Difference Between Central and Peripheral Tolerance

The key difference between central and peripheral tolerance is that thymus and bone marrow are the places that induce the state of central tolerance while lymph nodes and other tissues are the places that induce the state of peripheral tolerance.

Immune tolerance is a state of unresponsiveness of the immune system to substances or tissues that possess the potential of eliciting an immune response in an organism. There are two types of immune tolerances based on the location in which the state is induced originally. They are central tolerance and peripheral tolerance. Central tolerance is a state of immune tolerance that is induced originally in the thymus and bone marrow. Whereas, peripheral tolerance is a state of immune tolerance that is induced originally in the lymph nodes and other tissues.

1. Overview and Key Difference
2. What is Central Tolerance
3. What is Peripheral Tolerance
4. Similarities Between Central and Peripheral Tolerance
5. Side by Side Comparison – Central vs Peripheral Tolerance in Tabular Form
6. Summary

What is Central Tolerance?

Central tolerance is a type of immune tolerance that occurs in the thymus and bone marrow (primary lymphoid organs). It is the main mechanism that helps the immune system to discriminate self from non-self. In simple words, central tolerance facilitates the identification of own mature B cells and T cells without misunderstanding these self-antigens as foreign microbes. Central tolerance eliminates the developing T and B lymphocytes that are reactive to self. Otherwise, the immune system becomes induced and attacks self-peptides. Hence, central tolerance is important in removing autoreactive lymphocyte clones before they develop into fully immunocompetent cells.

Figure 01: Central Tolerance

Central tolerance occurs via two mechanisms: B cell tolerance and T cell tolerance. B cell tolerance occurs in the bone marrow while T cell tolerance occurs in the thymus. However, central tolerance is not a perfect process. Some mature autoreactive T or B lymphocytes can escape from primary lymphoid organs. At that time, peripheral tolerance takes place as a secondary mechanism ensuring that T and B cells are not self-reactive.

What is Peripheral Tolerance?

Peripheral tolerance is the second type of immune tolerance. It occurs in the peripheral tissues and lymph nodes. Since central tolerance is not a perfect process, peripheral tolerance operates as a secondary mechanism to ensure the deletion of self-reactive T and B lymphocytes or the conversion of T and B cells into the anergic state.

Figure 02: Peripheral Tolerance

In order to delete or convert T and B lymphocytes into an anergic state, peripheral tolerance occurs via three mechanisms. They are induction of anergy, deletion of autoreactive T cells via apoptosis and development of “induced” regulatory T cells (Tregs).

What are the Similarities Between Central and Peripheral Tolerance?

Central and peripheral tolerance are two states of immune tolerance.
However, their resultant effects are similar.
Moreover, peripheral tolerance exists as a secondary mechanism to central tolerance in order to ensure that T and B cells are not self-reactive once they leave thymus and bone marrow.
Besides, deficits in both tolerances can cause autoimmune diseases.

What is the Difference Between Central and Peripheral Tolerance?

Central tolerance and peripheral tolerance are two types of immune tolerance. Central tolerance occurs in the thymus and bone marrows while peripheral tolerance occurs in the peripheral tissues and lymph nodes. Therefore, this is the key difference between central and peripheral tolerance. Furthermore, central tolerance operates on the developing T and B lymphocytes which are reactive to self. Whereas, peripheral tolerance operates on the self-reactive T and B lymphocytes that have escaped from the primary lymphoid organs to peripheral tissues. So, this is the functional difference between central and peripheral tolerance.

Below infographic provides more details on the difference between central and peripheral tolerance.

Summary – Central and Peripheral Tolerance

Self-tolerance can be achieved through central tolerance and peripheral tolerance. Central tolerance occurs in the thymus and bone marrow while peripheral tolerance occurs in the peripheral tissues and lymph nodes. Hence, this is the key difference between central and peripheral tolerance. However, their resultant effects are similar. Moreover, central tolerance occurs via two mechanisms as T cell tolerance and B cell tolerance. Meanwhile, peripheral tolerance occurs via three mechanisms: induction of anergy, deletion of autoreactive T cells via apoptosis, and development of “induced” regulatory T cells (Tregs). However, it is important to note that both processes prevent the harmful immune responses within the host.

Reference:

1. “Central Tolerance.” Wikipedia, Wikimedia Foundation, 19 July 2018, Available here.
2. “Immune Tolerance.” Wikipedia, Wikimedia Foundation, 6 Apr. 2019, Available here.

Image Courtesy:

1. “Tregs in mouse pregnancy” By Maria Grazia Ruocco, Gérard Chaouat, Laura Florez, Armand Bensussan, David Klatzmann – (CC BY-SA 4.0) via Commons Wikimedia
2. “T cell negative selection” By Immcarle64 – Own work (CC BY-SA 4.0) via Commons Wikimedia