Re-educate The Immune System: Gerald T. Nepom at TEDxRainier (Transcript)

Gerald T. Nepom – TEDx Talk TRANSCRIPT

I’m here to talk with you today about a remarkable part of our bodies: the immune system.

It’s a story that has some drama to it, it has some mystery, it even has a little bit of science. The immune system protects us, right? Protects us from viruses, bacteria, other forms of infection.

But the story I’m going to tell you is about when the immune system makes mistakes. When it runs amok and when it actually causes disease.

So let’s think a little bit about the immune system as a process of shape recognition. Picture immune cells running around the body, through the blood, through the tissues, rubbing up against other cells and other tissues and reading the signals of those other tissues by contact.

It’s a little bit like reading a Braille message with your fingers. Cells of the immune system have a couple hundred thousand of these molecular fingers, reaching out, contacting the cells and tissues of the body, running across the bumps, the valleys, and reading the messages.

What you’re looking at here are some of these messages. Just a couple of examples.

Now, if you look carefully at these images, you’ll notice that there’s a subtle difference, the bottom image has this yellow blob, right in the middle, that’s different than the top image. These signals can be quite complex.

What do these signals say?

Some of them say “Stop” to the rest of the immune system. Some of them say “Come here.” Some of them say “Leave me alone.”

Some of them cry for help, “Bring the reinforcements.” Signals that bring reinforcements are good if you’re fighting off an infection.

Signals that say “Come here and attack and bring reinforcements” are not good if they’re telling the immune system to attack normal tissues and normal cells. That’s what you’re looking at here in the top image.

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This is one of those signals that the immune system sees in patients who have a disease called type 1 diabetes. Auto-immune diabetes. We’ll talk a little bit more about that in a minute.

But the bottom image, with that subtle change in the middle, that little yellow blob, is enough to change the signal to a “Go away and leave me alone” signal to the same immune cells. Let me tell you a little bit about the scale.

I already told you that some immune cells have a couple hundred thousand of these little fingers reaching out and reading these messages as they run through the body.

There are also hundreds of millions of these immune cells, running around in our bodies. All this is going on all the time, 24/7. It’s quite a remarkable set of reading material for the immune system and, unfortunately, it makes mistakes.

So when the mistake has to do with seeing tissue in the body that should be left alone, bad things happen. This example is a picture of a piece of the pancreas, that’s a little gushy organ that sits right here in our abdomen, this cluster that you’re looking at of cells in there, are the cells that make insulin in the body.

Insulin is required for life, it’s an essential hormone. What happens if the immune system reads signals that say “Attack the normal tissue that makes insulin”? A mistaken signal or a misreading of the signal, what happens is the immune cells, these little blue dots, start swarming in and start attacking that normal tissue.

It progresses to the point where they damage these cells so badly that they can no longer make insulin. This is actually the cause of type I diabetes, juvenile diabetes or auto-immune diabetes, it has several names. It’s not a disease caused by some metabolic problem, it’s a disease of the immune system making mistakes.

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Unfortunately, there are a lot of these signals and there are a lot of mistakes to be made and our immune systems aren’t perfect. In fact, our immune systems are these error-prone complex biologic systems that can attack any normal tissue in the body.

In the case of rheumatoid arthritis, the immune system attacks the cartilage around the joints. In the case of multiple sclerosis, the immune system attacks the insulating layers around the nerves in the brain and in the spinal chord.

Crohn’s disease or inflammatory bowel disease, that’s the immune system attacking the lining of the gut. Pemphigus, vitiligo, those are examples of the immune system attacking the skin. And on, and on, and on, there are over 80 of these auto-immune diseases.

Auto-immune because the immune system is attacking our own self-tissue. It’s made a mistake. About 5% of us have one of these auto-immune diseases.

There’s a lot of mistakes to be made out there, and the immune system makes them. If you include immune-mediated diseases like asthma and allergy, where the immune system is also over-active and making mistakes, between 15% and 20% of us have these diseases. Now, that’s the bad news.

The good news is that the immune system has developed to try to regulate itself. It’s ordinarily a balanced system with cells that damage tissue and cells that try to repair tissue. Cells that cause the inflammation, cells that try to regulate the inflammation.

When things are in balance, we’re healthy, our immune systems are healthy. So this balance goes on all the time. Let me give you a bit of an analogy for this.

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