Immune Tolerance - Online Tutor, Practice Problems & Exam Prep

Immune tolerance is the immune system's ability to distinguish between harmful and harmless antigens, preventing inappropriate responses that could lead to autoimmune diseases. Central immune tolerance occurs in primary lymphoid organs, eliminating self-reacting T and B cells through apoptosis. Peripheral immune tolerance, occurring in secondary lymphoid organs, involves both positive and negative selection, promoting cells that bind to MHC while eliminating those that react to harmless antigens. This strict selection process ensures that only about 5% of T and B cells effectively target harmful pathogens.

Immune Tolerance

In this video, we're going to begin our lesson on immune tolerance. It's important to note that our immune system must be able to build what is known as immune tolerance in order to prevent an inappropriate response of our immune system to harmless antigens. Immune tolerance can be defined as the ability of our immune system to ignore or, in other words, to tolerate any given molecule. The goal of immune tolerance is to generate immune tolerance only to harmless antigens. In other words, we want our immune system to ignore harmless antigens, and we don't want our immune system to ignore dangerous or harmful antigens. Without immune tolerance, our immune system would have a really hard time distinguishing between harmless and harmful. That would leave our immune system more likely to attack our own healthy, uninfected cells leading to diseases known as autoimmune diseases. We'll get to talk more about autoimmune diseases later in our course in a different video.

Now, if we take a look at our image down below, we can get a better understanding of immune tolerance, which is really the ability for our immune system to distinguish harmless antigens from harmful antigens. Notice here what we have in the middle is one of our adaptive immune system cells, perhaps a T cell. This T cell has learned to tolerate all of the things listed on the left, which include the normal microflora or our normal microbiota, normal self cells, or our own healthy cells, as well as other harmless antigens. It's the harmless antigens that our immune system has built a tolerance for. Immune system tolerance is built towards harmless antigens. Notice that this T cell has not built a tolerance towards these harmful antigens and pathogens, including pathogens, cancer cells that are infected, and also other harmful antigens. Ultimately, what we're saying here again is that immune system tolerance is the ability for our immune system to distinguish harmless from harmful and to practically ignore all of the harmless substances but attack all of the harmful substances.

This concludes our brief introduction to immune tolerance, and we'll be able to continue to learn more and more about it as we move forward in our course. So I'll see you all in our next video.

Football Analogy for Immune Tolerance

In this video, we have a football analogy for immune tolerance. First, we need to recall from our previous lesson video that immune tolerance is the ability of our immune system to distinguish between harmful and harmless antigens. In this football analogy, the immune system is represented as the quarterback (QB) of the team. The harmful antigens are represented as the opponent team, and the harmless antigens are represented as the teammates. Without immune system tolerance, our immune system cannot distinguish between harmful and harmless antigens. That means that the immune system will not be able to perform its job very well.

If we look at our image below at our football analogy, notice that without immune tolerance, our immune system will be unable to distinguish harmful from harmless substances. That means that our immune system, represented as the QB, will be unable to distinguish his teammates from the opposing team. Notice that all these players are on the field; however, the QB, which represents our immune system, cannot distinguish between the harmful and harmless substances. Because the QB can't figure out who's on his team, he won't be able to do his job properly. Without immune tolerance, the immune system cannot do its job properly, and it could lead to autoimmune diseases.

On the other hand, with immune system tolerance, our immune system can distinguish between harmful and harmless substances properly, and that means that our immune system will be able to perform its job properly. If we look at our image on the right-hand side, notice it's representing with immune tolerance. That means that our immune system will be able to distinguish between harmful and harmless substances, which means that our QB, here our QB immune system, will be able to distinguish his teammates from the opposing team. Notice here that his teammates are all colorful, and because the QB can distinguish the teammates from the opposing team, the immune system will be able to perform its job properly. The QB is saying, "Oh, now that I have immune tolerance, I can do my job properly."

This football analogy demonstrates how immune tolerance allows our immune system to distinguish harmful from harmless substances and to perform its job properly, building immune tolerance towards harmless substances and targeting and attacking harmful and dangerous antigens. This concludes our football analogy for immune tolerance, and we'll be able to get some practice applying these concepts and learn even more about immune tolerance as we move forward in our course. I'll see you all in our next video.

Central vs. Peripheral Tolerance

In this video, we're going to introduce and differentiate central immune tolerance and peripheral immune tolerance. It's important to note that sometimes our adaptive immune response can make a mistake, and it can mistakenly produce what are known as self-reacting T and B cells. Self-reacting here just means that these T and B cells will react to our own healthy, uninfected cells. These self-reacting T and B cells will actually harm our own healthy cells, which is a bad thing. Again, this is a mistake that our adaptive immune system can occasionally make. To prevent this mistake from happening, our body strictly controls T and B cell development to ensure that these self-reacting T and B cells are not produced.

There are two types of tolerance mechanisms that control T and B cell development: central immune tolerance and peripheral immune tolerance. Central immune tolerance occurs via negative selection of mature T and B cells before they leave the primary lymphoid organs. Recall that the primary lymphoid organs include the bone marrow for B cells and the thymus for T cells. This negative selection involves the elimination or removal of self-reacting T and B cells by apoptosis, essentially killing any cell that binds self or harmless antigens. Peripheral immune tolerance, on the other hand, involves the selection of mature T and B cells after leaving the primary lymphoid organs and making their way to the secondary lymphoid organs. Peripheral immune tolerance involves both negative selection as well as positive selection, positively selecting T cells that bind any MHC and negatively selecting T cells that bind harmless antigens.

