Immunity

Question 1

What is the ideal environment for a pathogen and why?

Answer 1

For a pathogen—a bacterium, fungus, virus, or other disease-causing agent—the internal environment of an animal is a nearly ideal habitat. The animal body offers a ready source of nutrients, a protected setting for growth and reproduction, and a means of transport to new environments

Question 2

What is the immune system?.

Answer 2

From the perspective of a cold or flu virus, we are wonderful hosts. From our vantage point, the situation is not so ideal. Fortunately, adaptations have arisen over the course of evolution that protect animals against many invaders. Dedicated immune cells in the body fluids and tissues of most animals specifically interact with and destroy pathogens. For example, Figure 35.1 shows an immune cell called a macrophage (brown) surrounding and engulfing a clump of bacteria (green). Immune cells also release defense molecules into body fluids, including proteins that punch holes in bacterial membranes or block viruses from entering body cells. Together, the body’s defenses make up the immune system, which enables an animal to avoid or limit many infections. A foreign molecule or cell doesn’t have to be pathogenic (disease-causing) to elicit an immune response, but we’ll focus in this chapter on the immune system’s role in defending against pathogens.

Question 3

What is the first line of defense of the immune system?

Answer 3

The first lines of defense offered by immune systems help prevent pathogens from gaining entrance to the body. For example, an outer covering, such as a shell or skin, blocks entry by many microbes. Sealing off the entire body surface is impossible, however, because gas exchange, nutrition, and reproduction require openings to the environment. Secretions that trap or kill microbes guard the body’s entrances and exits, while the linings of the digestive tract, airway, and other exchange surfaces provide additional barriers to infection.

Question 4

What is the primary function of the immune system once the pathogen has breached barrier defenses? How does it do that?

Answer 4

If a pathogen breaches barrier defenses and enters the body, the problem of how to fend off attack changes substantially. Housed within body fluids and tissues, the invader is no longer an outsider. To fight infections, an animal’s immune system must detect foreign particles and cells within the body. In other words, a properly functioning immune system distinguishes nonself from self. How is this accomplished? Immune cells produce receptor molecules that bind specifically to molecules from foreign cells or viruses and activate defense responses. The specific binding of immune receptors to foreign molecules is a type of molecular recognition and is the central event in identifying nonself particles and cells.

Question 5

What are the two major components of molecular recognition and defense?

Answer 5

Animal immune systems rely on either one or two major components for molecular recognition and defense. All animals have the component called innate immunity, which includes barrier defenses. Besides innate immunity, an additional component, called adaptive immunity, is found only in vertebrates. Figure 35.2 provides an overview of the basic components of both innate and adaptive immunity.

Question 6

What is innate immunity?

Answer 6

Molecular recognition in innate immunity relies on a small set of receptors that bind to molecules or structures that are absent from animal bodies but common to a group of viruses, bacteria, or other microbes. Binding of an innate immune receptor to a foreign molecule activates internal defenses, enabling responses to a very broad range of pathogens.

Question 7

What is adaptive immunity?

Answer 7

In adaptive immunity, molecular recognition relies on a vast arsenal of receptors, each of which recognizes a feature typically found only on a particular part of a particular molecule in a particular pathogen. As a result, recognition and response in adaptive immunity occur with tremendous specificity.
The adaptive immune response, also known as the acquired immune response, is activated after the innate immune response and develops more slowly. The names adaptive and acquired reflect the fact that this immune response is enhanced by previous exposure to the infecting pathogen. Examples of adaptive responses include the synthesis of proteins that inactivate a bacterial toxin and the targeted killing of a virus-infected body cell.

Question 8

Which type of immunity do vertebrates have?

Answer 8

In innate immunity, recognition and response rely on traits common to groups of pathogens Innate immunity is found in all animals (as well as in plants). In exploring innate immunity, we’ll begin with invertebrates, which repel and fight infection with only this type of immunity. We’ll then turn to vertebrates, in which innate immunity serves both as an immediate defense against infection and as the foundation for adaptive immune defenses.

Question 9

Which enzyme acts as a chemical barrier against pathogens ingested with food and how does it work? Which immune response is it part of?

Answer 9

Innate Immunity of Invertebrates The great success of insects in terrestrial and freshwater habitats teeming with diverse microbes highlights the effectiveness of invertebrate innate immunity. In each of these environments, insects rely on their exoskeleton as a first line of defense against infection. Within the digestive system, lysozyme, an enzyme that breaks down bacterial cell walls, acts as a chemical barrier against pathogens ingested with food.

Question 10

What immune defenses are found by a pathogen that breaches an insect’s barrier defenses?

Answer 10

Any pathogen that breaches an insect’s barrier defenses encounters a number of internal immune defenses. Immune cells called hemocytes travel throughout the body in the hemolymph, the insect circulatory fluid. Some hemocytes ingest and break down bacteria and other foreign substances, a process known as phagocytosis (Figure 35.3). Other hemocytes release chemicals that kill pathogens and help entrap large invaders, such as Plasmodium, the parasite of mosquitoes that causes malaria in humans. One major class of defense molecules consists of antimicrobial peptides, which circulate throughout the body and inactivate or kill fungi and bacteria by disrupting their plasma membranes.

Question 11

Explain the immune system identification process of insects.

Answer 11

Immune cells of insects bind to molecules found only in the outer layers of fungi or bacteria. Fungal cell walls contain certain unique polysaccharides, whereas bacterial cell walls have polymers containing combinations of sugars and amino acids not found in animal cells. Such macromolecules serve as “identity tags” in the process of pathogen recognition. Insect immune cells secrete recognition proteins, each of which binds to a macromolecule characteristic of a broad class of bacteria or fungi. Once bound to a macromolecule, the recognition protein triggers an innate immune response specific for that class.

