reach the success to boost the immune response in the treatment of irritant directly. Fluid from the blood plasma also leaks malignancies, such as melanoma, leukemia, and Kaposi out of the vessels into the tissues and begins to clot. sarcoma, a cancer associated with AIDS. Interestingly, in- When this response occurs in a local area, it helps terferon is used to treat the autoimmune disorder mul- prevent the spread of the foreign agent. The mixture of tiple sclerosis (MS), because it stimulates cells that de- leukocytes and fluid, the inflammatory exudate, causes press the immune response. pressure on the nerve endings, which combined with the increased amount of blood in the vessels, causes the pain Checkpoint 17-3 What are some nonspecific factors that help of inflammation. to control infection? As the phagocytes do their work, large numbers of them are destroyed, so that eventually the area becomes filled with dead leukocytes. The mixture of exudate, liv- ◗ Immunity ing and dead white blood cells, pathogens, and destroyed tissue cells is pus. Immunity is the final line of defense against disease. Im- Meanwhile, the lymphatic vessels begin to drain fluid munity to disease can be defined as an individual’s power from the inflamed area and carry it toward the lymph to resist or overcome the effects of a particular disease nodes for filtration. The regional lymph nodes become agent or its harmful products. In a broader sense, the im- 348 ✦ CHAPTER SEVENTEEN mune system will recognize any foreign material and at- Some members of a given group have a more highly tempt to rid the body of it, as occurs in tissue transplan- developed individual immunity to specific diseases. For tation from one individual to another. Immunity is a se- example, some people are prone to cold sores (fever blis- lective process; that is, immunity to one disease does not ters) caused by herpes virus, whereas others have never necessarily cause immunity to another. This selective shown signs of this type of infection. Newspapers and characteristic is called specificity (spes-ih-FIS-ih-te). magazines sometimes feature the advice of an elderly per- There are two main categories of immunity: son who is asked to give his or her secret for living to a ripe old age. Some elderly people may say that they lived ◗ Inborn immunity is inherited along with other charac- a carefully regulated life with the right amount of rest, ex- teristics in a person’s genes. ercise, and work, whereas others may boast of drinking ◗ Acquired immunity develops after birth. Acquired im- alcohol, smoking, not exercising, and other kinds of un- munity may be obtained by natural or artificial means; healthy behavior. However, it is possible that the latter in addition, acquired immunity may be either active or group resisted infection and maintained health despite passive. their habits, rather than because of them, thanks to in- herited resistance factors. Figure 17-1 summarizes the different types of immu- nity. Refer to this diagram as we investigate each category Acquired Immunity in turn. Unlike inborn immunity, which is due to inherited fac- tors, acquired immunity develops during a person’s life- Inborn Immunity time as that person encounters various specific harmful Both humans and animals have what is called a species agents. immunity to many of each other’s diseases. Although cer- If the following description of the immune system tain diseases found in animals may be transmitted to hu- seems complex, bear in mind that from infancy on, your mans, many infections, such as chicken cholera, hog immune system is able to protect you from millions of cholera, distemper, and other animal diseases, do not af- foreign substances, even synthetic substances not found fect human beings. However, the constitutional differ- in nature. All the while, the system is kept in check, so ences that make human beings immune to these disorders that it does not usually overreact to produce allergies or also make them susceptible to others that do not affect mistakenly attack and damage your own body tissues. different species. Such infections as measles, scarlet fever and diphtheria do not appear to affect animals who come Checkpoint 17-4 What is the difference between inborn and acquired immunity? in contact with infected humans. Antigens An antigen (AN-te-jen) Immunity (Ag) is any foreign substance that en- ters the body and induces an immune response. (The word is formed from Inborn Acquired antibody gen because an antigen stimulates production of antibody.) Species Most antigens are large protein mole- Individual cules, but carbohydrates and some lipids may act as antigens. Antigens Natural Artificial may be found on the surface of patho- genic organisms, on the surface of red blood cells and tissue cells, on pollens, in toxins, and in foods. The critical feature of any substance described as Active Passive Active Passive an antigen is that it stimulates the ac- tivity of certain lymphocytes classified Contact with Placenta Vaccine: Immune as T or B cells. the disease Mother's milk Killed serum Attenuated T Cells Both T and B cells come from Toxoid hematopoietic (blood-forming) stem Component cells in bone marrow, as do all blood Recombinant DNA cells. The T and B cells differ, how- ever, in their development and their Figure 17-1 Types of immunity. method of action. Some of the imma- BODY DEFENSES, IMMUNITY, AND VACCINES ✦ 349 ture stem cells migrate to the thymus and become T cells, cytic vesicles (Fig. 17-2). They then insert fragments of which constitute about 80% of the lymphocytes in the cir- the foreign antigen into their plasma membrane. The for- culating blood. While in the thymus, these T lymphocytes eign antigens are displayed on the macrophage’s surface multiply and become capable of combining with specific in combination with antigens that a T cell can recognize foreign antigens, at which time they are described as sen- as belonging to the “self.” Self antigens are known as sitized. These thymus-derived cells produce an immunity MHC (major histocompatibility complex) antigens be- that is said to be cell-mediated immunity. cause of their importance in cross-matching for tissue There are several types of T cells, each with different transplantation. They are also known