_{Defenses Against Disease}

Chapter

26

Outline

26.1 Organs, Tissues, and Cells of the Immune System

• Lymphocytes and other white blood cells are produced in the red bone marrow and mature there except for the T lymphocytes, which mature in the thymus gland.456-–57

• Lymphocytes proliferate and congregate in the lymph nodes and spleen. The tonsils and appendix are patches of lymphatic tissue.456-

26.2 Nonspecific Defenses

• Nonspecific defenses include barriers to entry, the inflammatory response, the complement system, and natural killer cells.458-–59

• In the inflammatory response, the area swells and becomes red, warm, and painful. In particular, neutrophils and macrophages phagocytize pathogens.458

26.3 Specific Defenses

• When a B-cell receptor binds to an antigen, the B cell divides and forms antibody-secreting plasma cells and memory B cells.460

• When a T-cell receptor binds to an antigen displayed on the surface of a macrophage, the T cell becomes a cytotoxic T cell (kills virus-infected or cancer cells) or a helper T cell (produces cytokines).462–63

26.4 Immunizations

• Injections of vaccines also result in immunity to a particular disease.464

26.5 Immune System Problems

• In allergic responses, the body responds to allergens to which most people do not respond.465

• In autoimmune diseases, such as rheumatoid arthritis, the immune system mistakenly attacks the body’s own tissues.465

• AIDS is caused by an HIV infection of helper
T cells in particular. In the untreated individual, the number of T cells declines, and the occurrence of infections increases until death occurs.466

If you were asked the purpose of a fever, what would your answer be? Many people think the heat generated by a fever actually “burns out” the pathogens in the body, thus killing them. In reality, the heat from increased body temperature does not directly kill the pathogens, but instead increases your metabolism so that your immune system defense mechanisms can work better to fight the pathogens. In fact, an increase of 1°C in body temperature causes about a 10% increase in metabolism. While a low-grade fever can be beneficial, a high-grade fever can be detrimental, as body temperature moves further away from normal. If a fever becomes too high and is not reduced, death will occur. For this reason, we often take medications to reduce fevers in case they start to elevate to potentially dangerous levels.

An interesting manipulation of body temperature is the basis for weight-loss supplements that claim to be “thermogenic.” These supplements raise the body temperature slightly (as would a natural fever), increasing metabolism as a way to bring about weight loss. However, some people have suffered serious consequences, including death, after taking such supplements. For this reason, the FDA has banned one of the major thermogenic supplemental ingredients—ephedra.

The immune system has an incredible array of defenses to help keep you free of infection, as well as to protect you from cancer. Most of these defenses work remarkably well and only rarely fail. In this chapter, you will learn about how the immune system protects you on a daily basis.

_{26.1 Organs, Tissues, and Cells
of the Immune System}

The immune system plays an important role in keeping us healthy because it fights infections and cancer. First and foremost, the immune system contains the lymphatic organs: red bone marrow, the thymus gland, the lymph nodes, and the spleen (Fig. 26.1). The tonsils, which are located in the pharynx, and the appendix, which is attached to a portion of the large intestine, are well known patches of lymphatic tissue that also belong to the immune system. The lymphatic system not only contains a network of lymphatic organs and lymphatic tissues, but it also includes cells. In particular, we will be discussing the cell types mentioned in Table 26.1. You will want to refer to this table as you read the chapter.

Immunity is the body’s capability to repel foreign substances, pathogens, and cancer cells. Nonspecific immunity indiscriminately repels pathogens, while specific immunity requires that a certain antigen be present. An antigen is any molecule, usually a protein or carbohydrate, that stimulates the immune system.

Lymphatic Organs

Each of the lymphatic organs has a particular function in immunity, and each is rich in lymphocytes, one of the types of white blood cells.

Red Bone Marrow

In a child, most bones have red bone marrow, but in an adult it is present only in the bones of the skull, the sternum (breastbone), the ribs, the clavicle, the pelvic bones, and the vertebral column. Red bone marrow produces all types of blood cells, but in this chapter we are interested in the cells listed in Table 26.1.

Lymphocytes differentiate into either B lymphocytes (B cells) or T lymphocytes (T cells), which are discussed at length later in the chapter. Bone marrow is not only the source of B lymphocytes, but also the place where B lymphocytes -mature. T lymphocytes mature in the thymus gland. We shall learn that B cells produce antibodies and that T cells kill antigen-bearing cells outright.

Thymus Gland

The soft, bilobed thymus gland varies in size, but it is larger in children and shrinks as we get older. The thymus gland plays a role in the maturity of T lymphocytes. Immature T lymphocytes migrate from the bone marrow through the bloodstream to the thymus, and then they -mature. Only about 5% of T lymphocytes ever leave the thymus. These T lymphocytes have survived a critical test: If any show the ability to react with “self” cells, they die. If they have potential to attack a foreign cell, they leave the -thymus.

The thymus gland also produces thymic hormones thought to aid in the maturation of T lymphocytes.

Lymph Nodes

Lymph nodes are small, ovoid structures occurring along lymphatic vessels. Lymph nodes filter lymph and keep it free of pathogens and antigens. Lymph is filtered as it flows through a lymph node because its many sinuses (open spaces) are lined by macrophages, large phagocytic cells that engulf and then devour as many as a hundred pathogens and still survive (see Fig. 26.4a). Lymph nodes are also instrumental in fighting infections and cancer because they contain many lymphocytes.

Some lymph nodes are located near the surface of the body, and such nodes are named for their location. For example, inguinal nodes are in the groin, and axillary nodes are in the armpits. Physicians often feel for the presence of swollen, tender lymph nodes in the neck as evidence that the body is fighting an infection. This method is a noninvasive, preliminary way to help make a diagnosis.

