Flashcards in Self, Non-self Discrimination Immune System Deck (13):
where is central tolerance acquired for B cells?
where is peripheral tolerance acquired?
peripheral tissues and secondary lymphoid organs (spleen, lymph nodes)
what are the four mechanisms used to induce tolerance?
1. delete (eliminate problem(
2. anergize (switch off problem)
3. ignore (ignore the problem)
4. regulate (contain the problem)
how is b cell tolerance exerted centrally? peripherally?
in terms of efficiency, how does it compare to t cell tolerance?
-ignorance, anergy, death
-lack of costimulation by T-cells
B cell tolerance less efficient than t cell tolerance.
2 signals for mature B cells to respond and survive?
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.
what happens when people lack cd40L for B cell stimulation?
cant generate an appropriate immune response. tend see hyper IgM levels.
t cell development occurs in the [...]. at this stage of early development immature t cells carry both [...] and [...] receptors.
Cd4+ and Cd8+ co-receptors (double positive)
following expression of a TCP, double positive thymocytes next undergo two types of selection processes....
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
t cell selection is dependant on receptor affinity for ?
self pMHC (sweet spot is between engaging too well and insufficient level of engagement).
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?
AIRE transcription factor
autoimmunity. potentially multiple autoimmune diseases.
Just as naiive B cells require stimulation from CD40L and surface Ag-Ig interaction, naiive T cells require two signals for activation and proliferation....
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.
[....] 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.
nTregs (immunosuppressive against self-reactive T cells)
CTLA4 (inhibitor of t cell responses)