as HLAs (human functions. The different types of T cells and some of their leukocyte antigens), because white blood cells are used in functions are as follows: testing tissues for compatibility. Macrophages and other cells that present antigens to T cells are known as APCs ◗ Cytotoxic T cells (Tc) destroy foreign cells directly. (antigen-presenting cells). ◗ Helper T cells (Th)release substances known as inter- For a T cell to react with a foreign antigen, that anti- leukins (in-ter-LU-kinz) (IL) that stimulate other lym- gen must be presented to the T cell along with the MHC phocytes and macrophages and thereby assist in the de- proteins. A special receptor on the T cell must bind with struction of foreign cells. (These substances are so both the MHC protein and the foreign antigen fragment named because they act between white blood cells). (see Fig. 17-2). The activated Th then produces inter- There are several subtypes of these helper T cells, one leukins (ILs), which stimulate other leukocytes, such as of which is infected and destroyed by the AIDS virus B cells. There are many different types of interleukins, (HIV). The HIV-targeted T cells have a special surface and they participate at different points in the immune re- receptor (CD4) to which the virus attaches. sponse. They are produced by white cells and also by fi- ◗ Regulatory T cells (Treg) suppress the immune re- broblasts (cells in connective tissue that produce fibers) sponse in order to prevent overactivity. These T cells and by epithelial cells. Because ILs stimulate the cells ac- may inhibit or destroy active lymphocytes. tive in immunity, they are used medically to boost the im- ◗ Memory T cells remember an antigen and start a rapid mune system. response if that antigen is contacted again. Checkpoint 17-5 What is an antigen? The T cell portion of the immune system is generally responsible for defense against cancer cells, certain 17 Checkpoint 17-6 List four types of T cells. viruses, and other pathogens that grow within cells (in- tracellular parasites), as well as for the rejection of tissue transplanted from another person. B Cells and Antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a substance pro- The Role of Macrophages Macrophages are phago- duced in response to an antigen. Antibodies are manufac- cytic white blood cells derived from monocytes (their tured by B cells (B lymphocytes), another type of lym- name means “big eater”). They act as processing centers phocyte active in the immune system. These cells must for foreign antigens. They ingest foreign proteins, such as mature in the fetal liver or in lymphoid tissue before be- disease organisms, and break them down within phago- coming active in the blood. Foreign antigen T cell receptor Helper T cell MHC protein Antigen fragment Activated helper Lysosome Phagocytic vesicle T cell Interleukin 1 Macrophage ingests 2 Macrophage presents 3 Activated T cell foreign antigen antigen fragment with produces interleukin, MHC proteins to which stimulates helper T cell other leukocytes Figure 17-2 Activation of a helper T cell by a macrophage (antigen-presenting cell). ZOOMING IN ✦ What is contained in the lysosome that joins the phagocytic vesicle? 350 ✦ CHAPTER SEVENTEEN Box 17-1 provides further information about the different types of antibodies. Some antibodies produced by B cells remain in the blood to give long- term immunity. In addition, some of B cell with specific antigen receptor the activated B cells do not become plasma cells but, like certain T cells, become memory cells. On repeated B cell binds to antigen contact with an antigen, these cells are ready to produce antibodies immedi- ately. Because of this “immunologic memory,” one is usually immune to a Activated childhood disease after having it. B cell multiplies Checkpoint 17-7 What is an antibody? Checkpoint 17-8 What type of cells pro- duce antibodies? The Antigen–Antibody B Reaction memory The antibody that is produced in re- cells sponse to a specific antigen, such as a Plasma bacterial cell or a toxin, has a shape cells that matches some part of that antigen, much in the same way that the shape of a key matches the shape of its lock. The antibody can bind specifically to the antigen that caused its production and thereby destroy or inactivate it. Antigen–antibody interactions are il- lustrated and their protective effects are described in Table 17-1. Complement The destruction of Antibodies foreign cells sometimes requires the en- Figure 17-3 Activation of B cells. The B cell combines with a specific antigen. The zymatic activity of a group of nonspe- cell divides to form plasma cells, which produce antibodies. Some of the cells develop cific proteins in the blood, together into memory cells, which protect against reinfection. ZOOMING IN ✦ What two types called complement. Complement pro- of cells develop from activated B cells? teins are always present in the blood, but they must be activated by antigen– antibody complexes or by foreign cell B cells have surface receptors that bind with a specific surfaces. Complement is so named because it assists with type of antigen (Fig. 17-3). Exposure to the antigen stim- immune reactions. Some of the actions of complement are: ulates the cells to multiply rapidly and produce large ◗ It coats foreign cells to help phagocytes recognize and numbers (clones) of plasma cells. Plasma cells produce engulf them. antibodies against the original antigen and release these ◗ It destroys cells by forming complexes that punch holes antibodies into the blood, providing the form of immu- in plasma membranes. nity described as humoral immunity (the term humoral ◗ It promotes inflammation by increasing capillary per- refers to body fluids). meability. Humoral immunity generally protects against circulating ◗ It attracts phagocytes to an area of inflammation. antigens and bacteria that grow outside the cells (extracellu- lar pathogens). All antibodies are contained in a portion of Checkpoint 17-9 What is complement? the blood plasma called the gamma globulin fraction. BODY DEFENSES, IMMUNITY, AND VACCINES ✦ 351 Box 17-1 A Closer Look Antibodies: A Protein Army That Fights Disease A ntibodies are proteins secreted by plasma cells (activated B cells) in response to specific antigens. They