Module 5: The Immune System and Disease Resistance

CommentaryTopicsThe Immune SystemInnate ImmunityAdaptive ImmunityTypes of ImmunityHIV and the Immune SystemConclusionClosing Remarks

The Immune SystemYour immune system is a collection of cells and defense mechanisms designed to protect you against viral, bacterial, and parasitic attack.

There are two branches to the human immune system:

1. innate immune system2. adaptive immune system

The innate immune system responds to foreign invaders (such as bacteria and viruses) with a nonspecific, or generalized, attack. This branch of the immune system functions to provide a rapid, widespread defense against disease. The response is immediate and short-lived, and it does not provide long-lasting protection or immunity to disease.

In contrast, the adaptive immune system mounts a strong, targeted response to a pathogenic invasion. This system takes longer to respond than does the innate immune system, but the response is more powerful, longer-lasting, and more specific. In addition, the adaptive immune response can confer long-term immunity to specific infections.

In this module, we will explore how the innate and adaptive immune systems work to battle infection and disease. Because this module has so many terms that you may not know, we have provided a Glossary tab for your reference.

Innate ImmunityYour innate immune system remains the same throughout your life; unlike your adaptive immune system, it does not have the ability to change over time. It is thought to be an evolutionarily older part of the immune system. Simpler organisms, such as insects and plants, lack an adaptive immune system, but have an innate immune system.

The innate immune system protects you by providing a quick, general response to pathogens. It fights infection in two stages, using a separate line of defense in each stage. Table 5.1 shows the stages of the innate immune response:

Table 5.1Innate Immune System

Stage Line of Defense

Purpose Components

Stage 1 first line of defense

to keep pathogens out of the body using physical barriers and inhibitory substances

skin mucus

membranes and bodily fluids

normal microbiota in the body

Stage 2 second line of defense

to provide a rapid defensive response to pathogens that pass through the first line of defense and enter the body

natural killer (NK) cells

phagocytic cells

inflammation fever complement

pathway

First Line of Defense

The first line of defense of the innate immune system is designed to block foreign microbes from gaining access to the deeper tissues of the body and the bloodstream. The defensive agents guard the places where microbes first encounter the body, such as the outside of the body and natural body openings such as the eyes and mouth. In the following sections, we will describe each of the first-line components.

Skin

The skin serves as a physical barrier to infection, denying pathogens access to the inside of the body. Pathogens can bypass this barrier through cuts, scrapes, and natural body openings. The skin provides defense against harmful microbes with the following:

Dryness: Most microbes require moisture to survive. For example, most fungal skin infections, such as athlete's foot and candidiasis (yeast infection), occur on warm, moist parts of the skin.

Sebum production: The skin produces sebum, an oily substance that contains fatty acids that inhibit the growth of certain microbes.

Skin secretions: Perspiration contains lysozyme, the enzyme that breaks down the peptidoglycan in the cell walls of Gram-positive bacteria. Skin secretions also lower the pH level of the skin to make it more acidic and less hospitable to pathogens.

Mucus Membranes and Bodily Fluids

Mucus membranes coat your gastrointestinal (GI), genitourinary (GU), and respiratory tracts. The cells that line these tracts secrete a layer of thick mucus that prevents many microbes from gaining access to the cells below. Some bacterial species, such as Salmonella, have developed ways to swim through the mucus and invade the cells underneath. Mucus is constantly washed through these tracts, and can carry pathogens out of the body before they can establish an infection.

The mucus membranes of the respiratory tract are lined with hairs (in the nose) and cilia (in the lungs) that trap pathogens and push them out of the body. Coughing and sneezing speed this process. Some substances, such as cigarette smoke, damage the cilia in the lungs, putting the individual at greater risk of lung infections such as bronchitis (an upper respiratory tract infection) and pneumonia (a lower respiratory tract infection).

Tears, saliva, and urine contain lysozyme (the same enzyme found in perspiration), which degrades Gram-positive bacteria. Vaginal secretions are acidic, and have a low pH level that encourages the growth of normal vaginal bacteria and inhibits the growth of unwanted microbes. These bodily fluids also stave off infection by constantly washing microbes out of the body through natural openings.

