L3: Immunological Memory Flashcards
Characteristics of the immune system’s ability to trigger an antibody-driven response to an antigen
Pre-existing, inducible, amplifiable
What is important for future development of safe and effective vaccines?
Immunological memory
What is haematopoiesis responsible for?
Development of the major immune cell lineages
Where do all immune cells (except T cells) develop?
Bone marrow
Where do T cells develop?
Thymus
Yellow vs red bone marrow
Yellow bone marrow: storage of fats in adipocytes
Red bone marrow: contains haematopoietic stem cells
Where does antigen-independent differentiation take place?
Bone marrow (pre-existing pool of B cells each expressing their antibody as a receptor on their cell surface)
Where does antigen-dependent differentiation take place?
Peripheral lymphoid tissues (upon exposure to antigen)
Structure of antibody
2 heavy chains and 2 light chains to form a Y-shaped molecule
What domain gives the antibody its specificity for binding antigen?
Variable domain (Fv)
Constant regions in antibodies play a role in:
- Antibody class switching
- Complement activation (CH2 domain)
- Fc receptor binding on APCs
- Serum half-life
Epitope vs paratope
Epitope: the binding site on the antigen for the antibody
Paratope: the binding site on the antibody for the antigen
What are responsible for antigen/epitope recognition?
The CDRs within the variable region
What do the framework regions do?
Provide a scaffold for the CDRs
What is structural convergence?
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.
Example of structural convergence
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
What are the 6 mechanisms for the generation of antibody diversity?
- Multiple germline V/D/J genes
- V-J and V-D-J recombinations
- N-nucleotide addition
- Recombinational inaccuracies
- Somatic hypermutation
- Class switching
How is V-D-J junctional diversity increased?
Nucleotides are randomly deleted and inserted at the junctional joining sites. This increases junctional diversity by increasing the complexity of antibodies.
What enzyme is involved in increasing V-D-J junctional diversity?
TdT = terminal deoxynucleotide transferase
P nucleotides are also removed by DNase, an endonuclease
Why do most B cells never reach circulation?
They fail positive/negative selection
Where do naive B cells migrate to?
Secondary lymphoid organs i.e. lymph nodes and spleen
How is SHM biased?
Mutations tend to occur more often in ‘hotspots’ in the H chain genes
What does the CDRH3 region do?
Adds and deletes nucleotides to the V-D junction on the H chain
Characteristics of naive B cells when they leave the bone marrow?
- They have successfully recombined their antibody genes and produced a functional BCR
- Been selected to ensure they don’t react with self-antigens
- They express both IgM and IgD on their surface
