Exam 2: Dr. Pinchuk Development of T Lymphocytes

Question 1

What do T cells derive from?

Answer 1

Bone marrow stem cells

Question 2

Look at figure of T cell lineage

Answer 2

Look at figure of T cell lineage

Question 3

Where are TCR genes rearranged?

Answer 3

Thymus (antigen-independent)

Question 4

What are the 2 lineages of T cells?

Answer 4

The majority are α:β and the minority are γ:δ

Question 5

What do T cells undergo?

Answer 5

Positive and negative selection (both are α:β only)

Question 6

What do B cells derive from?

Answer 6

Bone marrow stem cells

Question 7

Where do BCR genes rearrange?

Answer 7

Bone marrow (antigen-independent)

Question 8

What do B cells undergo?

Answer 8

Somatic hypermutation (antigen-dependent)

Question 9

Describe the thymus

Answer 9

Primary lymphoid organ
T cell development only
Blood is the only route to enter and leave

Question 10

What are the T cells that leave the thymus like?

Answer 10

Naive

Question 11

When is the thymus most active?

Answer 11

When you are very young

Question 12

What is the thymus fully developed?

Answer 12

At birth

Question 13

What happens to the thymus with increasing age?

Answer 13

Atrophies with thymocytes replaced by fat (involution)

Question 14

How long does it take for involution of thymus to be complete?

Answer 14

30 years

Question 15

Do involution or thymectomy compromise T cell immunity in adults?

Answer 15

No

Question 16

What is DiGeorge’s syndrome?

Answer 16

Genetic disease where the thymus fails to develop

Question 17

What are the 2 major signals for T cell lineage commitment?

Answer 17

IL-7 and Notch-1

Question 18

Look at T cell lineage and T cell selection in the thymus figures

Answer 18

Look at T cell lineage and T cell selection in the thymus figures

Question 19

What is positive selection?

Answer 19

Selection of T cells that can recognize peptides presented by a self-MHC molecules
Small population of T cells is signaled to mature further, leaving the vast majority go double-poisitve cells to die by apoptosis
Control expression of the CD4 or CD8 co-receptor

Question 20

What is negative selection?

Answer 20

Deletion of T cells whose antigen receptors bind too strongly to the complexes of self-peptides and self-MHC molecules presented

Question 21

What can negative selection not eliminate?

Answer 21

T cells whose receptors are specific for self-peptides that are present only in tissues other than the thymus

Question 22

What does autoimmune regulatory (AIRE) transcription factor cause?

Answer 22

Several hundred of other tissue specific genes to be transcribed by a subpopulation of the thymus epithelial cells

Question 23

What does AIRE gene mutation cause?

Answer 23

Autoimmune polyglandular syndrom type I or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

Question 24

Because of the AIRE gene, what do APCs in the thymus do?

Answer 24

Express and present many peptides derived from nonthymic tissues

Question 25

What is the major mechanism of immunological tolerance in the thymus?

Answer 25

Negative selection

Question 26

What are mechanisms that contribute to immunological central self-tolerance?

Answer 26

Negative selection in the bone marrow and thymus

Expresson of tissue-specific proteins in the thymus

Question 27

What are mechanisms that contribute to immunological peripheral self-tolerance?

Answer 27

No lymphocyte access to some tissue
Suppression of autoimmune response by regulatory T cells
Induction of anergy in auto-reactive B and T cells

Question 28

What are mechanisms of malignant transformations and generation of lymphomas?

Answer 28

High division rate of maturing lymphocytes

Activity of DNA recombination mechanisms responsible for generating antigen receptor diversity

Question 29

What is the immunological analysis of XLSCID in basset hounds?

Answer 29

Roles of IL-2 in T cell proliferation in the thymus and proliferation and differentiation in the secondary lymphoid organs
Roles of IL-4 in differentiation of B cells and Th2 cells
Roles of IL-7 in the development of lymphoid progenitor cells in the bone marrow