Normal Microbiota

Normal microbiota are the bacteria that inhabit parts of your body without causing harm or disease. Your normal microbiota actually inhibit the colonization of disease-causing microbes by competing with them for space, limiting the nutrients available to them, and secreting antimicrobial chemicals.

Second Line of Defense

The second line of defense of the innate immune system comes into play when the first line of defense fails to prevent pathogens from entering the body. The second line of defense responds to infection with immune cells (including phagocytic and NK cells), inflammation, fever, and the antimicrobial substances of the complement pathway. We will explore each of these components in the following sections, but first, we will take a moment to discuss the cells of the immune system.

In module 2, you learned about the general structure of eukaryotic cells. The human body has many types of eukaryotic cells. Those involved in the immune response are known as leukocytes, or white blood cells (WBCs).

There are several types of leukocytes, each with its own specific role in the immune response. Neutrophils, for example, act as phagocytic cells, engulfing and destroying pathogens, whereas eosinophils respond to parasitic infection. All leukocytes originate from a common progenitor cell known as a hematopoietic stem cell. Hematopoietic stem cells form in the bone marrow and eventually differentiate into the various blood (red) and immune (white) cells.

Figure 5.1 shows the major types of leukocytes:

Figure 5.1Major Types of Leukocytes

Source of cell illustrations: Rad, 2006, Wikipedia Web site. Used with permissionunder the terms of the GNU Free Documentation License.

Neutrophils, basophils, and eosinophils contain large numbers of proteins and enzyme-filled granules in their cytoplasm, which are released as part of the immune response. In the case of eosinophils, the granules work to destroy parasites, and in the case of neutrophils and basophils, they aid in promoting inflammation. Inflammation is actually caused by the body's response to a pathogen or injury, not by the pathogen or injury itself. Leukocytes promote inflammation by increasing blood flow to the site of infection and bringing in additional immune cells to fight the pathogen. We will discuss inflammation in greater detail below.

Lymphocytes differentiate into several types of immune cells, including various types of T cells, B cells, and NK cells. T cells and B cells play an important role in the adaptive immune

response. In the following sections, we will focus on some of the key cells involved in the innate immune response.

Natural Killer (NK) Cells

Natural killer (NK) cells, found in the blood, spleen, lymph nodes, and bone marrow, fight tumor and viral infected cells by releasing enzyme-filled granules onto the infected cell. The enzymes cause the cell to undergo apoptosis, the natural process of programmed cell death for old or damaged cells. Apoptosis causes the infected cell to shrivel and die without emptying its contents into the body. Killing an infected cell via apoptosis prevents the invading microbes from escaping the cell and subsequently infecting neighboring cells.

Phagocytic Cells

Phagocytic cells function by engulfing and destroying invading microbes. They lie dormant in the blood, lymph nodes, and body tissues until activated by specific signals. These signals include lipopolysaccharide (LPS) from Gram-negative bacteria and cytokines, protein or chemical signals secreted by certain cells of the immune system during an infection. Once activated, phagocytic cells exert their effects and destroy pathogens.

The process of phagocytosis can be broken down into five steps:

1. Engulfment of the pathogen: The plasma membrane of the phagocytic cell extends outward and surrounds the pathogen, bringing it inside the cell.

2. Phagosome formation: As the pathogen is brought inside the cell, the plasma membrane fuses together, creating a phagosome "bubble" around the pathogen.

3. Phagolysosome formation: A lysosome fuses with the phagosome, forming a compartment called a phagolysosome.

4. Digestion of the pathogen: Inside the phagolysosome, the digestive enzymes digest and destroy the pathogen.

5. Elimination of undigested debris: The phagolysosome fuses with the plasma membrane, emptying the undigested pathogenic debris into the external environment.

