Immunology 4 - Autoimmunity Flashcards
What is immunologic tolerance?
Unresponsiveness to an antigen that is induced by previous exposure to said antigen
What are tolerogens?
Antigens that induce tolerance
What is Self-tolerance?
System that prevents the immune system to react to itselfa
How are autoimmune diseases avoided?
T + B cells bearing self-reactive molecules are eliminated or downregulated
What are the mechanisms for downregulation of self-reactive B and T cells?
- Thymic destruction
- Clearing of antigens which are normally only present in cells via complement
- Physical barriers
- Inhibition by T-regulatory cells
Outline Central tolerance?
Thymus destroys T-cells with high affinity to self-antigens
Outline Peripheral Tolerance
Mature Lymphocytes which recognise self-antigens in peripheral tissues become incapable of activation or die
What are the mechanisms of peripheral tolerance?
- Anergy (unresponsiveness)
- Antigen recognition without co-stimulation
- Treg suppression
- Deletion (by apoptosis)
- Anatomical barriers
What are the responses of immature lymphocytes to recognition of self-antigens?
Apoptosis
Change in receptors (B-cell editing)
Development of regulatory T cells
How can peripheral tolerance be overcome?
- Inappropriate access to self-antigens
- Increased expression of co-stimulatory molecules
- Alterations in how self-molecules are presented
Overcoming peripheral tolerance is more likely to happen when?
Inflammation/tissue damage is present or Increased proteolytic enzymes leading to high concentrations of peptides being presented to T-cells
- Tolerance breaks down leading to further inflammation
- Immune response broadens (epitope spreading)
What is the major source of antoantibodies?
B1 cells
How can natural antibodies become autoantigens?
- Cross-reaction with inherited A and B antigens (normal - forms Anti-A and Anti-B antibodies)
- Can bind to cellular constituents (by-products of normal apoptosis)
What factors lead to the breakdown of T-cell tolerance?
Inheritance of HLA with poor binding to self-antigens
Poor expression of self-antigens in the thymus
Infections/drugs
What is the role of HLA?
Encode MHC
