Thursday, 26 April 2012

Education: The Th1 v Th2 paradigmn

The T cells can be divided in killing cells (CD8) that are programmed to kill viruses inside the cell and CD4 T helper (Th) cells. These helper produce growth factors that help B cells to make antibodies or growth factors to help macrophages kill pathogens (disease causing agents).  Th1 are designed to get rid of intracellular (inside the cell) parasites, bacteria, virus, Th2 are designed to help get rid of external parasites and parasitic worms, Th17 are designed to help get rid of extracellular (outsie the cell) parasites, bacteria. 

Initially it was thought that Th1 cells are involved in the generation of autoimmunity, whilst Th2 cells were responsible for the development of allergy. These were thought to cross regulate each other so Th1 responses could down regulate Th2 responses and Th2 responses could down regulate Th1 response. This balance of Th1 verses Th2 cells became the dogmatic mechanism for the control of many autoimmune responses such that if you generated a Th2 response it would stop autoimmunity. However now dogma suggests that it is not Th1 that is important but Th17 cells, which have been shown in animals that these convert to Th1 like cells. 

Each cell type produces growth factors such as interleukins (IL). IL-4, IL-5 (in mice), IL-10, IL-13 are B cell growth and maturation facors, IL5 is an eosinophil (worm killing cell) growth factor. Interferon (IFN) gamma inhibits viral replication but also activates macrophages to eat and kill things, IL-2, IL4, IL-12 and IL-17 are T cell growth and maturation factors.

Many Immunologist think that if you can skew the immune response towards a Th2 response that you will block the development of autoimmunity.  

This is a major dogma and most papers aim to do this. I think that this perhaps too simplistic for the reality and an exisiting immune response may not behave the same way as an immune response that is generating and human cells do not polarise quite as much as can be seen in mice.


  1. Is it right that alemtuzumab targets CD52 knocking out lymphocytes and CD4 are very slow ot recover. So it hits TH1,TH2, TH17 etc. and do they all take different times to recover? Why does alemtuzumab have as a side effect new autoimmune diseases? Why doesn't MS symptoms return when CD4 has totally regenerated? Has there been a shift in the balance between TH1,TH2, TH17 etc?

  2. Wow lots of questions yes alemtuzumab does target CD52 and knocks out T cells for a long time.

    It hits everything to start and then cells recover at different rates, when B cells recovery there is an overshoot in B cell numbers and maybe Th2 response recovers cause the adverse effects are due to a number of B cell autoimmunities, e.g graves disease, ITP, goodpasteurs etc.

    I don't think they have looked specifically at Th2, Th17, responses etc, it will come.

    I think they believe that Alemtuzumab induces Treg (T regulatory cells-another cell type) that then protects against further MS.


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