Exam 2: Tolerance and MHC Restriction Flashcards
T/F. The thymus does not have afferent lymphatics or HEVs.
True
How do the T cells enter the thymus?
through blood
Where are T cells made and what do they lack, expressed little of, or express lots of?
made i bone marrow
- lack TCRs, CD4s, and CD8s
- expressed very little Fas protein
- expresses lots of Bcl-2 (protein that protects against apoptosis)
What do T cells mature into in the thymus?
double positive (DP) cells
What do DP (double positive) cells contain, express little or, or expressed lots of?
- BOTH CD4 and CD8 co-receptor molecules
- expresses lots of Fas protein
- expresses very little Bcl-2 (can die easier)
T/F. DP cells are very resilient to death.
False– they are very vulnerable to death
What are the two tests a DP cell must pass to live? give both names
- MHC Restriction (positive selection)
2. Tolerance to Self (negative selection)
Describe the different in expression of molecules by T cells fresh from the bone marrow and those that are mature in the thymus.
T Cells fresh from bone marrow:
- lack TCRs, CD4s, CD8s
- Express little Fas protein
- Express lots of Bcl-2
Mature T cells = DP Cells:
- Contain both CD4 and CD8
- Express lots of Fas protein
- Express little Bcl-2
Where does MHC Restriction (positive selection) take place of T cells? What must the maturing T cell do?
takes place in cortex of thymus
must recognize peptides presented on self MHCs
Where does the Tolerance to Self (negative selection) or T cells take place? What must the maturing T cells do?
takes place in medulla of thymus
must NOT recognize peptides presented on self MHCs
During MHC restriction of maturing T cells, what cell type is involved and what are they asking the T cells?
Cortical epithelial cells ask T cells:
- Do you have receptors that recognize one of the MHC molecules on my surface?
- YES = correct
- NO = dies
Describe what the Cortical Epithelial Cells of the thymus are displaying peptides of.
peptides on MHC I –> made w/in cell
peptides on MHC II –> sampled from area
peptides on MHC II –> made w/in cell (yes, breaking the “rules”)
What must all mature T cells recognize in order to “pass” the MHC Restriction test?
must recognize antigen presented my MHC molecules
of don’t–> they are eliminated (apoptosis)
What does it mean when a T cell is a Double Positive cell? What about a Single Positive Cell?
DP cell = expresses BOTH CD4 and CD8
SP cell = chooses either CD4 or CD8
What are the two cell types that give the Tolerance to Self (Negative Selection) “Test” to the maturing T cells?
- Thymic Dendritic Cells
- Medullary Thymic Epithelial Cells
(occurs in medulla of thymus)
After Positive Selection (MHC Restriction), when do T cells become?
choose either CD4 or CD8 and are now called Single Positive Cell (SP cell)
How do Thymic Dendritic Cells fit into the picture for the Negative Selection test of maturing T cells?
Display self peptides on MHC molecules
- if recognize = death of T cell
- if “answer” No = correct answer
How are Medullary Thymic Epithelial Cells involved in Negative Selection process of maturing T cells?H
Have 2 features that make them good at testing self tolerance:
- break MHC peptide expression rules and display endogenous Ag on MHC II (just like cortical cells)
- Express several thousand tissue-specific proteins (“acts like another tissue”)_
What can Medullary Thymic Epithelial Cells do that is unique and is benificia to helping in Negative Selection of maturing T cells?
- display endogenous Ag on MHC II
- Express thousands of tissue-specific proteins –> are shared proteins that cell produce –> AIRE transcription factor drives expression of tissue-specific proteins
T/F. Medullary Thymic Epithelial Cells make sure we create T cells that do NOT recognize out tissue-specific proteins that Thymic Dendritic Cells missed
True
Describe what “Passing the Test” of maturing T cells means.
- Positive Selection = T cells DO recognize MHC-peptide complexes
- Negative Selection = T cells do NOT recognize self Ags on MHC
What cells are testing the T cells during Positive Selection and Negative Selection?
Positive Selection –> Cortical Thymic Epithelial Cells
Negative Selection –> Thymic Dendritic Cells and Medullary Thymic Epithelial Cells
How long does the test take for T cell maturation?
How many Double Positive T cells begin the test each day?
How many pass?
What does failing the test mean?
What percentage of the maturing T cells do we recover?
~ 2 weeks long 60 million DP T cells begin each day 2 million will pass Fail = apoptosis 3%
If self-reactive T cells happen to get through the Positive and Negative Selection, what are the four ways we deal with them?
- Naive Cell Trafficking
- nTregs (regulatory T cells, aka tTregs)
- Peripheral Tolerance (low B7 and MHC expression)
- AICD (activated-induced cell death)
Where do Niave T cells primarily traffic through? Why would this be good for not activating Naive T cells?
through secondary lymphoid tissues–> secondary lymphoid tissues tend to express same Ag set as found in thymus–> therefore Naive T cells are unlikely to see self Ag from extra lymphoid tissues and won’t activate T cells
What type of cell does the thymus produce that will leave and enter secondary lymphoid tissues and when activated they INHIBIT self-reactive T cells?
regulatory T cells (nTregs, and type of CD4 T cell (AKA tTregs or thymic regulatory T cells)
What is the different between tTregs and pTregs?
tTregs–> control cells react against self (deals with self Ag rxn)
pTregs–> prevent over active immune response (deals with foreign Ags)
When it comes to Peripheral Tolerance, what are the “two key” activations that T cells require?
- enough Ag to cluster receptors
2. Co-stimulatory signals
T cells that recognize Ag, but do not get co-stimulation are anergized, where does this often happen?
in peripheral tissue where B7 and MHC expression is low
What is AICD? Why does this help us control self reactive T cells?
= Activation-Induced Cell Death
when a naive T cell escapes deletion in thymus and enter peripheral tissues and there is enough MHC and costimulation for T cell activation
—> since it reacts to self it will get activated OVER and OVER
—> AICD occurs (expresses more Fas protein) and death from chronic re-stimulation happens
Where does B cell tolerance occur?
in bone marrow
What is it called when B cells that recognize “self” are give a change to change?
“receptor editing”
Some B cells that react to self proteins can be released, why is this okay?
- restricted travel from bone marrow to 2 lymphoid organs prevents exposure to “rare” self Ags
AND - B cells that get into tissues may be anergized or deleted b/c no T cell help (T cell must recognize self Ag too….but we don’t want that)
Can B cells undergo somatic hypermutation change and recognize self?
yes
but if a B cell does internalize self proteins and presents it with MHC –> a T cell will not recognize it and there a B cell won’t work as well w/o T cell help
