Immune tolerance facts for kids

Our bodies have an amazing defense system called the immune system. Its job is to find and get rid of harmful invaders like germs. But sometimes, the immune system needs to learn not to react to certain things. This special ability is called immune tolerance. It means the immune system ignores things that are not harmful, even if they look a bit foreign. This happens after the body has seen these things before.

Immune tolerance is super important for our health. It helps our immune system tell the difference between our own body parts and outside invaders. This stops our body from attacking itself, which is called autoimmunity. It also helps us not overreact to things in our environment, like harmless stuff in our food or the good germs in our gut. If our immune tolerance doesn't work right, it can lead to diseases where the immune system attacks the body, like type 1 diabetes.

Immune tolerance is also important when a mother is pregnant. It helps her body accept the baby, even though the baby has genes from both parents. This helps prevent problems during pregnancy.

However, immune tolerance can sometimes be a problem. It can let some bad germs hide from our immune system. Also, some unwanted cells (like those in cancer) can use immune tolerance to avoid being found and destroyed by the body's defenses.

How We Learned About Immune Tolerance

Scientists first noticed immune tolerance in 1945. A scientist named Ray D. Owen saw that twin calves, who shared blood before birth, kept some of each other's red blood cells their whole lives. This showed that their bodies could accept these "foreign" cells without attacking them.

Later, in 1953, other scientists like Peter Medawar did experiments with baby mice. They injected foreign cells into these mice. They found that the mice would then accept new tissues from the same donor later on. This meant the baby mice had learned to tolerate the foreign cells.

These discoveries helped scientists like Sir Frank McFarlane Burnet understand how the immune system learns what to tolerate. Burnet and Medawar won the Nobel Prize in Physiology or Medicine in 1960 for their work on this "acquired immune tolerance." They helped us understand how the body learns to accept certain things.

What Immune Tolerance Means

Immune tolerance is when your body's defense system doesn't react to something it normally would. It's like your immune system learning to be "indifferent" or "non-reactive" to certain substances.

This special ability helps our body in many ways:

• It helps us tell the difference between our own body parts and outside invaders.
• It stops us from having allergic reactions to harmless things.
• It allows friendly germs to live in our bodies without being attacked.
• It protects a baby inside its mother from being rejected by her immune system.

It's important to remember that immune tolerance is a natural change in the body. It's not the same as using medicines to weaken the immune system.

Scientists talk about two main types of immune tolerance: central tolerance and peripheral tolerance. These names describe where in the body this tolerance is learned.

Central Tolerance: Learning in the "Schools"

Central tolerance is like the immune system's first lesson. It happens in special "schools" where immune cells are made: the thymus for T cells and the bone marrow for B cells.

In these schools, young immune cells are shown many of the body's own proteins. If a young immune cell reacts too strongly to these "self" proteins, it's usually removed. This often happens through a process where the cell gets rid of itself. This step is very important. It makes sure that most T and B cells that could attack our own body are stopped before they become fully active.

Some T cells that react a little bit to self-proteins are turned into special "peacekeeper" cells. These are called regulatory T cells (or nTreg cells). They travel to other parts of the body to help calm down any potential immune overreactions.

This process ensures that our immune system learns not to attack our own body from the very beginning. It's a key step in preventing autoimmune diseases.

Peripheral Tolerance: Learning in the "Field"

Peripheral tolerance happens after immune cells leave their "schools" and go into the rest of the body, like our tissues and lymph nodes. This is where the immune system learns to tolerate things it didn't meet in the thymus or bone marrow.

Sometimes, T cells might escape central tolerance and still be able to react to our own body's proteins. Peripheral tolerance steps in to control these cells. The "peacekeeper" regulatory T cells (nTreg cells) that came from the thymus help to quiet down these potentially harmful T cells.

Peripheral tolerance also develops when the body is repeatedly exposed to certain harmless things. For example, when we eat food, our gut immune system learns not to attack the food proteins. In these cases, other types of regulatory T cells, called induced regulatory T cells (iTreg cells), are created. These iTreg cells help to calm down immune responses in the body's tissues.

Other immune cells also help with peripheral tolerance. Some dendritic cells can make T cells ignore certain signals. Some B cells have special signals that dampen their own activity. All these mechanisms work together to make sure our immune system doesn't overreact to harmless things or attack our own body.

Types of Regulatory T Cells

Regulatory T cells, especially those with the FoxP3 marker, are very important for keeping immune tolerance in the body.

Scientists discovered in 1995 that special T cells, later called Treg cells, were vital for immune tolerance. These cells stop the immune system from attacking the body.

There are two main types of Treg cells:

• nTreg cells (natural regulatory T cells): These are made in the thymus (the "school" for T cells). They are like the original peacekeepers.
• iTreg cells (induced regulatory T cells): These are made in other parts of the body, like the gut or lymph nodes, after the immune system meets certain things. They are like peacekeepers trained on the job.