The immune system has several types of phagocytic cells. Table 5.2 summarizes the major phagocytic cell types:

Table 5.2Major Phagocytic Cells

Cell Role in Innate Immunity

Role in Adaptive Immunity

Neutrophil plays a major role in the digestion of foreign microbes during infection

does not play a role in adaptive immunity

Macrophage plays a major role in the digestion of foreign microbes

plays a role in antigen presentation to cells of the

Cell Role in Innate Immunity

Role in Adaptive Immunity

during infection adaptive immune system

Dendritic cell plays only a minor phagocytic role

plays a role in antigen presentation to cells of the adaptive immune system

Some pathogens can prevent phagocytosis. For example, Mycobacterium tuberculosis (the causative agent of tuberculosis) and human immunodeficiency virus (HIV) (the causative agent of acquired immunodeficiency syndrome [AIDS]) are able to prevent lysosome fusion with the phagosome. Shigella species (the causative agents of the gastrointestinal illness shigellosis) are able to escape the phagosome before phagolysosome formation. These evasive maneuvers prevent the lysosome from dumping digestive enzymes onto the pathogen, and enable the pathogen to survive in the cell.

To test your understanding of phagocytosis, try the following activity:

Activity 5.1Phagocytosis

Click on the link to see the completed version of this activity. This can serve as a study guide.

Inflammation

Damage to the body's cells and tissues can instigate a local inflammatory response characterized by redness, pain, swelling, and heat. Inflammation stemming from an infection can be either acute or chronic. Acute inflammation occurs at the site of infection, such as a scrape or boil. Chronic inflammation tends to accompany chronic infections such as tuberculosis caused by M. tuberculosis. This type of inflammation is longer-lasting than the acute type, and can eventually cause more harm than good.

During an infection, inflammation has the following functions:

to destroy and eliminate the infecting microbes by bringing in phagocytes to wall off the site of infection and prevent the spread of the microbes to other parts

of the body to facilitate the repair of tissues damaged during the infection

Inflammation starts almost immediately following the injury to the skin barrier, when the pathogens start gaining access to the deeper tissues of the body. Table 5.3 shows the three stages of inflammation:

Table 5.3Stages of Inflammation

Stage Process Effects on the Body

1dilation of blood vessels (vasodilation)

Blood vessel dilation increases blood flow to the site of infection, causing redness.

Neutrophils and basophils at the site of infection release chemical signals to increase vasodilation.

Blood vessel dilation enables leukocytes to leave the blood and enter the injured tissues, causing fluid accumulation and swelling.

Blood vessel dilation allows clotting factors to leave the blood and enter the injured tissues, helping to wall off the site of infection.

2 phagocyte migration

Chemical signals attract phagocytes, which travel through the blood to the site of infection.

Phagocytes destroy as many microbes as they can and eventually die off, leading to pus formation.

3 tissue repair

Body tissues repair and replace damaged cells. The effectiveness of tissue repair is tissue-type dependent. For example, skin has a high rate of repair, whereas cardiac tissue has a low rate of repair.

Fever

Fever is a systemic response to infection. During some bacterial and viral infections, the body responds to chemical signals released from leukocytes by increasing the body temperature. It accomplishes this by tightening the blood vessels (in a process called vasoconstriction—the opposite of vasodilation), raising the metabolism, and causing shivering in the skeletal muscles. The uncontrollable shivering you experience during a fever actually helps to raise your body temperature.

Anyone who has had a fever knows that the condition can be uncomfortable and hard to tolerate. However, low-grade fevers help you by

slowing the growth of pathogens, giving the immune system a better chance to eliminate them

increasing the number of iron-binding proteins in the blood, limiting the amount of free iron available to bacteria

enhancing the effectiveness of interferons in the blood

increasing the rate of tissue repair increasing the activity of T cells in the adaptive immune response

Complement Pathway

The complement system is a part of the innate immune system that consists of different proteins made by the liver to fight and destroy invading pathogens. This system is called complement because the proteins work with antibodies to bolster their effectiveness in the fight against infection.

Complement proteins circulate in the body in inactive form until they are needed. They become activated either through direct interaction with antibodies bound to a pathogen, or through the detection of a signal produced by another immune cell. Once activated, complement proteins work in tandem to target and eliminate pathogens.

Complement activation has three possible outcomes:

1. Opsonization: Complement proteins stick to the outside of the pathogen. Phagocytes recognize this "complement coat" and target the cell for destruction via phagocytosis.

2. Lysis: Complement proteins come together to form a membrane attack complex (MAC), which pokes holes in the pathogen's plasma membrane, resulting in microbial lysis.

