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11 BMD 430 lecture 11

1.

1. Which statement is not one of the tenets of the clonal selection theory?

A. Each lymphocyte bears a single type of receptor with unique specificity.

B. Binding to antigen activates the lymphocyte.

C. All lymphocytes are eliminated after activation.

D. Self-reactive lymphocytes are deleted during development.

C. All lymphocytes are eliminated after activation.

2.

2. Stromal cells in the bone marrow support B-cell development through:

A. Antibody secretion

B. Physical contact and soluble growth factors

C. Phagocytosis of immature cells

D. Expression of MHC II only

B. Physical contact and soluble growth factors

3.

3. The interaction between SCF on stromal cells and Kit on developing B cells provides:

A. Apoptosis signal

B. Physical contact survival signal

C. Negative selection

D. Antigen presentation

B. Physical contact survival signal

4.

4. Which cytokine is secreted by stromal cells to promote B cell development?

A. IL-2

B. IL-7

C. TNF-α

D. IFN-γ

B. IL-7

5.

5. The first checkpoint in B cell development tests:

A. The light chain rearrangement

B. The heavy chain rearrangement

C. The ability to bind antigen

D. The ability to exit the bone marrow

B. The heavy chain rearrangement

6.

6. The surrogate light chains that test heavy chain structure are:

A. λ5 and VpreB

B. κ and λ

C. β and α

D. Igα and Igβ

A. λ5 and VpreB

7.

7. What happens if a heavy chain rearrangement is non-productive on both chromosomes?

A. The cell retries until successful

B. The cell undergoes apoptosis

C. The cell switches to light chain rearrangement

D. The cell expresses only IgM

B. The cell undergoes apoptosis

8.

8. How many chances (total) does a light chain have to successfully rearrange?

A. 1

B. 2

C. 3

D. 4

D. 4

9.

9. Receptor editing occurs only in:

A. Heavy chains

B. Light chains

C. Both heavy and light chains

D. T cell receptors

B. Light chains

10.

10. Negative selection of B cells ensures:

A. Reactivity to self-antigens

B. Death or inactivation of self-reactive B cells

C. Expression of both IgM and IgD

D. Isotype switching

B. Death or inactivation of self-reactive B cells

11.

11. What happens to a B cell that becomes anergic?

A. It proliferates uncontrollably

B. It becomes functionally unresponsive

C. It dies immediately

D. It becomes a plasma cell

B. It becomes functionally unresponsive

12.

12. Where does T cell development begin and end?

A. Thymus → Spleen

B. Bone marrow → Thymus

C. Thymus → Lymph node

D. Bone marrow → Lymph node

B. Bone marrow → Thymus

13.

13. The Notch receptor directs a progenitor cell to develop into a:

A. B cell

B. Macrophage

C. T cell

D. NK cell

C. T cell

14.

14. Positive selection ensures:

A. Self-reactive T cells survive

B. T cells recognize self-MHC molecules

C. T cells bind antigen with high affinity

D. T cells bind to foreign MHC molecules

B. T cells recognize self-MHC molecules

15.

15. Negative selection primarily occurs in the:

A. Thymic cortex

B. Bone marrow

C. Thymic medulla

D. Lymph node

C. Thymic medulla

16.

16. The AIRE gene helps promote:

A. Cytotoxic T cell activation

B. Expression of tissue-specific antigens in the thymus

C. Antibody class switching

D. B cell proliferation

B. Expression of tissue-specific antigens in the thymus

17.

17. Which best describes “death by neglect”?

A. Strong self-MHC binding

B. No binding to self-MHC

C. Weak binding to self-MHC

D. Excessive cytokine exposure

B. No binding to self-MHC

18.

18. Which fate results from TCR binding with intermediate affinity?

A. Apoptosis

B. Death by neglect

C. Treg formation

D. Survival

D. Survival

19.

19. ___ Programmed cell death

Apoptosis

20.

20. ___ Functional unresponsiveness

Anergy

21.

21. ___ Process of changing variable regions in light chains

Receptor Editing

22.

22. ___ Occurs during development in bone marrow/thymus

Central Tolerance

23.

23. ___ Occurs after immune cells leave the primary organs

Peripheral Tolerance

24.

24. ___ Antigen binding activates a specific lymphocyte

Clonal Selection

25.

25. ___ Provides survival and growth signals in bone marrow

Stromal Cell

26.

26. Define clonal selection theory and explain why it is important in adaptive immunity.

Each lymphocyte has a unique receptor; only those binding antigen are selected. Ensures specificity.

27.

27. Compare and contrast stem cells and stromal cells.

Stem: differentiate into many types; Stromal: provide signals/support

28.

28. Describe the key events of the Pro-B cell and Pre-B cell stages.

Pro-B: heavy chain rearrangement (DJ then VDJ). Pre-B: pre-BCR expression, light chain rearrangement.

29.

29. What is a Pre-B cell receptor, and why is it important?

μ heavy chain + surrogate light chains (VpreB & λ5); tests heavy chain function.

30.

30. Explain what is meant by a productive vs non-productive rearrangement.

Productive = functional gene in-frame; Non-productive = out-of-frame, no signal.

31.

31. Describe the two checkpoints in B cell development.

1st = functional heavy chain; 2nd = functional light chain.

32.

32. What are the consequences of negative selection of B cells in the bone marrow?

Removes or inactivates self-reactive B cells → prevents autoimmunity

33.

33. Why can receptor editing only occur in light chains and not heavy chains?

12/23 rule prevents editing in heavy chains.

34.

34. Compare central vs. peripheral tolerance in terms of location and function.

Central = in bone marrow/thymus, early; Peripheral = after circulation, catches escaped self-reactive cells

35.

35. What is the purpose of Notch signaling in T cell development?

Notch drives progenitors toward T cell lineage.

36.

36. Outline the general stages of T cell development and where each occurs.

HSC commitment (BM) → DN1–DN4 (thymus cortex) → positive (cortex) → negative (medulla).

37.

37. Define positive selection, negative selection, and the “Goldilocks model” of affinity.

Positive: binds self-MHC (just right); Negative: too strong = deletion; Goldilocks = moderate survives.

38.

38. What is AIRE, and why is it crucial for self-tolerance?

AIRE = transcription factor exposing tissue antigens in thymus → deletes self-reactive T cells.