 In this video, I will describe the functions of natural killer cells in innate immunity to viral infection, describe how phagocytosis works to defend against extracellular pathogens, and list the major phagocytic leukocytes, describe the characteristics, chemicals and cells involved in the inflammatory response, and describe the functions of the complement system. Natural killer cells are a type of lymphocyte that's involved in the innate immunity, in contrast to the T lymphocytes and B lymphocytes that are involved in the adaptive immunity to specific infections. Natural killer cells defend against viral infection, but not specific viral infections. Natural killer cells are fairly similar to T lymphocytes in that natural killer cells will stimulate apoptosis of viral infected cells, and a specific type of T lymphocyte known as a cytotoxic T lymphocyte also can stimulate apoptosis of viral infected cells. The main difference is that with natural killer cells, the natural killer cell does not recognize a specific antigen associated with a specific virus. The T lymphocyte would be activated by a specific antigen and be able to recognize a specific type of virus. A natural killer cell instead recognizes a molecular signal that one of our cells has become infected with a virus. Then the natural killer cell can release granules full of perforins and granzymes. Perforins are proteins that will punch holes in the membrane of the infected cell, and granzymes are enzymes that will then enter through these pores and stimulate apoptosis. Natural killer cells have receptors that recognize a viral infected cell. A healthy cell would express a MHC protein on its surface known as MHC1, and this MHC1 would bind to an inhibitory receptor on a natural killer cell, preventing that natural killer cell from becoming activated and trying to kill it. But when one of our cells becomes infected with a virus, it will express an activating molecule on its surface that will stimulate receptors on the natural killer cell, and so the infected cell will stop expressing the MHC1 protein and will not be able to activate the inhibitory receptor, but will express a different protein that stimulates the activating receptor in order to activate a natural killer cell. Then the natural killer cell can stimulate apoptosis of the infected cell. Phagocytosis is a major defense against infection where leukocytes will engulf foreign materials such as a bacterial cell. The major phagocytic leukocytes are the neutrophils, monocytes, macrophages, and dendritic cells. The illustration here shows a macrophage engulfing a bacterial cell. Macrophages and dendritic cells are both differentiated from monocytes, whereas neutrophils are a different lineage of leukocytes. All neutrophils, monophils, macrophages, and dendritic cells are capable of performing phagocytosis to engulf pathogens. Inflammation is a response triggered whenever the body tissues are injured or whenever there is an infection detected. There are four cardinal signs of inflammation, which are redness, swelling, heat, and pain. The redness and heat are a result of increased blood flow to the tissue, and swelling is in part a result of increased blood flow and also increased vascular permeability, increasing the amount of fluid that leaks from the blood plasma into the interstitial space. Pain is a result of pro-inflammatory mediators, chemical messages that are released by damaged cells in the tissue or activated leukocytes, and pro-inflammatory mediators can bind to afferent nerve fibers, nociceptors, activating these receptors leading to the perception of pain or itching sensations. Pro-inflammatory mediators are chemical messages that stimulate inflammation. Histamine is one of these pro-inflammatory mediators. Histamine is a small water soluble molecule, which is synthesized from the amino acid histidine. Histamine is secreted by basophils and mast cells, and histamine will stimulate vasodilation and increase vascular permeability as well as leukocyte activation and stimulation of nociceptors contributing to the perception of pain and itch. Antihistamine medications like Benadryl are commonly used to inhibit histamine signaling in order to decrease inflammation. Lugotrienes are another class of inflammatory mediators, and lugotrienes are in the chemical class of ecosanoids that are synthesized from fatty acids. Cytokines are another category of inflammatory mediators. Cytokines are glycoproteins with a carbohydrate post-translational modification, but cytokines are glycoproteins secreted by a variety of cells including leukocytes, fibroblasts and endothelial cells. Cytokines can function as autocrine, paracrine, or endocrine signals in order to regulate the functions of the immune system. Chemokines are a specific type of cytokine. Interleukin A here is an example of a chemokine. Chemokines are cytokines that attract leukocytes. In response to chemokines that are released by a damaged tissue, more leukocytes are attracted to the damaged tissue in order to help defend against infection. Cytokines are molecular messengers that can either participate in autocrine, paracrine, or endocrine signaling. These cytokines are glycoproteins that are important for regulating leukocytes to coordinate the immune response. Interferons are a type of cytokine which is released by virus-infected cells. Interferons can stimulate antiviral defense in neighboring cells to help protect these cells from infection with that virus. Interferons will also help stimulate natural killer cells to come and activate the apoptosis mechanism in a viral infected cell. Pyrogens are chemical messengers that stimulate an increase in the body temperature producing a fever. Exogenous pyrogens are pyrogens that come from outside of our body. LPS stands for lipopolysaccharide which is a chemical found in the cell walls of bacteria. The exogenous pyrogens could be chemicals that are part of a pathogen that can then be recognized by leukocytes leading to activation of the leukocytes that then secrete cytokines that function as endogenous pyrogens meaning pyrogens that are produced within our body by our own cells. Interleukin-1, interleukin-6, interferon gamma and TNF which is tumor necrosis factor are all endogenous pyrogens that will stimulate a signaling mechanism in the hypothalamus leading to an increase in the homeostatic set point for body temperature producing a fever. Emigration also known as diapidesis is the process where leukocytes squeeze through adjacent endothelial cells of a blood vessel wall in order to migrate, in order to move out of the blood and into a tissue. So emigration is the movement of leukocytes out of the blood as they're attracted by chemokines they'll be migrating out of the blood and into an inflamed tissue and then when the leukocytes move into this inflamed tissue and recognize a pathogen they can defend against that pathogen by either performing phagocytosis and golfing a pathogen or releasing cytotoxic chemicals that can destroy the pathogen and prevent it from spreading infection. The complement system is a system of defense proteins that functions to kill microorganisms such as bacteria and it works as part of the innate immunity although we will see many aspects of the innate immunity can also be stimulated by the adaptive immunity. The complement system can be activated by bacterial cells and these proteins on the surface of a bacteria can activate the complement protein cascade starting with the C3 complement protein that becomes activated and then leading to a cascade of other complement proteins C5 and C6, C7, C8 and C9 that form together a structure known as the membrane attack complex. This membrane attack complex makes a hole in the plasma membrane of the bacterial cell and then this will cause that cell to be destroyed by water rushing into the cell by a hypotonic lysis the cell will be destroyed. The complement proteins of the membrane attack complex also function as a target on the surface of this pathogenic cell that will recruit phagocytic leukocytes so opsonization is the activation of phagocytosis by a defense protein that's functioning as a tag or label on the surface of a pathogen so this bacterial cell that has been labeled with complement proteins stimulates phagocytic cells like macrophages or dendritic cells or neutrophils to come in and gulf the bacterial cell and break that cell down clean it up.