13.4: Innate Immune System

Paper Cut

It’s just a paper cut, but the break in your skin could provide an easy way for pathogens to enter your body. If bacteria were to enter through the cut and infect the wound, your innate immune system would quickly respond with a dizzying array of general defenses.

Figure \(\PageIndex{1}\): Papercut

The innate immune system is a subset of the human immune system that produces rapid but non-specific responses to pathogens. Innate responses are generic rather than tailored to a particular pathogen. Every pathogen that is encountered is responded to in the same general ways by the innate system. Although the innate immune system provides immediate and rapid defenses against pathogens, it does not confer long-lasting immunity to them. In most organisms, the innate immune system is the dominant system of host defense. Other than most vertebrates including humans, the innate immune system is the only system of host defense.

In humans, the innate immune system includes surface barriers, inflammation, the complement system, and a variety of cellular responses. Surface barriers of various types generally keep most pathogens out of the body. If these barriers fail, then other innate defenses are triggered. The triggering event is usually the identification of pathogens by pattern-recognition receptors on cells of the innate immune system. These receptors recognize molecules that are broadly shared by pathogens but distinguishable from host molecules. Alternatively, the other innate defenses may be triggered when damaged, injured, or stressed cells send out alarm signals, many of which are recognized by the same receptors as those that recognize pathogens.

Barriers to Pathogens

The body’s first line of defense consists of three different types of barriers that keep most pathogens out of body tissues. The types of barriers are mechanical, chemical, and biological barriers.

Mechanical Barriers

Mechanical barriers are the first line of defense against pathogens, and they physically block pathogens from entering the body. The skin is the most important mechanical barrier. In fact, it is the single most important defense the body has. The outer layer of skin, the epidermis, is tough and very difficult for pathogens to penetrate. It consists of dead cells that are constantly being shed from the body surface. This helps remove bacteria and other infectious agents that have adhered to the skin. The epidermis also lacks blood vessels and is usually lacking moisture, so it does not provide a suitable environment for most pathogens. Hair, which is an accessory organ of the skin, also helps to keep out pathogens. Hairs inside the nose may trap larger pathogens and other particles in the air before they can enter the airways of the respiratory system.

Mucous membranes provide a mechanical barrier to pathogens and other particles at body openings. These membranes also line the respiratory, gastrointestinal, urinary, and reproductive tracts. Mucous membranes secrete mucus, which is a slimy and somewhat sticky substance that traps pathogens. Many mucous membranes also have hair-like cilia that sweep mucus and trapped pathogens toward body openings where they can be removed from the body. When you sneeze or cough, mucus, and pathogens are mechanically ejected from the nose and throat, as you can see in the photo below. Other mechanical defenses include tears, which wash pathogens from the eyes, and urine, which flushes pathogens out of the urinary tract.

Figure \(\PageIndex{2}\): A sneeze can expel many pathogens from the respiratory tract. That’s why you should always cover your mouth and nose and when you sneeze.

Chemical Barriers

Chemical barriers also protect against infection by pathogens. They destroy pathogens on the outer body surface, at body openings, and on inner body linings. Sweat, mucus, tears, saliva, and breastmilk all contain antimicrobial substances, such as the enzyme lysozyme, that kill pathogens, especially bacteria. Sebaceous glands in the dermis of the skin secrete acids that form a very fine, slightly acidic film on the surface of the skin that acts as a barrier to bacteria, viruses, and other potential contaminants that might penetrate the skin. Urine and vaginal secretions are also too acidic for many pathogens to endure. Semen contains zinc, which most pathogens cannot tolerate, as well as defensins, which are antimicrobial proteins that act mainly by disrupting bacterial cell membranes. In the stomach, stomach acid and digestive enzymes called proteases, which break down proteins, kill most pathogens that enter the gastrointestinal tract in food or water.

Biological Barriers

Biological barriers are living organisms that help protect the body from pathogens. Trillions of harmless bacteria normally live on the human skin and in the urinary, reproductive, and gastrointestinal tracts. These bacteria use up food and surface space that help prevent pathogenic bacteria from colonizing the body. Some of these harmless bacteria also secrete substances that change the conditions of their environment, making it less hospitable to potentially harmful bacteria. For example, they may release toxins or change the pH. All of these effects of harmless bacteria reduce the chances that pathogenic microorganisms will be able to reach sufficient numbers to cause illness.

