Exam 2 - Chapter 9, Tolerance induction and MHC restriction

does the thymus have HEV or afferent lymphatics

no

how do t cells enter the thymus

through blood

t/f

t cells in the thymus express CD4, CD8, TCR

false - prevents activation

t cells that travel to the bone marrow express a lot of what protein? what is the role of this protein?

Bcl-2, protect against apoptosis

what do t cells mature into in the thymus

double positive cells (DP)

what do DP cells express

CD4 and CD8, TCRs, Fas protein, little Bcl-2

what two tests must DP cells pass in order to live

MHC restriction

tolerance to self

aka of mhc restriction

positive selection

what is the role of the MHC restriction test

teach t cells to only read MHC

where does positive selection take place

in cortex of thymus

aka of tolerance to self

negative selection

what is the role of the tolerance to self test

t cells read MHC, see if they activate against self-peptide

if they do= death

if they don't = live and go to secondary lymph organs

where does negative selection take place

medulla of thymus

what cells examine the t cells to see if they can read MHC (positive selection)

cortical thymic epithelial cells

what happens if the t cells do not recognize the MHC molecules on cortical epithelial cells

they die

which MHC receptors are on cortical epithelial cells? what do they present?

MHC I and II

self-peptides (cross presentation)

how is it determined whether a T cell will have a CD4 or CD8

whichever MHC it binds to

MHC II= CD4

MHC I = CD8

what classifies a single positive cell (SP)

when t cell chooses CD4 or CD8

what two cells give the tolerance to self test

thymic dendritic cells and medullary thymic epithelial cells (mTEC)

what do thymic dendritic cells display

current self peptide

what do medullary thymic epithelial cells express

tissue specific antigens from different regions of the body

what MHC molecule is used to present self proteins on a medullary thymic epithelial cell

MHC II (cross presentation)

if a t cell undergoing negative selection has a high affinity for binding the self peptide, what happens to it? What if it has a low affinity?

apoptosis

may differentiate into nTreg/tTreg cells

what is the transcription factor specific to mTEC cells that causes random synthesis of self-peptides in the thymus to allow thymic cells to display peptides from other body locations

AIRE

why do females have a higher chance of developing autoimmune disease

AIRE expression is suppressed by estrogens

60 million DP t cells begin a test each day, how many will pass? Why would we waste energy on this?

2 million

prevent autoimmunity

T cells with high affinity receptors for self antigens are disposed of during what process

central tolerance induction testing

some t cells with low affinity receptors for self antigens may leave the thymus, the naive t cells circulate through secondary lymph organs but are not allowed into the tissues because of what

lack of adhesion molecules

what gene is expressed to turn a CD4 cell into a regulatory t cell

Foxp3

what allows nTregs to enter secondary lymphoid organs from the thymus

adhesion molecules

how do nTregs suppress activation of potentially self-reactive t cells

downregulating B7 on APCs= anergy

upregulating CTLA-4 on nTregs and CTLs

what cytokine restrains foxp3 and leads to a proinflammatory effect

il-23

what two things do t cells require for activation

TCR clustering

co-stimulatory signals

t/f

ordinary cells such as heart, kidney, or liver cells generally do not express many MHC molecules or B7 so a t cells that recognizes one of these cells is likely to be anergized due to the lack of co-stimulation

true

if a t cell escapes deletion in the thymus, enters peripheral tissue, and has enough MHC and co-stimulation for activation, it will get activated over and over due to abundant antigen. _____ occurs which adds more and more fas protein expression. This increases sensitivity to ligation and ultimately ends in ____

AICD (activation induced cell death), apoptosis

failure of positive and negative selection results in

apoptosis

failure of peripheral tolerance tests such as tolerance by ignorance, tolerance by induction in secondary lymphoid organs, and missing signals

anergized t cells

where does b cell tolerance take place

bone marrow

what is the process called where b cells that recognize self are given a chance to change by rearranging light chain genes

receptor editing