Question 12

Which immune response(s) do jawed vertebrates have?

Answer 12

Innate Immunity of Vertebrates Among jawed vertebrates, innate immune defenses coexist with the more recently evolved system of adaptive immunity. Because most of the recent discoveries regarding vertebrate innate immunity have come from studies of mice and humans, we’ll focus here on mammals. We’ll consider first the innate defenses that are similar to those found among invertebrates: barrier defenses, phagocytosis, and antimicrobial peptides. We’ll then examine some unique aspects of vertebrate innate immunity, such as natural killer cells, interferons, and the inflammatory response.

Question 13

What are some examples of barrier defenses in mammals? (immune system)

Answer 13

Barrier Defenses In mammals, barrier defenses block the entry of many pathogens. These defenses include the skin and the mucous membranes lining the digestive, respiratory, urinary, and reproductive tracts. The mucous membranes produce mucus, a viscous fluid that traps microbes and other particles. In the airway, ciliated epithelial cells sweep mucus and any entrapped microbes upward, helping prevent infection of the lungs.

Question 14

Which enzyme is important to the immune system’s barrier in mammals? What other chemical responses are there?

Answer 14

Beyond their physical role in inhibiting microbial entry, body secretions create an environment that is hostile to many microbes. Lysozyme in tears, saliva, and mucous secretions destroys the cell walls of susceptible bacteria as they enter the openings around the eyes or the upper respiratory tract. Microbes in food or water and those in swallowed mucus must also contend with the acidic environment of the stomach, which kills most of them before they can enter the intestines. Similarly, secretions from oil and sweat glands give human skin a pH ranging from 3 to 5, acidic enough to prevent the growth of many bacteria.

Question 15

How do phagocytic cells detect fungal or bacterial components? What do phagocytic cells to start the response once a pathogen enters the mammalian body?

Answer 15

Cellular Innate Defenses Pathogens entering the mammalian body are engulfed by phagocytic cells that detect fungal or bacterial components using several types of receptors. Some mammalian receptors are very similar to Toll, a key activator of innate immunity in insects.

Question 16

How does a TLC receptor work? What does it do?

Answer 16

Each mammalian Toll-like receptor (TLR) binds to fragments of molecules characteristic of a set of pathogens (Figure 35.4). For example, TLR3 binds to double-stranded RNA, a form of nucleic acid characteristic of certain viruses. Similarly, TLR4 recognizes lipopolysaccharide, a molecule found on the surface of many bacteria, and TLR5 recognizes flagellin, the main protein of bacterial flagella. In each case, the recognized macromolecule is normally absent from the vertebrate body and is an essential component of certain groups of pathogens.

Question 17

What does the detection of invading pathogen trigger in mammals?

Answer 17

As in invertebrates, detection of invading pathogens in mammals triggers phagocytosis and destruction.

Question 18

What are the two main types of phagocytic cells in the mammalian body?

Answer 18

The two main types of phagocytic cells in the mammalian body are neutrophils and macrophages.

Question 19

What are neutrophils?

Answer 19

Neutrophils, which circulate in the blood, are attracted by signals from infected tissues.

Question 20

What are macrophages?

Answer 20

Macrophages (“big eaters”) are larger phagocytic cells. Some migrate throughout the body, whereas others reside in organs and tissues where they are likely to encounter pathogens. For example, some macrophages are located in the spleen, where pathogens in the blood become trapped.

Question 21

What are the two secondary types of phagocytic cells in the mammalian immune response? What do they do?

Answer 21

Two other types of cells—dendritic cells and eosinophils— provide additional functions in innate defense. Dendritic cells mainly populate tissues, such as skin, that contact the environment.
They stimulate adaptive immunity against pathogens they encounter and engulf, as we’ll explore shortly. Eosinophils, often found beneath mucous membranes, are important in defending against multicellular invaders, such as parasitic worms. Upon encountering such parasites, eosinophils discharge destructive enzymes.

Question 22

What are natural killer cells? What do they do?

Answer 22

Cellular innate defenses in vertebrates also involve natural killer cells. These cells circulate through the body and detect the abnormal array of surface proteins characteristic of some virus-infected and cancerous cells. Natural killer cells do not engulf stricken cells. Instead, they release chemicals that lead to cell death, inhibiting further spread of the virus or cancer.

Question 23

How is the lymphatic system involved in cellular innate defenses in vertebrates?

Answer 23

Many cellular innate defenses in vertebrates involve the lymphatic system (see Figure 34.12). Some macrophages reside in lymph nodes, where they engulf pathogens that have entered the lymph from the interstitial fluid. Dendritic cells reside outside the lymphatic system but migrate to the lymph nodes after interacting with pathogens. Within the lymph nodes, dendritic cells interact with other immune cells, stimulating adaptive immunity.

Question 24

How are peptides and proteins involved in the immune system?

Answer 24

Antimicrobial Peptides and Proteins In mammals, pathogen recognition triggers the production and release of a variety of peptides and proteins that attack pathogens or impede their reproduction. Some of these defense molecules function like the antimicrobial peptides of insects, damaging broad groups of pathogens by disrupting membrane integrity. Others, including the interferons and complement proteins, are unique to vertebrate immune systems.

Question 25

What are interferons? What do they do? Where do they come from?

Answer 25

Interferons are proteins that provide innate defense by interfering with viral infections. Virus-infected body cells secrete interferons, which induce nearby uninfected cells to produce substances that inhibit viral reproduction. In this way, interferons limit the cell-to-cell spread of viruses in the body, helping control viral infections such as colds and influenza.
Some white blood cells secrete a different type of interferon that helps activate macrophages, enhancing their phagocytic ability. Pharmaceutical companies now use recombinant DNA technology to mass-produce interferons to help treat certain viral infections, such as hepatitis C.

