L7: T Cell Activation Flashcards
What is immunological tolerance needed for?
- random generation of a range of BCR& TCR
- self reactive specifcities to be produced
- without it autoreactivity would lead to a serious pathology
TCR gene rearrangement leads to T cells expressing TCR that what?
- fails to recognise self MHC
- recognises self MHC and peptide generated from Ag present in the thymus (potentially dangerous)
- recognises self MHC and any other peptide present in thymus (potentially useful)
What will happen to T cells expressing TCR that fails to recognise self MHC?
It will die by neglect as there will be no +ve selection survival signal
What will happen to T cells expressing TCR recognises self MHC?
Cell are expanded by +ve selection. Then if:
- recognises peptides in thymus, eliminated by -ve selection
- recgonises peptides not present in thymus, survives
What population T cell is desired to survive selection and why?
Those recognising self MHC and antigens not present in Ag because
- will have medium affinity for self MHC so shouldn’t give autoimmune response
- cells also capable of responding to self MHC when it contains peptides found in pathogens
Give an example of a self Ag not expressed in the thymus
Insulin
What is the role of AIRE (autoimmune regulatory protein)?
Its a txn factor with a key role in tolerance induction
- allows expression of normally tissue specific Ag in thymus and thus deletion of T cells that recgonise these Ag
What can deficiency of AIRE result in?
Major autoimmune syndrome
Random Ig gene rearrangment can lead to what 2 main outcomes?
- B cells expressing self reactive BCR
- B cells expresing BCR that recognise Ag present in bone marrow
What can happen to immature B/T cells that bind self Ag and why?
They may undergo further light chain gene or TCR alpha locus rearrangements, in the possibility of expressing a BCR/ TCR that is no longer self reactive respectively
Name 3 methods by which tolerance can be acquired/ developed?
- gene rearrangement
- clonal anergy
- immunological ignorance
- privelleged sites
How can tolerance be acquired through clonal anergy?
Lymphocytes that recognise self Ag can become unresponsive (anergic)
- T cells that encounter Ag in the absence of co stimulation become anergic
- anergy can lead toperipheral tolerance of T cells
How can immunological ignorance cause tolerance?
Many Ag aren’t presented at sufficient levels to activate T cells
How can privelleged sites lead to tolerance?
These are sites of body that are able to tolerate introduction of Ag without eliciting an inflammatory immune response, so Ag is sequestered from immune system
- BB barrier stops lymphocytes going into CNS where it might recognise self Ag
What will happen if Ag-specific T cells are absent/tolerant?
There will be no Ab response as many B cell responses are T cell dependent
