Tolerance Flashcards (Immuno 2)

Question 1

Central Tolerance (T- cells)
Anergy

Answer 1

Co-stimulation is important for the activation of T cells:
Normal Signal 2: CD28 on T cell binds to B7 on APC

A: Disruption of the CD28/B7 signal (CTLA-4). CTLA-4 is a molecule that also interacts with greater affinity to B7, leading to disruption of the costimulatory signal and anergy.

B: Failure to express B7 can lead to anergy

Question 2

Peripheral Tolerance (T- cells)
Deletion

Answer 2

T lymphocytes that recognize self-antigens with high affinity or are repeatedly stimulated by antigens may die by the ApC giving apoptopic signals leading to apoptosis.

Question 3

Peripheral Tolerance (T- cells)
Suppression

Answer 3

Tregs can suppressTh cellsvia direct cell-cell contact, or by secretion of inhibitory cytokines (IL-10, TGF-B)

Direct Cell:cell contact
The Treg has CTLA-4 on cell surface and this moves B7 and binds to this so that the CD28 can not bind to it leading to suppression

Question 4

Central Tolerance (B-cells) 
Receptor editing

Answer 4

BCR binds strongly to multivalent self-antigen / self-antigen present in high concentrations
Development arrested
BCR of autoreactive immature B cell is modified
- self reactive light chain deleted and replaced with new one

If new BCR no longer self-reactive it continues to develop

If new BCR still self-reactive further light chain rearrangement may occur
If does not resolve – apoptosis
= CLONAL DELETION

Question 5

Central Tolerance (B-cells) 
Anergy

Answer 5

If immature B cells do not bind or bind weakly to monovalent antigens on cells in the BM, they successfully leave the BM and migrate to secondary lymphoid organs

If immature B cells bind strongly to monovalent antigens present in cells in the BM, the BCR’s cross link and they do not develop further (anergy) and do not leave the BM
- down regulation of BCR
expression
- block in BCR signalling

Question 6

Peripheral Tolerance (B-cells)

Answer 6

T cell independent activation:
- Weak/no interaction = normal
- Strong interaction
apoptotic signals = Clonal deletion

T cell dependant activation
- Auto reactive T cells are eliminated by Central tolerance in the thymus
- B cell remains unresponsive
= ANERGY