Inflammation

If pathogens manage to breach the barriers protecting the body, then one of the first active responses of the innate immune system kicks in. This response is inflammation. The main function of inflammation is to establish a physical barrier against the spread of infection. It also eliminates the initial cause of cell injury, clears out dead cells and tissues damaged from the original insult and the inflammatory process, and initiates tissue repair. Inflammation is often a response to infection by pathogens, but there are other possible causes, including burns, frostbite, and exposure to toxins.

The signs and symptoms of inflammation include redness, swelling, warmth, pain, and frequently some loss of function. These symptoms are caused by increased blood flow into infected tissue and a number of other processes, illustrated in Figure \(\PageIndex{3}\) and described below in the text.

Figure \(\PageIndex{3}\): This drawing shows what happens during the inflammatory response.

Inflammation is triggered by chemicals such as cytokines and histamines, which are released by injured or infected cells or by immune system cells such as macrophages (described in Figure \(\PageIndex{5}\)) that are already present in tissues. These chemicals cause capillaries to dilate and become leaky, increasing blood flow to the infected area and allowing blood to enter the tissues. Pathogen-destroying leukocytes, complement proteins, and tissue-repairing proteins migrate into tissue spaces from the bloodstream to attack pathogens and repair their damage. Cytokines also promote chemotaxis, which is migration to the site of infection by leukocytes that destroy pathogens. Some cytokines have anti-viral, antifungal, and antibacterial effects, such as shutting down protein synthesis in host cells, which viruses need in order to survive and replicate.

Complement System

The complement system is a complex biochemical mechanism named for its ability to “complement” the killing of pathogens directly by creating holes in the body of the pathogen and by assisting antibodies. Antibodies are produced as part of an adaptive immune response. The complement system consists of more than two dozen proteins that are normally found in the blood and synthesized in the liver. The proteins usually circulate as non-functional precursor molecules until activated.

Cellular Responses

Cellular responses of the innate immune system involve a variety of different types of leukocytes. Many of these leukocytes circulate in the blood and act like independent, single-celled organisms, searching out and destroying pathogens in the human host. These and other immune cells of the innate system identify pathogens or debris and then help to eliminate them in some way. One way is phagocytosis.

Phagocytosis

Phagocytosis is an important feature of innate immunity that is performed by cells classified as phagocytes. In the process of phagocytosis, phagocytes engulf and digest pathogens or other harmful particles. Phagocytes generally patrol the body searching for pathogens, but they can also be called to specific locations by the release of cytokines when inflammation occurs. Some phagocytes reside permanently in certain tissues.

As shown in Figure \(\PageIndex{4}\), when a pathogen such as a bacterium is encountered by a phagocyte, the phagocyte extends a portion of its plasma membrane, wrapping the membrane around the pathogen until it is enveloped. Once inside the phagocyte, the pathogen becomes enclosed within an intracellular vesicle called a phagosome. The phagosome then fuses with another vesicle called a lysosome, forming a phagolysosome. Digestive enzymes and acids from the lysosome kill and digest the pathogen in the phagolysosome. The final step of phagocytosis is the excretion of soluble debris from the destroyed pathogen through exocytosis.

Figure \(\PageIndex{4}\): Phagocytosis is a multi-step process in which a pathogen is engulfed and digested by immune cells called phagocytes.

Leukocytes

Types of leukocytes that kill pathogens by phagocytosis include neutrophils, macrophages, and dendritic cells. Macrophages and dendritic cells are the derivatives of monocytes. Figure \(\PageIndex{5}\) shows five major types of leukocytes, lymphocytes, basophils, eosinophils, neutrophils, and monocytes. Because lymphocytes are mainly involved in the adaptive immune system, they are not discussed in this concept.

Figure \(\PageIndex{5}\): Five types of leukocytes: from left to right, lymphocyte, basophil, eosinophil, neutrophil, and monocytes.

Neutrophils

Neutrophils are leukocytes that travel throughout the body in the blood and are usually the first immune cells to arrive at the site of an infection. As shown in Figure \(\PageIndex{5}\), these cells contain granules and carry a multilobed nucleus. They are the most numerous types of phagocytes and normally make up at least half of the total circulating leukocytes. The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day. During acute inflammation, more than 10 times that many neutrophils may be produced each day. Many neutrophils are needed to fight infections because after a neutrophil phagocytizes just a few pathogens, it generally dies.