are all con- tained in a fraction of the blood plasma known as gamma immunoglobulins that vary in molecular size and in function (see below). Studies of these antibody fractions can be helpful in making a diagnosis. For example, high levels of IgM anti- globulin. Because the plasma contains other globulins as well, bodies, because they are the first to be produced in an immune antibodies have become known as immunoglobulins (Ig). Im- response, indicate a recent infection. munologic studies have shown that there are several classes of CLASS ABUNDANCE CHARACTERISTICS AND FUNCTION IgG 75% Found in the blood, lymph, and intestines Enhances phagocytosis, neutralizes toxins, and activates complement Crosses the placenta and confers passive immunity from mother to fetus IgA 15% Found in glandular secretions such as sweat, tears, saliva, mucus, and digestive juices Provides local protection in mucous membranes against bacteria and viruses Also found in breast milk, providing passive immunity to newborn IgM 5–10% Found in the blood and lymph The first antibody to be secreted after infection Stimulates agglutination and activates complement IgD 1% Located on the surface of B cells 17 IgE 0.1% Located on basophils Active in allergic reactions and parasitic infections Naturally Acquired Immunity infant for about 6 months, at which time the child’s own immune system begins to function. Nursing an infant can Immunity may be acquired naturally through contact lengthen this protective period because of the presence of with a specific disease organism, in which case, antibod- specific antibodies in breast milk and colostrum (the first ies manufactured by the infected person’s cells act against breast secretion). These are the only known examples of the infecting agent or its toxins. The infection that trig- naturally acquired passive immunity. gers the immunity may be so mild as to cause no symp- toms (subclinical). Nevertheless, it stimulates the host’s Checkpoint 17-10 What is the difference between the active cells to produce an active immunity. and passive forms of naturally acquired immunity? Each time a person is invaded by disease organisms, his or her cells manufacture antibodies that provide im- munity against the infection. Such immunity may last for Artificially Acquired Immunity years, and in some cases for life. Because the host is ac- A person who has not been exposed to repeated small tively involved in the production of antibodies, this type doses of a particular organism has no antibodies against of immunity is called active immunity. See Box 17-2 for that organism and may be defenseless against infection. information on how stress affects the immune system. Therefore, medical personnel may use artificial measures Immunity also may be acquired naturally by the pas- to cause a person’s immune system to manufacture anti- sage of antibodies from a mother to her fetus through the bodies. The administration of virulent pathogens obvi- placenta. Because these antibodies come from an outside ously would be dangerous. Instead, laboratory workers source, this type of immunity is called passive immunity. treat the harmful agent to reduce its virulence before it is The antibodies obtained in this way do not last as long as administered. In this way, the immune system is made to actively produced antibodies, but they do help protect the produce antibodies without causing a serious illness. This 352 ✦ CHAPTER SEVENTEEN protective process is known as vacci- Table 17•1 Antigen-Antibody Interactions and Their nation (vak-sin-A-shun), or immu- Effects nization, and the solution used is Interaction Effects called a vaccine (vak-SENE). Ordinar- ily, the administration of a vaccine is Prevention of attachment A pathogen coated with antibody is a preventive measure designed to pro- Antibody prevented from attaching to a cell. vide protection in anticipation of inva- Virus sion by a certain disease organism. Originally, the word vaccination meant inoculation against smallpox. Clumping of antigen Antibodies can link antigens together, (The term even comes from the Latin forming a cluster that phagocytes word for cow, referring to cowpox, Foreign cell can ingest. which is used to vaccinate against smallpox.) According to the World Antibody Health Organization, however, small- pox has now been eliminated as a Neutralization of toxins Antibodies bind to toxin molecules to result of widespread immunization Toxin prevent them from damaging cells. programs. Mandatory vaccination has Antibody been discontinued because the chance of adverse side effects from the vaccine is thought to be greater than the prob- Help with phagocytosis Phagocytes can attach more easily to ability of contracting the disease. Foreign cell antigens that are coated with anti- All vaccines carry a risk of adverse Antibody body. side effects and may be contraindicated in some cases. People who are im- munosuppressed, for example, should Phagocyte not be given vaccines that contain live virus. Also pregnant women should not Activation of complement When complement attaches to anti- receive live virus vaccine because the Complement body on a cell surface, a series of virus could cross the placenta and harm Antibody reactions begins that activates com- the fetus. Foreign cell plement to destroy cells. Types of Vaccines Vaccines can Activation of NK cells NK cells respond to antibody adhering be made with live organisms or with NK cell to a cell surface and attack the cell. organisms killed by heat or chemicals. Antibody If live organisms are used, they must Foreign cell be nonvirulent for humans, such as the cowpox virus used for smallpox Box 17-2 Clinical Perspectives Too Much Stress Makes The Immune System Sick T he impact of stress on the immune system is the most wide-ranging and significant of its many effects on the body. Stressors such as trauma, infection, debilitating disease, ◗ inhibit histamine release from damaged tissues, thereby blocking inflammation and the arrival of phagocytic leuko- cytes. surgery, pain, extreme environmental conditions, and emo- ◗ reduce phagocytosis in damaged tissues, thus preventing tional distress all hamper immune function. The mechanisms antigen presentation to (and activation of) both killer T responsible for these changes are