Hudig: T and B cell Development

Question 1

What are the two primary lymphoid organs?

Answer 1

bone marrow

thymus

Question 2

Where are B cells made?

Answer 2

in the bone marrow

Question 3

Where are many (but not all) self-reactive B cells eliminated?

Answer 3

in the bone marrow

**if they undergo VDJ recombination of the heavy and light chain and are STILL self-reactive, they will die

Question 4

Where are T cell precursors made? Where do they migrate to?

Answer 4

in the bone marrow; migrate to the thymus

Question 5

In the thymus, what happens to pre-T cells?

Answer 5

they divide and become T cells
those that bind to MHC:peptide weakly are selected positively, while those that bind to MHC:peptide TOO well are eliminated

Question 6

Where do NK lymphocytes develop?

Answer 6

in the bone marrow as well

Question 7

So, what cells originate from pluripotent hematopoietic stem cells in the bone marrow?

Answer 7

B cells
T cells
NK cells

**this process is continuous throughout life

Question 8

What happens to anti-self reacting B cells in the bone marrow? What is this referred to as?

Answer 8

they die; central tolerance

Question 9

What is negative selection?

Answer 9

If a T cell reacts TOO STRONGLY to self-MHCs, it will die

Question 10

What is positive selection?

Answer 10

if a T cell reacts WEAKLY with self-MHCs, it will live

Question 11

Do preT stem cells have CD3, CD4 or CD8?

Answer 11

no, not yet

Question 12

What do preT stem cells express in the thymus in order to divide?

Answer 12

CD25, an IL-2 high affinity receptor

**need IL-2 to proliferate

Question 13

Explain what happens to a pre-T cell as it begins along the pathway to maturity.

Answer 13

pre-T cell comes from the bone marrow to the thymus (double negative at this point); they express CD25 once in the thymus which allows them to bind IL-2 and divide; the T cell will first express CD3 and then both CD4 & CD8 (double positive); they then undergo VDJ recombination of their TCRs; finally, they undergo positive or negative selection depending on their TCRs self-binding to MHC peptides

Question 14

Mutations/defects in what proteins can result in SCID?

Answer 14

defects in RAG-1 and RAG-2 proteins (initaite V(D)J recombination) and TdT (fills in splicing gaps) will not allow you to properly make B cells and T cells and will lead to SCID

Question 15

What occurs first, positive or negative selection?

Answer 15

positive selection first - selects those T cells that bind weakly to self MHC; then, negative selection for those T cells that bind too well to self

Question 16

Why does positive selection select for TCRs that will bind to self MHCs?

Answer 16

T cells need to be able to see MHC molecules so that later, foreign peptides will not have to provide ALL of the binding strength to the TCR

**dual recognition

Question 17

What happens to cells with TCRs that fail to bind to self-MHCs?

Answer 17

they die!

Question 18

Why does negative selection select AGAINST TCRs that will bind too well to MHCs alone?

Answer 18

so that later, foreign peptides are able to add binding strength to the TCRs - dual recognition

**avoids self-reactive T cells

Question 19

This induces expression of organ-specific proteins in the thymus to support deletion of “self”-reacting T cells

Answer 19

AIRE gene

Question 20

Deletion of anti-self T cells in the thymus

Answer 20

central tolerance

Question 21

Where is AIRE found? What do cells with AIRE make in their cytoplasm? If T cells bind to the peptides of this product that are presented on MHC class I molecules, what happens to them?

Answer 21

in the thymic medullary epithelial cells; proinsulin; if T cells bind to MHC class I molecules with proinsulin peptide expressed, they will die because they are “anti-self”

Question 22

When is the thymus of maximal size? What happens to it after it has reached max size?

Answer 22

age 11-15; it begins to atrophy but does persist for life

Question 23

What is central tolerance? Where does central tolerance occur?

Answer 23

the killing off of anti-self T and B cells; in the primary lymhoid organs

Question 24

Where does peripheral tolerance occur?

Answer 24

in the circulation

Question 25

What is peripheral tolerance? How can anti-self T and B cells “escape” peripheral tolerance?

Answer 25

this occurs when anti-self T and B cells see antigens WITHOUT signal 2 - they may die on site or become anergic; these cells can survive if they are un-stimulated; can circulate because they have low reactivity with self and low affinity so they go incognito