Spleen

The spleen, which is about the size of your fist, is in the upper left abdominal cavity. The spleen’s unique function is to filter the blood. This soft, spongy organ contains so-called red pulp and white pulp. Blood passing through the many sinuses in the red pulp is filtered of pathogens and debris, including worn out red blood cells, because the sinuses are lined by macrophages. The white pulp contains lymphocytes that are actively engaged in fighting infections and also cancer.

The spleen’s outer capsule is relatively thin, and an -infection or a severe blow can cause the spleen to burst. The spleen’s functions can be fulfilled by other organs, but a person without a spleen is often slightly more susceptible to infections and may have to receive antibiotic therapy indefinitely.

_{26.2 Nonspecific Defenses}

The body has various types of nonspecific defenses that are our first line of defense against most types of infections. The nonspecific defenses are barriers to entry, the inflammatory response, the complement system, and natural killer cells.

Barriers to Entry

Skin and the mucous membranes lining the respiratory, -digestive, and urinary tracts serve as mechanical barriers to entry by pathogens (Fig. 26.2). Oil gland secretions contain chemicals that weaken or kill certain bacteria on the skin. The upper respiratory tract is lined by ciliated cells that sweep mucus and trapped particles up into the throat, where they can be swallowed or expectorated (spit out). The stomach has an acidic pH, which inhibits growth or kills many types of bacteria. The various bacteria that normally reside in the intestine and other areas, such as the vagina, prevent pathogens from taking up residence.

The Inflammatory Response

Whenever tissue is damaged, a series of events occurs that is known as the inflammatory response (Fig. 26.3). The inflamed area has four outward signs: redness, warmth, swelling, and pain. The inflammatory response involves the first three cell types listed in Table 26.1.

When an injury occurs, damaged tissue cells and mast cells release chemical mediators, such as histamine, which cause the capillaries to dilate and become more permeable. Excess blood flow due to enlarged capillaries causes the skin to redden and become warm. -Increased permeability allows proteins and fluids to escape into the tissues, resulting in swelling. The swollen area stimulates free nerve endings, causing the sensation of pain.

Neutrophils are phagocytic white blood cells that migrate to the site of injury. They are amoeboid and can change shape to squeeze through capillary walls and enter tissue fluid. When neutrophils phagocytize pathogens, they are enclosed within a vesicle. The pathogens are later destroyed by hydrolytic enzymes when this vesicle combines with a lysosome, one of the cellular organelles.

Also present are macrophages (Fig. 26.4a). As stated, lymph nodes contain macrophages, but so do some tissues, particularly connective tissues, which have resident macrophages that routinely act as scavengers, devouring old blood cells, bits of dead tissue, and other debris. During the inflammatory response, macrophages can also bring about an explosive increase in the number of leukocytes by liberating growth factors, which pass by way of blood to the red bone marrow. There, they stimulate the production and release of white blood cells, primarily neutrophils. As the infection is being overcome, some neutrophils may die. These—along with dead cells, dead bacteria, and living white blood cells—form pus, a whitish material. The presence of pus indicates that the body is trying to overcome an -infection. When a blood vessel ruptures or is torn, the blood forms a clot to seal the break and prevent any further pathogen invasion.

The macrophages that have been fighting the infection move through the tissue fluid and lymph to the lymph nodes. Now lymphocytes are activated to react to the threat of an infection. Sometimes inflammation persists, and the result is chronic inflammation that is often treated by administering anti-inflammatory agents such as aspirin, ibuprofen, or cortisone. These medications act against the chemical mediators such as histamine released by the white blood cells in the area.

The Complement System

The complement system, often simply called complement, is composed of a number of blood plasma proteins designated by the letter C and a subscript. A limited amount of activated complement protein is needed because a domino effect occurs: As soon as a protein is activated, it in turn stimulates many more.

The complement proteins are activated when pathogens enter the body. The proteins “complement” certain immune responses, which accounts for their name. For example, they are involved in and amplify the inflammatory response because complement proteins attract phagocytes to the scene. Some complement proteins bind to the surfaces of pathogens already coated with antibodies, which ensures that the pathogens will be phagocytized by a neutrophil or macrophage.

Certain other complement proteins join to form a membrane attack complex that produces holes in the surfaces of bacteria and viruses (Fig. 26.4b). Fluids and salts then enter the pathogen to the point that it bursts.

Natural Killer Cells

Natural killer (NK) cells are large, granular lymphocytes that kill virus-infected cells and tumor (cancer) cells by cell-to-cell contact (see Table 26.1).

What makes an NK cell attack and kill a cell? The cells of your body ordinarily have “self” proteins on their surface that bind to receptors on NK cells. Sometimes virus-infected cells and cancer cells undergo alterations and lose their ability to produce self proteins. When NK cells can find no self proteins to bind to, they kill the cell by the same method as T lymphocytes do (see Fig. 26.8).

NK cells are not specific—their numbers do not increase when exposed to a particular antigen, and they have no means of “remembering” the antigen from previous contact.

_{26.3 Specific Defenses}

When nonspecific defenses have failed to prevent an infection, specific defenses come into play. Specific defenses -respond to antigens. Pathogens have antigens, but antigens can also be part of a foreign cell or a cancer cell. When our body learns to destroy a particular antigen, we have become immune to it. Because our immune system does not ordinarily respond to the proteins on the surface of our own cells (as if they were antigens), the immune system is said to be able to distinguish “self” from “nonself.” Only in this way can the immune system aid, rather than disrupt, homeostasis.

Lymphocytes are capable of recognizing an antigen -because they have plasma membrane receptor proteins shaped to allow them to combine with a specific antigen. It is often said that the receptor and the antigen fit together like a lock and a key. Because we -encounter a million different antigens during our lifetime, we need a great diversity of lymphocytes to protect us against them. Remarkably, diversification occurs to such an extent during the maturation process that a lymphocyte type exists for any possible antigen.

