Hashimotos-A case of rogue immune cells

So far this blog has focused heavily on the immune system’s role in fighting infections.  Preventing the invasion of these foreign “aliens” is arguably the reason we have immune systems in the first place.  The other main reason for the immune system that I haven’t discussed yet but will one of these days is it’s role in getting rid of cancerous cells. Each of these is a way in which the immune system is helpful, protecting us from bad things either external or internal.  Sometimes our immune system turns on us though and becomes the bad guy, destroying our healthy tissues and therefore causing us serious harm.  This takes the form of many autoimmune diseases including Type I Diabetes, Rheumatoid Arthritis, and lupus to name a few.

When our immune system destroys cells in our thyroid, we can develop Hashimoto’s disease named for the doctor who discovered it.

The thyroid

The thyroid is a large endocrine gland in our necks that produces thyroid hormone which regulates a vast number of processes including the consumption of energy, production of proteins, and the body’s sensitivity to other hormones.  The destruction of thyroid cells leads to hypothyroidism with symptoms including fatigue, sensitivity to cold, and weight gain to name a few.

Hashimoto’s disease is the result of both genetic and environmental causes.  There is usually a genetic predispostion (mutations in one more more genes that would normally control the immune response) but symptoms don’t develop simply because of this.  Many environmental factors can cooperate with those genetic factors to cause the development of Hashimoto’s including excessive consumption of iodine, deficiency in Vitamin D, infection with certain viruses, environmental pollutants, drugs, being female, and having gone through pregnancy. The immune component of Hashimoto’s (as well as a lot of other autoimmune diseases) is the result of T cells and B cells that are autoreactive, or capable of attacking our own healthy cells.

Normally, we are very good at preventing autoreactive immune cells from causing us harm.  If they are made during development, they are killed but if they escape the development process, other cells including regulatory T cells are able to keep them in check.  During Hashimoto’s autoreactive immune cells cause hypothyroidism due to the destruction of the thyroid cells.  But how do they do that?

Autoreactive B cells

B cells are components of the adaptive immune system that are responsible for making antibodies (see figure). During infection, antibodies can grab viruses or bacteria and block them from entering our cells or they can target them to be killed by other immune cells.  Antibodies have regions (called antigen-binding sites in the figure) that allow them to recognize and grab hold of very specific parts of cells.  In the case of Hashimoto’s disease, these antibodies bind to two different unique parts of thyroid cells not found on liver cells or immune cells or heart cells: thyroglobulin and thyroid peroxidase. Both thyroblobulin and thyroid peroxidase are important in the main function of this endocrine gland, the production of thyroid hormone.  When antibodies grab hold of these two different components of a thyroid cell, they are setting the cell up for destruction by something called the membrane attack complex.  This complex basically pokes holes in the surface of the thyroid cell, allowing lots of water to rush inside.  When the volume gets to be too much, the cell essentially dies because it has burst open like a water balloon.  This is a very messy form of cell death called necrosis, and distinct from the kind of cell death that autoreactive T cells cause discussed in the next section.


Autoreactive T cells

Like B cells, T cells are also a component of the adaptive immune system.  These cells can come in two forms: they either help other cells including B cells to be better at their job (these are CD4+ T cells, kind of like a cheerleader or career counselor), or they kill virally infected or cancerous cells (CD8+ T cells).  In Hashimoto’s disease, autoreactive CD8+ T cells recognize components of the thyroid cell in a similar way to B cells.  Instead of antibodies though, T cells use their “T cell receptors” which actually look somewhat similar to an antibody.  Instead of causing the thyroid cells to explode as happens when an antibody binds to the cell, T cells cause a very orchestrated cell death.  T cells latch on to thyroid cells, make pores, and introduce enzymes that cause the cell to die.  Unlike the explosive “necrosis” caused by antibodies, T cells cause a very contained cell death called apoptosis.  Explosive cell death as discussed above can cause a lot of inflammation which can lead to more cell death while the contained cell death is done in such a way that inflammation does not occur.  Follow the link below to see an amazing video of a T cell killing a target cell.  The blue cell is the T cell and it holds on tight to the cell it is killing.

Regardless of whether or not thyroid cells die in the explosive or contained manner, the end result is the same: decreased numbers of thyroid cells capable of making the thyroid hormone that controls so many of our functions.  Treatment for Hashimoto’s disease usually comes once enough thyroid cells have died and hormone levels have decreased dramatically.  In this case, it may be necessary to treat with synthetic thyroid hormone. Hashimoto’s disease is one of many examples of the immune system causing autoimmune disease.