148 17.4 Innate Immune System
Created by CK-12 Foundation/Adapted by Christine Miller
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.
What Is the Innate Immune System?
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. The innate system responds in the same general way to every pathogen it encounters. 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 shed from the body surface, a process that 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 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 Figure 17.4.2).
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 Figure 17.4.3. A sneeze can travel as fast as 160 Km/hr (about 99 mi/hour) and expel as many as 100,000 droplets into the air around you (a good reason to cover your sneezes!). Other mechanical defenses include tears, which wash pathogens from the eyes, and urine, which flushes pathogens out of the urinary tract.
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. This film 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 of the 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. They may release toxins or change the pH, for example. All of these effects of harmless bacteria reduce the chances that pathogenic microorganisms will be able to reach sufficient numbers and cause illness.
Inflammation
If pathogens manage to breach the barriers protecting the body, 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 17.4.4.
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 pathogen-destroying leukocytes. Some cytokines have anti-viral effects. They may shut down protein synthesis in host cells, which viruses need in order to survive and replicate.
See the video “The inflammatory response” by Neural Academy to learn about inflammatory response in more detail:
The inflammatory response, Neural Academy, 2019.
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 normally found in the blood and synthesized in the liver. The proteins usually circulate as non-functional precursor molecules until activated.
As shown in Figure 17.4.5, 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.
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 Figure 17.4.6, 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 excretion of soluble debris from the destroyed pathogen through exocytosis.
Types of leukocytes that kill pathogens by phagocytosis include neutrophils, macrophages, and dendritic cells. You can see illustrations of these and other leukocytes involved in innate immune responses in Figure 17.4.7.
Neutrophils
Neutrophils are leukocytes that travel throughout the body in the blood. They are usually the first immune cells to arrive at the site of an infection. They are the most numerous types of phagocytes, and they 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 ten 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 body tissues. They are the most efficient phagocytes, and they can phagocytize substantial numbers 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.
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.
Eosinophils
Eosinophils are non-phagocytic leukocytes that are related to neutrophil. 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.
Mast Cells
Mast cells are non-phagocytic leukocytes that help 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 human hosts’ innate immune systems. 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 characterizes some species of bacteria and fungi. You can see an example of a bacterial biofilm on teeth in Figure 17.4.8.
17.4 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.
17.4 Review Questions
- What is the innate immune system?
- Identify the body’s first line of defense.
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- What are biological barriers? How do they protect the body?
- State the purposes of inflammation. What triggers inflammation, and what signs and symptoms does it cause?
- Define the complement system. How does it help destroy pathogens?
- Describe two ways that pathogens can evade the innate immune system.
- What are the ways in which phagocytes can encounter pathogens in the body?
- Describe two different ways in which enzymes play a role in the innate immune response.
17.4 Explore More
How mucus keeps us healthy – Katharina Ribbeck, TED-Ed, 2015.
Human Physiology – Innate Immune System, Janux, 2015.
Myriam Sidibe: The simple power of handwashing, TED, 2014.
Everything You Didn’t Want To Know About Snot, Gross Science, 2017.
Cough Grosser Than Sneeze? | Curiosity – World’s Dirtiest Man, Discovery, 2011.
Attributions
Figure 17.4.1
Oww_Papercut_14365 by Laurence Facun on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) license.
Figure 17.4.2
hairy-nose by Piotr Siedlecki on publicdomainpictures.net is used under a CC0 1.0 Universal Public Domain Dedication (http://creativecommons.org/publicdomain/zero/1.0/) license.
Figure 17.4.3
1024px-Sneeze by James Gathany/ CDC Public Health Image library (PHIL) ID# 11162 on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/public_domain).
Figure 17.4.4
OSC_Microbio_17_06_Erythema by CNX OpenStax on Wikimedia Commons is used under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0) license.
Figure 17.4.5
2212_Complement_Cascade_and_Function by OpenStax College on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.