Question 26

What is the infection-fighting complement system?

Answer 26

The infection-fighting complement system consists of roughly 30 proteins in blood plasma. These proteins circulate in an inactive state and are activated by substances on the surface of many microbes. Activation results in a cascade of biochemical reactions that can lead to lysis (bursting) of invading cells. The complement system also functions in the inflammatory response, our next topic, as well as in the adaptive defenses discussed later in the chapter.

Question 27

What is the inflammatory response? What s the most important inflammatory signaling molecule and how does it work?

Answer 27

Inflammatory Response The pain and swelling that alert you to a splinter under your skin are the result of a local inflammatory response, the changes brought about by signaling molecules released upon injury or infection (Figure 35.5). One important inflammatory signaling molecule is histamine, which is stored in the granules (vesicles) of mast cells, found in connective tissue. Histamine released at sites of damage triggers nearby blood vessels to dilate and become more permeable. Activated macrophages and neutrophils discharge cytokines, signaling molecules that in an immune response promote blood flow to the site of injury or infection. The increase in local blood supply causes the redness and increased skin temperature typical of the inflammatory response (from the Latin inflammare, to set on fire). Blood-engorged capillaries leak fluid into neighboring tissues, causing swelling.

Question 28

Describe cycles of signaling and response during inflammation.

Answer 28

During inflammation, cycles of signaling and response transform the site. Activated complement proteins promote further release of histamine, attracting more phagocytic cells that enter injured tissues (see Figure 35.5) and carry out additional phagocytosis. At the same time, enhanced blood flow to the site helps deliver antimicrobial peptides. The result is an accumulation of pus, a fluid rich in white blood cells, dead pathogens, and cell debris from damaged tissue.

Question 29

What is a systemic inflammatory response? How is it different than a local inflammatory response?

Answer 29

A minor injury or infection causes a local inflammatory response, but severe tissue damage or infection may lead to a response that is systemic (throughout the body). Cells in injured or infected tissue often secrete molecules that stimulate the release of additional neutrophils from the bone marrow. In a severe infection, such as meningitis or appendicitis, the number of white blood cells in the blood may increase several-fold within a few hours.

Question 30

What type of immune response is fever and why might it occur?

Answer 30

Another systemic inflammatory response is fever. In response to certain pathogens, substances released by activated macrophages cause the body’s thermostat to reset to a higher temperature (see Concept 32.1). The benefits of the resulting fever are still a subject of debate. One hypothesis is that an elevated body temperature may enhance phagocytosis and, by speeding up chemical reactions, accelerate tissue repair.

Question 31

What is septic shock? How is it caused?

Answer 31

Certain bacterial infections can induce an overwhelming systemic inflammatory response, leading to a life-threatening condition called septic shock. Characterized by very high fever, low blood pressure, and poor blood flow through capillaries, septic shock occurs most often in the very old and the very young. It is fatal in more than one-third of cases and kills more than 90,000 people each year in the United States alone.

Question 32

What is chronic inflammation?

Answer 32

Chronic (ongoing) inflammation can also threaten human health. For example, millions of individuals worldwide suffer from Crohn’s disease and ulcerative colitis, often debilitating disorders in which an unregulated inflammatory response disrupts intestinal function.

Question 33

How can pathogens evade innate immunity?

Answer 33

Evasion of Innate Immunity by Pathogens Adaptations have evolved in some pathogens that enable them to avoid destruction by phagocytic cells. For example, the outer capsule that surrounds certain bacteria interferes with molecular recognition and phagocytosis. One such bacterium, Streptococcus pneumoniae, played a critical role in the discovery that DNA can convey genetic information (see Figure 13.2). Other bacteria, after being engulfed by a host cell, resist breakdown within lysosomes. An example is the bacterium that causes tuberculosis (TB). Rather than being destroyed within host cells, this bacterium grows and reproduces, effectively hidden from the body’s innate immune defenses. These and other mechanisms that prevent destruction by the innate immune system make certain fungi and

Question 34

What are lymphocytes?

Answer 34

Vertebrates are unique in having adaptive immunity in addition to innate immunity. The adaptive response relies on T cells and B cells, which are types of white blood cells called lymphocytes. Like all blood cells, lymphocytes originate from stem cells in the bone marrow. Some lymphocytes migrate from the bone marrow to the thymus, an organ in the thoracic cavity above the heart (see Figure 34.12). These lymphocytes mature into T cells. Lymphocytes that remain and mature in the bone marrow develop as B cells.

Question 35

What is an antigen and what is its role in immunity?

Answer 35

Any substance that elicits a response from a B cell or T cell is called an antigen. In adaptive immunity, recognition occurs when a B cell or T cell binds to an antigen, such as a bacterial or viral protein, via a protein called an antigen receptor. An antigen receptor is specific enough to bind to just one part of one molecule from a particular pathogen, such as a species of bacteria or strain of virus. Although the cells of the immune system produce millions of different antigen receptors, all of the antigen receptors made by a single B or T cell are identical. Infection by a virus, bacterium, or other pathogen triggers activation of B and T cells with antigen receptors specific for parts of that pathogen. B and T cells are shown in this text with only a few antigen receptors, but there are actually about 100,000 antigen receptors on the surface of a single B or T cell.

Question 36

What is an epitope?

Answer 36

Antigens are usually foreign and are typically large molecules, either proteins or polysaccharides. The small, accessible portion of an antigen that binds to an antigen receptor is called an epitope, or antigenic determinant. An example is a group of amino acids in a particular protein. A single antigen usually has several different epitopes, each of which binds to a receptor with a different specificity. Because all antigen receptors produced by a single B cell or T cell are identical, they bind to the same epitope. Each B or T cell thus displays specificity for a particular epitope, enabling it to respond to any pathogen that produces molecules containing that same epitope.

