Tolerance Induction Flashcards Preview

Term 3: Immunology/Pathology > Tolerance Induction > Flashcards

Flashcards in Tolerance Induction Deck (15):

When do T cells begin to express TCR, CD4, and CD8 molecules?

-Must enter thymus and Migrate to cortex of thymus

-TCR alpha and beta chain rearrangement

-express CD3 TCR complex

-Finally express the good stuff


What puts the T cell in a vulnerable condition to be tested for self and MHC restriction?

-once T cell reaches thymic cortex and starts proliferating, it expresses lots of Fas on its surface, and little Bcl-2

-very easy to send into apoptosis


How does positive selection of T cells work?

-Testing for MHC restriction

-Tested by epithelial cells in thymic cortex

-If TCRs do not recognize any of the self MHC molecules (not antigens!), the T cell dies


How does testing of T Cells for tolerance of self work?

-T cells that recognize self MHC plus peptide proceed from thymic cortex to medulla

-tested for tolerance of self (negative selection)

-Tested by thymic dendritic cell displaying self peptides on MHC

-T cells that react to self antigens are killed


Why do thymic dendritic cells have a short lifespan?

-present only current self antigen

-if foreign antigens reach thymus (infection) then dentritic cells could falsely present them as self antigens

-short lifetime protects against this possibility


What two cell types perform negative selection of T cells in the thymus? Which MHC do they each use?

-Thymic dendritic cells (primarily MHC I)

-Medullary Thymic Epithelial cells (Primarily MHC II)


What do nTreg Cells do?

-work in secondary lymphoid organs

-express Foxp3

-suppress the activation of potentially self-reactive T cells that slipped through the cracks in the thymus


So nTreg cells keep self-reactive T cells from being activated in the secondary lymphoid organs, but what if that self-reactive T cell slips into random tissues of the body?

-still needs dual stimulation, usually provided by dendritic cells

-ordinary tissue cells do not expresss high levels of MHC or co-stimulatory molecules

-When a T cell recognizes its cognate antigen, but does not receive required costimulation, it is "anergized," and dies by apoptosis


Ok, Ok, so what if the self-reactive T cells manage to slip into the tissues, and find a high enough density of its cognate to activate? What then?

-there is another layer of tolerance induction to save us

-activation-induced cell death


Enough about T cells, are B cells tolerized too?

Yes, in the bone marrow


How are B cells tolerized?

-in bone marrow

-tested to see if they recognize self antigens

-if they do, they are given a second chance at gene rearrangement

=Receptor Editing


After somatic hypermutation, what if the B cells have mutated their receptors to recognize self antigens?

-does not happen very often

-B cells in germinal centers are fragile and die by apoptosis unless they receive rescue signals

-also need costimulation from T cells, and it is very unlikely for a B cell to bump into a T cell that recognizes the same self antigen


Why is it unlikely that a self-recognizing B cell will find a self antigen on a follicular dendritic cell?

-FDC's only display antigens that have been opsonized


What do Thymic dendritic cells do?

-Display self peptides in the thymus for presentation to maturing T cells

-Present only current self antigen

-T cell that react to self antigens are killed


What is the difference between nTregs and iTregs?

-nTregs provide protection against T cells which have the potential to react against self antigens and cause autoimmunity

-iTregs are tasked with restraining the immune system to keep it from overreacting to the foreign antigens of invaders