cytokines are tiny proteins that are secreted by both immune and non-immune cells to communicate with one another cytokines bind to receptors and trigger a response in the receiving cell oftentimes cytokines promote activation proliferation and differentiation of immune cells but they can do other things like help increase the body temperature causing a fever now cytokines signal to other cells mainly through autocrine and paracrine signaling but to a lesser extent endocrine signaling can also be employed now autocrine means the cell producing the cytokine is also the cell responding to the cytokine an example is interleukin-2 or il2 which is secreted by cd4 positive t helper cells interleukin 2 promotes the proliferation of t lymphocytes including the cd4 positive t helper cell that produced it paracrine means that the cytokine is produced by one cell and that it affects cells in the near vicinity once again an example is interleukin-2 because it helps nearby cd8 positive cytotoxic t cells proliferate that's important because the cd8 positive cytotoxic t cells aren't good at making their own interleukin 2. finally there's endocrine which is when the cytokine affects a cell that's far away perhaps in a different organ an example would be the inflammatory triad of interleukin-1 beta or il-1 beta interleukin-6 or il-6 and tumor necrosis factor alpha or tnf-alpha these cytokines are produced by macrophages and dendritic cells during acute inflammation these cytokines travel to the liver and brain in response the liver produces acute phase reactants like c-reactive protein and manos binding lectin and the brain increases the body's temperature triggering a fever at the same time interleukin-1 beta and tumor necrosis factor alpha also help to recruit other immune cells to the site of injury enhancing the inflammatory response overall there are five main classes of cytokines the first and most varied group are the interleukins which are numbered in the order they were identified so the numbers actually don't tell us anything about what they do it used to be thought that interleukins were only sent between leukocytes or white blood cells but it turns out that they're released and act on both leukocytes as well as non-leukocytes the second group are the tumor necrosis factors or tnfs tnfs are named because they were discovered by their ability to kill tumor cells now known to be because they elicit inflammation in the inflammatory cells neutrophils and macrophages actually do the killing [Music] tumor necrosis factor alpha tumor necrosis factor beta also called lymphotoxin alpha or lt alpha and the lymphotoxin beta or lt beta are known to have a wide variety of biological effects in the inflammatory response including activating endothelial cells to upregulate expression of adhesion molecules and increasing their vascular permeability the third group are the interferons and as their name implies they interfere with processes like viral replication there are two types of interferons type 1 and type 2. type 1 interferons include interferon alpha and interferon beta and they're usually produced by virally infected cells and some dendritic cells responding to the viral infection in order to limit viral replication now the only type 2 interferon is interferon gamma this molecule is the most powerful macrophage activator and it also activates cd4 positive helper t cells which then secrete their own interferon gamma and interleukin 2. the fourth group includes the colony stimulating factors these cytokines bind to surface receptors on hematopoietic stem cells causing them to proliferate and differentiate some examples include granulocyte macrophage colony stimulating factor or gmcsf what is a cytokine secreted by a wide variety of immune and non-immune cells that stimulates the development of granulocytes and macrophages the fifth and final group includes the transforming growth factors there are more than 30 different tgfs and the most important in the immune system is tgf beta tgf beta is an inhibitory factor that suppresses proliferation and differentiation of various cells it also helps cd4 positive t cells to develop into a regulatory cell that can slow down or stop the overall immune response you can think of transforming growth factor beta as helping to put on the breaks so broadly speaking there are hundreds of cytokines some are pro-inflammatory some are anti-inflammatory and regulate the immune response and some are growth factors it's kind of like cooking where each cytokine is like an ingredient one meal might call for onions garlic asparagus mushrooms and rice whereas another meal might call for garlic tomatoes and pasta ultimately in response to an event like damage or infection we're combining different cytokines to get the desired immune response and that's why you'll see one cytokine included in different pathways each one resulting in a different immune response the highly pro-inflammatory response for fighting intracellular pathogens include cytokines that enhance the innate or adaptive immune response these include interferon alpha and interferon beta which are produced by virally infected cells and work on various immune cells to help interfere with viral replication in addition there's interleukin-1 beta 2-necrosis factor alpha and interleukin-6 which are produced by macrophages and dendritic cells interleukin-6 can additionally be produced by t and b cells their major targets are various immune cells as well as endothelial cells where they promote migration of leukocytes and the liver and brain where they cause production of acute phase reactants and cause fever as time passes the immune system moves into the adaptive immune response and cytokines are what help cd4 positive helper cells differentiate into specialized subsets called th1 th2 or th17 cells going one by one interleukin 2 is produced by cd4 positive helper cells and it also acts on cd4 positive helper cells as well as on cd8 positive cytotoxic t cells and b cells interleukin-12 is produced largely by dendritic cells and macrophages and it activates natural killer cells interleukin-12 also helps cd4-positive t-cells differentiate into cd4-positive th1 cells which produce interferon gamma and lymphotoxin on the other hand the cytokines interleukin-6 interleukin-23 and transforming growth factor beta help cd4-positive t cells differentiate into cd4-positive th17 cells which produce interleukin-17 interleukin-17 is a cytokine that helps recruit neutrophils to the site of inflammation this collection of cytokines are effective against viruses bacteria and some cancers the inflammatory response that's geared toward parasitic infections is created using interleukin-4 interleukin-5 and interleukin-13. these cytokines help the immune system handle large unwieldy parasites and also induce asthma and allergy responses they induce t cells to differentiate into th2 helper t cells and stimulate mast cells basophils and eosinophils the th2 cells secrete even more of these cytokines which perpetuates the response the regulatory immune response is immunosuppressive in this case we use one cytokine from an inflammatory response in your leuken 10 along with transforming growth factor beta the overall effect is to inhibit the inflammatory response by getting t cells to develop into regulatory t cells regulatory t cells produce more interleukin 10 and transforming growth factor beta and that perpetuates the anti-inflammatory state the key is that interleukin-10 and transforming growth factor beta make nearby cells reduce their expression of co-stimulatory receptors and ultimately that inhibits immune cell growth the fourth type of cytokine response is a little different from the other immune responses because its main goal is to replenish the immune cells growth factors like gm csf mcsf and interleukin-7 are produced by bone marrow stromal cells where they get bone marrow progenitor cells to differentiate gm csf and mcsf promote the differentiation of monocytes in granulocytes while interleukin-7 promotes the differentiation of progenitor cells into lymphocytes like b cells t cells and natural killer cells the last type of cytokine response is also a process that happens constantly these are the air traffic controllers of the cytokine world and they tell everyone where to go the group of cytokines are called chemokines and these are chemotactic agents meaning that they help cells move toward the site of inflammation one such chemokine is interleukin-8 which is generated by fibroblasts neutrophils and macrophages to recruit phagocytes to the site of inflammation finally a potent inductor of chemokine production is interleukin-17 which is generated by cd4-positive th17 cells during inflammation all right as a quick recap cytokines help facilitate communication mainly through autocrine and pericurine signaling but also through endocrine signaling there are five main classes interleukins tumor necrosis factors interferons transforming growth factors and colony stimulating factors and they can be mixed to create different functional responses the main response types are the acute inflammatory pro-inflammatory parasite slash allergy regulatory growth and differentiation and chemotactic agents helping current and future clinicians focus learn retain and thrive learn more