Question 37

The antigen receptors of B cells and T cells have similar components, but they encounter antigens in different ways. How do B cells recognize antigens?

Answer 37

We’ll consider the two processes in turn. Antigen Recognition by B Cells and Antibodies Each B cell antigen receptor is a Y-shaped molecule consisting of four polypeptide chains: two identical heavy chains and two identical light chains, with disulfide bridges linking the chains together (Figure 35.6). A transmembrane region near one end of each heavy chain anchors the receptor in the cell’s plasma membrane. A short tail region at the end of the heavy chain extends into the cytoplasm.
The light and heavy chains each have a constant (C) region, where amino acid sequences vary little among the receptors on different B cells. Within the two tips of the Y shape (see Figure 35.6), each chain has a variable (V) region, so named because its amino acid sequence varies extensively from one B cell to another. Together, parts of a heavy-chain V region and a light-chain V region form an asymmetric binding site for an antigen. As shown in Figure 35.6, each B cell antigen receptor has two identical antigen-binding sites.
The binding of a B cell antigen receptor to an antigen is an early step in B cell activation, leading eventually to formation of cells that secrete a soluble form of the receptor (Figure 35.7a). This secreted protein is called an antibody, or immunoglobulin (Ig). Antibodies have the same Y-shaped organization as B cell antigen receptors, but they are secreted rather than membrane-bound. It is the antibodies, rather than the B cells themselves, that actually help defend against pathogens. The antigen-binding site of a membrane-bound receptor or antibody has a unique shape that provides a lock-and-key fit for a particular epitope. Many noncovalent bonds between an epitope and the binding surface provide a stable and specific interaction. Differences in the amino acid sequences of variable regions provide the variation in binding surfaces that enables this highly specific binding.
B cell antigen receptors and antibodies bind to intact antigens in the blood and lymph. As illustrated in Figure 35.7b for antibodies, they can bind to antigens on the surface of pathogens or free in body fluids.

Question 38

What is an Immunoglobulin? How is it produced?

Answer 38

The binding of a B cell antigen receptor to an antigen is an early step in B cell activation, leading eventually to formation of cells that secrete a soluble form of the receptor (Figure 35.7a). This secreted protein is called an antibody, or immunoglobulin (Ig). Antibodies have the same Y-shaped organization as B cell antigen receptors, but they are secreted rather than membrane-bound. It is the antibodies, rather than the B cells themselves, that actually help defend against pathogens. The antigen-binding site of a membrane-bound receptor or antibody has a unique shape that provides a lock-and-key fit for a particular epitope. Many noncovalent bonds between an epitope and the binding surface provide a stable and specific interaction. Differences in the amino acid sequences of variable regions provide the variation in binding surfaces that enables this highly specific binding.

Question 39

Describe the antigen receptor of a T cell.

Answer 39

Antigen Recognition by T Cells For a T cell, the antigen receptor consists of two different polypeptide chains, an α chain and a β chain, linked by a disulfide bridge (Figure 35.8). Near the base of the T cell antigen receptor (often called simply a T cell receptor) is a transmembrane region that anchors the molecule in the cell’s plasma membrane. At the outer tip of the molecule, the variable (V) regions of α and β chains together form a single antigen-binding site. The remainder of the molecule is made up of the constant (C) regions.

Question 40

How are T and B cell antigen recognitions different?

Answer 40

Whereas the antigen receptors of B cells bind to epitopes of intact antigens on pathogens or circulating in body fluids, those of T cells bind only to fragments of antigens that are displayed, or presented, on the surface of host cells. The host protein that displays the antigen fragment on the cell surface is called a major histocompatibility complex (MHC) molecule.

Question 41

How does a T cell recognize antigens?

Answer 41

Recognition of protein antigens by T cells begins when a pathogen or part of a pathogen either infects or is taken in by a host cell (Figure 35.9). Inside the host cell, enzymes in the cell cleave the antigen into smaller peptides. Each peptide, called an antigen fragment, then binds to an MHC molecule inside the cell. Movement of the MHC molecule and bound antigen fragment to the cell surface results in antigen presentation, the display of the antigen fragment in an exposed groove of the MHC protein.
In effect, antigen presentation advertises the fact that a host cell contains a foreign substance. If the cell displaying an antigen fragment encounters a T cell with the right specificity, the antigen receptor on the T cell can bind to both the antigen fragment and the MHC molecule. This interaction of an MHC molecule, an antigen fragment, and an antigen receptor is necessary for a T cell to participate in an adaptive immune response, as you’ll see later.

Question 42

What are the four major characteristics of adaptive immunity?

Answer 42

B Cell and T Cell Development Now that you know how B cells and T cells recognize antigens, let’s consider four major characteristics of adaptive immunity. First, there is an immense diversity of lymphocytes and receptors, enabling the immune system to detect pathogens never before encountered. Second, adaptive immunity normally has self-tolerance, the lack of reactivity against an animal’s own molecules and cells. Third, cell proliferation triggered by activation greatly increases the number of B and T cells specific for an antigen. Fourth, there is a stronger and more rapid response to an antigen encountered previously, due to a feature known as immunological memory.

Question 43

In what order do the four major characteristics of adaptive immunity form?

Answer 43

Receptor diversity and self-tolerance arise as a lymphocyte matures. Cell proliferation and the formation of immunological memory occur later, after a mature lymphocyte encounters and binds to a specific antigen. We’ll consider these four characteristics in the order in which they develop.