Macrophages

Macrophages are large phagocytic leukocytes that develop from monocytes. Macrophages spend much of their time within the interstitial fluid in tissues of the body. As shown in Figure \(\PageIndex{5}\), monocytes do not contain granules and carry a big kidney-shaped nucleus. They are the most efficient phagocytes and can phagocytize a substantial number of pathogens or other cells. Macrophages are also versatile cells that produce a wide array of chemicals — including enzymes, complement proteins, and cytokines — in addition to their phagocytic action. As phagocytes, macrophages act as scavengers that rid tissues of worn-out cells and other debris as well as pathogens. In addition, macrophages act as antigen-presenting cells that activate the adaptive immune system. (To learn more about antigen-presenting cells, see the concept Adaptive Immune System.)

Eosinophils

Eosinophils are non-phagocytic leukocytes that are related to neutrophils. They specialize in defending against parasites. As shown in Figure \(\PageIndex{5}\), these cells contain granules and carry a bilobed earmuff-shaped nucleus. These leukocytes are very effective in killing large parasites such as worms by secreting a range of highly toxic substances when activated. Eosinophils may become overactive and cause allergies or asthma.

Basophils

Basophils are non-phagocytic leukocytes that are also related to neutrophils. They are the least numerous of all white blood cells. As shown in Figure \(\PageIndex{5}\), these cells contain granules and carry a bilobed nucleus. Basophils secrete two types of chemicals that aid in body defenses: histamines and heparin. Histamines are responsible for dilating blood vessels and increasing their permeability in inflammation. Heparin inhibits blood clotting and also promotes the movement of leukocytes into an area of infection.

Dendritic Cells

Like macrophages, dendritic cells develop from monocytes (see Figure \(\PageIndex{6}\). They reside in tissues that have contact with the external environment, so they are located mainly in the skin, nose, lungs, stomach, and intestines. Their plasma membrane has extensions. Besides engulfing and digesting pathogens, dendritic cells also act as antigen-presenting cells that trigger adaptive immune responses.

Figure \(\PageIndex{6}\): dendritic cell

Mast Cells

Mast cells are non-phagocytic leukocytes that help to initiate inflammation by secreting histamines. In some people, histamines trigger allergic reactions as well as inflammation. Mast cells may also secrete chemicals that help defend against parasites.

Natural Killer Cells

Natural killer cells are in the subset of leukocytes called lymphocytes, which are produced by the lymphatic system. Natural killer cells destroy cancerous or virus-infected host cells, although they do not directly attack invading pathogens. Natural killer cells recognize these host cells by a condition they exhibit called “missing self.” Cells with missing self have abnormally low levels of cell-surface proteins of the major histocompatibility complex (MHC), which normally identify body cells as self.

Review

1. What is the innate immune system?
2. Identify the body’s first line of defense.
3. Define and give examples of mechanical and chemical barriers of the innate immune system.
4. What are biological barriers, and how do they protect the body?
5. State the purposes of inflammation.
6. What triggers inflammation, and what signs and symptoms does it cause?
7. Define the complement system. How does it help destroy pathogens?
8. List six different types of leukocytes and state their roles in innate immune responses.
9. Describe two ways that pathogens may evade the innate immune system.
10. Explain how mucus can contribute to the immune system as both a mechanical barrier and a chemical barrier.
11. Which type of immune system cell can both phagocytize pathogens and produce chemicals that promote inflammation?

    A. Macrophages

    B. Natural killer cells

    C. Basophils

    D. Mast cells

12. What are the ways in which phagocytes can encounter pathogens in the body?
13. Describe different two ways in which enzymes play a role in the innate immune response.
14. True or False. Complement proteins can be produced by macrophages.
15. True or False. The main function of inflammation is to secrete repair proteins at the site of damage.

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Attributions

1. Oww Papercut by Laurence Facun (Flickr), CC BY 2.0, via Wikimedia Commons
2. Sneeze by James Gathany; CDC Public Health Image library ID 11162, Public domain via Wikimedia Commons
3. Inflammatory Response by OpenStax, CC BY 3.0
4. Phagocytosis by OpenStax, CC BY 3.0
5. Leukocytes by Suzanne Wakim licensed CC BY 4.0 adapted from:
   • White Blood Cells, CC BY 3.0, Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436.
   • Leukocyte Key by OpenStax College, CC BY 3.0 via Wikimedia Commons
6. S8-Dendritic Cells Dragging Conidia in Collagen by Judith Behnsen, Priyanka Narang, Mike Hasenberg, Frank Gunzer, Ursula Bilitewski, Nina Klippel, Manfred Rohde, Matthias Brock, Axel A. Brakhage, Matthias Gunzer, CC BY 2.5 via wikimedia.org
7. Text adapted from Human Biology by CK-12 licensed CC BY-NC 3.0