Tolerance Flashcards
What is the definition of tolerance in immunology?
Tolerance is a specific state of immunologic unresponsiveness to a certain antigen, although the immune system is functioning normally.
What are the two types of immune tolerance?
- Self-tolerance (the ability of the immune system to recognize and not respond to self-antigens).
- Induced tolerance (the immune system actively avoids responding to external antigens, e.g., to avoid rejection of transplanted organs).
What is central tolerance in T-cells, and where does it occur?
Central tolerance occurs within the thymus and involves clonal deletion (negative selection), where T-cells that react to self-antigens are killed by apoptosis during embryonic life.
What is peripheral tolerance, and why is it important?
Peripheral tolerance occurs outside the thymus and is important because not all antigens are exposed and expressed in the thymus, leading to some auto-reactive T-cells escaping and not being killed in the thymus.
What are the mechanisms of peripheral T-cell tolerance?
- Clonal Anergy: T-cells are not activated due to a lack of co-stimulatory signals (e.g., no B7-CD28 interaction) or inhibitory receptors like CTLA-4.
- Suppression by regulatory T-cells: These cells produce inhibitory cytokines like TGF-β and IL-10.
- Ignorance: T-cells ignore self-antigens due to physical separation (e.g., blood-brain barrier) or because antigens are present in small amounts.
- Deletion of auto-reactive cells by apoptosis (e.g., via Fas-FasL interaction).
What is B-cell tolerance, and where does central tolerance for B-cells occur?
B-cell tolerance involves central tolerance by clonal deletion of B-cells in the bone marrow and peripheral tolerance by clonal anergy of B-cells.
What factors determine the induction and maintenance of tolerance?
- Immunologic maturity: Neonates are more easily induced to tolerance than adults.
- The structure & dose of antigens: Simple molecules and very high or very low doses of antigens can induce tolerance.
- T-cells remain tolerant longer than B-cells.
- Administration of cross-reacting antigens can fail tolerance.
- Immunosuppressive drugs improve and maintain tolerance.
- Continuous presentation of the antigen maintains tolerance.
What happens if an exogenous antigen is injected into a fetus during immune system maturation?
The exogenous antigen is recognized as a self-antigen, inducing tolerance to it rather than an immune response.
What is clonal anergy in T-cells, and what causes it?
Clonal anergy in T-cells occurs when T-cells are not activated due to a lack of co-stimulatory signals (e.g., no B7-CD28 interaction) or inhibitory receptors like CTLA-4, leading to a failure of IL-2 production, which is required for full T-cell activation.
How do regulatory T-cells suppress immune responses?
Regulatory T-cells suppress immune responses by producing inhibitory cytokines such as TGF-β and IL-10.
What is the role of Fas-FasL in peripheral tolerance?
Fas-FasL interaction leads to the deletion of auto-reactive T-cells by apoptosis, contributing to peripheral tolerance.
Why are neonates more easily induced to tolerance than adults?
Neonates are immunologically immature and do not respond well to foreign antigens, making them more easily induced to tolerance compared to adults with a fully mature immune system.