Question 44

Describe generation of B Cell and T Cell Diversity

Answer 44

Each person makes more than 1 million different B cell antigen receptors and 10 million different T cell antigen receptors. Yet there are only about 20,000 protein-coding genes in the human genome. How, then, do we generate such remarkable diversity in antigen receptors? The answer lies in combinations. Think of selecting a car with a choice of three interior colors and six exterior colors. There are 18 (3 × 6) color combinations to consider. Similarly, by combining variable elements, the immune system assembles many different receptors from a much smaller collection of parts.
To understand the origin of receptor diversity, let’s consider an immunoglobulin (Ig) gene that encodes the light chain of both secreted antibodies (immunoglobulins) and membranebound B cell antigen receptors. Although we’ll analyze only a single Ig light-chain gene, all B and T cell antigen receptor genes undergo very similar transformations.
The capacity to generate diversity is built into the structure of Ig genes. A receptor light chain is encoded by three gene segments: a variable (V) segment, a joining (J) segment, and a constant (C) segment. The V and J segments together encode the variable region of the receptor chain, while the C segment encodes the constant region. The light-chain gene contains a single C segment, 40 different V segments, and 5 different J segments. These alternative copies of the V and J segments are arranged within the gene in a series (Figure 35.10). Because a functional gene is built from one copy of each type of segment, the pieces can be combined in 200 different ways (40 V × 5 J × 1 C). The number of different heavy-chain combinations is even greater, resulting in even more diversity. Assembling a functional Ig gene requires rearranging the DNA. Early in B cell development, an enzyme complex called recombinase links one light-chain V gene segment to one J gene segment. This recombination event eliminates the long stretch of DNA between the segments, forming a single exon that is part V and part J. Because there is only an intron between the J and C DNA segments, no further DNA rearrangement is required. Instead, the J and C segments of the RNA transcript will be joined when splicing removes the intervening RNA (see Figure 14.12 to review RNA splicing).
Recombinase acts randomly, linking any one of the 40 V gene segments to any one of the 5 J gene segments. Heavychain genes undergo a similar rearrangement. In any given cell, however, only one allele of a light-chain gene and one allele of a heavy-chain gene are rearranged. Furthermore, the rearrangements are permanent and are passed on to the daughter cells when the lymphocyte divides.

After both a light-chain and a heavy-chain gene have rearranged, antigen receptors can be synthesized. The rearranged genes are transcribed, and the transcripts are processed for translation. Following translation, the light chain and heavy chain assemble together, forming an antigen receptor (see Figure 35.10). Each pair of randomly rearranged heavy and light chains results in a different antigen-binding site. For the total population of B cells in a human body, the number of such combinations has been calculated as 3.5 × 106. Furthermore, mutations introduced during VJ recombination add additional variation, making the number of possible antigen-binding specificities even greater.

Question 45

Describe the origin of self-tolerance in adaptive immunity.

Answer 45

In adaptive immunity, how does the body distinguish self from nonself? Because antigen receptor genes are randomly rearranged, some immature lymphocytes produce receptors specific for epitopes on the organism’s own molecules. If these self-reactive lymphocytes were not eliminated or inactivated, the immune system could not distinguish self from nonself and would attack body proteins, cells, and tissues. Instead, as lymphocytes mature in the bone marrow or thymus, their antigen receptors are tested for self-reactivity. Some B and T cells with receptors specific for the body’s own molecules are destroyed by programmed cell death. The remaining self-reactive lymphocytes are typically rendered nonfunctional, leaving only those lymphocytes that react to foreign molecules. Since the body normally lacks mature lymphocytes that can react against its own components, the immune system is said to exhibit self-tolerance.

Question 46

Describe the proliferation of B and T cells in adaptive immunity.

Answer 46

Proliferation of B Cells and T Cells Despite the enormous variety of antigen receptors, only a tiny fraction are specific for a given epitope. How, then, does an effective adaptive response develop? To begin with, an antigen is presented to a steady stream of lymphocytes in the lymph nodes (see Figure 34.12) until a match is made. A successful match then triggers changes in cell number and activity for the lymphocyte to which an antigen has bound.
The binding of an antigen receptor to an epitope initiates events that activate the lymphocyte. Once activated, a B cell or T cell undergoes multiple cell divisions. For each activated cell, the result of this proliferation is a clone, a population of cells that are identical to the original cell. Some cells from this clone become effector cells, short-lived cells that take effect immediately against the antigen and any pathogens producing that antigen. The effector forms of B cells are plasma cells, which secrete antibodies. The effector forms of T cells are helper T cells and cytotoxic T cells, whose roles we’ll explore in Concept 35.3. The remaining cells in the clone become memory cells, long-lived cells that can give rise to effector cells if the same antigen is encountered later in the animal’s life.
Figure 35.11 summarizes the proliferation of a lymphocyte into a clone of cells in response to binding to an antigen, using B cells as an example. This process is called clonal selection because an encounter with an antigen selects which lymphocyte will divide to produce a clonal population of thousands of cells specific for a particular epitope.

Question 47

Describe immunological memory in adaptive immunity.

Answer 47

Immunological Memory Immunological memory is responsible for the long-term protection that a prior infection provides against many diseases, such as chickenpox. This type of protection was noted almost 2,400 years ago by the Greek historian Thucydides. He observed that individuals who had recovered from the plague could safely care for those who were sick or dying, “for the same man was never attacked twice—never at least fatally.” Prior exposure to an antigen alters the speed, strength, and duration of the immune response. The production of effector cells from a clone of lymphocytes during the first exposure to an antigen is the basis for the primary immune response.
The primary response peaks about 10–17 days after the initial exposure. During this time, selected B cells and T cells give rise to their effector forms. If an individual is exposed again to the same antigen, the response is faster (typically peaking only 2–7 days after exposure), of greater magnitude, and more prolonged. This is the secondary immune response, a hallmark of adaptive, or acquired, immunity. Because selected B cells give rise to antibody-secreting effector cells, measuring the concentrations of specific antibodies in blood over time distinguishes the primary and secondary immune responses (Figure 35.12).

Question 48

What does the primary response of immunological memory peak?

