Lecture #126: Mechanisms of Autoimmunity in Rheumatologic Disease

What is autoimmunity?

A condition in which self-tolerance is broken, leading the immune system to attack the body’s own tissues.

What are the two key requirements for autoimmunity to occur?

Breakdown of self-tolerance and loss of previously established immune tolerance.

What is central tolerance?

A mechanism in primary lymphoid organs where self-reactive lymphocytes are eliminated during development.

What is peripheral tolerance?

A mechanism outside primary lymphoid organs that controls self-reactive cells that escape central tolerance.

What happens to some autoreactive T cells despite central tolerance?

A proportion escape deletion and enter the periphery, requiring additional regulation.

What is receptor editing in B cells?

A process in central tolerance where B cells change their antigen receptor specificity to avoid self-reactivity.

What is anergy?

A state of functional inactivation in lymphocytes when they recognize antigen without proper co-stimulation.

What is apoptosis in immune tolerance?

Programmed cell death used to eliminate self-reactive lymphocytes.

What is immunologic ignorance?

A state where self-reactive lymphocytes do not encounter antigen and therefore remain inactive.

What are regulatory T cells (Tregs)?

A subset of T cells that suppress immune responses and maintain self-tolerance.

What markers are associated with regulatory T cells?

CD4, CD25, and FOXP3 expression.

What happens with FOXP3 mutation?

Impaired regulatory T cell function leading to loss of immune regulation and autoimmunity.

What role do Tregs play in preventing autoimmunity?

They suppress autoreactive lymphocytes and maintain immune homeostasis.

What is the role of Th17 cells in immune responses?

They are proinflammatory and contribute to autoimmune disease when dysregulated.

What is the significance of the Th1/Th2 balance?

It regulates immune responses, and imbalance can contribute to autoimmune or allergic diseases.

What is a key mechanism of autoimmune disease involving B cells?

Autoreactive B cells fail to respond to inhibitory signals and produce autoantibodies.

What is the consequence of defective inhibitory signaling in B cells?

Persistent activation and production of antibodies against self-antigens.

What are superantigens?

Molecules that cause nonspecific activation of large numbers of T cells, potentially triggering autoimmune responses.

How can superantigens contribute to autoimmunity?

They bypass normal antigen processing and activate T cells excessively.

What is the role of antigen dose and T-cell receptor affinity in tolerance?

They influence whether T cells are deleted, become anergic, or differentiate into regulatory cells.

What happens to high-affinity self-reactive T cells?

They may be deleted or converted into regulatory T cells.

What is the importance of immune tolerance mechanisms?

They prevent the immune system from attacking self-tissues.

What is the consequence of defective immune tolerance?

Development of autoimmune diseases.

What is the relationship between central and peripheral tolerance?

Central tolerance removes most autoreactive cells, while peripheral tolerance controls those that escape.

What is the overall goal of immune regulation?

Maintain balance between immune activation and suppression to prevent disease.