Module 5: The Immune System and Disease Resistance

Commentary

Topics

The Immune System
Innate Immunity
Adaptive Immunity
Types of Immunity
HIV and the Immune System
Conclusion
Closing Remarks

The Immune System

Your 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 system
  2. adaptive immune system

Theinnate immune systemresponds 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, theadaptive immune systemmounts 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 aGlossarytab for your reference.

Innate Immunity

Your 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 5.1
Innate 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

Thefirst line of defenseof 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 producessebum, 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 asSalmonella, 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 microbiotaare 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

Thesecond line of defenseof 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 asleukocytes, orwhite 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, whereaseosinophilsrespond to parasitic infection. All leukocytes originate from a common progenitor cell known as ahematopoietic stem cell.Hematopoietic stem cellsform 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 5.1
Major Types of Leukocytes

Source of cell illustrations: Rad, 2006, Wikipedia Web site. Used with permission
under 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 undergoapoptosis, 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 cellsfunction 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 andcytokines, 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 ofphagocytosiscan 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: Alysosomefuses with the phagosome, forming a compartment called aphagolysosome.
  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 5.2
Major 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 during infection / plays a role in antigen presentation to cells of the 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.Shigellaspecies (the causative agents of the gastrointestinal illnessshigellosis) 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 5.1
Phagocytosis

Click on the link to see thecompleted versionof 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 eitheracuteorchronic.Acute inflammationoccurs at the site of infection, such as a scrape or boil.Chronic inflammationtends to accompany chronic infections such as tuberculosis caused byM. 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 5.3
Stages of Inflammation

Stage / Process / Effects on the Body
1 / dilation 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 calledvasoconstriction—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 ofinterferonsin the blood
  • increasing the rate of tissue repair
  • increasing the activity of T cells in the adaptive immune response

Complement Pathway

Thecomplement systemis 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 calledcomplementbecause 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 amembrane 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 cellsare 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 5.2
Complement Activation

Source of mast cell illustration: Arcadian, 2006, Wikipedia Web site. Used with
permission 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 astudy guidebased on the above activity.

Adaptive Immunity

Theadaptive immune systemprovides 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 infection
  2. 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 termhumoralcomes from the Latin wordhumororumor, meaning "bodily fluid." Antibodies were first discovered circulating in the bodily fluids, hence the phrasehumoral immunity. Humoral immunity is also known asantibody-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.

Antigensare 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.