Restraining the Immune System/Tolerance Flashcards
Under normal conditions, what immune fighters deals with commensal bacteria which occasionally enter tissues from intestines?
Macrophages and IgA antibodies
What other CD4+ T cell helps turn immune response off? What cytokines do they produce that restrain immune system?
Inducible regulatory T cell (iTreg)
Produce IL-10 and TGF-beta
IL-10 binds to T cells and blocks co-stim signals
TGF-beta encourages naive T cells in Peyer’s patches to become iTregs
Under normal conditions, what types of cells produce TGF-beta?
Intestinal epithelial cells
What cytokine do dendritic cells produce with a pathogenic fungal invasion? What does it stimulate?
IL-6: encourages Th cells to become Th17 cells
What other T cell receptor can B7 proteins bind to that represses activation of T cell by antagonizing CD28 activation signal within the T cell?
CTLA-4
What are the general lifespans of the following cells? Neutrophils NKCs DC's in lymph node Plasma B cells Antibodies
Neutrophils - few days NKCs - half-life of a week DC's - about a week Plasma B cells - 5 days Antibodies - longest half life (IgG) - 3 weeks
What cytokine do NKC’s produce to keep macrophages activated?
IFN-gamma
What process handles elimination of obsolete T cells?
Activation-induced cell death (AICD) - CTL’s use Fas/FasL mechanism to induce apoptosis
Can virgin T cells be killed by CTL’s through the FasL/Fas mechanism?
NO! Only activated T cells can be killed
Where does T cell central tolerance induction (tolerance of self) take place?
Thymus
Where in the thymus do T cells proliferate?
Cortex
What type of selection involves testing T cells for MHC restriction?
What cells in the thymus perform this testing?
Positive selection - if TCRs do not recognize a self MHC molecule + self peptide, the T cell goes through apoptosis
Cortical thymic epithelial cells
What type of selection involves testing T cells for tolerance induction (tolerance of self)?
What cells in the thymus perform this testing? What MHC class do they use for presentation?
Negative selection - T cells that react to self antigens are killed
- Thymic dendritic cells derived from bone marrow (presentation of shared proteins) - on MHC I
- Medullary thymic epithelial cells (presentation of tissue-specific self antigens) - on MHC II
Approximately how long does the entire T cell testing process take?
2 weeks
What subset of thymic CD4+ T cells search for self-reactive T cells that have slipped through the testing process? What molecule do they express?
nTregs (natural regulatory T cells)
Express Foxp3
