L3: Immunological Memory

Question 1

Characteristics of the immune system’s ability to trigger an antibody-driven response to an antigen

Answer 1

Pre-existing, inducible, amplifiable

Question 2

What is important for future development of safe and effective vaccines?

Answer 2

Immunological memory

Question 3

What is haematopoiesis responsible for?

Answer 3

Development of the major immune cell lineages

Question 4

Where do all immune cells (except T cells) develop?

Answer 4

Bone marrow

Question 5

Where do T cells develop?

Answer 5

Thymus

Question 6

Yellow vs red bone marrow

Answer 6

Yellow bone marrow: storage of fats in adipocytes
Red bone marrow: contains haematopoietic stem cells

Question 7

Where does antigen-independent differentiation take place?

Answer 7

Bone marrow (pre-existing pool of B cells each expressing their antibody as a receptor on their cell surface)

Question 8

Where does antigen-dependent differentiation take place?

Answer 8

Peripheral lymphoid tissues (upon exposure to antigen)

Question 9

Structure of antibody

Answer 9

2 heavy chains and 2 light chains to form a Y-shaped molecule

Question 10

What domain gives the antibody its specificity for binding antigen?

Answer 10

Variable domain (Fv)

Question 11

Constant regions in antibodies play a role in:

Answer 11

1. Antibody class switching
2. Complement activation (CH2 domain)
3. Fc receptor binding on APCs
4. Serum half-life

Question 12

Epitope vs paratope

Answer 12

Epitope: the binding site on the antigen for the antibody
Paratope: the binding site on the antibody for the antigen

Question 13

What are responsible for antigen/epitope recognition?

Answer 13

The CDRs within the variable region

Question 14

What do the framework regions do?

Answer 14

Provide a scaffold for the CDRs

Question 15

What is structural convergence?

Answer 15

Paratope structures that recognise the same substantially overlapping epitopes can arise either by using the same or closely similar CDRH3 sequences, or by using different VH, D and JV sequences that produce the same epitope binding specificity. Net result is that they have evolved/been selected because of their antigen-binding specificity.

Question 16

Example of structural convergence

Answer 16

Convergent classes of Abs have been seen in different individuals to Influenza A. 2 different Abs, NC10 and NC41, have significantly different aa sequences but recognise ~80% of the same epitope on the surface of Influenza neuraminidase protein. NC10 CDRH3 has 15 residues while NC41 has 13

Question 17

What are the 6 mechanisms for the generation of antibody diversity?

Answer 17

1. Multiple germline V/D/J genes
2. V-J and V-D-J recombinations
3. N-nucleotide addition
4. Recombinational inaccuracies
5. Somatic hypermutation
6. Class switching

Question 18

How is V-D-J junctional diversity increased?

Answer 18

Nucleotides are randomly deleted and inserted at the junctional joining sites. This increases junctional diversity by increasing the complexity of antibodies.

Question 19

What enzyme is involved in increasing V-D-J junctional diversity?

Answer 19

TdT = terminal deoxynucleotide transferase
P nucleotides are also removed by DNase, an endonuclease

Question 20

Why do most B cells never reach circulation?

Answer 20

They fail positive/negative selection

Question 21

Where do naive B cells migrate to?

Answer 21

Secondary lymphoid organs i.e. lymph nodes and spleen

Question 22

How is SHM biased?

Answer 22

Mutations tend to occur more often in ‘hotspots’ in the H chain genes

Question 23

What does the CDRH3 region do?

Answer 23

Adds and deletes nucleotides to the V-D junction on the H chain

Question 24

Characteristics of naive B cells when they leave the bone marrow?

Answer 24

1. They have successfully recombined their antibody genes and produced a functional BCR
2. Been selected to ensure they don’t react with self-antigens
3. They express both IgM and IgD on their surface