Positive selection refers to promoting cells that do something, and negative selection refers to inhibiting or killing cells that do something. We'll distinguish that a little bit better down below when we get to this interesting image of Jigsaw from the scary movie Saw. In this context, self-reacting T and B cells will become anergic or unresponsive and will eventually undergo apoptosis, negatively selecting for those T cells that bind harmless antigens. These two tolerance mechanisms are so strict that approximately 95% of all T and B cells that we initially create undergo apoptosis, and only 5% of the T and B cells will make it through these mechanisms. This small percentage of cells that make it through are very effective at doing their job appropriately and targeting harmful antigens.

Now, negative selection, as its name implies, involves something negative: if you do something specific — in this case, if T and B cells bind to harmless and self antigens — then they will die. Positive selection, on the other hand, is somewhat positive: if you do something specific — in this case, bind any MHC — then you get to survive. In the images below focused on T cells, notice that central tolerance occurs before the immune cells leave the primary lymphoid organs like the thymus for T cells, and peripheral tolerance occurs after they reach secondary lymphoid organs like the lymph nodes.

In central tolerance, if T cells bind to harmless or self antigens, they are eliminated via apoptosis. However, if negative selection fails, some self-reacting T cells may not be eliminated and can leave the primary lymphoid organ. These T cells are then exposed to peripheral tolerance mechanisms involving both positive and negative selection. Positive selection promotes cells that sufficiently bind and recognize antigens on MHC, allowing them to survive, while negative selection eliminates those that do not.

Ultimately, of all the T cells produced, only a small percentage can make it through both central and peripheral tolerance mechanisms and generate an immune response. The T cells and B cells that we have in our secondary lymphoid organs are those that have undergone these strict tolerance mechanisms and are capable of generating an appropriate immune response.

This concludes our brief lesson on central versus peripheral tolerance mechanisms. We'll get some practice applying these concepts as we move forward in our course. I'll see you all in our next video.

The most important function of peripheral tolerance is to:

• A. Eliminate mature B & T lymphocytes that bypassed central tolerance from reacting to self-cells.
• B. Eliminate inactive B & T lymphocytes from peripheral blood.
• C. Eliminate self-reacting B & T lymphocytes before they enter central tolerance.
• D. Eliminate mature B & T lymphocytes from the bone marrow.

Where do T cells undergo central tolerance selection?

• A. Bone marrow.
• B. Pancreas.
• C. Thymus.
• D. Liver.
• E. Brain.

What is immunological tolerance?

• A. The ability of the immune system to remove lymphocytes that recognize and attack foreign antigens.
• B. The ability of the immune system to differentiate between self and non-self antigens.
• C. The ability of the immune system to create antibodies that most effectively bind foreign antigens.
• D. The ability of the immune system to tolerate a certain amount of pathogens before triggering an immune response.

Which of the following is NOT a consequence of the immune system lacking an immune tolerance?

• A. The immune system cells will only recognize and attack foreign antigens.
• B. The immune system cells will recognize and attack foreign and self-antigens.
• C. The immune system will attack self-cells causing autoimmune diseases.
• D. The immune system will not remove T and B lymphocytes that bind to self-antigens.

Here’s what students ask on this topic:

What is immune tolerance and why is it important?

Immune tolerance is the immune system's ability to distinguish between harmful and harmless antigens, preventing inappropriate immune responses. This is crucial because without immune tolerance, the immune system might attack the body's own healthy cells, leading to autoimmune diseases. By ignoring harmless antigens, such as normal microflora and self-cells, the immune system can focus on targeting harmful pathogens and infected cells. This selective response ensures that the immune system functions effectively without causing damage to the body's own tissues.

What are the differences between central and peripheral immune tolerance?

Central immune tolerance occurs in primary lymphoid organs (bone marrow for B cells and thymus for T cells) and involves the elimination of self-reacting T and B cells through apoptosis. This process is known as negative selection. Peripheral immune tolerance, on the other hand, occurs in secondary lymphoid organs (such as lymph nodes) and involves both positive and negative selection. Positive selection promotes cells that bind to MHC, while negative selection eliminates cells that react to harmless antigens. Together, these mechanisms ensure that only a small percentage of T and B cells, which can effectively target harmful pathogens, survive.

How does the immune system distinguish between harmful and harmless antigens?

The immune system distinguishes between harmful and harmless antigens through a process called immune tolerance. This involves both central and peripheral tolerance mechanisms. Central tolerance occurs in primary lymphoid organs, where self-reacting T and B cells are eliminated. Peripheral tolerance occurs in secondary lymphoid organs, where cells that bind to MHC are promoted (positive selection) and those that react to harmless antigens are eliminated (negative selection). These processes ensure that the immune system can effectively target harmful pathogens while ignoring harmless substances.

What role do T cells and B cells play in immune tolerance?

T cells and B cells are crucial in immune tolerance. During their development in primary lymphoid organs, self-reacting T and B cells are eliminated through central tolerance. This prevents them from attacking the body's own healthy cells. In secondary lymphoid organs, peripheral tolerance further refines this process by promoting cells that bind to MHC (positive selection) and eliminating those that react to harmless antigens (negative selection). This strict selection process ensures that only T and B cells capable of effectively targeting harmful pathogens survive, maintaining a balanced immune response.

What happens if immune tolerance fails?

If immune tolerance fails, the immune system may not properly distinguish between harmful and harmless antigens. This can lead to the immune system attacking the body's own healthy cells, resulting in autoimmune diseases. Without proper immune tolerance, self-reacting T and B cells are not eliminated, causing inappropriate immune responses. This failure can lead to chronic inflammation, tissue damage, and various autoimmune conditions, highlighting the importance of effective immune tolerance mechanisms in maintaining immune system balance and preventing disease.