Figure 17.4.6
512px-Phagocytosis2 by Graham Colm at English Wikipedia on Wikimedia Commons is used under a CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) license.
Figure 17.4.7
Innate_Immune_cells.svg by Fred the Oyster on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).
Figure 17.4.8
1024px-Gingivitis-before-and-after-3 by Onetimeuseaccount on Wikimedia Commons is used under a CC0 1.0 Universal Public Domain Dedication (http://creativecommons.org/publicdomain/zero/1.0/) license.
References
Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 21.13 Complement cascade and function [digital image]. In Anatomy and Physiology (Section 21.2). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/21-2-barrier-defenses-and-the-innate-immune-response
Discovery. (2011, October 27). Cough grosser than sneeze? | Curiosity – World’s dirtiest man. YouTube. https://www.youtube.com/watch?v=dy1D3d1FBcw&feature=youtu.be
Gross Science. (2017, January 31). Everything you didn’t want to know about snot. YouTube. https://www.youtube.com/watch?v=shEPwQPQG4I&feature=youtu.be
Janux. (2015, January 10). Human physiology – Innate immune system. YouTube. https://www.youtube.com/watch?v=sYjtMP67vyk&feature=youtu.be
Mayo Clinic Staff. (n.d.). Anthrax [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/anthrax/symptoms-causes/syc-20356203
Mayo Clinic Staff. (n.d.). Influenza (flu) [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/flu/symptoms-causes/syc-20351719
Mayo Clinic Staff. (n.d.). Salmonella infection [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/salmonella/symptoms-causes/syc-20355329
Mayo Clinic Staff. (n.d.). Staph infection [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/staph-infections/multimedia/staph-infection/img-20008600
Mayo Clinic Staff. (n.d.). Tuberculosis [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/tuberculosis/symptoms-causes/syc-20351250
OpenStax. (2016, November 11). Figure 17.23 A typical case of acute inflammation at the site of a skin wound – Erythema [digital image]. In OpenStax, Microbiology (Section 17.5). https://openstax.org/details/books/microbiology?Bookdetails
TED. (2014, October 14). Myriam Sidibe: The simple power of handwashing. YouTube. https://www.youtube.com/watch?v=c64M1tZyWPM&feature=youtu.be
TED-Ed. (2015, November 5). How mucus keeps us healthy – Katharina Ribbeck. YouTube. https://www.youtube.com/watch?v=WW4skW6gucU&feature=youtu.be
A microorganism which causes disease.
Any member of a large group of unicellular microorganisms which have cell walls but lack organelles and an organized nucleus, including some which can cause disease.
A subset of the immune system that makes generic attacks such as inflammation against invading pathogens.
A physical barrier which pathogens cannot cross, protecting the body. These barriers include: The outer layer of the skin and mucous membranes.
The major organ of the integumentary system that covers and protects the body and helps maintain homeostasis, for example, by regulating body temperature.
The outer layer of skin that consists mainly of epithelial cells and lacks nerve endings, blood vessels, and other structures.
A filament made of tightly packed, keratin-filled keratinocytes that grows out of a hair follicle in the dermis of the skin.
Epithelial tissue that lines inner body surfaces and body openings and produces mucus.
Tiny hairlike organelles, identical in structure to flagella, that line the surfaces of certain cells and beat in rhythmic waves, providing locomotion to ciliate protozoans and moving liquids along internal epithelial tissue in animals.
The response of the innate immune system that establishes a physical barrier against the spread of infection and repairs tissue damage while causing redness, swelling, and warmth.
A chemical released by injured, infected, or immune cells that triggers inflammation or other immune responses.
A chemical released by injured or infected cells or by certain immune system cells that triggers inflammation or an allergic reaction.
The movement of a living structure in response to a chemical signal, (example, as when chemical signals from an egg direct the movement of sperm toward the egg).
An innate immune response that consists of a cascade of proteins that complement the killing of pathogens by antibodies.
An antibody, also known as an immunoglobulin, is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses.
An organ of digestion and excretion that secretes bile for lipid digestion and breaks down excess amino acids and toxins in the blood.