not yet fully understood. Sci- cells and helper T cells. entists do know that stress causes the hypothalamus to pro- ◗ inhibit interleukin secretion from helper T cells, thus pre- mote the release of ACTH from the anterior pituitary. This venting the immune system from mounting a coordinated hormone stimulates the adrenal cortex to release the hormone cortisol, which influences a person’s immediate ability to response to infection. overcome any challenge, even stress itself. However, the ab- Box 12-3, Stress: Mechanisms for Coping, suggests some normally high levels of cortisol that appear during periods of strategies for reducing stress. intense stress can actually be harmful. Such levels can: BODY DEFENSES, IMMUNITY, AND VACCINES ✦ 353 immunization, or they must be treated in the laboratory their toxins. Because of whooping cough’s seriousness in to weaken them as human pathogens. An organism weak- young infants, early inoculation with whooping cough, or ened for use in vaccines is described as attenuated. In pertussis (per-TUS-is), vaccine, is recommended. A new some cases, just an antigenic component of the pathogen form of the vaccine containing pertussis toxoid causes is used as a vaccine. Another type of vaccine is made from fewer adverse reactions than older types that contained the toxin produced by a disease organism. The toxin is al- heat-killed organisms. This acellular (aP) vaccine usually tered with heat or chemicals to reduce its harmfulness, is given in a mixture with diphtheria toxoid and tetanus but it can still function as an antigen to induce immunity. toxoid. The combination, referred to as DTaP, may be Such an altered toxin is called a toxoid. given as early as the second month of life and should be The newest types of vaccines are produced from anti- followed by additional injections at 4, 6, and 15 months genic components of pathogens or by genetic engineering. and again when the child enters day care, a school, or any By techniques of recombinant DNA, the genes for specific other environment in which he or she might be exposed disease antigens are inserted into the genetic material of to one of these contagious diseases. Diphtheria and harmless organisms. The antigens produced by these or- tetanus toxoid (Td) is given again at 11 to 12 years of age. ganisms are extracted and purified and used for immuniza- A tetanus booster is given when there is a disease risk and tion. The hepatitis B vaccine is produced in this manner. the last booster was administered more than 10 years prior to exposure. Boosters In many cases, an active immunity acquired Routine inoculation against Haemophilus influenzae by artificial (or even natural) means does not last a life- type B (Hib) has nearly eliminated the life-threatening time. Circulating antibodies can decline with time. To meningitis caused by this organism among preschool chil- help maintain a high titer (level) of antibodies in the dren. Hib also causes pneumonia and recurrent ear infec- blood, repeated inoculations, called booster shots, are ad- tions in young children. Depending on the type used, the ministered at intervals. The number of booster injections vaccine is given in either two doses or three doses begin- recommended varies with the disease and with an indi- ning at 2 months of age. vidual’s environment or range of exposure. On occasion, Pneumococcal vaccine (PCV) protects against infec- epidemics in high schools or colleges may prompt rec- tion with pneumococcus, an organism that can cause ommendations for specific boosters. Table 17-2 lists the pneumonia and meningitis. Four doses are given between vaccines currently recommended in the United States for the ages of 2 and 15 months. 17 childhood immunizations. The number and timing of doses varies with the different vaccines. Examples of Viral Vaccines Intensive research on viruses has resulted in the development of vaccines for an Examples of Bacterial Vaccines Children are increasing number of viral diseases. The medical commu- routinely immunized with vaccines against bacteria or nity has achieved spectacular results in eliminating po- liomyelitis by the use of vaccines. The first of these was an inactivated polio Table 17•2 Childhood Immunizations* vaccine (IVP) developed by Dr. Jonas Salk and made with killed poliovirus. A VACCINE DISEASE(S) SCHEDULE more convenient oral vaccine (OPV), made with live attenuated virus, was DTaP Diphtheria, tetanus, 2, 4, 6, and 15–18 months pertussis (whooping Booster at 4–6 years then developed by Dr. Albert Sabin. cough) Diphtheria and tetanus Both vaccine types are presently used toxoid (Td) at 11–12 years in worldwide immunization programs, Hib Haemophilus influenza 2 and 4 months or 2, 4, and 6 but IPV is preferred for routine child- type b (spinal months depending on type hood immunizations. A series of three meningitis) used PCV Pneumococcus (pneu- 2, 4, 6, and 12–15 months doses is given between 2 and 18 monia, meningitis) months, and a fourth dose is given be- MMR Measles, mumps, rubella 15 months and 4–6 years fore entry into school. HBV Hepatitis B Birth, 1–2 months, 6–18 MMR, made with live attenuated months viruses, protects against measles Polio vaccine Poliomyelitis 2 and 4 months, 6–18 months, (IPV) and 4–6 years (rubeola), mumps, and rubella (Ger- Varicella Chickenpox 12–18 months man measles). Rubella is a very mild disease, but it causes birth defects in a *Recommended by the Advisory Committee on Immunization Practices (www.cdc.gov/nip/acip), developing fetus (see Table 2 in Ap- the American Academy of Pediatrics (www.aap.org), and the American Academy of Family pendix 5). A first dose of MMR is Physicians (www.aafp.org). Information available through the National Immunization Program given at 15 months and a second be- website (www2a.cdc.gov/nip). tween 4 and 6 years of age. 354 ✦ CHAPTER SEVENTEEN Infants are now routinely immunized against hepati- used in emergencies, that is, in situations in which there tis B, receiving the first of three shots just after birth and is no time to wait until an active immunity has developed. two more before the age of 18 months. The vaccine is also recommended for people at high risk of hepatitis B infec- Preparation of Antisera Immune sera often are de- tion, including healthcare