Cytokines

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Cytokines

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Cytokines

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Cytokines promote (3 processes) of immune cells.

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A 32-year-old African American female presents to your clinic with a temperature of 104 deg Fahrenheit and generalized fatigue and lethargy. The cytokine most likely responsible for her increased temperature is secreted by which of the following cells?

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Content Reviewers:

Rishi Desai, MD, MPH

You can think of cytokines as being the hormones of the immune system.

They’re 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.

There are three main ways by which cells use cytokines to signal to other cells - autocrine, paracrine, and endocrine.

Autocrine means the cell producing the cytokine is also the cell responding to the cytokine.

An example is Interleukin-2, or IL-2 which is secreted by CD4+ T helper cells.

IL-2 promotes the proliferation of all lymphocytes - including the CD4+ 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 IL-2 because it helps nearby CD8+ cytotoxic T cells proliferate.

That’s important because the CD8+ cytotoxic T cells aren’t good at making their own IL-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-1beta, Interleukin-6 or IL-6, and Tumor Necrosis Factor-alpha, or TNF-alpha.

These cytokines are produced by epithelial cells that are injured or infected, and then the cytokines travel to the liver and the brain.

In response, the liver produces acute phase reactants like C-reactive protein, Mannose Binding Lectin, and complement proteins, and the brain increases the body’s temperature triggering a fever.

Overall, there are 5 types of cytokines.

The first and most varied group are the Interleukins, which are numbered in the order they were identified, so the numbers 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 that because they can bind to some cell receptors on tumor cell lines and cause those cells to die.

TNF-alpha, TNF-beta, and lymphotoxin, which is sometimes called LT-beta are also heavily involved in the inflammatory responses made to pathogens.

The TNF family members are known to have a wide variety of biological effects in the inflammatory response including activating endothelial cells to upregulate expression of adhesion molecules, increasing vascular permeability, and helping to induce fever.

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 I and Type II. Type I interferons include Interferon alpha and Interferon beta, and they’re usually produced by virally infected cells.

When surrounding cells detect these type I interferons, they start trying to protect themselves.

They start to degrade mRNA which blocks viruses from rapidly making copies of themselves, inhibit protein synthesis which blocks viral proteins from being produced, and they increase expression of MHC molecules, which makes it easier for cytotoxic CD8+ T cells and NK cells to do surveillance and kill them if they’re infected.

Now, the only Type II Interferon is interferon gamma.

Like the type I interferons, interferon gamma also promotes an anti-viral state, but it also helps activate macrophages and CD4+ helper T cells which then secrete their own interferon gamma and IL-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 GM-CSF, which 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 is TGF-beta.

TGF-beta is an inhibitory factor that controls proliferation and differentiation of various cells.

It also helps CD4+ T cells to develop into a regulatory cell that can slow down or stop the overall immune response.

You can think of TGF-beta as helping to put on the brakes.