3. Inflammation: Complement proteins trigger mast cells to release histamine granules, which induce inflammation. Mast cells are non-leukocyte cells that function in a similar manner to basophils.

Figure 5.2 shows the process of complement activation, and the three possible outcomes:

Figure 5.2Complement Activation

Source of mast cell illustration: Arcadian, 2006, Wikipedia Web site. Used withpermission under the terms of the GNU Free Documentation License.

Summary of the Innate Immune System

The innate immune system comprises several physical deterrents and cellular components that function to battle microbial infection. Click on the link below to test your understanding of the innate immune system.

Test Your Understanding 5.1

Click on the link for a study guide based on the above activity.

Adaptive ImmunityThe adaptive immune system provides a highly specific response to harmful microbes, both free-floating and intracellular. It gives your body the ability to recognize and remember individual pathogens. If you get the measles vaccine, for example, this part of your immune system recognizes the vaccine and arms you with a specific immune cell memory response that protects you from future measles infections.

Your adaptive immune system takes over once your innate immune system has responded to the initial stages of infection. This typically occurs several days after the infection has begun (in contrast to the few hours it takes the innate immune system to respond), and involves a specific set of immune cells.

The adaptive immune system confers two types of immunity:

1. humoral immunity, which involves B cells and their antibody response to infection2. cell-mediated immunity, which involves T cells (T helper [Th or CD4+] cells and

cytotoxic T [Tc or CD8+] cells) and antigen-presenting cells (APCs), including dendritic cells, B cells, and macrophages

Humoral Immunity

Humoral immunity involves the production of antibodies in response to a specific foreign antigen (see definitions below). The term humoral comes from the Latin word humor orumor, meaning "bodily fluid." Antibodies were first discovered circulating in the bodily fluids, hence the phrase humoral immunity. Humoral immunity is also known as antibody-mediated immunity.

Antibodies travel in the blood to access sites of infection via inflammation and vasodilation. Because antibodies can only recognize and bind to exposed surface antigens, they can only affect pathogens roaming freely in the body, and not those living inside the host cell.

Antigens are proteins or complex sugar molecules (polysaccharides) expressed on the surface of most eukaryotic cells, bacteria, and viruses. Your body sees the antigens expressed on the surface of bacteria and viruses as "foreign," and these antigens therefore become a target for the immune system. Your body is able to recognize "self" antigens on the surface of your cells and normal microbiota, and typically does not mount an antibody response against these cells. In some cases, such as in autoimmune diseases, this self-recognition fails to operate in some way, and the body mounts an immune response against its own cells.

Antibody Structure

Antibodies, also called immunoglobulins (Ig), are large, globular protein complexes produced by B cells. They are made for the purpose of binding to specific antigens. An antibody binds to its antigen when it encounters a foreign invader expressing that antigen. Figure 5.3 shows the structure of an antibody and the location of antibodies on the surface of a B cell, where they reside until secreted in response to a recognized antigen.

Figure 5.3Antibody Structure

All antibodies share the same basic Y-shaped structure. The tips of the "Y" bind to the antigen, and the bottom of the "Y" anchors the antibody to the B cell surface until it is ready to be secreted. Some antibodies are composed of several "Y" structures that enhance their ability to bind to antigens. For example, IgM antibodies contain five of the "Y" structures, which enable them to bind to up to ten antigens at a given time.

There are five classes of human antibodies, each with a characteristic shape and function. Figure 5.4 shows these classes:

Figure 5.4Antibody Classes

Activation of B Cells

Newly formed B cells already contain a variety of antibodies on their surface. For example, one B cell might have 200 different IgM and 50 different IgD antibodies. Each one of these will differ slightly from the others in its antigen-binding regions. B cells make these initial surface antibodies randomly in the hopes that one of them will recognize a foreign antigen. In a B cell expressing 250 antibodies, there are 250 different antigen-binding possibilities.

Bacterial antigens are the major target of circulating B cells. On occasion, viral antigens can elicit an antibody response, but only when the antigens are found outside the host cells. Viruses (and viral surface antigens) are exposed to bodily fluids and circulating immune cells for a short period of time before they enter a host cell.