Both types of Treg cells work to calm down other immune cells. They do this by:

• Releasing special calming signals.
• Stopping other immune cells from growing and multiplying too much.
• Taking away important nutrients that other immune cells need.

nTreg cells mainly help with tolerance to our own body's parts. iTreg cells help us tolerate things like food, friendly germs, and even some unwanted cells.

How Tolerance Helps Our Bodies

Accepting New Organs

When someone gets a new organ, like a kidney, their immune system usually sees it as foreign and tries to attack it. This is called graft rejection. But sometimes, the body can learn to accept the new organ. This is called allograft tolerance.

This can happen if the new organ is placed in a special "immune-privileged" area, where the immune system is less active. More often, doctors try to help the body develop tolerance. Some patients can even stop taking medicines that weaken their immune system and still keep their new organ. This is called "operational tolerance." Special regulatory T cells help the body accept these new organs.

Protecting Babies During Pregnancy

A baby growing inside its mother has genes from both parents. This means the baby's cells are different from the mother's. Normally, the mother's immune system might see the baby as foreign. But during pregnancy, the mother's body develops strong immune tolerance to protect the baby.

The placenta, which connects the mother and baby, plays a big role. It has special cells that hide from the mother's immune system. It also creates signals that calm down the mother's immune cells. This creates a safe space for the baby to grow. If this tolerance breaks down, it can lead to problems during pregnancy.

Living with Friendly Germs

Our bodies are home to many tiny living things, especially in our gut and on our skin. This community of germs is called the microbiome. Most of these germs are friendly and even helpful! Our immune system learns to tolerate their presence.

Special immune cells in our gut help to create this tolerance. They make sure our body doesn't overreact to these friendly germs. This is why we don't constantly have inflammation in our gut. If this tolerance breaks down, it can lead to problems like inflammatory bowel disease.

Oral Tolerance: What We Eat

Oral tolerance is a special type of tolerance that happens when we eat food. Our gut is exposed to many different food proteins that are "foreign." The immune system in our gut needs to learn not to attack these harmless food parts. This stops us from having constant inflammation or allergies to food.

How Oral Tolerance Works

When we eat, tiny pieces of food proteins are taken up by special immune cells called dendritic cells in our gut. These dendritic cells then travel to nearby lymph nodes. There, they teach young T cells to become regulatory T cells (iTregs). These new regulatory T cells then go back to the gut. They help to calm down any immune reactions to the food proteins.

This process helps prevent allergic reactions to food. It also makes sure our immune system is still ready to fight off bad germs that might enter through our food.

Immune Tolerance and Unwanted Growths

Unfortunately, immune tolerance can also be used by unwanted growths, like cancer. These sick cells can change their surroundings to make the immune system ignore them. They create a special area around themselves called the "tumor microenvironment."

In this area, the sick cells release chemicals and signals that stop immune cells from attacking them. They can make regulatory T cells, which then calm down other immune cells that would normally fight the growth. Scientists are working on new medicines that can block these tolerance signals. This helps the immune system find and destroy the sick cells.

Why Immune Tolerance Developed

Scientists believe immune tolerance developed over a long time because it helps organisms survive. Instead of always fighting off every single foreign thing, it's sometimes better to just tolerate it. Fighting takes a lot of energy and can damage the body.

Imagine a friendly germ that lives in your gut. If your body constantly fought it, you'd be tired and sick. It's better to tolerate it, especially if it helps you, like by digesting food.

However, tolerance also has downsides. Some bad germs can take advantage of this tolerance to hide from our immune system. Also, as we saw with unwanted growths, they can use tolerance to avoid being destroyed. So, there's a balance between fighting off invaders (resistance) and tolerating them.

Balancing Resistance and Tolerance

Our immune system has two main ways to deal with foreign things:

• Resistance: This means fighting and getting rid of the invader. It's like a full-on battle.
• Tolerance: This means accepting the invader and trying to reduce any harm it causes, without destroying it. It's like a truce.

Both strategies have pros and cons:

• Fighting (Resistance):
  • Good: Gets rid of bad germs, stops them from causing harm.
  • Bad: Can cause pain, swelling, and damage to our own tissues. Uses a lot of energy. Can sometimes lead to our immune system attacking itself.
• Tolerating (Tolerance):
  • Good: Less damage to our own body from the immune response. Saves energy. Helps friendly germs live with us.
  • Bad: The invader might still cause some direct harm or use up our resources.

Evolution has shaped our bodies to choose the best strategy for different situations. If an invader is very dangerous, our body will fight it. If it's harmless or even helpful, our body will likely tolerate it. This balance helps us stay healthy.

See also

In Spanish: Tolerancia inmunitaria para niños

• Evolutionary medicine § tradeoffs
• Immunotherapy
• Infectious tolerance
• Mithridatism
• Plant tolerance to herbivory