Answer 48

10-17 days after initial exposure

Question 49

How do memory cells function in the secondary immune response?

Answer 49

The secondary immune response relies on the reservoir of T and B memory cells generated following initial exposure to an antigen. Because these cells are long-lived, they provide the basis for immunological memory, which can span many decades. (Effector cells have much shorter life spans, which is why the immune response diminishes after an infection is overcome.) If an antigen is encountered again, memory cells specific for that antigen enable the rapid formation of clones of thousands of effector cells also specific for that antigen, thus generating a greatly enhanced immune defense. Although the processes for antigen recognition, clonal selection, and immunological memory are similar for B cells and T cells, these two classes of lymphocytes fight infection in different ways and in different settings, as we’ll explore next.

Question 50

How are the humoral and cell-mediated immune responses different?

Answer 50

Adaptive immunity defends against infection of body fluids and body cells Having considered how clones of lymphocytes arise, we now explore how these cells help fight infections and minimize damage by pathogens. The defenses provided by B and T lymphocytes can be divided into a humoral immune response and a cell-mediated immune response. The humoral immune response occurs in the blood and lymph (once called body humors, or fluids). In the humoral response, antibodies help neutralize or eliminate toxins and pathogens in the blood and lymph. In the cell-mediated immune response, specialized T cells destroy infected host cells. Both responses include a primary immune response and a secondary immune response, with memory cells enabling the secondary response.

Question 51

What are helper T cells?

Answer 51

Helper T Cells: A Response to Nearly All Antigens A type of T cell called a helper T cell triggers both the humoral and cell-mediated immune responses. Helper T cells themselves do not carry out those responses. Instead, signals from helper T cells initiate production of antibodies that neutralize pathogens and activate T cells that kill infected cells.

Question 52

What two requirements must be met for a helper T cell to activate adaptive immune responses?

Answer 52

Two requirements must be met for a helper T cell to activate adaptive immune responses. First, a foreign molecule must be present that can bind specifically to the antigen receptor of the T cell. Second, this antigen must be displayed on the surface of an antigen-presenting cell. The antigen-presenting cell can be a dendritic cell, macrophage, or B cell.

Question 53

When host cells are infected, they, too, display antigens on their surface. What, then, distinguishes an antigen-presenting cell?

Answer 53

The answer lies in the existence of two classes of MHC molecules. Most body cells have only class I MHC molecules, but antigen-presenting cells have both class I and class II MHC molecules. The class II molecules provide a molecular signature by which an antigen-presenting cell is recognized.

Question 54

How do helper T cells and antigen presenting cells interact?

Answer 54

A helper T cell and the antigen-presenting cell displaying its specific epitope have a complex interaction (Figure 35.13). The antigen receptors on the surface of the helper T cell bind to the antigen fragment and to the class II MHC molecule displaying that fragment on the antigen-presenting cell. At the same time, an accessory protein called CD4 on the helper T cell surface binds to the class II MHC molecule, helping keep the cells joined. As the two cells interact, signals in the form of cytokines are exchanged.
Antigen-presenting cells interact with helper T cells in several different contexts. Antigen presentation by a dendritic cell or macrophage activates a helper T cell, which then proliferates, forming a clone of activated cells. B cells present antigens to already activated helper T cells, which in turn activate the B cells themselves. Activated helper T cells also help stimulate cytotoxic T cells, as we’ll discuss next.

Question 55

What is a cytotoxic T cell? How does it become activated?

Answer 55

Cytotoxic T Cells: A Response to Infected Cells In the cell-mediated immune response, cytotoxic T cells use toxic proteins to kill cells infected by viruses or other intracellular pathogens. To become active, cytotoxic T cells require signals from helper T cells and interaction with an antigen-presenting cell. Fragments of foreign proteins produced in infected host cells associate with class I MHC molecules and are displayed on the cell surface, where they can be recognized by activated cytotoxic T cells (Figure 35.14). As with helper T cells, cytotoxic T cells have an accessory protein that binds to the MHC molecule. This accessory protein, called CD8, helps keep the two cells in contact while the cytotoxic T cell is activated.

Question 56

How does a cytotoxic T cell destroy an infected host cell?

Answer 56

The targeted destruction of an infected host cell by a cytotoxic T cell involves the secretion of proteins that disrupt membrane integrity and trigger cell death (see Figure 35.14). The death of the infected cell not only deprives the pathogen of a place to reproduce, but also exposes cell contents to circulating antibodies, which mark released antigens for disposal. B Cells and Antibodies: A Response to Extracellular Pathogens The secretion of antibodies by clonally selected B cells is the hallmark of the humoral immune response. As illustrated in Figure 35.15, activation of B cells involves both helper T cells and proteins on the surface of pathogens. Stimulated by both an antigen and cytokines, the B cell proliferates and differentiates into memory B cells and antibody-secreting plasma cells.

Question 57

What does an activated B cell do?

Answer 57

A single activated B cell gives rise to thousands of identical plasma cells. Each plasma cell secretes approximately 2,000 antibodies every second during its 4- to 5-day life span. The antibodies do not kill pathogens, but by binding to antigens, they mark pathogens in various ways for inactivation or destruction.

Question 58

What are four things antibodies can do?

Answer 58

In the simplest of these activities, neutralization, antibodies bind to proteins on the surface of a virus (see Figure 35.7b). The bound antibodies prevent infection of a host cell, thus neutralizing the virus. Similarly, antibodies sometimes bind to toxins released in body fluids, preventing the toxins from entering body cells. Because each antibody has two antigen-binding sites, antibodies can also facilitate phagocytosis by linking bacterial cells, viruses, or other foreign substances into aggregates.
Antibodies sometimes work together with the proteins of the complement system. (The name complement reflects the fact that these proteins increase the effectiveness of antibodydirected attacks on bacteria.) Binding of a complement protein to an antigen-antibody complex on a foreign cell triggers events leading to formation of a pore in the membrane of the cell. Ions and water rush into the cell, causing it to swell and lyse.