B cell activation occurs in the following stages:

1. Recognition: One of the random antibodies on the B cell surface recognizes and binds to a foreign antigen. B cells typically bind to free-floating antigens released naturally from the bacterial cell (or virion), or released during phagocytosis by immune cells.

2. Internalization: The antigen is taken inside the B cell, where it interacts with and binds to a protein called major histocompatability complex (MHC).

3. MHC-antigen complex formation: The antigen is placed on the surface of the B cell in conjunction with the MHC protein.

4. Th cell recognition: The MHC-antigen complex is recognized by a Th cell.

5. B cell activation: The Th cell binds to the MHC-antigen complex and secretes cytokines to activate the B cell.

6. Plasma cell formation: Once activated, the B cell develops into a plasma cell and begins secreting large quantities of the antibody that can bind to the specific antigen.

Figure 5.5 illustrates the process of B cell activation:

Figure 5.5B Cell Activation

Source: partially adapted from Tortora, Funke, & Case, 2007, figure 17.1

Memory Response

During B cell activation, an individual B cell replicates itself in a process called clonal expansion to make many identical copies. Some of these B cells become memory cells, whereas others become antibody-producing and -secreting plasma cells. Memory cells are responsible for initiating the response to an antigen (and the pathogen expressing that antigen) the second time you encounter it.

Memory cells respond quickly to an antigen the second time the pathogen invades your body, having been programmed to respond to it during the first round of exposure. This means a faster and stronger immune response, which means a faster elimination of the invading microbe. Figure 5.6 illustrates the process of clonal expansion and memory cell formation:

Figure 5.6B Cell Clonal Expansion and Memory Cell Formation

Source: partially adapted from Tortora, Funke, & Case, 2007, figure 17.5

Unfortunately, not all pathogens cause a memory response to develop. With these microbes, no immunity is conferred, and your body treats each exposure as if you are seeing the harmful microbe for the first time. In the case of the Norwalk virus (the causative agent of the 24-48 hour "stomach flu"), antibodies circulate for a few weeks, providing short-term protection, but no long-term memory results. This means that you can become re-infected with the Norwalk virus a few weeks to a month after an earlier infection.

Antibody Function

Now that we understand the production and structure of antibodies, let's see how they function to fight infection. After an antibody has bound to its target antigen, it works in one of four ways to aid the immune system.

Figure 5.7 illustrates the four ways in which antibodies can work:

Figure 5.7Four Possible Antibody Responses to Pathogens

Antibodies function to mobilize other agents of the immune system, such as complement and phagocytic cells, to thwart and eventually destroy the pathogen. These "killer cells" of the immune system recognize parts of the antibody-antigen complex and engulf and/or eliminate the cell containing the complex.

Cell-Mediated Immunity

Cell-mediated immunity involves T cells—primarily, Th and Tc cells. Humoral immunity (B cells and antibodies) works well against bacteria and viruses roaming freely in the blood or attached to the outer surface of cells. However, antibodies cannot detect a pathogen once it has entered a cell. Because of this, the humoral immune system is ineffective against intracellular bacteria and viruses. This is where the cell-mediated adaptive immune system comes into play.

There are three types of T cells involved in cell-mediated immunity:

1. T helper cells (also known as Th or CD4+ cells) aid the humoral immune system by releasing cytokines to activate B cells and turn them into plasma cells. Th cells also use cytokines to stimulate Tc cells, macrophages, and NK cells.

2. Cytotoxic T cells (also known as Tc or CD8+ cells) aid in the clearing of intracellular bacteria and viruses from the body.

3. Regulatory T cells (also known as Tr cells) play a role in suppressing inflammation, organ rejection, and autoimmune diseases. These are not thought to play a major role in fighting bacterial and viral infections.

Like antibodies, T cells react to specific foreign antigens. They use the MHC molecules on their cell surface to bind to antigens. T cells must be activated before they can fully exert their effects. This activation occurs when the MHC binds to the antigen.

Whereas antibodies can bind to both free-floating and pathogen-bound antigens, Th cells can bind only to antigens on the surface of an antigen-presenting cell (APC). APCs are leukocytes (often phagocytic cells, such as dendritic cells or macrophages, but sometimes other types of cells, such as B cells) that have engulfed a foreign microbe and placed parts of that microbe on their surface. As their name suggests, APCs "present" antigens to Th cells, aiding them in their transformation into cytokine-secreting Th cells.

