Self, Non-self Discrimination Immune System

Question 1

where is central tolerance acquired for B cells?

T lymphocytes?

Answer 1

bone marrow

thymus

Question 2

where is peripheral tolerance acquired?

Answer 2

peripheral tissues and secondary lymphoid organs (spleen, lymph nodes)

Question 3

what are the four mechanisms used to induce tolerance?

Answer 3

1. delete (eliminate problem(
2. anergize (switch off problem)
3. ignore (ignore the problem)
4. regulate (contain the problem)

Question 4

how is b cell tolerance exerted centrally? peripherally?

in terms of efficiency, how does it compare to t cell tolerance?

Answer 4

central tolerance

• anergy
• deletion

peripheral

• ignorance, anergy, death
• lack of costimulation by T-cells

B cell tolerance less efficient than t cell tolerance.

Question 5

2 signals for mature B cells to respond and survive?

Answer 5

1. signals via surface Ig-Ag interaction (cross-linking)
2. T cell help via CD40 ligand and some cytokines

without t cell interaction, b cells have very short lifespan.

Question 6

what happens when people lack cd40L for B cell stimulation?

Answer 6

cant generate an appropriate immune response. tend see hyper IgM levels.

Question 7

t cell development occurs in the […]. at this stage of early development immature t cells carry both […] and […] receptors.

Answer 7

thymus

Cd4+ and Cd8+ co-receptors (double positive)

Question 8

following expression of a TCP, double positive thymocytes next undergo two types of selection processes….

Answer 8

positive selection: thymocytes that recognize self-antigen and tolerate it, are selected to survive

negative selection: removal of immature thymocytes that have strong reactivity to self-antigen

Question 9

t cell selection is dependant on receptor affinity for ?

Answer 9

self pMHC (sweet spot is between engaging too well and insufficient level of engagement).

Question 10

Some proteins are only expressed in specific tissues/in the periphery. We must ensure thymocytes are exposed to them in the thymus:
Tissue specific antigens are expressed in the thymus under the control of […] (an autoimmune regulator of expression).

Patients with mutation of AIRE might present with?

Answer 10

AIRE transcription factor

autoimmunity. potentially multiple autoimmune diseases.

Question 11

Just as naiive B cells require stimulation from CD40L and surface Ag-Ig interaction, naiive T cells require two signals for activation and proliferation….

Answer 11

1) TCR-peptide MHC interaction
2) Co-stimulation (eg. CD28 with CD80/86)

NB: both signals must act together to allow proliferation/differentiation or else inactivation/tolerance results.

Question 12

[….] are the most prominent suppressors of immune function (in regulating immune response).

[…] are derived from the thymus during t cell development..

[…] are derived following activation of naiive CD4 t cells in presence of TGF-beta. Express […] and inhibit co-stimulation.

Answer 12

Tregs

nTregs (immunosuppressive against self-reactive T cells)

iTregs
CTLA4 (inhibitor of t cell responses)

Question 13

how does CTLA4 inhibit costimulation

Answer 13

CTLA4 binds B7 receptor on APC more avidly than CD28