17.4 Innate Immune System

Created by CK-12 Foundation/Adapted by Christine Miller

17.4.1 Paper Cut
Figure 17.4.1 Darn it!  Paper cuts are the worst!

Paper Cut

It’s just a paper cut, but the break in your skin could provide an easy way for  to enter your body. If  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  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

17.4.2 Hairy Nose
Figure 17.4.2 Nasal hairs are a mechanical barrier to larger particles in the air.

are the first line of defense against pathogens, and they physically block pathogens from entering the body. The is the most important mechanical barrier. In fact, it is the single most important defense the body has. The outer layer of skin — the  — 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.  — 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).

17.4.3 Sneeze
Figure 17.4.3 A sneeze can expel many pathogens from the respiratory tract, which is why you should always cover your mouth and nose and when you sneeze.

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 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.


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 . 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.

17.4.4 Inflammatory Response
Figure 17.4.4 This drawing shows what happens during the inflammatory response.

Inflammation is triggered by chemicals such as  and ,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 , 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  is a complex biochemical mechanism named for its ability to “complement” the killing of pathogens by , 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 . 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 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.

17.4.5 Complement Cascade
Figure 17.4.5 The complement system is a cascade of proteins that complements the killing of pathogen cells by antibodies.

Cellular Responses

Cellular responses of the innate immune system involve a variety of different types of . 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 .


 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  when 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 , 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 .

17.4.6 Phagocytosis
Figure 17.4.6 Phagocytosis is a multi-step process in which a pathogen is engulfed and digested by immune cells called phagocytes.

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.

17.4.7 Innate Immune Cells
Figure 17.4.7 Types of leukocytes evolved in innate immune responses are illustrated here.


 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 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.


 are large phagocytic leukocytes that develop from monocytes. Macrophages spend much of their time within the 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  — 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 .

Dendritic Cells

Like macrophages,  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.


are non-phagocytic leukocytes that are related to . They specialize in defending against . 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 or .


 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: and heparin. Histamines are responsible for dilating blood vessels and increasing their permeability in inflammation.  inhibits blood clotting, and also promotes the movement of leukocytes into an area of infection.

Mast Cells

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

Natural Killer Cells

 are in the subset of leukocytes called , which are produced by the lymphatic system. Natural killer cells destroy  or -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 , 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 and fungi. You can see an example of a bacterial biofilm on teeth in Figure 17.4.8.
17.4.8 Gingivitis
Figure 17.4.8 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.


17.4 Summary

  • The is a subset of the human immune system that produces rapid, but non-specific responses to pathogens. Unlike the , the innate system does not confer . The innate immune system includes surface barriers, , the , 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 , , and fluids such as tears and — physically block pathogens from entering the body. Chemical barriers — such as enzymes in , , and  — 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, occurs. This creates a physical barrier against the spread of infection, and repairs tissue damage. Inflammation is triggered by chemicals such as  and , and it causes swelling, redness, and warmth.
  • The is a complex biochemical mechanism that helps 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 . For example, , , and  phagocytize pathogens.  and  release chemicals that trigger inflammation.  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

  1. What is the innate immune system?
  2. Identify the body’s first line of defense.
  3. What are biological barriers? How do they protect the body?
  4. State the purposes of inflammation. What triggers inflammation, and what signs and symptoms does it cause?
  5. Define the complement system. How does it help destroy pathogens?
  6. Describe two ways that pathogens can evade the innate immune system.
  7. What are the ways in which phagocytes can encounter pathogens in the body?
  8. 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.



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.


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


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Human Biology Copyright © 2020 by Christine Miller is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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