Figure 5.8 shows the process of Th cell activation:

Figure 5.8Th Cell Activation

In module 4, we learned that viruses are obligate intracellular parasites that cannot survive for long outside of a host cell. Their intracellular lifestyle makes viruses (and some intracellular bacteria) inaccessible to APCs. Tc cells, however, have adapted specifically to target cells infected with an intracellular pathogen.

Like B cells, Tc cells become activated with the aid of Th cells. Once flooded by cytokines from a Th cell, Tc cells are able to bind directly to cells infected with an intracellular

pathogen. All the cells in your body that have a nucleus (red blood cells lack a nucleus) express a form of MHC. When a cell is infected with an intracellular pathogen, the cell starts to display foreign antigens on its surface-bound MHC. The MHC of the Tc cell is able to recognize and bind to the MHC of the cell expressing the foreign antigen. This MHC-antigen-MHC interaction tells the Tc cell that the host cell is infected. Once the Tc cell recognizes the infected host cell as abnormal, it secretes cytokines and induces apoptosis in the cell.

Figure 5.9 shows the process by which a Tc cell kills an infected host cell:

Figure 5.9Mode of Killing Infected Cells by Tc Cells

Summary of the Adaptive Immune System

The adaptive immune system provides both humoral and cell-mediated immunity, and comprises different types of cells that work with one another to protect the body. Click on the link below to test your understanding of the adaptive immune system.

Test Your Understanding 5.2

Click on the link for a study guide based on the above activity.

Types of ImmunityIn module 1, we discussed Edward Jenner's development of the first recognized vaccine. This vaccine against the human smallpox virus was highly effective and was used for over 150 years before people began to understand why and how it actually worked. We now know that immunological memory is involved in providing the long-term protection offered by vaccines.

Jenner made his vaccine out of the cowpox virus knowing that milkmaids who had contracted cowpox were naturally immune to smallpox. What Jenner did not know is that cowpox and smallpox have very similar antigens, which the human immune system sees as identical. Exposure to cowpox (occurring naturally or through a vaccine) activates the

immune system and creates long-term memory cells able to respond to the smallpox virus quickly and to prevent it from infecting cells.

Immunity can be acquired actively, through exposure to a pathogen or vaccine, or passively, through the transmission of antibodies taken from an animal, created in a lab, or donated by another person. Active immunity can last for years or even a lifetime. Passive immunity only lasts as long as the antibodies are circulating in the body—typically, a few weeks.

Immunity is classified based on how it is conferred to the individual. There are four types:

1. Naturally acquired active immunity occurs when an individual is naturally exposed to a pathogen.

2. Naturally acquired passive immunity occurs in the passing of antibodies from mother to fetus through the placenta or through breast milk via colostrum.

3. Artificially acquired active immunity occurs as a result of vaccination.4. Artificially acquired passive immunity occurs when antibodies are directly

transferred to an individual. This type of immunity can also be effective for neutralizing toxins.

Artificially acquired passive immunity is usually conferred only in severe situations (such as when a person contracts rabies or tetanus) where there is not enough time to stimulate the patient's own adaptive immune response to fight the infection (a process that can take several days). Because the B cells that originally made the antibodies are not present, you do not retain immunity given passively.

HIV and the Immune SystemThe ability of the human immunodeficiency virus (HIV) to infect and damage the host is directly linked to the cells of the immune system. In module 4, we learned that viruses bind to specific cell receptors to gain entry into the cell. Th, or CD4+, cells are one of the main cell types that HIV infects. HIV uses a protein marker on the surface of the cell (CD4) to gain entry into the cell.

Th cells play a key role in activating both the humoral and cell-mediated immune responses. Once infected with HIV, a Th cell cannot function properly, and eventually dies. Without Th cells, the body cannot activate B cells to make antibodies, nor can it activate Tc cells to fight virally infected cells (including those infected with HIV).