workers, people on kidney rived from animals, mainly horses. It has been found that dialysis, people receiving blood clotting factors, injecting the horse’s tissues produce large quantities of antibodies drug users, and those with multiple sexual partners. A in response to the injection of organisms or their toxins. vaccine against hepatitis A virus is recommended for trav- After repeated injections, the horse is bled according to elers and others at high risk for infection. careful sterile technique; because of the animal’s size, it is A vaccine against chicken pox (varicella) has been possible to remove large quantities of blood without caus- available since 1995. Children who have not had the ing injury. The blood is allowed to clot, and the serum is disease by 1 year of age should be vaccinated. Although removed and packaged in sterile containers. chicken pox is usually a mild disease, it can cause en- Injecting humans with serum derived from animals is cephalitis, and infection in a pregnant woman can cause not without its problems. The foreign proteins in animal congenital malformation of the fetus. Because varicella is sera may cause an often serious sensitivity reaction, called the same virus that causes shingles, vaccination may pre- serum sickness. To avoid this problem, human antibody vent this late-life sequel. in the form of gamma globulin may be used. A number of vaccines have been developed against in- fluenza, which is caused by a variety of different viral Checkpoint 17-13 What is an immune serum and when are im- mune sera used? strains. Laboratories produce a new vaccine each year to combat what they expect will be the most common strains in the population. The elderly, the debilitated, and Examples of Antisera Some immune sera contain anti- children with certain risk factors, including asthma, heart bodies, known as antitoxins, that neutralize toxins but disease, sickle cell disease, HIV infection, and diabetes, have no effect on the toxic organisms themselves. Certain should be immunized yearly against influenza. antibodies act directly on pathogens, engulfing and de- The rabies vaccine is an exception to the rule that a stroying them or preventing their continued reproduc- vaccine should be given before invasion by a disease or- tion. Some antisera are obtained from animal sources, ganism. Rabies is a viral disease transmitted by the bite of others from human sources. Examples of immune sera wild animals such as raccoons, bats, foxes, and skunks. are: Mandatory vaccination of domestic animals has practi- cally eliminated this source of rabies in some countries, ◗ Diphtheria antitoxin, obtained from immunized horses. including the United States, but worldwide, a variety of ◗ Tetanus immune globulin, effective in preventing lock- wild and domestic animals are host to the virus. There is jaw (tetanus), which is often a complication of neg- no cure for rabies; it is fatal in nearly all cases. The dis- lected wounds. Because tetanus immune globulin is of ease develops so slowly, however, that affected people human origin, it carries less risk of adverse reactions vaccinated after transmission of the organism still have than do sera obtained from horses. time to develop an active immunity. The vaccine may be ◗ Immune globulin (human) is given to people exposed given preventively to people who work with animals. to hepatitis A, measles, polio, or chickenpox. It is also given on a regular basis to people with congenital (pres- Checkpoint 17-11 What are some bacterial diseases for which ent at birth) immune deficiencies. there are vaccines? ◗ Hepatitis B immune globulin, used after hepatitis B ex- posure, is given principally to infants born to mothers Checkpoint 17-12 What are some viral diseases for which who have hepatitis. there are vaccines? ◗ The immune globulin Rho(D) (trade name RhoGAM), a concentrated human antibody given to prevent an Rh- Passive Immunization It takes several weeks to pro- negative mother from forming Rh antibodies. It is given duce a naturally acquired active immunity and even during pregnancy if maternal antibodies develop and longer to produce an artificial active immunity through after the birth of an Rh-positive infant (or even after a the administration of a vaccine. Therefore, a person who miscarriage of a presumably Rh-positive fetus) (see receives a large dose of virulent organisms and has no es- Chapter 13). It is also given when Rh transfusion in- tablished immunity to them is in great danger. To prevent compatibilities occur. illness, the person must quickly receive counteracting an- ◗ Anti–snake bite sera, or antivenins (an-te-VEN-ins) are tibodies from an outside source. This is accomplished used to combat the effects of certain poisonous snake through the administration of an immune serum, or an- bites. tiserum. The “ready-made” serum gives short-lived but ◗ Botulism antitoxin, an antiserum from horses offers the effective protection against the invaders in the form of an best hope for botulism victims, although only if given artificially acquired passive immunity. Immune sera are early. BODY DEFENSES, IMMUNITY, AND VACCINES ✦ 355 ◗ Rabies antiserum, from humans or horses, is used with Anaphylaxis Anaphylaxis (an-ah-fih-LAK-sis) is a se- the vaccine to treat victims of rabid animal bites. vere, life-threatening allergic response in a sensitized indi- vidual. (The term actually means excess “guarding,” in this case, immune protection, from the Greek word phylaxis.) ◗ Disorders of the Immune System Any allergen can result in an anaphylactic response, but common causes are drugs, insect venom, and foods. Symp- Immune system disorders may result from overactivity or toms appear within seconds to minutes after contact and underactivity. Allergy and autoimmune diseases fall into include breathing problems, swelling of the throat and the first category; hereditary, infectious, and environ- tongue, urticaria, edema, and decreased blood pressure mental immune deficiency disease fall into the second. with cardiovascular shock. Anaphylaxis is treated with in- jectable epinephrine, antihistamine, administration of Allergy oxygen, and plasma expanders to increase blood volume. Allergy involves antigens and antibodies, and its chemi- People subject to severe allergic reactions