Immunity usually lasts for some time. For example, once we recover from the measles, we usually do not get the illness a second time. Immunity is primarily the result of the action of the B lymphocytes and the T lymphocytes. B lymphocytes mature in the bone marrow, and T lymphocytes mature in the thymus gland. B lymphocytes, also called B cells, give rise to plasma cells, which produce antibodies. These antibodies are secreted into the blood, lymph, and other body fluids. In contrast, T lymphocytes, also called T cells, do not produce antibodies. Some T cells regulate the immune response, and other T cells directly attack cells that bear antigens (see Table 26.1).

B Cells and the Antibody Response

Each B cell can bind only to a specific antigen—the antigen that fits the binding site of its receptor. The receptor is called a B-cell receptor (BCR). Some B cells never have anything to do because an antigen that fits the binding site of their type of receptor never shows up. But if an antigen does bind to a BCR, that particular B cell is activated, and it divides, producing many plasma cells and also memory B cells (Fig. 26.5). A B cell is stimulated to divide and produce plasma cells by helper T-cell secretions called cytokines, which are discussed later in this section. Plasma cells are larger than regular B cells because they have extensive rough endoplasmic reticulum for the mass production and secretion of antibodies specific to the antigen. The antibodies produced by plasma cells and secreted into the blood and lymph are identical to the BCR of the activated B cell.

Memory B cells are the means by which long-term immunity is possible. If the same antigen enters the system again, memory B cells quickly divide and give rise to more plasma cells capable of producing the correct antibodies.

Once the threat of an infection has passed, the development of new plasma cells ceases, and those present undergo apoptosis. Apoptosis is a process of programmed cell death (PCD) involving a cascade of specific cellular events leading to the death and destruction of the cell (see Fig. 8.11, p. 120).

Table 26.2 summarizes the activities of B cells.

The Function of Antibodies

Antibodies, as stated, are immunoglobulin proteins that are capable of combining with a specific antigen (Fig. 26.6). The antigen-antibody reaction can take several forms, but quite often the reaction produces complexes of antigens combined with antibodies. Such antigen-antibody complexes, sometimes called immune complexes, mark the antigens for destruction (see Fig. 26.5). An antigen-antibody complex may be engulfed by neutrophils or macrophages, or it may activate complement. Complement makes pathogens more susceptible to phagocytosis, as discussed previously.

ABO Blood TypeMost likely you know your ABO blood type—whether you have type A, B, AB, or O blood. These letters stand for antigens on your red blood cells. If you have type O blood, you don’t have either antigen A or B on your red cells. Some blood types have antibodies in the plasma (Table 26.3). As an example, type O blood has both anti-A and anti-B antibodies in the plasma. You can’t give a person with type O blood a transfusion from an individual with type A blood. If you do, the antibodies in the plasma will react to type A red blood cells, and agglutination will occur. Agglutination, the clumping of red blood cells, causes blood to stop circulating and red blood cells to burst. On the other hand, you can give type O blood to a person with any blood type because type O red blood cells bear neither A nor B antigens.

It’s possible to determine who can give blood to whom based on the ABO system. However, there are other red blood cell antigens in addition to A and B that are used in typing blood. Therefore, it is best to physically put the donor’s blood on a slide with the recipient’s blood to observe whether the two types match (no agglutination occurs) before blood can be safely transfused from one person to another.

T Cells and the Cellular Response

When T cells leave the thymus gland, they have unique T-cell receptors (TCRs) just as B cells do. Unlike B cells, however, T cells are unable to recognize an antigen without help. The antigen must be presented to them by an antigen-presenting cell (APC), such as a macrophage. After a macrophage phagocytizes a virus it is digested in a lysosome. An antigen from the virus is combined with an MHC “self” protein, and the complex appears on the cell surface. Then the MHC 1 antigen is presented to a T cell. The importance of self proteins in plasma membranes was first recognized when it was discovered that they contribute to the specificity of tissues and make it difficult to transplant tissue from one human to another.

In Figure 26.7, the antigen is represented by a red triangle, and the T cell that binds to the antigen has the specific TCR that can -combine with this particular MHC 1 antigen. Now the T cell is activated and divides to produce more T cells. T cells that are destined to become cytotoxic T cells are activated by a macrophage that presents an antigen with an MHC I. T cells that are destined to become helper T cells are activated by a macrophage that presents an antigen with an MHC II. If the macrophage presents an antigen with an MHC II, the activated T cell will form helper T cells as in Figure 26.7.

As the illness disappears, the immune reaction wanes, and the activated T cells become susceptible to apoptosis. Apoptosis contributes to homeostasis by regulating the number of cells present in an organ, or in this case, the immune system. When apoptosis does not occur as it should, T-cell cancers (e.g., lymphomas and leukemias) can result. Also, in the thymus gland, any T cell that has the potential to destroy the body’s own cells undergoes apoptosis.

Types of T Cells

The two main types of T cells are cytotoxic T cells and helper T cells. Cytotoxic T cells have storage vacuoles containing perforins or enzymes called granzymes. After a cytotoxic T cell binds to a virus-infected or cancer cell presenting the same antigen it has learned to recognize, it releases perforin molecules that perforate the plasma membrane, forming a pore. Cytotoxic T cells then deliver a supply of granzymes into the pore, and these cause the cell to undergo apoptosis and die. Once cytotoxic T cells have released the perforins and granzymes, they move on to the next target cell. Cytotoxic T cells are responsible for a cellular response to virus-infected and cancer cells (Fig. 26.8).