Question 59

What different types of immunoglobulin can B cells express?

Answer 59

B cells can express five different types of immunoglobulin. For a given B cell, each type has an identical antigen-binding specificity but a distinct heavy-chain C region. One type of B cell Ig, the B cell antigen receptor, is membrane bound. The other four lg types consist of soluble antibodies, including those found in blood, tears, saliva, and breast milk. Summary of the Humoral and Cell-Mediated Immune Responses

Question 60

What is passive immunity?

Answer 60

Active and Passive Immunization Our discussion of adaptive immunity has focused to this point on active immunity, the defenses that arise when a pathogen infects the body. A different type of immunity results when, for example, antibodies in the blood of a pregnant female cross the placenta to her fetus. This protection is called passive immunity because the antibodies in the recipient (in this case, the fetus) are produced by another individual (the mother). Antibodies present in breast milk provide additional passive immunity to the infant’s digestive tract while the infant’s immune system develops. Because passive immunity does not involve the recipient’s B and T cells, it persists only as long as the transferred antibodies last (a few weeks to a few months).

Question 61

How can active and passive immunity be induced artificially?

Answer 61

Both active immunity and passive immunity can be induced artificially. Active immunity is induced when antigens are introduced into the body in vaccines, which may be made from inactivated bacterial toxins, killed or weakened pathogens, or even genes encoding microbial proteins. This process, called immunization (or vaccination), induces a primary immune response and immunological memory. As a result, any subsequent encounter with the pathogen from which the vaccine was derived triggers a rapid and strong secondary immune response (see Figure 35.12).
In artificial passive immunization, antibodies from an immune animal are injected into a nonimmune animal. For example, humans bitten by venomous snakes are sometimes treated with antivenin, serum from sheep or horses that have been immunized against a snake venom. When injected immediately after a snakebite occurs, the antibodies in antivenin can neutralize toxins in the venom before the toxins do massive damage.

Question 62

Describe misinformation about vaccine safety and consequences as it relates to measles.

Answer 62

Misinformation about vaccine safety and disease risk has led to a substantial and growing public health problem. Consider measles as just one example. Side effects of immunization are remarkably rare, with fewer than one in a million children suffering a significant allergic reaction to the measles vaccine. The disease, however, is quite dangerous, killing more than 200,000 people each year. Declining vaccination rates in parts of the United Kingdom, Russia, and the United States have resulted in a number of recent measles outbreaks and many preventable deaths.

Question 63

What is the difference between polyclonal and monoclonal antibodies?

Answer 63

Antibodies as Tools Antibodies produced after exposure to an antigen are polyclonal: They are the products of many different clones of plasma cells, each specific for a different epitope. Antibodies can also be prepared from a clone of B cells grown in culture. The monoclonal antibodies produced by such a culture are identical and specific for the same epitope on an antigen.

Question 64

How are monoclonal antibodies used? Why are they important?

Answer 64

Monoclonal antibodies have provided the basis for many recent advances in medical diagnosis and treatment. For example, home pregnancy test kits use monoclonal antibodies to detect human chorionic gonadotropin (hCG). Because hCG is produced as soon as an embryo implants in the uterus (see Chapter 36), the presence of this hormone in a woman’s urine is a reliable indicator for a very early stage of pregnancy. Monoclonal antibodies are also produced in large amounts and injected as a therapy for a number of human diseases.

Question 65

Why is the blood type of a blood donor important?

Answer 65

Immune Rejection Like pathogens, cells from another person can be recognized as foreign and attacked by immune defenses. For example, skin transplanted from one person to a genetically nonidentical person will look healthy for a week or so but will then be destroyed (rejected) by the recipient’s immune response. Carbohydrates on the surface of transfused blood cells can also be recognized as foreign by the recipient’s immune system, triggering an immediate and devastating reaction. To avoid this danger, the so-called ABO blood groups of the donor and recipient must be taken into account.

Question 66

How are tissue and organ transplants carried out in a way that does not cause immune rejection?

Answer 66

In the case of tissue and organ transplants, or grafts, MHC molecules stimulate the immune response that leads to rejection. Each vertebrate species has many alleles for each MHC gene, enabling presentation of antigen fragments that vary in shape and net electrical charge. This diversity of MHC molecules almost guarantees that no two people, except identical twins, will have exactly the same set. Thus, in the vast majority of graft and transplant recipients, some MHC molecules on the donated tissue are foreign to the recipient. To minimize rejection, physicians use donor tissue bearing MHC molecules that match those of the recipient as closely as possible. In addition, the recipient takes medicines that suppress immune responses (but as a result leave the recipient more susceptible to infections).

Question 67

What are allergies?

Answer 67

Allergies Allergies are exaggerated (hypersensitive) responses to certain antigens called allergens. Hay fever, for instance, occurs when plasma cells secrete antibodies specific for antigens on the surface of pollen grains, as illustrated in Figure 35.17. The interaction of pollen grains and these antibodies triggers immune cells in connective tissue to release histamine and other inflammatory chemicals. The results can include sneezing, teary eyes, and smooth muscle contractions in the lungs that inhibit effective breathing. Drugs called antihistamines block receptors for histamine, diminishing allergy symptoms (and inflammation).

Question 68

What is anaphylactic shock?

Answer 68

In some instances, an acute allergic response leads to a lifethreatening reaction called anaphylactic shock. Inflammatory chemicals trigger abrupt dilation of peripheral blood vessels, causing a precipitous drop in blood pressure, as well as constriction of bronchioles. Death may occur within minutes due to lack of blood flow and the inability to breathe. Substances that can cause anaphylactic shock in allergic individuals include bee venom, penicillin, peanuts, and shellfish. People with severe hypersensitivities often carry syringes containing the hormone epinephrine, which counteracts this allergic response.

