M: Immuno2 Autoimmune - Week 5 Flashcards
Why does autoimmune disease occur?
because of the tissue damage due to the activation of self-reactive T and B cells (i.e. failure of T and B cell tolerance)
What mediates autoimmune disease?
Type II-IV hypersensitivity responses
Regarding autoimmune diseases:
A) does genetic background determine development and severity?
B) Are they organ specific or non-organ specific
A: yes
B: can be either, depends on the disease
What central tolerance mechanism is in place for T cells to control how the react? (1)
- deletion of T cells which recognise self peptide
How can self-peptides be derived? (so that we can test T cell reactivity to them) (2)
May be derived from:
- thymic dendritic cell associated proteins
- ectopically expressed proteins on thymic epithelium (AIRE)
What does AIRE stand for?
autoimmune regulator gene
Why might T cell tolerance fail?
May fail if antigens are not expressed in the thymus to react with
Name 2 types of proteins that are ocular specific antigens against which circulating T and B cells have been detected
- retinal proteins
2. iris/choroid proteins - melanin assoc. proteins
Name 4 retinal proteins
- S-antigen (arrestin)
- IRBP (interphotoreceptor retinoid binding protein)
- Rhodopsin
- Recoverin
Name 4 peripheral tolerance mechanisms for T cells
- Ignorance
- Deletion
- Anergy
- Suppression
Explain Ignorance (the peripheral tolerance mechanism)
Mature T cells do not enter healthy tissues, so do not meet their antigen
Explain Deletion (the peripheral tolerance mechanism)
corneal endothelium and pigmented epithelial cells express Fas-L which binds Fas expressing activated lymphocytes – lead to apoptosis
Explain Anergy (the peripheral tolerance mechanism)
T cell recognition of peptides in the absence of co-stimulation leads to “anergy” of the T cell
Define Anergy
absence of the normal immune response to a particular antigen or allergin
Explain Suppression (the peripheral tolerance mechanism)
suppression of T cells due to expansion of specific regulatory T cells (Tregs)
What does failure of co-stimulation of T cells lead to?
T cell anergy
Why might there be a failure of co-stimulation of T cells?
due to absence of PAMPs and/or DAMPs
Name 2 co-stimulatory molecules essential for T cell activation
CD80 and CD86
What must APCs do in order to activate CD4 T cells effectively?
Differentiate
What is considered a “critical checkpoint” in adaptive immunity?
co-stimulation
Briefly describe a normal adaptive immune response
- Antigen is uptaken and the PAMPs bind the TLR, which activates the APC
- Activated APC migrates to LN and expresses co-stimulatory molecules as well as expressing peptides with MHC – this is done to activate CD4 T cells
- activated CD4 T cells can now proliferate and differentiate
What happens to the CD4 T cells when co-stimulatory molecules are not induced?
Anergy and apoptosis