Helper T cells regulate immunity by secreting cytokines. Cytokines are signaling chemicals that stimulate various immune cells (e.g., macrophages, B cells, and other T cells) to perform their functions. B cells cannot be activated without T cell help. Because HIV, the virus that causes AIDS, infects helper T cells and other cells of the immune system, it inactivates the immune response and makes HIV-infected individuals susceptible to opportunistic infections. Infected macrophages serve as reservoirs for the HIV virus. AIDS is discussed in Section 26.5.

Table 26.4 summarizes the activities of T cells.

Tissue Rejection

Certain organs, such as the skin, the heart, and the kidneys, could be transplanted easily from one person to another if the body did not attempt to reject them. Rejection occurs because cytotoxic T cells and also antibodies bring about destruction of foreign tissues in the body. When rejection occurs, the immune system is correctly distinguishing between self and nonself.

Organ rejection can be controlled by carefully selecting the organ to be transplanted and administering immunosuppressive drugs. It is best if the transplanted organ has the same type of MHC proteins as those of the recipient because otherwise the transplanted organ will be antigenic to T cells. Two well-known immunosuppressive drugs, cyclosporine and tacrolimus, act by inhibiting the response of T cells to cytokines. Without cytokines, all types of immune responses are weak.

_{26.4 Immunizations}

After you have had an infection, you are sometimes immune to getting it again. Good examples are the childhood diseases measles and mumps. Unfortunately, few sexually transmitted diseases stimulate lasting immunity; for example, a person can get gonorrhea over and over again. If lasting immunity is possible, a vaccine for the disease likely exists or can be developed. Vaccines are substances that usually don’t cause illness, but even so, the immune system responds to them. Traditionally, vaccines are the pathogens themselves, or their products, that have been treated so that they are no longer virulent (able to cause disease). Today, it is possible to genetically engineer bacteria to mass-produce a protein from pathogens, and this protein can be used as a vaccine. This method has now produced a vaccine against hepatitis B, a virus-induced disease, and it is being used to prepare a vaccine against malaria, a protozoan-induced -disease.

Immunization promotes active immunity. After a vaccine is given, it is possible to follow an active immune response by determining the amount of antibody present in a sample of plasma; this is called the antibody titer. After the first exposure to a vaccine, a primary response occurs. For a period of several days, no anti-bodies are present; then their concentration rises slowly, levels off, and gradually declines as the antibodies bind to the antigen or simply break down (Fig. 26.9). After a second exposure to the vaccine, a secondary response is expected. The concentration now rises rapidly to a level much greater than before; then it slowly declines. The second exposure is called a “booster” because it boosts the antibody concentration to a high level. The high antibody concentration now is expected to help prevent disease symptoms if the individual is exposed to the disease-causing antigen.

Active immunity is dependent upon the presence of memory B cells and possibly memory T cells that are capable of -responding to lower doses of antigen. Active immunity is usually long-lasting, but a booster may be required after a certain number of years.

Although the body usually makes its own antibodies, it is sometimes possible to give an individual prepared antibodies (immunoglobulins) to combat a disease. Because these antibodies are not produced by the individual’s plasma cells, this so-called passive immunity is temporary. For example, newborn infants are passively immune to some diseases -because antibodies have crossed the placenta from the mother’s blood. These antibodies soon disappear, however, so that within a few months, infants become more suscep-tible to infections. Breast-feeding prolongs the natural passive immunity an infant receives from the mother because antibodies are present in the mother’s milk.

Even though passive immunity does not last, it is sometimes used to prevent illness in a patient who has been -unexpectedly exposed to an infectious disease. Usually, the patient receives an injection of gamma globulin, a portion of blood that contains antibodies, preferably taken from an individual who has recovered from the illness. In the past, horses were -immunized, and gamma globulin was taken from them to provide the needed antibodies against such diseases as diphtheria, botulism, and tetanus. Unfortunately, patients who -received these anti-bodies became ill about 50% of the time, because the serum contained proteins that the individual’s immune system recognized as foreign. This condition was called serum sickness.

_{26.5 Immune System Problems}

The immune system usually protects us from disease because it can distinguish self from nonself. Sometimes, however, it responds in a manner that harms the body, as when individuals develop allergies or have an autoimmune disease.

Allergies

Allergies are hypersensitivities to substances in the environment, such as pollen, food, or animal hair, that ordinarily would not cause an immune reaction. The response to these antigens, called allergens, usually includes some unpleasant symptoms (Fig. 26.10). An allergic -response is regulated by cytokines secreted by both T cells and macrophages.

Immediate allergic responses are caused by receptors attached to the plasma membrane of mast cells in the tissues. When an allergen attaches to receptors on mast cells, they release histamine and other substances that bring about the symptoms.

An immediate allergic response can occur within seconds of contact with the antigen. The symptoms can vary, but a dramatic example, anaphylactic shock, is a severe -reaction characterized by a sudden and life-threatening drop in blood pressure.

Allergy shots sometimes prevent the onset of an allergic response. It has been suggested that injections of the allergen may cause the body to build up high quantities of antibodies released by plasma cells, and these combine with allergens received from the environment before they have a chance to reach the receptors located in the membranes of mast cells.

Delayed allergic responses are probably initiated by memory T cells at the site of allergen contact in the body. A classic example of a delayed allergic response is the skin test for tuberculosis (TB). When the test result is positive, the tissue where the antigen was injected becomes red and hardened. This shows that the person has been previously exposed to tubercle bacilli, the cause of TB. Contact dermatitis, which occurs when a person is allergic to poison ivy, jewelry, cosmetics, and so forth, is also an example of a delayed allergic response.

Autoimmune Diseases

When cytotoxic T cells or antibodies mistakenly attack the body’s own cells as if they bear antigens, the resulting condition is known as an autoimmune disease. Exactly what causes autoimmune diseases is not known. However, sometimes they occur after an individual has recovered from an infection.

