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Innate immunity

Every day we are alive, humans encounter potentially harmful disease causing organisms, or “pathogens”, like bacteria or viruses. Yet most of us are still able to function properly and live life without constantly being sick. That’s because the human body requires a multilayered immune system to keep it running smoothly. The two main classes of the immune system are the innate immune system and the adaptive immune system, or “acquired immunity”. In this article, we’ll discuss the first line of defense: the innate immune system.

Self vs. Non-self: How does the body know?

In order to be effective, the immune system needs to be able to identify which particles are foreign, and which are a part of your body. Let’s define some terms before we jump in to how this works:
  • Self refers to particles, such as proteins and other molecules, that are a part of, or made by, your body. They can be found circulating in your blood or attached to different tissues. Something that is self should not be targeted and destroyed by the immune system. The non-reactivity of the immune system to self particles is called tolerance.
  • Non-self refers to particles that are not made by your body, and are recognized as potentially harmful. These are sometimes called foreign bodies. Non-self particles or bodies can be bacteria, viruses, parasites, pollen, dust, and toxic chemicals. The non-self particles and foreign bodies that are infectious or pathogenic, like bacteria, viruses, and parasites, make proteins called antigens that allow the human body to know that they intend to cause damage.
  • Antigens are anything that causes an immune response. Antigens can be entire pathogens, like bacteria, viruses, fungi, and parasites, or smaller proteins that pathogens express. Antigens are like a name tag for each pathogen that announce the pathogens’ presence to your immune system. Some pathogens are general, whereas others are very specific. A general antigen would announce “I’m dangerous”, whereas a specific antigen would announce “I’m a bacteria that will cause an infection in your gastrointestinal tract” or “I’m the influenza virus”.
  • Cytokines are molecules that are used for cell signaling, or cell-to-cell communication. Cytokines are similar to chemokines, wherein they can be used to communicate with neighboring or distant cells about initiating an immune response. Cytokines are also used to trigger cell trafficking, or movement, to a specific area of the body.
  • Chemokines are a type of cytokines that are released by infected cells. Infected host cells release chemokines in order to initiate an immune response, and to warn neighboring cells of the threat.

Innate Immune System

The innate immune system is made of defenses against infection that can be activated immediately once a pathogen attacks. The innate immune system is essentially made up of barriers that aim to keep viruses, bacteria, parasites, and other foreign particles out of your body or limit their ability to spread and move throughout the body. The innate immune system includes:
  • Physical Barriers
    • such as skin, the gastrointestinal tract, the respiratory tract, the nasopharynx, cilia, eyelashes and other body hair.
  • Defense Mechanisms
    • such as secretions, mucous, bile, gastric acid, saliva, tears, and sweat.
  • General Immune Responses
    • such as inflammation, complement, and non-specific cellular responses. The inflammatory response actively brings immune cells to the site of an infection by increasing blood flow to the area. Complement is an immune response that marks pathogens for destruction and makes holes in the cell membrane of the pathogen. Check out our video that explains inflammation and complement, which we will touch on later.
The innate immune system is always general, or nonspecific, meaning anything that is identified as foreign or non-self is a target for the innate immune response. The innate immune system is activated by the presence of antigens and their chemical properties.

