11:9: Autoimmunity Flashcards
What is autoimmunity?
- Immune rxn against self antigen
- Can be directed against single tissue/organ or against many
What is self tolerance?
- Lack of responsiveness to self antigens
What is immunologic tolerance?
- Making lymphocytes unresponsive to self antigen
- “Self tolerance”
- Result of central tolerance
What is central tolerance?
- Clonal deletion of self reactive T and B cells
- Occurs in thymus for T cells
- Occurs in marrow for B cells
What is peripheral tolerance?
- Removal of self reactive T cells that escape intrathymic negative selection
What happens to T cells that to not recognize self antigen?
Allowed to undergo clonal proliferation
What is AIRE?
“Autoimmune regulator”
- Transcription factor promoting expression of self antigen by thymic epithelial cells
- Allows for elimination of self directed T cells
What is APECED?
- Occurs when you lack AIRE
- Develop organ specific autoimmune disease
- Often shows problems with eyes, teeth and fingers
What is receptor editing?
- Rearrangements altering specificity of B cell receptor to avoid autoreactivity
- Occurs in bone marrow
4 mechanisms of peripheral tolerance?
- Anergy
- Suppression by Tregs
- Clonal deletion by induced cell death
- Antigen sequestration
What is anergy?
- A reaction between self reactive T cell and its antigen that leads to expression of proapoptotic proteins and silencing of those T cells
- Most self antigens do not possess stimulatory molecules necessary to mount T cells response
How to Tregs impact T cells?
- Release cytokines to suppress function of autoreactive T cells
What is Fas-FasL ligand?
Leads to apoptosis of self reactive T cells in periphery
What is antigen sequestration?
- Certain areas such as brain eyes and testis have limited exposure to T cells so the celf antigens here are protected
- Can lead to prolonged inflammation / infection because of this as well
What is molecular mimicry?
- Virus or bacteria shares epitopes with self proteins expressed on human
- Leads to immune response against human as well
- Rheumatic fever is example of this
What is exposure of cryptic self?
- Infection in area usually not exposed to immune system allows self antigen to spread to areas it is not normally present
- Can lead to autoimmune rxn
What is SLE?
“Systemic lupus erythematosus”
- Multisystem autoimmune disease caused by variety of antibodies