How Do Autoimmune Diseases Occur?

Autoimmune disease sounds like a very fancy term, but it doesn’t take a genius to understand that it has something to do with our immune system.

Most of us have heard of rheumatoid arthritis,as it’s a pretty common disease, but also quite painful. Similarly, there are diseases like Myasthenia gravis, Hashimoto’s Thyroiditis, etc., all of which are diseases that have one thing in common… they are all autoimmune diseases!

Autoimmune Disease

Autoimmune diseases occur when our own immune system cells attack us. Our immune system is like an army that prevents the entry, spread, and colonization of invaders. However, sometimes, our army has traitors. These Judas cells, instead of attacking the enemy, attack our own body’s cells instead.

Autoimmmune desease

This causes great damage to our body. It can affect specific organs, in which case it’s called organ-specific autoimmune disease, or it could affect an entire system, which is called systemic autoimmune disease

So why do our own cells attack us? Before we can hope to understand that, we need to first understand which cells are involved in this, and how our cells learn to differentiate between our body’s cells and outside cells.

Immune Tolerance

Cells produce molecules called antigens. These are found on the surface of cells, and can either be self-antigens, i.e., produced by our cells, or non-self-antigens, i.e., produced by pathogens.
From all the different types of immune cells, those involved in autoimmune diseases are the T-lymphocytes and B-lymphocytes. During their development, these cells must go through a rigorous assessment period, to ensure that they don’t harm us. During this period, the ability of these cells to distinguish between self and non-self is put to the test. Cells that fail the selection process are killed. This process of selection and training helps to develop and build our immune tolerance. Immune tolerance is the ability of our immune system’s cells to distinguish between self and non-self.

T lymphocytes

These cells are formed in the thymus gland. While there are various types of T cells, they have the same precursor, called thymocytes. These thymocytes are formed in the bone marrow and then proceed to the thymus gland for their selection and maturation.

T cell

Photo Credit : Wikimedia Commons

The thymocytes must go through 2 stages of selection that pertain to their role in autoimmune diseases. This is the positive and negative selection. In positive selection, the immature T cells are exposed to self antigens on MHC class I and II proteins. This is on the epithelial cells of the thymus cortex. T cells that bind strongly or weakly to this are rejected, and not given a survival signal. Those that bind moderately are given a survival signal and proceed to the next round of selection. This selection essentially selects cells that can bind to MHC molecules sufficiently.

The next round is the negative selection. In this round, the T cells are also presented with self-antigens on MHC molecules. However, this time it is done by the Medullary epithelial cells of the thymus gland. The cells that bind to the self-antigens very strongly are given an apoptotic signal, or a signal for cell death. The remaining ones are called naïve T cells. These have cleared the selection and are inducted into our immune system.

B lymphocytes

B lymphocytes, or B cells, are formed and mature in the bone marrow itself. They are the cells that produce antibodies in the normal functioning of the body. To ensure that they do not produce antibodies against the self-antigens, they must also go through a selection process.

In positive selection, the B Cell precursors need to develop the correct receptors that they require. Failure to do so results in apoptosis. The cells that clear this are then exposed to self-antigens. The cells that bind strongly to the self-antigens have failed the selection process. They can either be killed, locked away, or their receptors are edited. The latter are now called naïve B Cells. The efficiency of their receptors is checked again. Eventually, all the cells that have cleared the selection process proliferate to form the various types of B cells.

B cell

Sometimes, however, some defective cells manage to escape detection during their selection process. These cells can lead to autoimmune diseases. There may also be times when a pathogen resembles our own cells. This leads to confusion of our immune system cells, which then attack our own body’s cells.

The exact cause behind autoimmune diseases is, however, not yet understood. There is still no clear reason why our immune system would attack our own body’s cells in the first place, which leads to these largely mysterious diseases.


  2. B Cell Development
  3. Positive and negative selection of T cells. – NCBI


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