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20.4: Innate Immune System

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    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.

    Papercut
    Figure \(\PageIndex{1}\): By Laurence Facun (Flickr) [CC BY 2.0], via Wikimedia Commons; Oww Papercut 14365.jpg)

    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 (see photo below).

    Nose hair
    Figure \(\PageIndex{2}\): Nasal hairs are a mechanical barrier to larger particles in the air. (By Thomy pc [Public domain], via Wikimedia Commons; Nasenhaare.jpg)

    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.

    Sneeze
    Figure \(\PageIndex{3}\): 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. (By James Gathany; CDC Public Health Image library ID 11162; [Public domain], via Wikimedia Commons; Sneeze.jpg)

    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 the figure below.

    inflammation process
    Figure \(\PageIndex{4}\): This drawing shows what happens during the inflammatory response. (Image copyright Athanasia Nomikou, CC BY 3.0; 2014, modified by CK-12 Foundation; shutterstock.com)

    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 below) 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 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 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 by antibodies, which 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.

    As shown in the figure below, when the first protein in the complement series is activated —typically by the binding of an antibody to an antigen on a pathogen — it sets in motion a domino effect. Each component takes its turn in a precise chain of steps known as the complement cascade. The end product is a cylinder that punctures a hole in the pathogen’s cell membrane. This allows fluids and molecules to flow in and out of the cell, which swells and bursts.

    Complement pathway
    Figure \(\PageIndex{5}\): The complement system is a cascade of proteins that complements the killing of pathogen cells by antibodies. (By Original work of the US Federal Government - public domain: English text by DO11.10; via Wikimedia Commons; Complement pathway.png)

    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 by 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 the figure below, 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.

    Phagocytosis
    Figure \(\PageIndex{6}\): Phagocytosis is a multi-step process in which a pathogen is engulfed and digested by immune cells called phagocytes. (GrahamColm at English Wikipedia [CC BY-SA 3.0]; Phagocytosis2.png)

    Leukocytes

    Types of leukocytes that kill pathogens by phagocytosis include neutrophils, macrophages, and dendritic cells. Macrophages and dendritic cells are the derivatives of monocytes.

    White Blood Cells
    Figure \(\PageIndex{7}\): Different types of leukocytes. (Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436.; CC BY 3.0: White Blood Cells)
    Leukocyte micrographs
    Figure \(\PageIndex{8}\): Microscope pictures of leukocytes. (OpenStax College; CC BY-NC 3.0; via Wikipedia.org: 1916 Leukocyte Key.jpg)

    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. 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. 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. They 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. 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. They reside in tissues that have contact with the external environment, so they are located mainly in the skin, nose, lungs, stomach, and intestines. Besides engulfing and digesting pathogens, dendritic cells also act as antigen-presenting cells that trigger adaptive immune responses.

    dendritic cell
    Figure \(\PageIndex{9}\): dendritic cell. (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; S8-Dendritic Cells Dragging Conidia in Collagen.ogv)

    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.

    Innate Immune Evasion

    Many pathogens have evolved mechanisms that allow them to evade the innate immune system of human hosts. Some of these mechanisms include:

    • invading host cells to replicate so they are “hidden” from the immune system. The bacterium that causes tuberculosis uses this mechanism.
    • forming a protective capsule around themselves to avoid being destroyed by immune system cells. This defense occurs in bacteria such as Salmonella species.
    • mimicking host cells so the immune system does not recognize them as foreign. Some species of Staphylococcus bacteria use this mechanism.
    • directly killing phagocytes. This ability evolved in several species of bacteria, including the species that causes anthrax.
    • producing molecules that prevent the formation of interferons, which are immune chemicals that fight viruses. Some influenza viruses have this capability.
    • forming complex biofilms that provide protection from the cells and proteins of the immune system. This ability characterizes some species of bacteria and fungi. You can see an example of a bacterial biofilm on teeth in the figure below.
    Gingivitis before and after
    Figure \(\PageIndex{10}\): The dental plaque on the top set of teeth is a biofilm that sticks to the teeth and consists of many species of bacteria. The plaque biofilm is difficult to remove, and it subjects the teeth and gums to high concentrations of bacterial metabolites, which result in dental disease. The same teeth after plaque removal are shown in the bottom picture. (By Onetimeuseaccount (Own work) [CC0], via Wikimedia Commons; Gingivitis before and after.jpg)

    Summary

    • The innate immune system is a subset of the human immune system that produces rapid but non-specific responses to pathogens. Unlike the adaptive immune system, the innate system does not confer immunity. The innate immune system includes surface barriers, inflammation, the complement system, and a variety of cellular responses.
    • 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 — which include the skin, mucous membranes, and fluids such as tears and urine — physically block pathogens from entering the body. Chemical barriers — such as enzymes in sweat, saliva, and semen — kill pathogens on body surfaces. Biological barriers are harmless bacteria that use up food and space so pathogenic bacteria cannot colonize the body.
    • If pathogens breach protective barriers, inflammation occurs. This creates a physical barrier against the spread of infection and repairs tissue damage. Inflammation is triggered by chemicals such as cytokines and histamines, and it causes swelling, redness, and warmth.
    • The complement system is a complex biochemical mechanism that helps antibodies kill pathogens. Once activated, the complement system consists of more than two dozen proteins that lead to disruption of the cell membrane of pathogens and bursting of the cells.
    • Cellular responses of the innate immune system involve various types of leukocytes. For example, neutrophils, macrophages, and dendritic cells phagocytize pathogens. Basophils and mast cells release chemicals that trigger inflammation. Natural killer cells destroy cancerous or virus-infected cells, and eosinophils kill parasites.
    • Many pathogens have evolved mechanisms that help them evade the innate immune system. For example, some pathogens form a protective capsule around themselves, and some mimic host cells so the immune system does not recognize them as foreign.

    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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