L4 - Adaptive immunity 1 Flashcards
Comparison of B-cell and T-cell development
- Both develop in specialised microenvironments
- bone marrow (B cells)
- Thymus (T cells)
Both have diverse repertoires of Ag receptors via gene rearrangements
B-cell vs T-cell production
B cell - production throughout life in BM
T cells - decrease in thymus at puberty
Adults:
- Thymus has soem residual corticomedullary tissue w/thymocytes
- New T cells also generated in ‘extrathymic’ sites
- Long lived peripheral T-cell pool
What is B and T cell development guided by
Both development guided by stromal cells
T cells: development is compartmentalised. Distinct types of stromal cells
B cells: stromal cells in the bone marrow
Both involve cell death via apoptosis
1st phase of B-cell development
- Generation of Ag receptor
- V(D)J gene rearrangement –> antigen receptor
2nd phase of B-cell development
Refinement of Ag receptor repertoire
- Ag receptor tested for Ag recognition
- Positive selection - for Ag receptor that recognises ‘self’ Ag weakly
- Negative selection - for Ag receptor binds strongly to self Ag’s, cells eliminated via apoptosis
3rd phase of B-cell development
- Clonal selection of lymphocytes
- Generation of effector and memory lymphocytes
Phases that occur in central and peripheral organs
1st and 2nd phases occur in central lymphoid organs
3rd phase occurs in peripheral lymphoid organs
Types of B-cell antigens
Thymus dependent antigens - dependent upon helper T cells to induce antibody production. Proteins
Thymus independent antigens - Does not need helper T cells to induce antibody production. Polysaccharides, lipids.
2 signal model
Engagement of antigen receptor (BCR signal 1) is not sufficient to activate B cell.
Also need co-stimulatory signal (signal 2)
Features of T-cell independent responses
- Simple, repetitive antigens (often carbs)
- Mostly IgM
- Modest affinity
- No memory
- B cells activated by direct BCR crosslinking
- B cells can also be activated via toll-like receptors (TLRs)
How do T-independent antigens activate B cells
- By direct BCR aggregation
Features of T-cell/B-cell collaboration
- Required for antibody response to complex antigens - proteins, lipids
- Requires direct, physical B-T interaction
- Involves multiple cell surface receptors on T and B cells
- Both B and T cell must recognise antigen (but not necessarily the same epitope)
- Both B and T cells need signal 1 (through antigen receptor) and signal 2 (co-stimulation)
T-cell dependent B-cell response
Sequence of events:
- Antigen binding to bCR provides ‘signal 1’ to B cell
- Antigen is internalised, processed and antigenic peptides are displayed on MHC for T cell recognition
- Th (helper T cell) recognises antigen-MHC complex via the T cell antigen receptor (TCR): provides ‘signal 1’ to T cell
- B7 on B cell binding to CD28 on T cell provides ‘signal 2’ to T cell
- T cell activation leads to up-regulation of CD40L which binds to CD40 providing ‘signal 2’ to B cell
- Cytokine production aby activated T cell also help to activate B cell
- B cell proliferates and differentiates into antibody secreting B cell (plasma cell)
How do B-cells and T-cells form their antigen receptors
- Both form their antigen receptors by V(D)J recombination
What do B-cell receptors consist of
- 2 HC and 2 LC (membrane and secreted Ig)