The body responds to Th cell infection and death by making more Th cells. Unfortunately, this increase in Th cell production provides even more cells for HIV to infect and kill. The battle between HIV and the immune system over the Th cells can go on for years. Eventually, the body can no longer make the quantities of Th necessary to maintain the immune system. The loss of Th cells leads to acquired immunodeficiency syndrome (AIDS), which renders the immune system unable to fight even the smallest of infections. People who succumb to AIDS typically die from complications caused by secondary infections.

ConclusionThe human immune system is a complex yet organized symphony of cells, proteins, and barriers designed to protect your body from infection. When harmful microbes breach the outer barriers of the body, inflammation begins. Within a few hours, the cells of the innate immune system arrive at the site of infection to attempt to control it and to eliminate the

invaders. Neutrophils are the first phagocytic cells to arrive, engulfing and destroying pathogens. Neutrophils are short-lived, however, and are eventually replaced by a second type of phagocytic cell, the macrophage. Macrophages are part of the adaptive immune system and serve a dual role: they destroy harmful microbes and they display antigens from the digested microbes on their surface to aid in the activation of Th cells. Once activated, Th cells secrete chemical signals (cytokines) to call even more cells of the immune system to the site of infection.

The B cell is one type of cell activated with the help of Th cells. Once stimulated, B cells secrete large quantities of highly specific antibodies that travel through the blood system and bind to pathogens. These antibodies mark each pathogen so that additional components of the immune system will know to destroy the infected cell. This system works well for microbes that reside in the body fluids or attached to the surface of host cells. Intracellular bacteria and viruses are not affected by antibodies, as they are shielded by the host cell. To battle intracellular pathogens, the immune system relies on Tc cells that, once activated by Th cells, destroy the infected host cell in the hopes of preventing the spread of the infection.

The immune system is fairly efficient in deterring and eliminating the many pathogens capable of infecting humans. However, as we learned in modules 3 and 4, some bacteria and viruses have developed ways of escaping or even exploiting the immune system in order to survive in the host. HIV invades the cells of the immune system—specifically, the Th cells—thereby crippling their ability to aid in the activation of B and Tc cells. By residing inside immune cells, HIV protects itself from immune attack and therefore lives unharmed in the body.

Closing RemarksWe designed this course to give you an overview of the microbial world and the types of cells and microorganisms it contains. Bacteria and viruses are among the smallest microbes capable of infecting humans and causing disease. These microorganisms are too small to be seen with the naked eye, but they are powerful enough to affect our bodies profoundly and to cause illness. Anyone who has had the flu or strep throat can attest to the impact these small life forms can have on our bodies.

Viruses and pathogenic bacteria have developed many ways in which to cause disease in humans. In some bacterial infections, secreted toxins and even parts of the bacterial cell itself cause disease symptoms. Viruses and some intracellular bacteria have evolved ways to invade and exploit human cells to propagate themselves and survive.

Rudimentary protective immune systems can be found in insects and plants; however, animals and humans have developed a more complex, multifaceted immune system that helps protect us when we cannot avoid exposure to pathogenic microbes.

The mechanisms by which beings so small can cause destruction and disease in humans are fascinating to study, and the knowledge we gain from such study can benefit everyone on the planet. Microorganisms are all around us, and cannot be easily avoided. We are exposed to them right after birth, and continue to be exposed throughout our lives. Understanding how microbes can both affect and infect our bodies is the first step in protecting ourselves and preventing infectious disease.

References

Arcadian. (2006). Mast cell [Illustration]. Retrieved April 22, 2008, from http://en.wikipedia.org/wiki/Image:Mast_cell.png. Used with permission under the terms of the GNU Free Documentation License.

Douek, D. (2007, Aug–Sep). HIV disease progression: Immune activation, microbes, and a leaky gut. Topics in HIV Medicine, 15(4), 114–117.

Rad, A. (2006). Major leukocytes [Illustration]. Retrieved April 21, 2008, from http://en.wikipedia.org/wiki/Image:Hematopoiesis_%28human%29_diagram.png. Used with permission under the terms of the GNU Free Documentation License.

Tortora, G., Funke, B., & Case, C. (2007). Microbiology and introduction (9th ed.). San Francisco: Pearson Education, Benjamin Cummings.

Weeks, B., & Alcamo, E. (2008). Microbes and society (2nd ed.). Sudbury, MA: Jones and Bartlett Publishers.