Question 69

What are autoimmune diseases?

Answer 69

Autoimmune Diseases In some people, the immune system is active against particular molecules of the body, causing an autoimmune disease. In systemic lupus erythematosus, commonly called lupus, the immune system generates antibodies against histones and DNA.
Other targets of autoimmunity are the insulin-producing beta cells of the pancreas (in type 1 diabetes) and the myelin sheaths that encase many neurons (in multiple sclerosis). Gender, genetics, and environment all influence susceptibility to autoimmune disorders. For example, many autoimmune diseases afflict females more often than males. Women are nine times as likely as men to suffer from lupus and two to three times as likely to develop rheumatoid arthritis, a damaging and painful inflammation of the cartilage and bone in joints (Figure 35.18). The cause of this sex bias, as well as the rise in autoimmune disease frequency in industrialized countries, are areas of active research and debate.

Question 70

What is antigenic variation?

Answer 70

Immune System Avoidance EVOLUTION Just as immune systems that ward off pathogens have evolved in animals, mechanisms that thwart immune responses have evolved in pathogens. In one such mechanism, a pathogen alters how it appears to the immune system. If a pathogen changes the epitopes it expresses to ones that a host has not previously encountered, it can reinfect or remain in the host without triggering the rapid and robust response mediated by memory cells. Such changes in epitope expression are called antigenic variation. The parasite that causes sleeping sickness provides an extreme example, periodically switching at random among 1,000 different versions of the protein found over its entire surface. In the Scientific Skills Exercise, you will interpret data related to this example of antigenic variation and the body’s response.

Question 71

How does the influenza remain a major public health problem?

Answer 71

Antigenic variation is the major reason the influenza, or “flu,” virus remains a major public health problem. As it replicates in one human host after another, the human flu virus undergoes frequent mutations. Because any change that lessens recognition by the immune system provides a selective advantage, the virus steadily accumulates such alterations. These changes are the reason that a new flu vaccine must be distributed each year. In addition, the human flu virus occasionally exchanges genes with influenza viruses that infect domesticated animals, such as pigs or chickens. If the new strain expresses surface epitopes of the animal rather than the human virus, it may not be recognized by any of the memory cells in the human population. The resulting outbreak can be deadly: The 1918–1919 influenza outbreak killed more than 20 million people.

Question 72

What is latency? How does it avoid an immune response? What is one example?

Answer 72

Some viruses avoid an immune response by infecting cells and then entering a largely inactive state called latency. The viral genome integrates into the chromosome of the host cell, which ceases making most viral proteins and typically releases no free viruses. Latency typically persists until conditions arise that are favorable for viral transmission or unfavorable for host survival.
Herpes simplex viruses provide a good example of latency. The type 1 virus causes most oral herpes infections, whereas the sexually transmitted type 2 virus is responsible for most cases of genital herpes. These viruses remain latent in sensory neurons until a stimulus such as fever, emotional stress, or menstruation reactivates the viruses. Activation of the type 1 virus can result in blisters around the mouth that are inaccurately called “cold” sores. Infections of the type 2 virus pose a serious threat to the babies of infected mothers and can increase transmission of HIV.

Question 73

How does HIV pose a threat to the immune system?

Answer 73

The human immunodeficiency virus (HIV), the pathogen that causes AIDS (acquired immune deficiency syndrome), both escapes and attacks the adaptive immune response. Once introduced into the body, HIV infects helper T cells with high efficiency. Although the body responds to HIV with an immune response sufficient to eliminate most viral infections, some HIV invariably escapes. One reason HIV persists is that it has a very high mutation rate. Altered proteins on the surface of some mutated viruses reduce interaction with antibodies and cytotoxic T cells. Such viruses survive, proliferate, and mutate further. The virus thus evolves within the body. The continued presence of HIV is also helped by latency.
Over time, an untreated HIV infection not only avoids the adaptive immune response but also abolishes it. Viral reproduction and cell death triggered by the virus lead to loss of helper T cells, impairing both humoral and cell-mediated immune responses. The result is a progression to AIDS, characterized by susceptibility to infections and cancers that a healthy immune system would usually defeat. For example, Pneumocystis carinii, a common fungus that does not cause disease in healthy individuals, can result in severe pneumonia in people with AIDS. Such opportunistic diseases, as well as nerve damage and wasting, are the primary causes of death from AIDS, not HIV itself.
HIV transmission requires the transfer of virus particles or infected cells via body fluids such as semen, blood, or breast milk. Unprotected sex (that is, without a condom) and transmission via HIV-contaminated needles (often among intravenous drug users) account for the vast majority of HIV infections. People infected with HIV can transmit the disease in the first few weeks of infection, before they express HIV-specific antibodies that can be detected in a blood test. Although HIV infection cannot be cured, drugs have been developed that can significantly slow HIV replication and the progression to AIDS. New drugs continue to be needed as HIV’s high mutation rate results in the frequent appearance of drug-resistant strains.

Question 74

How does cancer implicate immunity?

Answer 74

Cancer and Immunity When adaptive immunity is inactivated, the frequency of certain cancers increases dramatically. For example, the risk of developing Kaposi’s sarcoma is 20,000 times greater for untreated AIDS patients than for healthy people. This observation was unanticipated. If the immune system recognizes only nonself, it should fail to recognize the uncontrolled growth of self cells that is the hallmark of cancer. It turns out, however, that viruses are involved in about 15–20% of all human cancers. Because the immune system can recognize viral proteins as foreign, it can act as a defense against viruses that can cause cancer and against cancer cells that harbor viruses.