In the autoimmune disease myasthenia gravis, neuromuscular junctions do not work properly, and muscular weakness results. In multiple sclerosis (MS), the myelin sheath of nerve fibers breaks down, causing various neu-romuscular disorders. A person with systemic lupus eryth-ematosus has various symptoms prior to death due to kidney damage. In rheumatoid arthritis, the joints are affected (Fig. 26.11). Researchers suggest that rheumatic fever and also diabetes type 1 are autoimmune illnesses. As yet, there are no cures for autoimmune diseases, but they can be controlled with drugs.

AIDS

Understanding why AIDS patients are so sick gives us a whole new level of appreciation for the workings of a healthy immune system. An immune system ravaged by AIDS (acquired immunodeficiency syndrome) can no longer fight off the onslaught of viruses, fungi, and bacteria that the body encounters every day. HIV (human immunodeficiency virus), which causes AIDS, lives in and destroys helper T cells, which promote the activity of all the other cells in the immune system. For years, the body is able to maintain an adequate number of T cells, but finally the virus gains the upper hand. Without drug therapy, the number of T cells eventually drops from thousands to hundreds as the immune system becomes helpless (Fig. 26.12). The symptoms of AIDS begin with weight loss, chronic fever, cough, diarrhea, swollen glands, and shortness of breath, and progress to those of rare diseases. Pneumocystic pneumonia, a respiratory disease found in cats, and Kaposi’s sarcoma, a very rare type of cancer, are often observed in patients with advanced AIDS. Death approaches rapidly and certainly.

HIV is transmitted by sexual contact with an infected person, including vaginal or rectal intercourse and oral/genital contact. Also, needle-sharing among intravenous drug users is high-risk behavior. Babies born to HIV-infected women may become infected before or during birth, or through breast-feeding after birth. To date, as many as 64 million people worldwide may have contracted HIV, and almost 2.2 million people have died. Male-to-male sexual contact still accounts for most new AIDS cases in the United States, but the greatest percentage of increase is now through heterosexual contact or intravenous drug use.

Advances in treatment have reduced the serious complications of an HIV infection and have prolonged life. The sooner drug therapy begins after infection, the better the chances that the immune system will not be destroyed by HIV. Also, medication must be continued indefinitely. Unfortunately, new strains of the virus have emerged that are resistant to the new drugs used for treatment. The likelihood of transmission from mother to child at birth can be lessened if the mother receives medication prior to birth and the child is delivered by cesarean section.

Many investigators are working on a vaccine for AIDS. Some are trying to develop a vaccine in the traditional way, using the entire virus. Others are working on vaccines that utilize just a single HIV protein as the vaccine. So far, no method has resulted in sufficient antibodies to keep an infection at bay. After many clinical trials, none too successful, most investigators agree that a combination of various vaccines may be the best strategy to bring about a response by both B cells and T cells.

HIV infection is preventable. Suggestions for preventing an infection are: (1) Abstain from sexual intercourse or develop a long-term monogamous (always same partner) sexual relationship with a person who is free of HIV; (2) be aware that having relations with an intravenous drug user is risky behavior; (3) avoid anal-rectal intercourse because the lining of the rectum is thin, and infected T cells easily enter the body there; (4) always use a latex condom during sexual intercourse if you do not know that your partner has been free of HIV for the past five years; (5) avoid oral sex because this can be a means of transmission; and (6) be cautious about the use of alcohol or any drug that may prevent you from being able to control your behavior.

The Chapter in Review

Summary

26.1 Organs, Tissues, and Cells of the Immune System

The immune system consists of lymphatic organs, tissues, and cells, as well as the products of these cells. The lymphatic organs are:

• Red bone marrow, where all blood cells are made and the
B lymphocytes mature.

• Thymus gland, where T lymphocytes mature (see Table 26.1).

• Lymph nodes, where lymph is cleansed of pathogens and debris.

• Spleen, where blood is cleansed of pathogens and debris.

• Other organs, such as the tonsils and appendix, are patches of lymphatic tissue.

26.2 Nonspecific Defenses

Immunity involves nonspecific and specific defenses. Nonspecific defenses include:

• Barriers to entry (e.g., skin).

• Inflammatory response involves mast cells, which release histamine to increase capillary permeability resulting in redness, warmth, swelling, and pain. Neutrophils and macrophages enter tissue fluid and engulf pathogens.

• The complement system has many functions. One is to attack bacteria outright by forming a pore in the surface of a bacterium. Water and salts then enter, and the bacterium bursts.

• Natural killer cells that can tell self proteins from nonself and cause virus-infected cells to undergo apoptosis.

26.3 Specific Defenses

Specific defenses require B lymphocytes and T lymphocytes, also called B cells and T cells.

B Cells and the Antibody Response

The BCR (B-cell receptor) of each type B cell is specific to a particular antigen. When the antigen binds to a BCR, that B cell divides to produce plasma cells and memory B cells.

• Plasma cells secrete antibodies and eventually undergo apoptosis. Plasma cells are responsible for antibody response to an antigen.

• Memory B cells remain in the body and produce antibodies if the same antigen enters the body at a later date.

T Cells and the Cellular Response

T cells are responsible for cellular response to an infection. Each TCR (T-cell receptor) is specific to a particular antigen. For a T cell to recognize an antigen, the antigen must be presented to it, usually by a macrophage, along with an MHC protein. Thereafter, the activated
T cell divides and produces either cytotoxic T cells or helper T cells.

• Cytotoxic T cells kill virus-infected or cancer cells on contact because these cells bear the MHC  antigen it has learned to recognize. First, perforin is secreted, and these molecules form a pore; then granzymes are secreted and cause the cell to undergo apoptosis.

• Helper T cells produce cytokines and stimulate other immune cells.

26.4 Immunizations

Immunity occurs after an infection or a vaccination.

