Overview
This lecture covers the mechanisms, types, and examples of autoimmune diseases, focusing on how the immune system loses self-tolerance and attacks the body.
Loss of Self-Tolerance in Autoimmunity
- Autoimmune diseases occur when the immune system attacks the body's own tissues.
- Loss of self-tolerance is due to failed thymic selection, letting self-reactive T cells survive.
- Autoantibodies and sensitized T cells target self-antigens, causing tissue damage.
Types of Autoimmune Reactions
Cytotoxic Autoimmune Reactions
- Antibodies react with cell surface antigens but usually do not destroy the cell.
- Example: Graves Disease—autoantibodies mimic thyroid-stimulating hormone (TSH), causing overactive thyroid (hyperthyroidism) symptoms like bulging eyes and rapid heartbeat.
Immune Complex Autoimmune Reactions
- Antibodies form complexes with antigens on self-tissues, triggering inflammation.
- Examples: Lupus and rheumatoid arthritis involve immune complexes depositing in tissues (e.g., joints), causing chronic inflammation and tissue damage.
Cell-Mediated Autoimmune Reactions
- T cells attack body’s own tissues, causing direct cell damage.
- Examples: Type 1 diabetes (T cells attack pancreas islets), multiple sclerosis (MS), and psoriasis (T cells increase skin cell production).
- Psoriasis can lead to psoriatic arthritis, similar in severity to rheumatoid arthritis.
Treatment Considerations
- Most autoimmune disease treatments suppress the immune system, reducing symptoms but increasing infection and cancer risks.
- Ideally, immune system modulation is preferred over broad suppression.
Key Terms & Definitions
- Autoimmunity — immune response against the body’s own cells or tissues.
- Self-tolerance — immune system's ability to avoid attacking the body’s own proteins.
- Autoantibody — antibody directed against self-antigens.
- Thymic selection — process eliminating self-reactive T cells during development.
- Immune complex — cluster of antigens and antibodies causing inflammation.
- Cytotoxic reaction — antibody reaction with cell surface antigens.
- Cell-mediated reaction — immune response led by T cells against self-tissue.
Action Items / Next Steps
- Review examples of each autoimmune reaction type.
- Prepare for discussion on immune system modulation strategies in the next class.