Innate immunity

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

• 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

• 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.

Cells 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.

• 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.

• 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

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.