• A vaccine brings about immunity to a particular infection. Two injections may be required because the number of antibodies is higher after the second injection, called a booster shot. A booster shot in the future also increases the number of antibodies.

• Passive immunity (receiving preformed antibodies) is short-lived because the antibodies are administered to, not made by, the individual.

26.5 Immune System Problems

Allergies

Allergic responses to various substances can be immediate or delayed. Anaphylactic shock is a dangerous immediate allergic response.

Autoimmune Diseases

In an autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, and perhaps diabetes type 1), the immune system mistakenly attacks the body’s tissues.

AIDS

The HIV virus lives in and destroys helper T cells. Without drug treatment, the number of T cells falls off, and the individual dies from infections that are rare in healthy individuals. Sexual contact and needle-sharing transmit AIDS from person to person. Combined drug therapy has prolonged the lives of some people infected with HIV. So far, vaccine research has met with limited success. However, AIDS is a preventable disease if certain behaviors are avoided.

Thinking Scientifically

1. The human body is exposed to many antigens over a lifetime. It is estimated that the mammalian genome contains the information needed to produce a million different antibodies. Considering that there are only about 30,000 genes in the human genome, how can it make a million different antibodies?

2. The transplantation of organs from one person to another was impossible until the discovery of immunosuppressive drugs. Now, with the use of drugs such as cyclosporine, organs can be transplanted without rejection. Transplant patients must take immunosuppressive drugs for the remainder of their lives. How can a person do this and not eventually succumb to disease?

Testing Yourself

Choose the best answer for each question.

1. This lymphatic tissue is associated with the respiratory system.

a. red bone marrow

b. spleen

c. tonsil

d. appendix

e. lymph node

2. Label the lymphatic organs in the following illustration.

3. Which of the following is not a barrier to pathogen entry?

a. oil gland secretions of the skin

b. acidic pH in the stomach

c. cilia in the upper respiratory tract

d. nonpathogenic bacteria in the digestive tract

e. saliva in the mouth

For questions 4–9, identify the lymphatic organ in the key that matches the description. Some answers may be used more than once.

Key:

a. red bone marrow

b. thymus gland

c. lymph nodes

d. spleen

4. Produces stem cells.

5. Located in every body cavity except the dorsal cavity.

6. Produces lymphocytes.

7. Site of maturation of T cell.

8. Contains red pulp and white pulp.

9. Shrinks with age.

10. During the inflammatory response,

a. T cells move to the site of injury.

b. capillaries become constricted.

c. histamine is produced.

d. capillaries become less permeable.

e. More than one of these are correct.

11. Which is a lymphatic organ?

a. spleen

b. tonsil

c. thymus gland

d. All of these are correct.

12. The _________ cleanses _________, and in its absence, problems associated with _________ may occur.

a. spleen, lymph, oxygen transport

b. liver, lymph, infection

c. spleen, blood, infection

d. spleen, blood, oxygen transport

13. Which cells will phagocytize pathogens?

a. neutrophils

b. macrophages

c. mast cells

d. Both a and b are correct.

14. Complement

a. is a general defense mechanism.

b. is involved in the inflammatory response.

c. is a series of proteins present in the plasma.

d. plays a role in destroying bacteria.

e. All of these are correct.

15. _{_________ release histamines.}

a. Mast cells

b. Neutrophils

c. Monocytes

d. All of these are correct.

16. Which applies to T lymphocytes?

a. mature in bone marrow

b. mature in thymus gland

c. Both a and b are correct.

d. None of these are correct.

17. AIDS is caused by which of the following viruses?

a. SIV

b. HSV

c. HPV

d. AIDS

e. HIV

18. Plasma cells are

a. the same as memory cells.

b. formed from blood plasma.

c. B cells that are actively secreting antibody.

d. inactive T cells carried in the plasma.

e. a type of red blood cell.

19. Vaccines are associated with

a. active immunity.

b. long-lasting immunity.

c. passive immunity.

d. Both a and b are correct.

20. MHC proteins play a role in

a. active immunity.

b. histamine release.

c. tissue transplantation.

d. All of these are correct.

21. Programmed cell death is known as

a. activation.

b. apoptosis.

c. clonal selection.

d. None of these are correct.

22. Type O blood has _________ antibodies in the plasma.

a. A

b. B

c. Both a and b are correct.

d. Neither a nor b is correct.

23. Label the following diagram of skin.

24. Which of the following is a nonspecific defense of the body?

a. immunoglobulin

b. B cell

c. T cell

d. vaccine

e. inflammatory response

25. Antibodies combine with antigens

a. at variable regions.

b. at other regions.

c. only if macrophages are present.

d. Both a and c are correct.

26. Which one of these pairs is mismatched?

a. helper T cells—help complement react

b. cytotoxic T cells—active in tissue rejection

c. macrophages—activate T cells

d. memory T cells—long-living line of T cells

e. T cells—mature in thymus

27. An antigen-presenting cell (APC)

a. presents antigens to T cells.

b. secretes antibodies.

c. marks each human cell as belonging to that particular person.

d. secretes cytokines.

28. Which of the following would not be a participant in cell-mediated immune responses?

a. helper T cells

b. macrophages

c. cytokines

d. cytotoxic T cells

e. plasma cells

29. Vaccines are

a. the same as monoclonal antibodies.

b. treated bacteria or viruses, or one of their proteins.

c. short-lived.

d. MHC proteins.

e. All of these are correct.

30. Which of the following is not an example of an autoimmune disease?

a. multiple sclerosis

b. myasthenia gravis

c. contact dermatitis

d. systemic lupus erythematosus

e. rheumatoid arthritis

31. Natural killer cells attack cells that

a. have been determined to contain a virus.

b. have lost their self proteins.

c. are malformed.

d. are dividing rapidly.