must avoid con- cal processes are much like those of immunity. Allergy— tact with known allergens. They should be sensitivity a broader term for which is hypersensitivity—can be de- tested before administration of a new drug and should also fined informally as a tendency to react unfavorably to carry injectable epinephrine and wear a medical bracelet certain substances that are normally harmless to most identifying their allergy. people. These reaction-producing substances are called aller- Autoimmunity gens (AL-er-jens), and like most antigens, they are usu- The term autoimmunity refers to an abnormal reactivity ally proteins. Examples of typical allergens are pollens, to one’s own tissues. In autoimmunity, the immune sys- house dust, animal dander (dander is the term for the tem reacts to the body’s own antigens, described as “self,” minute scales that are found on hairs and feathers), and as if they were foreign antigens, or “nonself.” Normally, certain food proteins. Many drugs can induce allergy, par- the immune system learns before birth to ignore (toler- ticularly aspirin, barbiturates, and antibiotics (especially ate) the body’s own tissues by eliminating or inactivating penicillin). those lymphocytes that will attack them. Some factors When a susceptible person’s tissues are repeatedly ex- that might result in autoimmunity include: 17 posed to an allergen—for example, exposure of the nasal mucosa to pollens—those tissues become sensitized; that ◗ A change in “self” proteins, as a result of disease, for ex- ample. is, antibodies are produced in them. When the next ex- ◗ Loss of immune system control, as through loss of reg- posure to the allergen occurs, there is an antigen–anti- ulatory T cell activity, for example. body reaction. Normally, this type of reaction takes place ◗ Cross-reaction of antibodies with “self” antigens. This in the blood without harm, as in immunity. In allergy, reaction occurs in rheumatic fever, for example, when however, the antigen–antibody reaction takes place antibodies to streptococci damage the valves of the within the cells of the sensitized tissues, with results that heart. are disagreeable and sometimes dangerous. In the case of the nasal mucosa that has become sensitized to pollen, Autoimmunity is involved in a long list of diseases, in- the allergic manifestation is hay fever, with symptoms cluding rheumatoid arthritis, multiple sclerosis, lupus much like those of the common cold. erythematosus, psoriasis, inflammatory bowel diseases, The antigen–antibody reaction in sensitive individu- Graves disease, glomerulonephritis, and Type I diabetes. als promotes the release of excessive histamine. Hista- All of these diseases probably result to varying degrees mine causes dilation and leaking from capillaries as well from the interaction of individual genetic makeup with as contraction of involuntary muscles (e.g., in the environmental factors, including infections. Autoimmune bronchi). Antihistamines are drugs that counteract hista- diseases are three times more prevalent in women than in mine and may be effective in treating the symptoms of men, perhaps related to hormonal differences. certain allergies. Sometimes, it is possible to desensitize Autoimmunity is treated with drugs that suppress the an allergic person by repeated intermittent injections of immune system and with antibodies to lymphocytes. Pure the offending allergen. Unfortunately, this form of pro- antibodies, such as these, are prepared in the laboratory and are known as monoclonal antibodies. A newer ap- tection does not last long. proach uses chemotherapy to destroy immune cells fol- Serum sickness is an example of an allergic manifes- lowed by their replacement with healthy stem cells from tation that may occur in response to various sera. People bone marrow. who are allergic to the proteins in serum from a horse or some other animal show such symptoms as fever, vomit- ing, joint pain, enlargement of the regional lymph nodes, Immune Deficiency Diseases and urticaria (ur-tih-KA-re-ah), also called hives. This An immune deficiency is some type of failure of the im- type of allergic reaction can be severe but is rarely fatal. mune system. This failure may involve any part of the 356 ✦ CHAPTER SEVENTEEN system, such as T cells, B cells, or the thymus gland, and tibodies. These cells produce an excess of a particular an- it may vary in severity. Such disorders may be congenital tibody, but the antibody is not effective. The disease (present at birth) or may be acquired as a result of mal- causes loss of resistance to infection, anemia, bone pain, nutrition, infection, or treatment with x-rays or certain and weakening of the bones, owing to production of a drugs. factor that accelerates loss of bone tissue. High blood lev- The disease AIDS (acquired immunodeficiency syn- els of calcium and proteins secreted by the plasma cells drome) is a devastating example of an infection that at- often lead to kidney failure. Multiple myeloma is treated tacks the immune system. It is caused by HIV (human im- with chemotherapy. A new approach is high-dose munodeficiency virus), which destroys the specific helper chemotherapy combined with bone marrow transplants. T cells that have a receptor (CD4) for the virus. Its first Blood-forming stem cells in the bone marrow replace appearance in the United States in the early 1980s was cells killed by the chemotherapy. This treatment is ex- among homosexual men and injecting drug users. It now pensive, and stem cell transplants in themselves are dan- occurs worldwide in heterosexual populations of all ages. gerous, but this combined treatment has improved sur- AIDS is considered to be a pandemic, especially in sub-Sa- vival rates. haran Africa and in some parts of Asia. It is spread through unprotected sexual activity and the use of con- Checkpoint 17-14 What are some disorders of the immune sys- tem? taminated injection needles. It can also be transmitted from a mother to her fetus. The testing of donated blood has virtually eliminated the spread of AIDS through blood transfusions. ◗ The Immune System and Cancer Diagnosis of HIV infection is based on the presence of Cancer cells differ slightly from normal body cells and HIV antibodies, the virus, or viral components in the