Lecture 24 - Adaptive Immunity

Question 1

What is the antibody structure nomenclature

Answer 1

The hinge region allows antibodies to be flexible so that the antibody binding sites can vary in distance from one another. This also makes the hinge region susceptible to proteolysis by proteases such as papain. When IgG is treated with papain get 3 antibody fragments 2 Fab fragments and an Fc fragment.

Light chain, heavy chain. Constant/variable domains. Fab and Fc fragments.
Fab= Fragment antigen binding
Fc= Fragment crystallisable

Question 2

What is the life of a B-cell

Answer 2

Before encountering an antigen, a mature B-cell expresses antibody in a membrane bound form

When a foreign antigen binds to this immunoglobulin, the B-cell is stimulated to proliferate and gives rise to plasma cells and memory cells. (Note: this usually involves T-cell help)

Question 3

Describe the phases of repertoire generation

Answer 3

Phase 1 - Generation of diverse and clonal expressed B-cell receptors in the bone marrow (Repertoire Assembly)

Phase 2 - Alteration, elimination or inactivation of B-cell receptors that bind to components of the human body (negative selection)

Phase 3 - Promotion of a fraction of immature B cells to become mature B cells in the secondary lymphoid tissues (positive selection)

Phase 4 - Recirculation of mature B cells between lymph blood and secondary lymphoid tissues (searching for infection)

Phase 5 - Activation and clonal expansion of B cells by pathogen-derived antigens in secondary lymphoid tissues (finding infection)

Phase 6 - Differentiation to antibody-secreting plasma cells and memory B cells in secondary lymphoid tissue (attacking infection)

Question 4

What are V and C regions?

Answer 4

V (variable) region → binds antigen
C (constant) region → mediates effector function

Question 5

What are CDRs

Answer 5

Complementarity Determining Regions — hypervariable loops in V regions that directly contact antigen.

Question 6

Which CDR is most variable and why?

Answer 6

CDR3 — formed at the V(D)J junction, includes junctional diversity.

Question 7

What is membrane-bound antibody called

Answer 7

B-cell receptor

Question 8

What does a mature naïve B cell express before antigen encounter?

Answer 8

Membrane-bound IgM and IgD with identical antigen specificity.

Question 9

What happens after antigen binds the BCR?

Answer 9

B cell activation → proliferation → differentiation into:
Plasma cells (antibody secretion)
Memory B cells
(Usually requires T cell help)

Question 10

Why is antibody diversity described as “virtually limitless”?

Answer 10

Multiple genetic mechanisms create enormous variability.

Question 11

What is the germline configuration?

Answer 11

Immunoglobulin genes in unrearranged form (non-B cells).

Question 12

How are functional Ig genes created?

Answer 12

By somatic gene rearrangement of gene segments.

Question 13

What gene segments form the heavy chain?

Answer 13

V + D + J segments.

Question 14

What gene segments form the light chain?

Answer 14

V + J segments (no D segment).

Question 15

What enzymes initiate V(D)J recombination?

Answer 15

RAG1 and RAG2 proteins.

Question 16

What guides RAG proteins to correct sites?

Answer 16

Recombination signal sequences (RSS).

Question 17

Do all B cells rearrange the same Ig genes identically?

Answer 17

No — each B cell rearranges independently, creating diversity.

Question 18

How much diversity arises from simple V(D)J combination?

Answer 18

~2 million possible combinations (large but not unlimited).

Question 19

What increases diversity beyond combinatorial joining?

Answer 19

Junctional flexibility (especially in heavy chain).

Question 20

What is junctional diversity?

Answer 20

Random nucleotide additions/deletions at V(D)J joining sites.

Question 21

Which enzyme adds random nucleotides?

Answer 21

TdT (Terminal deoxynucleotidyl transferase).

Question 22

When is TdT highly expressed?

Answer 22

During heavy chain rearrangement in early B cell development.

Question 23

What region of the antibody does the V(D)J junction encode?

Answer 23

CDR3

Question 24

What is a potential issue with adding random N-nucleotides?

Answer 24

Non-functional rearrangements
Frameshifts
Risk of self-reactivity

Question 25

What is the difference between DNA rearrangement and RNA splicing?

Answer 25

DNA rearrangement: Permanent genomic change (V(D)J recombination) RNA splicing: Post-transcriptional processing of mRNA

Question 26

List the main sources of antibody diversity.

Answer 26

Multiple V, D, J segments Random segment recombination Heavy + light chain pairing Junctional diversity (TdT activity)