32. A person with type A blood can receive a transfusion from someone with type

a. A blood only.

b. A or B blood.

c. A or AB blood.

d. A or O blood.

e. A, B, AB, or O blood.

33. Unlike B cells, T cells

a. require help to recognize an antigen.

b. are components of a specific defense response.

c. are types of lymphocytes.

d. contribute to homeostasis.

34. Passive immunity

a. is permanent.

b. may result from immunoglobulin injections.

c. requires memory B cells.

d. may be induced by vaccines.

35. Anaphylactic shock is an example of

a. an immediate allergic response.

b. an autoimmune disease.

c. a type of serum shock.

d. a delayed allergic response.

36. The HIV virus lives in and destroys

a. B cells.

b. cytotoxic T cells.

c. helper T cells.

d. All of these are correct.

37. AIDS patients generally die due to which of the following causes?

a. rare diseases and infections

b. HIV virus

c. strokes

d. heart attacks

e. cancer

Go to www.mhhe.com/maderessentials for more quiz questions.

Bioethical Issue

Over 36 million people worldwide are living with AIDS. This disease is deadly without proper medical care, but can be chronic if treated. Drug companies typically charge a high price for AIDS medications because Americans and their insurance companies can afford them. However, these drugs are out of reach in many countries, such as those in Africa, where AIDS is a widespread problem. Some people argue that drug companies should use the profits from other drugs (such as those for heart disease, depression, and impotence) to make AIDS drugs affordable to those who need them. That has not happened yet. In some countries, governments have allowed companies to infringe on foreign patents held by major drug companies so that they can produce affordable AIDS drugs. Do drug companies have a moral obligation to provide low-cost AIDS drugs, even if they have to do so at a loss of revenue? Is it right for governments to ignore patent laws in order to provide their citizens with affordable drugs?

Understanding the Terms

active immunity464

agglutination461

AIDS (acquired immunodeficiency
syndrome)466

allergen465

allergy465

antibody456

antigen456

antigen-presenting cell
(APC)462

appendix456

autoimmune disease465

B-cell receptor (BCR)460

B lymphocyte (B cell)457

complement system459

cytokine463

cytotoxic T cell462

delayed allergic response465

helper T cell463

histamine458

HIV (human immunodeficiency
virus)466

immediate allergic response465

immune system456

immunity456

inflammatory response458

lymph node457

lymphatic organs456

macrophage457

mast cell458

natural killer (NK) cell459

neutrophil458

passive immunity464

red bone marrow457

spleen457

T-cell receptor (TCR)462

T lymphocyte (T cell)457

thymus gland457

tonsils456

vaccine464

Match the terms to these definitions:

a. _______________ Region of lymphatic tissue attached to the large intestine.

b. _______________ Site of blood cell production.

c. _______________ Large white blood cell that phagocytizes pathogens and presents antigens to T cells.

d. _______________ Chemical that causes capillaries to dilate and become more permeable.

e. _______________ White blood cell produced in the bone marrow that gives rise to plasma cells.

f. _______________ Clumping of red blood cells.

g. _______________ Secretes granzymes into infected cells to cause apoptosis.

h. _______________ Substance that doesn’t cause illness, but results in immunity.

i. _______________ Antigens that cause allergies.

j. _______________ Condition that results when cytotoxic T cells attack the body’s own cells.

A fever increases metabolism, enabling the immune system to fight infection more efficiently.

People who have had organ transplants must take immunosuppressive drugs for the rest of their lives.

Figure 26.1Lymphatic organs.

The red bone marrow, the thymus gland, the lymph nodes, and the spleen are lymphatic organs essential to immunity. The cells of the immune system, including lymphocytes, are found in these organs and also in the lymph of lymphatic vessels.

Check Your Progress

1. List the components of the immune system.

2. List the lymphatic organs, and identify their functions.

3. What does an antibody do?

Answers:1. The immune system is composed of lymphatic organs, tissues, and cells as well as the products of those cells, including antibodies.2. Red bone marrow: produces blood cells, including white blood cells; thymus: aids in maturation of T lymphocytes and testing of their ability to function; spleen: filters blood of pathogens and debris; lymph nodes: filter lymph of pathogens and debris.3. An antibody combines with and destroys an antigen.

Check Your Progress

1. Describe the steps in the inflammatory response.

2. Describe the function of the complement system.

3. Explain how natural killer cells “know” what to attack.

Answers:1. Damaged cells and mast cells release chemicals that cause capillaries to dilate and become more permeable. Neutro-phils and macrophages phagocytize pathogens.2. The complement system produces proteins that complement other forms of immunity.3. Natural killer cells attack cells that have lost their ability to produce self proteins, often because of a viral infection.

Figure 26.2Skin.

The cells of the epidermis harden and die as they progress to the outer layer of skin. These outer dead cells form a protective barrier against invasion by pathogens. The sweat and oil glands are acidic enough to inhibit invasion by bacteria.

Figure 26.3The inflammatory response.

If you cut your skin, the inflammatory response occurs immediately. As blood flow increases, the area gets red and warm. As mast cells, a type of white blood cell, release chemicals such as histamine, the capillary becomes more permeable, localized swelling occurs, and pain receptors are stimulated. Neutrophils and macrophages begin phagocytizing the bacteria.

Figure 26.4Ways to get rid of pathogens.

a. Macrophages, the body’s scavengers, engulf pathogens and chop them up inside lysosomes. b. Complement proteins come together and form a membrane attack complex in the surface of a pathogen. Water and salts enter, and the pathogen bursts.

Check Your Progress

1.
Explain how antibodies are produced in response to an antigen.

2. Explain what the letters in an ABO blood type refer to.

Answers:1. The B-cell receptor binds to the antigen and activates the B cell carrying that receptor. This causes the B cell to produce many plasma cells. The plasma cells secrete antibodies against the antigen.2. The letters A, B, AB, and O refer to the antigens carried on red blood cells. Type A produces antigen A, type B produces antigen B, type AB produces both antigens A and B, and type O does not produce antigen A or B.

