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.
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.
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.
Picture a game of ping-pong between two professional players. The ball going fast and furious across the net, back and forth, it’s a very well-orchestrated, beautiful, synchronized game.
Picture a stadium now, full of hundreds of these tables, all in play at the same time, all with players, you’re watching from above, it can be quite an orchestrated, synchronized athletic program.
But now somebody in the middle of the field misreads the ball, hits it off, disrupt the play, sometimes the ball even bounces off across the neighboring tables a few times and disrupts their play, there’s a little focus of chaos right in the middle.
That sort of thing happens all the time in our immune system. Most of the time it’s regulated, most of the time our natural systems keep balance, chime in and control that, bring it back into a normal balanced situation.
But when it doesn’t, we have to do something about that, therapeutically. And I guess I would say it’s about time, because for the last 50 years the way that we have treated these kinds of auto-immune diseases is through something called immunosuppression. It basically is an approach that says “Let’s block the immune system. Let’s interfere with the process and stop the immune system.” Sort of like blindfolding a person.
If you had a student who was having trouble reading, you could fix the errors that they made in reading by putting a blindfold on them, they wouldn’t make any mistakes. Yeah. They wouldn’t be learning to read. That is essentially what we’ve been doing for 50 years in immune therapies.
What we’re doing now, in the last few years, is taking the knowledge of how the immune system works, some of the signals and pathways that I’ve been just alluding to here in the last few minutes, and putting all these pieces of the puzzle together to understand what this orchestrated set of events and signals and recognition is supposed to look like and how the game is supposed to be played, how to keep it in an orchestrated normal mode, something we call tolerance, but it’s basically re-educating the immune response to do what it’s supposed to do in the first place, to be in a balanced state that’s tightly regulated.
What do I mean by these kinds of therapeutics? Sometimes they’re drugs, they go in and create new signposts, new messages for the immune system to read in the body. Sometimes they’re just teaching the immune system to read the signs that are already there a little better.
Sometimes they’re therapies that remove some of the signs that are causing the problem and have been used in the process of the disease. But each of them is focused on trying to re-educate the immune system and get back to where it’s supposed to be.
Besides being sort of more sophisticated and elegant, there’s a real reason for this and that is that the immunosuppression, over here, is dangerous, because blocking the immune system means that it blocks the immune system from protecting you from infection. So we don’t want to do that.
We’d much rather re-educate the immune system to be selective, to do what we want it to do and let the rest of the immune system do what it’s supposed to do in terms of protecting us.
Probably the most important thing I’m going to tell you today is that what I’ve been saying is not hypothetical, it’s not theoretical, it’s not futuristic. It’s actually happening now.
There are many people in our community who are participating in the research studies and the clinical trials to test these new therapeutics, to attempt to re-direct the immune system, to help us learn how to approach these diseases in this orchestrated, regulated fashion.
Even just in the last few years, patients with diseases like rheumatoid arthritis and multiple sclerosis and inflammatory bowel disease have a whole new set of therapeutic options that are directed at this re-education process. It’s a very exciting era for patients, for physicians, for scientists.
I want to thank you for listening to me for these few minutes and if any of you are interested in further information, here’s a couple of websites for you, immunetolerance.org and benaroyaresearch.org.
The story that I’ve told you is a remarkable story. But the next chapter is still to be written.
Thank you very much.
Download This Transcript as PDF here: Re-educate The Immune System_ Gerald T. Nepom at TEDxRainier (Transcript)