Lecture 7 Flashcards
Why do we need immuological tolerance?
Many self reactive specificities would be produced, and autoimmune diseases would results from the immune system attacking urself
What happens if we don’t have tolerance?
Would lead to serious pathology
What are the two types of bad tolerance for TCR?
- T cells fail to recognise self MHC
- T cells recognise self MHC + peptide (autoreactive)
What is a useful type of T cell tolerance?
Recognise self MHC + any other peptide not present in thymus
What is negative selection of TCR tolerance?
When the T cells recognise their own self-MHC
What is T cell survival and tolerance based on?
TCR affinity
What is the best mechanism for T cell survival?
A population with TCRs that have a medium affinity - capable of binding peptides derived from antigens NOT present in the thymus
Not all self antigen are expressed in thymus, what else can be?
Insulin
What does AIRE stand for?
Autoimmune regulator protein
What is AIRE?
A transcription factor
What is the job of AIRE?
Allows lots of tissues specific genes to be expressed in the thymus at low levels
What is the reasons for insulin being expressed in the thymus?
Deletes autoreactive T cells
What does a global transcription factor allow?
Allows us to become tolerant as it controls expression
What is AIRE deficiency?
When People have major autoimmune syndromes
What leads to b cell tolerance?
Random Ig gene arrangements leads to self reactive BCRs
Where are autoreactive B cells negatively selected?
In the bone marrow
What is different about b cells than T cells in tolerance?
B cells get another change to re-arrange the self-reactive BCR
What is it called when self-reactive BCR can rearrange?
Receptor editing
What is receptor editing?
A new chain may remove self-reactivity changing the specific of the BCR
What does binding of self antigen by immature B cells lead to?
Death or anergy
What happens in anergy?
Sneak out the bone marrow by lowering the B cell receptor so they don’t get killed
What are the levels of BCR like in a anergic B cell?
Low levels of BCR become unresponsive
What happens when receptors encounter an AG that is not multivalent?
They done regulate BCR and leave the bone marrow unresponsive
Can T cells be made anergic?
Yes - if a T cell encounters an Ag in the absence of co-stimulation becomes anergic
What happens if a T cell only gets signal 1?
The T cell will override and not work
What are some other mechanisms of tolerance?
Immunological ignorance and privileged sites
What is immunological ignorance?
When the T cells don’t get enough expression to drive signal 1 or 2
What are privileged sites?
Stops immune cells going into the central nervous system with barriers
Where are the barriers in privileged sites?
Eyes, testis, CNS
What do B cells hope in tolerance?
They are dependent on T cell tolerance, they hope they will never get help from an autoreactive T cell