Figure 26.5B cell and the antibody response.

When an antigen combines with a BCR, the B cell divides to produce plasma cells and memory B cells. Plasma cells produce antibodies but eventually disappear. Memory B cells remain in the body ready to produce the same antibody in the future.

Figure 26.6Why an antibody is specific.

a. During a lifetime, a person will encounter a million different antigens that differ in shape. An antibody has two variable regions that end in an antigen-binding site. The variable regions vary so much that the binding site of each antibody has a shape that will fit only one specific antigen. b. Computer model of an antibody molecule. The antigen combines with the two side branches.

Check Your Progress

1. Compare and contrast B cells with T cells.

2. What happens to plasma cells and cytotoxic T cells when an infection has passed?

Answers:1. Both are involved with specific defenses against disease.
B cells are produced in the bone marrow and give rise to plasma cells that produce antibodies. T cells are produced in the thymus gland and when activated become either cytotoxic or helper T cells.2. They undergo programmed cell death, called apoptosis.

Figure 26.7Activation of a T cell.

For a T cell to be activated, the antigen must be presented along with an MHC protein to the T cell by an APC, often by a macrophage. Each type of T cell bears a specific receptor, and if its TCR fits the MHC 1 antigen complex, it is activated to divide and produce more T cells—in this case, helper T cells, which also have this type TCR.

Figure 26.8Cytotoxic T cells and the cellular
response.

a. Scanning electron micrograph of cytotoxic T cell attacking a target cell, which is either a virus-infected or cancer cell.
b. A cytotoxic T cell attacks any cell that presents it with an
MHC I  antigen it has learned to recognize. First, vesicles release perforin, which forms a pore in the target cell. Then vesicles release granzymes, which cause the cell to undergo apoptosis.

Check Your Progress

1. Explain why you cannot be vaccinated for most sexually transmitted diseases.

2. Describe the function of a booster shot.

3. Explain the function of gamma globulin injections to prevent illness in a patient who is unexpectedly exposed to an infectious disease.

Answers:1. People cannot become immune to sexually transmitted diseases, so vaccines are ineffective.2. A booster shot is an injection of the same vaccine to increase the antibody concentration to a high level.3. Gamma globulin from someone who had the same disease will contain antibodies against the pathogen in question.

Figure 26.9Active immunity due to immunizations.

a. Immunization often requires more than one injection.
b. A minimal primary response occurs after the first vaccine injection, but after a second injection, the secondary response usually shows a dramatic rise in the amount of antibody present in plasma.

Figure 26.10Allergies.

When people are allergic to pollen, they develop symptoms that include watery eyes, sinus headaches, increased mucus production, labored breathing, and sneezing.

Figure 26.11Rheumatoid arthritis.

Rheumatoid arthritis is due to recurring inflammation in skeletal joints. Complement proteins, T cells, and B cells all participate in deterioration of the joints, which eventually become immobile.

Check Your Progress

1. Describe the relationship between allergies and allergens.

2.
Contrast an immediate allergic response with a delayed allergic response.

3. Explain why AIDS patients cannot fight pathogens.

Answers:1. Allergies are hypersensitive responses to antigens called allergens.2. An immediate allergic response occurs within seconds of exposure to an allergen and is caused by chemicals released by mast cells. Delayed allergic responses take longer to develop and are probably initiated by memory T cells.3. The HIV virus lives in and destroys helper T cells, which are necessary for the activity of all other immune system cells.

Figure 26.12HIV infection.

a. An HIV infection leads to AIDS, characterized by a number of associated illnesses, including a cancer that results in skin lesions. b. At first the body produces enough helper T cells to keep the HIV infection under control, but then as the number of helper T cells declines, the HIV infection takes over.

Table 26.1

Immunocell Type and Function

Cell	Function
Macrophages	Phagocytize pathogens; inflammatory response and specific immunity
Mast cells	Release histamine, which promotes blood flow to injured tissues; inflammatory response
Neutrophils	Phagocytize pathogens; inflammatory response
Natural killer cells	Kill virus-infected and tumor cells by cell-to-cell contact
Lymphocytes	Responsible for specific immunity
B cells	Produce plasma cells and memory cells
Plasma cells	Produce specific antibodies
Memory cells	Ready to produce antibodies in the future
T cells	Regulate immune response; produce cytotoxic T cells and helper T cells
Cytotoxic T cells	Kill virus-infected and cancer cells
Helper T cells	Regulate immunity

Table 26.3

Blood Types

Blood Type	Antigens on Red Blood Cells	Antibodies in Plasma
A	A	Anti-B
B	B	Anti-A
AB	A,B	Neither anti-A nor anti-B
O	—	Both anti-A and anti-B

Table 26.2

Characteristics of B Cells

• Provide an antibody response to a pathogen

• Produced and become mature in bone marrow

• Reside in lymph nodes and spleen; circulate in blood and lymph

• Directly recognize antigen and then undergo cell division

• Cell division produces antibody-secreting plasma cells as well as memory B cells

Table 26.4

Characteristics of T Cells

• Provide a cellular response to virus-infected cells and cancer cells

• Produced in bone marrow, mature in thymus gland

• Antigen must be presented in groove of an MHC^1 molecule

• Cytotoxic T cells destroy nonself protein-bearing cell

• Helper T cells secrete cytokines that control the immune response

¹ MHC 5 major histocompatibility complex. The MHC genes encode MHC proteins that are displayed on the cell surface and define an individual’s tissue type. When tissues/organs have like MHC proteins, they are histocompatible, and transplants between individuals are possible.

SEM of pollen