Lymphocyte Development and Central Tolerance (Satti)

Question 1

What is the origin of T-cells?

Answer 1

Start from pluripotent stem cells in the bone marrow

Question 2

Where do pre-T cells migrate to?

Answer 2

Thymus

Question 3

What do immature T-cells lack?

Answer 3

Antigen receptors

Question 4

What process generates receptor diversity in T-cells?

Answer 4

V(D)J recombination

Question 5

What happens to cells with nonfunctional or self-reactive TCRs?

Answer 5

They are eliminated via apoptosis (central tolerance)

Question 6

What is the outcome for surviving T-cells?

Answer 6

They become functional, self-tolerant T-cells

Question 7

Where do mature T-cells circulate after leaving the thymus?

Answer 7

Secondary lymphoid organs (lymph nodes, spleen)

Question 8

What occurs during T-cell activation in secondary organs?

Answer 8

Clonal selection when TCR recognizes foreign antigen

Question 9

What do activated T-cells differentiate into?

Answer 9

• Helper T-cells (cytokine secretion)
• Cytotoxic T-cells (kill infected cells)

Question 10

What is the origin of B-cells?

Answer 10

Start from pluripotent stem cells in the bone marrow

Question 11

Where does B-cell maturation occur in birds?

Answer 11

Bursa of Fabricius

Question 12

What do pre-B cells lack?

Answer 12

Antigen receptors

Question 13

What process generates receptor diversity in B-cells?

Answer 13

V(D)J recombination

Question 14

What happens to self-reactive BCRs?

Answer 14

They are eliminated (central tolerance)

Question 15

What is the outcome for surviving B-cells?

Answer 15

They become mature B-cells

Question 16

Where do mature B-cells circulate after exiting the bone marrow?

Answer 16

Secondary lymphoid organs

Question 17

What occurs during B-cell activation in secondary organs?

Answer 17

Clonal selection when BCR binds antigen

Question 18

What do activated B-cells differentiate into?

Answer 18

• Plasma cells (antibody secretion)
• Memory B-cells

Question 19

Where does T-cell central tolerance occur?

Answer 19

In the thymus (primary lymphoid organ)

Question 20

Developing T-cells (thymocytes) randomly generate ______ through ______ recombination.

Answer 20

Developing T-cells (thymocytes) randomly generate TCRs through V(D)J recombination.

Question 21

What is the process of clonal deletion in T-cell central tolerance?

Answer 21

• Some new TCRs strongly bind self-antigens presented in the thymus.
• If binding is too strong, the cell is instructed to undergo apoptosis

Question 22

What is the outcome of T-cell central tolerance?

Answer 22

• Self-reactive T-cells are removed before they enter circulation.
• Only T-cells with functional, non–self-reactive receptors survive and mature.

Question 23

Where does B-cell central tolerance occur?

Answer 23

In the bone marrow (or bursa in birds, Peyer’s patches in pigs)

Question 24

What happens to self-reactive B-cells during central tolerance?

Answer 24

• They are eliminated by apoptosis.
• Some may also undergo receptor editing (try rearranging light chain genes to create a non-self-reactive BCR)

Question 25

What is V(D)J recombination?

Answer 25

Process by which BCR/TCRs generate diversity through random reorganization of genes that code antigen-binding sites and determines specificity or antibody variable region.

Question 26

What can V(D)J recombination result in?

Answer 26

Non-functional or self-antigen-reactive receptors * Gene-switch multiple times to fix and create functional receptors or eventually deleted

Question 27

For the heavy chain, a Variable (V), Diversity (D), and Joining (J) segment combine through V(D)J recombination. For the light chain, only __ and __ segments rearrange, as light chains lack __ segments.

Answer 27

For the heavy chain, a Variable (V), Diversity (D), and Joining (J) segment combine through V(D)J recombination. For the light chain, only **V** and **J** segments rearrange, as light chains lack **D** segments.

Question 28

Heavy chain generates ________ in ______ regions through V(D)J recombination.

Answer 28

Heavy chain generates **greater diversity** in **variable** regions through V(D)J recombination.

Question 29

Where does V(D)J recombination occur?

Answer 29

Occurs in primary lymphoid organs, determines antibody specificity.

Question 30

Light chain has ________ sequences (not in heavy chain).

Answer 30

Light chain has **enhancer** sequences (not in heavy chain)

Question 31

What does the C region in BCRs produce?

Answer 31

Different immunoglobulin classes (IgM, IgG, IgA, IgE, IgD)

Question 32

Can TCRs undergo class switching?

Answer 32

No

Question 33

Can BCRs undergo class switching?

Answer 33

Yes

Question 34

What is class switching?

Answer 34

* Gene rearrangement that changes constant region * Switching between different immunoglobulin classes

Question 35

1st portion of V(D)J recombinatin occurs in developing lymphocytes in __________; 2nd portion (somatic hypermutation) occurs in _________________ when encountering ________.

Answer 35

1st portion of V(D)J recombinatin occurs in developing lymphocytes in **bone marrow**; 2nd portion (somatic hypermutation) occurs in **lymph nodes, thymus, or spleen** when encountering **antigen**.

Question 36

Somatic mutations can only occur in _______.

Answer 36

B-cell receptors

Question 37

How is antigen receptor diversity generated in B and T cells?

Answer 37

By DNA rearrangements during development: * **Germline diversity**: many inherited V, D, J segments * **Combinatorial diversity**: random V(D)J recombination * **Junctional diversity**: random nucleotides added/deleted at joins * **Chain pairing**: heavy+light (BCR) or α+β (TCR)

Question 38

What is somatic hypermutation?

Answer 38

Point mutations in V region that create a better fitting variable region with antigens

Question 39

What extra mechanism adds diversity in B cells (not T cells)?

Answer 39

Somatic hypermutation (point mutations in V region) + affinity maturation (selection of best binders).

Question 40

What enzyme drives B cell hypermutation?

Answer 40

Activation-induced cytidine deaminase (AID): converts cytosine → uracil → mutations.

Question 41

What is the outcome of clonal selection?

Answer 41

Lymphocytes create antigen-specific responses

Question 42

What happens to cells with BCR/TCR that bind strongly to antigen?

Answer 42

They are activated and replicate into clones

Question 43

What do activated B-clones become?

Answer 43

Plasma cells (secrete antigen-specific Abs) or Memory B-cells

Question 44

What do activated T-clones become?

Answer 44

* T-helper/CD4 (cytokine secretion) * T-cytotoxic/CD8 (kills host cells)