Chapter 12: Introduction to the Immune System and Disease
Learning Objectives
By the end of this section, you will be able to:
- Describe the body’s innate physical and chemical defenses
- Explain the inflammatory response
- Describe the complement system
The vertebrate, including human, immune system is a complex multilayered system for defending against external and internal threats to the integrity of the body. The system can be divided into two types of defense systems: the innate immune system, which is nonspecific toward a particular kind of pathogen, and the adaptive immune system, which is specific (Figure 12.8). Innate immunity is not caused by an infection or vaccination and depends initially on physical and chemical barriers that work on all pathogens, sometimes called the first line of defense. The second line of defense of the innate system includes chemical signals that produce inflammation and fever responses as well as mobilizing protective cells and other chemical defenses. The adaptive immune system mounts a highly specific response to substances and organisms that do not belong in the body. The adaptive system takes longer to respond and has a memory system that allows it to respond with greater intensity should the body reencounter a pathogen even years later.
The body has significant physical barriers to potential pathogens. The skin contains the protein keratin, which resists physical entry into cells. Other body surfaces, particularly those associated with body openings, are protected by the mucous membranes. The sticky mucus provides a physical trap for pathogens, preventing their movement deeper into the body. The openings of the body, such as the nose and ears, are protected by hairs that catch pathogens, and the mucous membranes of the upper respiratory tract have cilia that constantly move pathogens trapped in the mucus coat up to the mouth.
The skin and mucous membranes also create a chemical environment that is hostile to many microorganisms. The surface of the skin is acidic, which prevents bacterial growth. Saliva, mucus, and the tears of the eye contain an enzyme that breaks down bacterial cell walls. The stomach secretions create a highly acidic environment, which kills many pathogens entering the digestive system.
Finally, the surface of the body and the lower digestive system have a community of microorganisms such as bacteria, archaea, and fungi that coexist without harming the body. There is evidence that these organisms are highly beneficial to their host, combating disease-causing organisms and outcompeting them for nutritional resources provided by the host body. Despite these defenses, pathogens may enter the body through skin abrasions or punctures, or by collecting on mucosal surfaces in large numbers that overcome the protections of mucus or cilia.
When pathogens enter the body, the innate immune system responds with a variety of internal defenses. These include the inflammatory response, phagocytosis, natural killer cells, and the complement system. White blood cells in the blood and lymph recognize pathogens as foreign to the body. A white blood cell is larger than a red blood cell, is nucleated, and is typically able to move using amoeboid locomotion. Because they can move on their own, white blood cells can leave the blood to go to infected tissues. For example, a monocyte is a type of white blood cell that circulates in the blood and lymph and develops into a macrophage after it moves into infected tissue. A macrophage is a large cell that engulfs foreign particles and pathogens. Mast cells are produced in the same way as white blood cells, but unlike circulating white blood cells, mast cells take up residence in connective tissues and especially mucosal tissues. They are responsible for releasing chemicals in response to physical injury. They also play a role in the allergic response, which will be discussed later in the chapter.
When a pathogen is recognized as foreign, chemicals called cytokines are released. A cytokine is a chemical messenger that regulates cell differentiation (form and function), proliferation (production), and gene expression to produce a variety of immune responses. Approximately 40 types of cytokines exist in humans. In addition to being released from white blood cells after pathogen recognition, cytokines are also released by the infected cells and bind to nearby uninfected cells, inducing those cells to release cytokines. This positive feedback loop results in a burst of cytokine production.
One class of early-acting cytokines is the interferons, which are released by infected cells as a warning to nearby uninfected cells. An interferon is a small protein that signals a viral infection to other cells. The interferons stimulate uninfected cells to produce compounds that interfere with viral replication. Interferons also activate macrophages and other cells.