therefore the immune system should recognize them as blood. The disease is monitored with CD4 T cell counts “nonself.” The fact that people with AIDS and other im- and measurement of HIV RNA in the blood. (See Box 17- mune deficiencies develop cancer at a higher rate than 3 for information on the type of virus that causes AIDS.) normal suggests that this is true. Cancer cells probably Patients with AIDS succumb easily to disease, includ- form continuously in the body but normally are de- ing rare diseases such as parasitic (Pneumocystis) pneu- stroyed by NK cells and the immune system, a process monia and an especially malignant skin cancer, Kaposi called immune surveillance (sur-VAY-lans). As a person (KAP-o-se) sarcoma. ages, cell-mediated immunity declines and cancer is more Drugs active against HIV stop viral growth at different likely to develop. stages of replication. These drugs, often used in combina- Some efforts are being made to treat cancer by stimu- tion, can slow the progress of AIDS, but so far, do not lating the patient’s immune system, a practice called im- cure it. An obstacle to the development of a vaccine munotherapy. In one approach, T cells have been removed against HIV is the tremendous variability of the virus. from the patient, activated with interleukin, and then rein- jected. This method has given some positive results, espe- Multiple Myeloma cially in treatment of melanoma, a highly malignant form Multiple myeloma is a cancer of the blood-forming cells of skin cancer. In the future, a vaccine against cancer may in bone marrow, mainly the plasma cells that produce an- become a reality. Vaccines that target specific proteins Box 17-3 A Closer Look Retroviruses: Working Backward to Cause Disease H IV, the virus that causes AIDS, belongs to a group of viruses that is unique in its method of reproduction. The group’s name, retroviruses, which means “backward viruses,” There, it may direct the formation of more viruses or lie dor- mant and undetected for long periods, even years, before being triggered to multiply and cause disease. Some retroviruses can refers to the way in which the viruses reverse the typical order transform the DNA of the host cell and produce cancer. These of genetic action. Retroviruses have RNA instead of DNA as viruses have been associated with leukemia in both humans their genetic material. Unlike other RNA viruses, however, and animals and with other types of tumors in animals. they transcribe (copy) the RNA into DNA to reproduce inside Some drugs that are used against retroviruses like HIV act the host. To accomplish this unusual feat, the virus has an en- by inhibiting reverse transcriptase and interrupting the repli- zyme called reverse transcriptase. cation cycle of the virus. The drug AZT is one such example. The DNA formed using reverse transcriptase enters the nu- While drugs like AZT can slow the rate of HIV replication, cleus of the host cell and becomes part of the genetic material. they do not cure or prevent HIV infection or AIDS. BODY DEFENSES, IMMUNITY, AND VACCINES ✦ 357 produced by cancer cells have already been tested in a few contain relatively few antigens that might cause trans- forms of cancer. plant rejection in a recipient, the person receiving the part. (One exception to the need for careful cross-match- ing is corneal transplantation in the eye. Corneal proteins ◗ Transplantation and the don’t enter the circulation to stimulate an immune re- Rejection Syndrome sponse.) Because it is impossible to match all of a donor’s anti- Transplantation is the grafting to a recipient of an organ gens with those of the recipient, physicians give the re- or tissue from an animal or other human to replace an in- cipient drugs that will suppress an immune response to jured or incompetent part of the body. Much experimen- the transplanted tissue. These include drugs that suppress tal work preceded transplantation surgery in humans. synthesis of nucleic acids, drugs or antibodies that inhibit Tissues that have been transplanted include: bone mar- lymphocytes, and adrenal glucocorticoid hormones, such row, lymphoid tissue, skin, corneas, parathyroid glands, as cortisol, that suppress immunity. These drugs cause a ovaries, kidneys, lungs, heart, and liver. variety of adverse side effects, such as hypertension, kid- The natural tendency of every organism to destroy ney damage, and osteoporosis (glucocorticoids). Most foreign substances, including tissues from another person importantly, they reduce a patient’s ability to fight infec- or any other animal, has been the most formidable obsta- tion. Because T cells cause much of the reaction against cle to complete success. This normal antigen–antibody the foreign material in transplants, scientists are trying to reaction has, in this case, been called the rejection syn- use drugs and antibodies to suppress the action of these drome. lymphocytes without damaging the B cells. B cells pro- In all cases of transplantation or grafting, the tissues duce circulating antibodies and are most important in of the donor, the person donating the part, should be preventing infections. Success with transplantation will typed in much the same way that blood is typed when a increase when methods are found to selectively suppress transfusion is given. Blood type antigens are much fewer the immune attack on transplants without destroying the in number than tissue antigens; thus, the process of ob- recipient’s ability to combat disease. taining matching blood is much less involved than is the Checkpoint 17-15 What is the greatest obstacle to tissue trans- process of obtaining matching tissues. Laboratories do plantation from one individual to another? tissue typing in an effort to obtain donors whose tissues 17 Word Anatomy Medical terms are built from standardized word parts (prefixes, roots, and suffixes). Learning the meanings of these parts can help you remember words and interpret unfamiliar terms. WORD PART MEANING EXAMPLE Factors in the Occurrence of Infection tox poison A toxin is a substance that is poisonous. Disorders of the Immune System erg work In cases of allergy, the immune system overworks. ana- excessive Anaphylaxis is a life-threatening condition that results from an excessive immune reaction. myel/o marrow