Autoimmunity Mechanisms

Establishing and Maintaining Self-Tolerance

Your immune system is designed to hunt down foreign germs while ignoring your own healthy cells. This peaceful coexistence is called self-tolerance. As you learned, T cells grow up in the thymus, while B cells mature in the bone marrow. During this training, the body tests these young cells. If a cell shows signs that it might attack your own tissues, it is usually destroyed right away.

However, the system is not perfect. Some self-reactive B cells escape destruction and enter the bloodstream. To keep us safe, the body uses a backup plan: it forces these dangerous cells into a state of permanent sleep. This functional silence is known as clonal anergy 1. These anergic cells float in the blood, but they are locked down and cannot release antibodies that would harm your tissues.

Molecular Mimicry and the Awakening of B Cells

So, how do these safety systems fail? One common way is a trick of disguise known as molecular mimicry. Sometimes, a virus or bacteria enters the body wearing proteins that look almost identical to the proteins on your own cells. Think of this like a spy wearing a stolen uniform to blend in with your own soldiers. Because the germ wears a uniform that matches your healthy cells, your immune system gets confused. The T cells and B cells start attacking your own tissues because they cannot tell the difference between the invader and your body.

We can see how this breakdown happens by looking at those sleeping, self-reactive B cells. Surprisingly, about 5 to 10% of the B cells in the human body have the potential to attack the self 1. Normally, clonal anergy keeps them quiet. But a severe viral infection can change the rules:

• If a virus enters the body and its shape matches the receptors on these sleeping B cells, the cells can suddenly wake up 1.
• The virus acts like an alarm clock.
• Once awake, the B cells multiply and mutate to build better antibodies against the virus.
• Within 16 days of an infection, these cells undergo intense genetic changes 1.

While this helps fight the virus, it can accidentally break the rules of self-tolerance, unleashing cells that attack the body.

Bystander Activation and Cryptic Antigens

Molecular mimicry is not the only way self-tolerance collapses. Sometimes, a severe infection causes massive inflammation in a specific tissue. This chaotic environment can accidentally activate nearby immune cells that were not supposed to be involved. This is known as bystander activation 2. Think of this like a peaceful crowd that gets swept up into a riot simply because they were standing too close to the chaos. The innocent bystanders are caught in the crossfire and begin acting aggressively.

In other cases, physical trauma or infection can expose hidden proteins the immune system has never seen before. Because these "cryptic antigens" were hidden during the immune system's early training, the body treats them as foreign invaders and attacks them 2. Through molecular mimicry, bystander activation, and the waking of sleeping B cells, the immune system can tragically lose its self-tolerance. While autoimmune diseases occur when the immune system is too active against the self, the opposite problem can also happen. In the next station, we will explore what occurs when the immune system is too weak to fight off any invaders at all.