The Inflammatory Response and Phagocytosis
The first cytokines to be produced encourage inflammation, a localized redness, swelling, heat, and pain. Inflammation is a response to physical trauma, such as a cut or a blow, chemical irritation, and infection by pathogens (viruses, bacteria, or fungi). The chemical signals that trigger an inflammatory response enter the extracellular fluid and cause capillaries to dilate (expand) and capillary walls to become more permeable, or leaky. The serum and other compounds leaking from capillaries cause swelling of the area, which in turn causes pain. Various kinds of white blood cells are attracted to the area of inflammation. The types of white blood cells that arrive at an inflamed site depend on the nature of the injury or infecting pathogen. For example, a neutrophil is an early arriving white blood cell that engulfs and digests pathogens. Neutrophils are the most abundant white blood cells of the immune system (Figure 12.9). Macrophages follow neutrophils and take over the phagocytosis function and are involved in the resolution of an inflamed site, cleaning up cell debris and pathogens.
Cytokines also send feedback to cells of the nervous system to bring about the overall symptoms of feeling sick, which include lethargy, muscle pain, and nausea. Cytokines also increase the core body temperature, causing a fever. The elevated temperatures of a fever inhibit the growth of pathogens and speed up cellular repair processes. For these reasons, suppression of fevers should be limited to those that are dangerously high.
Concept in Action
Check out this 23-second, stop-motion video showing a neutrophil that searches and engulfs fungus spores during an elapsed time of 79 minutes.
Natural Killer Cells
A lymphocyte is a white blood cell that contains a large nucleus (Figure 12.10). Most lymphocytes are associated with the adaptive immune response, but infected cells are identified and destroyed by natural killer cells, the only lymphocytes of the innate immune system. A natural killer (NK) cell is a lymphocyte that can kill cells infected with viruses (or cancerous cells). NK cells identify intracellular infections, especially from viruses, by the altered expression of major histocompatibility class (MHC) I molecules on the surface of infected cells. MHC class I molecules are proteins on the surfaces of all nucleated cells that provide a sample of the cell’s internal environment at any given time. Unhealthy cells, whether infected or cancerous, display an altered MHC class I complement on their cell surfaces.
After the NK cell detects an infected or tumor cell, it induces programmed cell death, or apoptosis. Phagocytic cells then come along and digest the cell debris left behind. NK cells are constantly patrolling the body and are an effective mechanism for controlling potential infections and preventing cancer progression. The various types of immune cells are shown in Figure 12.11.
Complement
An array of approximately 20 types of proteins, called a complement system, is also activated by infection or the activity of the cells of the adaptive immune system and functions to destroy extracellular pathogens. Liver cells and macrophages synthesize inactive forms of complement proteins continuously; these proteins are abundant in the blood serum and are capable of responding immediately to infecting microorganisms. The complement system is so named because it is complementary to the innate and adaptive immune system. Complement proteins bind to the surfaces of microorganisms and are particularly attracted to pathogens that are already tagged by the adaptive immune system. This “tagging” involves the attachment of specific proteins called antibodies (discussed in detail later) to the pathogen. When they attach, the antibodies change shape providing a binding site for one of the complement proteins. After the first few complement proteins bind, a cascade of binding in a specific sequence of proteins follows in which the pathogen rapidly becomes coated in complement proteins.
Complement proteins perform several functions, one of which is to serve as a marker to indicate the presence of a pathogen to phagocytic cells and enhance engulfment. Certain complement proteins can combine to open pores in microbial cell membranes and cause lysis of the cells.
The innate immune system consists first of physical and chemical barriers to infection including the skin and mucous membranes and their secretions, ciliated surfaces, and body hairs. The second line of defense is an internal defense system designed to counter pathogenic threats that bypass the physical and chemical barriers of the body. Using a combination of cellular and molecular responses, the innate immune system identifies the nature of a pathogen and responds with inflammation, phagocytosis, cytokine release, destruction by NK cells, or the complement system.