Multiple myeloma is a cancer (-oma) of blood-forming cells in bone marrow. Summary I. Factors in the occurrence of infection II. Nonspecific defenses A. Tissue preference of pathogen A. Chemical and mechanical barriers B. Portal of entry of pathogen 1. Skin C. Virulence of pathogen 2. Mucous membranes 1. Invasive power 3. Body secretions 2. Production of toxins (poisons) 4. Reflexes—coughing, sneezing, vomiting, diarrhea D. Dose (number) of pathogens B. Phagocytosis—mainly by neutrophils and macrophages E. Predisposition of host C. Natural killer (NK) cells—attack tumor cells and virus-in- fected cells 358 ✦ CHAPTER SEVENTEEN D. Inflammation (2) Damages plasma membranes E. Fever (3) Promotes inflammation F. Interferon (4) Attracts phagocytes 1. Substances released from virus-infected cells D. Naturally acquired immunity 2. Prevent virus production in nearby cells 1. Active—acquired through contact with the disease 3. Stimulate the immune response nonspecifically 2. Passive—acquired from antibodies obtained through placenta and mother’s milk III. Immunity—specific defense against E. Artificially acquired immunity disease 1. Active—immunization with vaccines A. Inborn immunity a. Types: live (attenuated), killed, toxoid, recombinant 1. Inherited DNA 2. Types: species, individual b. Boosters—keep antibody titers high B. Acquired immunity—develops after birth c. Examples of bacterial vaccines 1. Antigens—stimulate immune response by lymphocytes d. Examples of viral vaccines 2. T cells (T lymphocytes) 2. Passive—administration of immune serum (antiserum) a. Processed in thymus b. Types: cytotoxic, helper, regulatory, memory IV. Disorders of the immune system c. Involved in cell-mediated immunity A. Allergy—hypersensitivity to normally harmless substances 3. Macrophages (allergens) a. Derived from monocytes 1. Anaphylaxis—severe, life-threatening allergic response b. Present antigen to T cells in combination with MHC B. Autoimmunity—abnormal response to body’s own tissues (“self”) proteins C. Immune deficiency disease—failure in the immune system c. Stimulate the release of interleukins (IL) 1. Congenital (present at birth) 4. B cells (B lymphocytes) 2. Acquired (e.g., AIDS) a. Mature in lymphoid tissue D. Multiple myeloma—cancer of blood-forming cells in bone b. Develop into plasma cells marrow (1) Produce circulating antibodies (2) Antibodies counteract antigens V. The immune system and cancer c. Also develop into memory cells A. Immune surveillance—ability of immune system to find d. Involved in humoral immunity and destroy abnormal cells (e.g., cancer cells) C. The antigen–antibody reaction B. Immunotherapy—stimulating the immune system to treat 1. Shape of antibody matches shape of antigen cancer 2. Results a. Prevention of attachment VII. Transplantation b. Clumping of antigen A. Grafting of an organ or tissue to replace injured or incom- c. Neutralization of toxins petent part d. Help in phagocytosis B. Requirements e. Activation of complement 1. Tissue typing f. Activation of NK cells 2. Suppression of immune system 3. Complement a. Group of proteins in blood b. Actions (1) Coats foreign cells Questions for Study and Review Building Understanding Fill in the blanks 1. The power of the organism to overcome its host’s de- 4. All antibodies are contained in a portion of the blood fenses is called ______. plasma termed the ______. 2. Heat, redness, swelling, and pain are classic signs of 5. Substances capable of inducing a hypersensitivity re- ______. action are called ______. 3. Any foreign substance that enters the body and in- duces an immune response is called a(n)______. BODY DEFENSES, IMMUNITY, AND VACCINES ✦ 359 Matching Match each numbered item with the most closely related lettered item. ___ 6. Destroy foreign cells directly. a. regulatory T cells ___ 7. Release interleukins, which stimulate other cells to join the immune response. b. memory T cells ___ 8. Suppress the immune response in order to prevent overactivity. c. cytotoxic T cells ___ 9. Remember an antigen and start a rapid response if the antigen is contacted again. d. B cells ___ 10. Manufacture antibodies when activated by antigens e. helper T cells Multiple choice 17. What causes the symptoms of inflammation? ___ 11. All of the following are part of the first line of 18. Differentiate between the terms in each of the defense against invaders except following pairs: a. tears a. interferon and interleukin b. saliva b. antibody and complement c. neutrophils c. inborn immunity and acquired immunity d. skin d. cell-mediated immunity and humoral immunity ___ 12. Damaged cells release a vasodilator substance e. active immunization and passive immunization called f. attenuated vaccine and toxoid a. interleukin 19. Describe the events that must occur for a T cell to b. interferon react with a foreign antigen. Once activated, what do the c. histamine T cells do? d. complement 20. What role do antibodies play in immunity? How are ___ 13. Which of the following cells mature in the they produced? How do they work? thymus? 21. Compare and contrast the four types of acquired im- a. T cell munity. b. B cell 22. What is an immune serum? Give examples. Define c. plasma cell antitoxin. d. natural killer cell 23. Define allergy. How is the process of allergy like that ___ 14. Sensitivity to animal-derived immune serum of immunity, and how do they differ? may lead to a serious condition called 24. What is meant by rejection syndrome, and what is a. serum sickness being done to offset this syndrome? 17 b. hay fever c. Kaposi sarcoma Conceptual Thinking d. rejection syndrome 25. While in the garden with his father Alek, a 4-year old ___ 15. An abnormal reactivity to one’s own tissues is Caucasian boy was, in his own words, “kicked by a bee.” called Shortly afterward, Alek developed hives near the affected a. allergy area, which he began to scratch. About ten minutes later, b. autoimmunity Alek’s father noticed that his son was wheezing. What is c. anaphylaxis happening to Alek? Describe the inflammatory events d. rejection that are occurring in his body. How should Alek’s father Understanding Concepts respond? 16. Describe four factors that influence the occurrence of 26. Why is HIV’s attack on helper T cells so devastating infection. to the entire immune system?