Introduction
Immune Tolerance Overview
- Definition: Immune tolerance is the absence of an immune response to substances that are normally recognized by the immune system, including self-antigens.
- Adaptiveness: It's an adaptive feature of the entire immune system, not just individual lymphocytes, which discerns self from non-self based on the context of antigen presentation.
- Developmental Dependence: Effective tolerance usually requires ongoing exposure to the antigen, particularly during developmental stages.
- Experimental Insight: Removal and reimplantation of an organ during development often leads to rejection, highlighting the role of early exposure in tolerance.
Types of Immune Tolerance
- Central Tolerance:
- Location: Takes place during lymphocyte development in central lymphoid organs like the thymus and bone marrow.
- Process: Self-reactive lymphocytes that recognize self-antigens with high affinity undergo apoptosis—a process called negative selection.
- B-Cell Specifics: Immature B-cells may edit their receptors to eliminate self-reactivity; failure results in apoptosis.
- T-Cell Risk: Autoreactive T-cells pose a higher threat compared to B-cells, which require additional T-cell help to become fully active.
- Peripheral Tolerance:
- Occurrence: Happens in the body's periphery when mature lymphocytes encounter self-antigens under non-stimulatory conditions.
- Mechanism: Involves the failure of self-reactive lymphocytes to receive necessary co-stimulatory signals during antigen recognition, leading to inactivation rather than activation.
Role of Regulatory T-Lymphocytes
- Function: Regulatory T-cells help maintain tolerance by suppressing overly active lymphocytes, preventing immune responses to both self and foreign antigens.
- Autoimmunity: Failures in either central or peripheral tolerance mechanisms can lead to autoimmune diseases, where the body mistakenly attacks its own tissues.