An antigen is any substance capable of triggering a response from the immune system. These substances can originate from outside the body, such as components of viruses, bacteria, or pollen. A self-antigen, however, is an antigen from the body’s own healthy cells and tissues. The immune system recognizes these self-antigens as harmless.
Consider a security team at a large company; they are trained to recognize employee ID badges, which represent self-antigens, signaling that the individual belongs and poses no threat. Conversely, an unfamiliar face without a badge, like a non-self antigen from an invading pathogen, would raise an alarm. This distinction allows the immune system to differentiate between the body’s own components and foreign invaders, attacking only what is harmful.
The Process of Immune Tolerance
The body’s ability to recognize and not react to its own self-antigens is known as immune tolerance. This process begins during the development of immune cells, primarily T-cells and B-cells, which are the main components of the adaptive immune system. The immune system undergoes an “education” phase to prevent it from attacking healthy tissues.
T-cells mature in the thymus, a gland located in the chest. During this maturation, T-cells are exposed to a wide variety of self-antigens presented by specialized cells. Those T-cells that show a strong reaction to these self-antigens are eliminated through a process called negative selection. This ensures that only T-cells that do not target the body’s own components circulate.
Similarly, B-cells develop and mature in the bone marrow. They also undergo a selection process where B-cells that produce antibodies strongly reactive to self-antigens are either inactivated or eliminated. This dual training mechanism in both the thymus and bone marrow prevents the immune system from launching an attack against the body’s own healthy tissues. This selection maintains the body’s integrity.
Presentation of Self-Antigens
Beyond the initial training phase, the continuous display of self-antigens maintains immune tolerance throughout life. This display is facilitated by specialized molecules known as Major Histocompatibility Complex (MHC) molecules. In humans, these molecules are also called Human Leukocyte Antigens (HLA). MHC molecules are found on the surface of most nucleated cells in the body.
MHC molecules function like molecular display cases, constantly presenting small protein fragments (antigens) from within the cell. These protein fragments are derived from the normal turnover of cellular proteins. When a healthy cell displays self-antigens via its MHC molecules, it signals to passing immune cells, particularly T-cells, that the cell is normal.
The continuous presentation of self-antigens reinforces the immune system’s understanding of “self.” If a cell displays a foreign antigen (e.g., from a virus), the immune system recognizes it as non-self and initiates a protective response.
When Self-Recognition Fails
A breakdown in immune tolerance occurs when the body’s immune system mistakenly identifies its own self-antigens as foreign invaders. This misidentification leads the immune system to launch an attack against the body’s own tissues and organs, a condition known as an autoimmune disease. The specific self-antigen targeted dictates the affected body part.
In Type 1 Diabetes, for example, the immune system targets and destroys the insulin-producing beta cells located in the pancreas. The self-antigens on these pancreatic cells are recognized as threats, leading to a loss of insulin production and impaired blood sugar regulation.
Rheumatoid Arthritis involves the immune system attacking self-antigens found in the lining of the joints, leading to inflammation, pain, and joint damage. The immune response targets components of the synovial membrane, which lubricates and protects the joints. The assault on joint tissues can impact mobility.
Lupus is a systemic autoimmune disease where the immune system can attack self-antigens found in various tissues and organs, including the skin, joints, kidneys, and brain. The broad attack on diverse self-antigens explains the wide range of symptoms experienced by individuals with Lupus, reflecting the widespread error.
Self-Antigens in Medical Contexts
Understanding self-antigens holds importance in medical applications, particularly organ transplantation and cancer immunotherapy. In organ transplantation, MHC molecules, which present self-antigens, are a concern. The recipient’s immune system can perceive the donor organ’s self-antigens as foreign if they are different from their own.
This difference in self-antigens, specifically the MHC/HLA types, can trigger an immune response that leads to organ rejection, where the body attacks the transplanted organ. Doctors strive to find the closest match between donor and recipient HLA types to minimize this risk. Matching HLA types helps the recipient’s immune system recognize the new organ as “more self” than “non-self.”
In cancer immunotherapy, the role of self-antigens is complex and exploited for therapeutic benefit. Cancer cells are derived from the body’s own cells, but can undergo genetic changes resulting in altered self-antigens on their surface. These altered antigens (neoantigens) can be recognized as abnormal by the immune system. New therapies aim to enhance the immune system’s ability to detect and target changes in self-antigen presentation on cancer cells.