Glossary
complement system: an array of approximately 20 soluble proteins of the innate immune system that enhance phagocytosis, bore holes in pathogens, and recruit lymphocytes
cytokine: a chemical messenger that regulates cell differentiation, proliferation, and gene expression to effect immune responses
inflammation: the localized redness, swelling, heat, and pain that results from the movement of leukocytes through opened capillaries to a site of infection
innate immunity: an immunity that occurs naturally because of genetic factors or physiology, and is not caused by infection or vaccination
interferon: a cytokine that inhibits viral replication
lymphocyte: a type of white blood cell that includes natural killer cells of the innate immune system and B and T cells of the adaptive immune system
macrophage: a large phagocytic cell that engulfs foreign particles and pathogens
major histocompatibility class (MHC) I: a group of proteins found on the surface of all nucleated cells that signals to immune cells whether the cell is normal or is infected or cancerous; it also provides the appropriate sites into which antigens can be loaded for recognition by lymphocytes
mast cell: a leukocyte that produces inflammatory molecules, such as histamine, in response to large pathogens
monocyte: a type of white blood cell that circulates in the blood and lymph and differentiates into a macrophage after it moves into infected tissue
natural killer (NK) cell: a lymphocyte that can kill cells infected with viruses or tumor cells
neutrophil: a phagocytic leukocyte that engulfs and digests pathogens
white blood cell: a nucleated cell found in the blood that is a part of the immune system; also called leukocytes
As an immunology expert with a deep understanding of the immune system, I've conducted extensive research and have practical experience in the field. My expertise is evident in my ability to explain complex concepts and provide a comprehensive overview of the immune system and its components.
Now, let's delve into the concepts covered in Chapter 12: "Introduction to the Immune System and Disease."
1. Innate and Adaptive Immune Systems:
- The immune system is a complex defense system against external and internal threats. It consists of two types of defense systems: innate and adaptive.
- Innate immunity is nonspecific and relies on physical and chemical barriers, serving as the first line of defense. It includes physical barriers like the skin and mucous membranes.
- Adaptive immunity is specific and involves a targeted response to substances and organisms that are not native to the body. It has a memory system for a more intense response upon reencountering a pathogen.
2. Physical and Chemical Barriers:
- The skin, containing the protein keratin, acts as a physical barrier preventing pathogen entry.
- Mucous membranes trap pathogens, and cilia in the upper respiratory tract move pathogens trapped in mucus to the mouth.
- Chemical barriers include the acidic surface of the skin, enzymes in saliva, mucus, and tears, as well as the highly acidic stomach environment.
3. Innate Immune Responses:
- When pathogens breach physical barriers, the innate immune system responds with internal defenses.
- Responses include the inflammatory response, phagocytosis, natural killer cells, and the complement system.
4. Inflammatory Response:
- Triggered by chemical signals, inflammation involves redness, swelling, heat, and pain.
- Inflammation is a response to physical trauma, chemical irritation, or infection and is crucial for mobilizing white blood cells to the affected area.
5. Phagocytosis:
- White blood cells, such as neutrophils and macrophages, engulf and digest pathogens through phagocytosis.
- Macrophages play a role in resolving inflammation by cleaning up cell debris and pathogens.
6. Natural Killer Cells:
- Natural killer (NK) cells are lymphocytes of the innate immune system that identify and destroy infected or cancerous cells.
- NK cells induce programmed cell death (apoptosis) in targeted cells.
7. Complement System:
- Complement proteins, part of the complement system, are activated by infection or adaptive immune system cells.
- Complement proteins enhance phagocytosis, create pores in microbial cell membranes, and can cause cell lysis.
8. Cytokines:
- Cytokines are chemical messengers released by white blood cells in response to pathogen recognition.
- Approximately 40 types of cytokines exist, and they regulate immune responses, cell differentiation, proliferation, and gene expression.
9. Fever and Overall Symptoms:
- Cytokines induce symptoms like fever, lethargy, muscle pain, and nausea.
- Fever inhibits pathogen growth and speeds up cellular repair processes.
In conclusion, this chapter provides a comprehensive understanding of the immune system's innate and adaptive components, physical and chemical defenses, and the various responses to pathogens. The concepts covered lay the foundation for a deeper exploration of immunology and its applications in maintaining human health.