Cells of the Innate Immune System

There are many types of white blood cells, or leukocytes, that work to defend and protect the human body. In order to patrol the entire body, leukocytes travel by way of the circulatory system.
The following cells are leukocytes of the innate immune system:
  • Phagocytes, or Phagocytic cells: Phagocyte means “eating cell”, which describes what role phagocytes play in the immune response. Phagocytes circulate throughout the body, looking for potential threats, like bacteria and viruses, to engulf and destroy. You can think of phagocytes as security guards on patrol.
This article explains how phagocytes know what to engulf, and how phagocytosis works.
  • Macrophages: Macrophages, commonly abbreviated as “Mφ”, are efficient phagocytic cells that can leave the circulatory system by moving across the walls of capillary vessels. The ability to roam outside of the circulatory system is important, because it allows macrophages to hunt pathogens with less limits. Macrophages can also release cytokines in order to signal and recruit other cells to an area with pathogens.
  • Mast cells: Mast cells are found in mucous membranes and connective tissues, and are important for wound healing and defense against pathogens via the inflammatory response. When mast cells are activated, they release cytokines and granules that contain chemical molecules to create an inflammatory cascade. Mediators, such as histamine, cause blood vessels to dilate, increasing blood flow and cell trafficking to the area of infection. The cytokines released during this process act as a messenger service, alerting other immune cells, like neutrophils and macrophages, to make their way to the area of infection, or to be on alert for circulating threats.
  • Neutrophils: Neutrophils are phagocytic cells that are also classified as granulocytes because they contain granules in their cytoplasm. These granules are very toxic to bacteria and fungi, and cause them to stop proliferating or die on contact.
The bone marrow of an average healthy adult makes approximately 100 billion new neutrophils per day. Neutrophils are typically the first cells to arrive at the site of an infection because there are so many of them in circulation at any given time.
  • Eosinophils: Eosinophils are granulocytes target multicellular parasites. Eosinophils secrete a range of highly toxic proteins and free radicals that kill bacteria and parasites. The use of toxic proteins and free radicals also causes tissue damage during allergic reactions, so activation and toxin release by eosinophils is highly regulated to prevent any unnecessary tissue damage.
    While eosinophils only make up 1-6% of the white blood cells, they are found in many locations, including the thymus, lower gastrointestinal tract, ovaries, uterus, spleen, and lymph nodes.
  • Basophils: Basophils are also granulocytes that attack multicellular parasites. Basophils release histamine, much like mast cells. The use of histamine makes basophils and mast cells key players in mounting an allergic response.
  • Natural Killer cells: Natural Killer cells (NK cells), do not attack pathogens directly. Instead, natural killer cells destroy infected host cells in order to stop the spread of an infection. Infected or compromised host cells can signal natural kill cells for destruction through the expression of specific receptors and antigen presentation.
  • Dendritic cells: Dendritic cells are antigen-presenting cells that are located in tissues, and can contact external environments through the skin, the inner mucosal lining of the nose, lungs, stomach, and intestines. Since dendritic cells are located in tissues that are common points for initial infection, they can identify threats and act as messengers for the rest of the immune system by antigen presentation. Dendritic cells also act as bridge between the innate immune system and the adaptive immune system.

The Complement System

The complement system (also called the complement cascade) is a mechanism that complements other aspects of the immune response. Typically, the complement system acts as a part of the innate immune system, but it can work with the adaptive immune system if necessary.
The complement system is made of a variety of proteins that, when inactive, circulate in the blood. When activated, these proteins come together to initiate the complement cascade, which starts the following steps:
  1. Opsonization: Opsonization is a process in which foreign particles are marked for phagocytosis. All of the pathways require an antigen to signal that there is a threat present. Opsonization tags infected cells and identifies circulating pathogens expressing the same antigens.
  2. Chemotaxis: Chemotaxis is the attraction and movement of macrophages to a chemical signal. Chemotaxis uses cytokines and chemokines to attract macrophages and neutrophils to the site of infection, ensuring that pathogens in the area will be destroyed. By bringing immune cells to an area with identified pathogens, it improves the likelihood that the threats will be destroyed and the infection will be treated.
  3. Cell Lysis: Lysis is the breaking down or destruction of the membrane of a cell. The proteins of the complement system puncture the membranes of foreign cells, destroying the integrity of the pathogen. Destroying the membrane of foreign cells or pathogens weakens their ability to proliferate, and helps to stop the spread of infection.
  4. Agglutination: Agglutination uses antibodies to cluster and bind pathogens together, much like a cowboy rounds up his cattle. By bringing as many pathogens together in the same area, the cells of the immune system can mount an attack and weaken the infection. Other innate immune system cells continue to circulate throughout the body in order to track down any other pathogens that have not been clustered and bound for destruction.
The steps of the complement cascade facilitate the search for and removal of antigens by placing them in large clumps, making it easier for other aspects of the immune system to do their jobs. Remember that the complement system is a supplemental cascade of proteins that assists, or “complements” the other aspects of the innate immune system.
The innate immune system works to fight off pathogens before they can start an active infection. For some cases, the innate immune response is not enough, or the pathogen is able to exploit the innate immune response for a way into the host cells. In such situations, the innate immune system works with the adaptive immune system to reduce the severity of infection, and to fight off any additional invaders while the adaptive immune system is busy destroying the initial infection.

Want to join the conversation?

