Exam 2: Tolerance and MHC Restriction

Question 1

T/F. The thymus does not have afferent lymphatics or HEVs.

Answer 1

True

Question 2

How do the T cells enter the thymus?

Answer 2

through blood

Question 3

Where are T cells made and what do they lack, expressed little of, or express lots of?

Answer 3

made i bone marrow

• lack TCRs, CD4s, and CD8s
• expressed very little Fas protein
• expresses lots of Bcl-2 (protein that protects against apoptosis)

Question 4

What do T cells mature into in the thymus?

Answer 4

double positive (DP) cells

Question 5

What do DP (double positive) cells contain, express little or, or expressed lots of?

Answer 5

• BOTH CD4 and CD8 co-receptor molecules
• expresses lots of Fas protein
• expresses very little Bcl-2 (can die easier)

Question 6

T/F. DP cells are very resilient to death.

Answer 6

False– they are very vulnerable to death

Question 7

What are the two tests a DP cell must pass to live? give both names

Answer 7

1. MHC Restriction (positive selection)

2. Tolerance to Self (negative selection)

Question 8

Describe the different in expression of molecules by T cells fresh from the bone marrow and those that are mature in the thymus.

Answer 8

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

Question 9

Where does MHC Restriction (positive selection) take place of T cells? What must the maturing T cell do?

Answer 9

takes place in cortex of thymus

must recognize peptides presented on self MHCs

Question 10

Where does the Tolerance to Self (negative selection) or T cells take place? What must the maturing T cells do?

Answer 10

takes place in medulla of thymus

must NOT recognize peptides presented on self MHCs

Question 11

During MHC restriction of maturing T cells, what cell type is involved and what are they asking the T cells?

Answer 11

Cortical epithelial cells ask T cells:

• Do you have receptors that recognize one of the MHC molecules on my surface?
• YES = correct
• NO = dies

Question 12

Describe what the Cortical Epithelial Cells of the thymus are displaying peptides of.

Answer 12

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”)

Question 13

What must all mature T cells recognize in order to “pass” the MHC Restriction test?

Answer 13

must recognize antigen presented my MHC molecules

of don’t–> they are eliminated (apoptosis)

Question 14

What does it mean when a T cell is a Double Positive cell? What about a Single Positive Cell?

Answer 14

DP cell = expresses BOTH CD4 and CD8

SP cell = chooses either CD4 or CD8

Question 15

What are the two cell types that give the Tolerance to Self (Negative Selection) “Test” to the maturing T cells?

Answer 15

1. Thymic Dendritic Cells
2. Medullary Thymic Epithelial Cells

(occurs in medulla of thymus)

Question 16

After Positive Selection (MHC Restriction), when do T cells become?

Answer 16

choose either CD4 or CD8 and are now called Single Positive Cell (SP cell)

Question 17

How do Thymic Dendritic Cells fit into the picture for the Negative Selection test of maturing T cells?

Answer 17

Display self peptides on MHC molecules

• • if recognize = death of T cell
• • if “answer” No = correct answer

Question 18

How are Medullary Thymic Epithelial Cells involved in Negative Selection process of maturing T cells?H

Answer 18

Have 2 features that make them good at testing self tolerance:

1. break MHC peptide expression rules and display endogenous Ag on MHC II (just like cortical cells)
2. Express several thousand tissue-specific proteins (“acts like another tissue”)_

Question 19

What can Medullary Thymic Epithelial Cells do that is unique and is benificia to helping in Negative Selection of maturing T cells?

Answer 19

1. display endogenous Ag on MHC II
2. Express thousands of tissue-specific proteins –> are shared proteins that cell produce –> AIRE transcription factor drives expression of tissue-specific proteins

Question 20

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

Answer 20

True

Question 21

Describe what “Passing the Test” of maturing T cells means.

Answer 21

1. Positive Selection = T cells DO recognize MHC-peptide complexes
2. Negative Selection = T cells do NOT recognize self Ags on MHC

Question 22

What cells are testing the T cells during Positive Selection and Negative Selection?

Answer 22

Positive Selection –> Cortical Thymic Epithelial Cells

Negative Selection –> Thymic Dendritic Cells and Medullary Thymic Epithelial Cells

Question 23

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?

Answer 23

~ 2 weeks long
60 million DP T cells begin each day
2 million will pass
Fail = apoptosis 
3%

Question 24

If self-reactive T cells happen to get through the Positive and Negative Selection, what are the four ways we deal with them?

Answer 24

1. Naive Cell Trafficking
2. nTregs (regulatory T cells, aka tTregs)
3. Peripheral Tolerance (low B7 and MHC expression)
4. AICD (activated-induced cell death)

Question 25

Where do Niave T cells primarily traffic through? Why would this be good for not activating Naive T cells?

Answer 25

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

Question 26

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?

Answer 26

regulatory T cells (nTregs, and type of CD4 T cell (AKA tTregs or thymic regulatory T cells)

Question 27

What is the different between tTregs and pTregs?

Answer 27

tTregs–> control cells react against self (deals with self Ag rxn)

pTregs–> prevent over active immune response (deals with foreign Ags)

Question 28

When it comes to Peripheral Tolerance, what are the “two key” activations that T cells require?

Answer 28

1. enough Ag to cluster receptors

2. Co-stimulatory signals

Question 29

T cells that recognize Ag, but do not get co-stimulation are anergized, where does this often happen?

Answer 29

in peripheral tissue where B7 and MHC expression is low

Question 30

What is AICD? Why does this help us control self reactive T cells?

Answer 30

= 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

Question 31

Where does B cell tolerance occur?

Answer 31

in bone marrow

Question 32

What is it called when B cells that recognize “self” are give a change to change?

Answer 32

“receptor editing”

Question 33

Some B cells that react to self proteins can be released, why is this okay?

Answer 33

• 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)

Question 34

Can B cells undergo somatic hypermutation change and recognize self?

Answer 34

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