Molecules on the surface of cells or viruses that the immune system identifies as either self (produced by your own body) or non-self (not produced by your own body).
a colorless cell that circulates in the blood and body fluids and is involved in counteracting foreign substances and disease; a white (blood) cell. There are several types, all amoeboid cells with a nucleus, including lymphocytes, granulocytes, monocytes, and macrophages.
The process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome.
An organelle in the cytoplasm of eukaryotic cells containing digestive enzymes enclosed in a membrane.
An important process of plant and animal cells as it performs the opposite function of endocytosis. In exocytosis, membrane-bound vesicles containing cellular molecules are transported to the cell membrane and released into the area surrounding the cell.
A type of immune cell that is one of the first cell types to travel to the site of an infection. Neutrophils help fight infection by ingesting microorganisms and releasing enzymes that kill the microorganisms. A neutrophil is a type of white blood cell, a type of granulocyte, and a type of phagocyte.
A soft connective tissue in spongy bone that produces blood cells.
A large phagocytic cell found in stationary form in the tissues or as a mobile white blood cell, especially at sites of infection.
Fluid found in the spaces around cells. ... It helps bring oxygen and nutrients to cells and to remove waste products from them. As new interstitial fluid is made, it replaces older fluid, which drains towards lymph vessels. When it enters the lymph vessels, it is called lymph. Also called tissue fluid.
A subset of the immune system that makes tailored attacks against specific pathogens or tumor cells such as the production of antibodies that match specific antigens.
A special type of immune cell that is found in tissues, such as the skin, and boosts immune responses by showing antigens on its surface to other cells of the immune system. A dendritic cell is a type of phagocyte and a type of antigen-presenting cell (APC).
A type of immune cell that has granules (small particles) with enzymes that are released during infections, allergic reactions, and asthma. An eosinophil is a type of white blood cell and a type of granulocyte.
A species that lives in or on another species, called the host, and causes harm to the host while benefitting from the relationship.
A damaging immune response by the body to a substance, especially pollen, fur, a particular food, or dust, to which it has become hypersensitive.
Chronic inflammatory disease of the respiratory system in which airways periodically become inflamed, causing swelling and narrowing of the airways, which makes breathing difficult.
A type of immune cell that has granules (small particles) with enzymes that are released during allergic reactions and asthma. A basophil is a type of white blood cell and a type of granulocyte.
A compound which is released by cells in response to injury and in allergic and inflammatory reactions, causing contraction of smooth muscle and dilation of capillaries.
A compound occurring in the liver and other tissues which inhibits blood coagulation.
A type of white blood cell found in connective tissues all through the body, especially under the skin, near blood vessels and lymph vessels, in nerves, and in the lungs and intestines. Mast cells play an important role in how the immune system responds to certain pathogens by releasing chemicals such as histamines and cytokines during allergic reactions and certain immune responses.
A type of immune cell that has granules (small particles) with enzymes that can kill tumor cells or cells infected with a virus. A natural killer cell is a type of white blood cell.
A type of leukocyte produced by the lymphatic system that is a key cell in the adaptive immune response to a specific pathogen or tumor cell.
A group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.
A tiny, nonliving particle that contains nucleic acids but lacks other characteristics of living cells and may cause human disease.
A set of molecules normally found on most human cells that provide a way for the immune system to recognize body cells as self.
The state of being immune from or insusceptible to a particular disease or the like. the condition that permits either natural or acquired resistance to disease. the ability of a cell to react immunologically in the presence of an antigen.
A liquid waste product of the body that is formed by the kidneys and excreted by the other organs of the urinary system.
Salty fluid secreted into ducts by sweat glands in the dermis that excretes wastes and helps cool the body; also called perspiration.
A fluid secreted by salivary glands that keeps the mouth moist and contains the digestive enzymes amylase and lipase.
Fluid containing sperm and glandular secretions, which nourishes sperm and carries them through the urethra and out of the body.