  • blobby green style avatar for user sarahmatthes1113
    I'm not very well versed in immunology, but when it talks about distinguishing self versus non-self, I was wondering where the body's natural flora falls in that scenario. How does the body know not to attack the bacteria that are not made from the body but are still supposed to be there? Especially when some bacteria are natural in one part of the body and pathogenic in another? If you have any links to scientific articles I'd be interested to read those as well
    (18 votes)
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    • aqualine ultimate style avatar for user Haben Gabir
      MHCs are proteins used to identify as "self". all cells have them.
      So the bacteria you are talking about are still technically still outside the body- GI is just a lumen with very specialized skin cells that do more than protected your insides. So no bacteria should be "inside" your body, which is how the immune system can tell.
      so MHC id self and ANY bacteria INSIDE you is an invader.
      (31 votes)
  • male robot johnny style avatar for user Gyroscope99
    The link to the article that is supposed to explain macrophages and phagocytosis is not there. Any chance somebody could post that if they know what the link is?
    (16 votes)
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  • blobby green style avatar for user JCMecklosky
    Just want to clarify since it doesn't say it explicitly, I know that mast cells have granules, so are they also categorized under granulocytes the same way neutrophils, eosinphils, and basophils are? Love this article too!
    (6 votes)
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  • blobby green style avatar for user K Taylor
    So is the innate immune system responsible for allergic reactions? (Like my annoying hay fever)
    (4 votes)
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    • piceratops ultimate style avatar for user Isaac Deatherage
      Yes, it is known that mast cells release histamine, which causes an allergic reaction. When pollen or dust enters the mucous membranes where there are mast cells, the mast cells know they are "nonself" and release histamine, which causes an inate inflammatory response. It is not specified in the adaptive response. This is a great discussion in most general biology classes. Many wonder what the function is since pollen etc, is not necessarily bad for us. When we have allergies, mucous is produced in order to physically wash away the foreign particles, as foreign particles are not beneficial to our respiratory system.
      (6 votes)
  • duskpin ultimate style avatar for user Derrick Liang
    I believe that in the first sentence of the paragraph on eosinophils is grammatically incorrect and should be: "Eosinophils are granulocytes [that] target multicellular parasites."
    (5 votes)
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  • blobby green style avatar for user Samantha Gibb
    Thanks for this - I am just a little confused - is the primary immune response the same as innate immunity, and the secondary response then the same as adaptive immunity, or are these two completely separate systems?
    (3 votes)
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    • blobby green style avatar for user dhimanbhuyan04
      innate immune system is non specific, that means it reacts all the same with all type of pathogens. whereas the primary immune response you mentioned is a part of active immunity (that is a part of adaptive immunity) primary immune response means the first exposure of pathogens to the adaptive immune cells, first exposure means, memory is yet to be created against that pathogen. so primary immune response is actually a part of adaptive immunity and not a part of innate immunity.
      (4 votes)
  • primosaur ultimate style avatar for user 사이라스
    I was taught that the complement cascade, that results in the formation of MAC, which punches holes in the cell membrane, works on bacteria and the like, but not viruses. Is this true, and why or why not? Is it because viruses do not have a cell membrane, or is it something else?
    (3 votes)
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  • blobby green style avatar for user virmilind007
    Is it possible to describe how immune response is beneficial and detrimental to human body with examples?
    (2 votes)
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    • female robot ada style avatar for user Angelica Chen
      One example of how an immune response can be detrimental is with fevers that rise to unsafe temperatures, causing tissue damage. Also, inflammation--an attempt to provide more cells to repair damage--can end up causing more damage, such as with meningitis. A third time immune responses are bad is when our bodies reject medical implants, such as a heart that has been transplanted. Arthritis and eczema are two conditions caused by autoimmune syndromes.

      Of course, the immune response is also beneficial. Without defenses against foreign bodies, we would easily die. The immune system protects us from viruses and bacteria that seek to turn our cells into their food, and the functions I mentioned eaelier have evolved to protect us from that. Fevers kill our own cells, but they also kill bacteria. Sneezing expells fluid buildup from our lungs. Pus is the result of white blood cells fighting off local infections.

      These are just a few examples. If you want more clarification, please ask!
      (3 votes)
  • starky sapling style avatar for user Danielle jahrmarkt
    What are signs your body is healing?
    (2 votes)
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  • blobby green style avatar for user chancedgoodspeed
    im glad yall have this posted as they are killing our people off I'm figuring out how to heal and what about us the control no one cares bout
    (2 votes)
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