Adaptive immunity Flashcards
Describe the principles of the adaptive immune response
- slow
- dependent on recognition via initially low affinity receptors via B and T cells
- based on memory
- requires gene rearrangements and clonal expansion
Outline the development of B cells
include cell lineage
- occur in bone marrow
- produced throughout life
- development guided by stromal cells
HPC –> pro B cell –> pre B cell –> immature b cell –> circulating naive b cell –> germinal centre produces plasma and memory B cell
Describe the development of T cells
- maturation in thymus
- production declines at puberty
- in adults thymus has some residual corticomedullary tissue with thymocytes and new t cells generated in extrathymic sites and long lived peripheral t cell pool
- developement is compartmentalised, distinct types of stromal cells
Consider the phases of development
What happens in stage 1?
Where does this occur?
GENERATION OF Ag RECEPTOR
- V(D)J gene rearrangement –> antigen receptor
Occurs in primary (central) lymphoid organs
Consider the phases of development
What happens in stage 2?
Where does this occur?
REFINEMENT OF Ag RECEPTOR REPERTOIRE
- Ag receptor tested for Ag recognition
- Positive selection: Ag receptor that recognises self Ag weakly
- Negative selection: Ag receptor that binds strongly to self Ag –> eliminated by apoptosis
Occurs in primary (central) lymphoid organs
Consider the phases of development
What happens in stage 3?
Where does this occur?
STIMULATION BY FOREIGN Ag
- Clonal selection of lymphocytes
- Generation of effector and memory lymphocytes
Occurs in secondary lymphoid organs
B cell development can be thymus antigen dependent or independent. Describe how thymus antigen dependent development occurs
- Dependent upon Th cells to induce antibody production
- Antigen: proteins
- MOA: T cell/ B cell collaboration, required in response to complex antigens (proteins, lipids) and requires direct contact between T and B cell
- Involves multiple surface receptors on both cells
- Both cells must recognise antigen (can be different epitome) and both require signal 1 (from antigen receptor) and signal 2 (co-stimulation)
What is the two-signal model?
Engagement of antigen receptor (BCR), known as signal 1, is insufficient to activate B cell. It requires a co-stimulatory signal, signal 2
B cell development can be thymus antigen dependent or independent. Briefly outline how thymus antigen independent development occurs
- doesnt need Th cells to induce antibody production
- polysaccharides, lipids
- MOA: Activation of B cell by direct BCR aggregation
State the 7 steps involved in T-cell dependent B cell response
- Antigen binding to BCR (signal 1)
- Antigen in internalised, processed and antigenic peptides displaced on MHC for T cell recognition
- Th recognises antigen-MHC complex via TCR (signal 1)
- CD80/CD86 (on B cell) bind to CD28 on T cell providing signal 2 to T cell
- T cell activation leads to upregulation of CD40L which binds to CD40 providing signal 2 to B cell
- Cytokine production by activated T cell also helps activate B cell
- B cell proliferates and differentiates into AB-secreting B cell (plasma cell)
How does antigen recognition by B cells differ to T cell?
BCR consists of 2 heavy chains and 2 light chains (membrane bound and secreted Ig). TCR consists of only membrane form only (a-b heterodimer)
Signalling complex in B cell membrane = Ig alpha & beta
Signalling compleS in T cell membrane = CD3
B cells can bind intact protein antigen in solution. T cells can only bind antigen derivates on antigen presenting cells
How does the primary and secondary antibody response differ?
PRIMARY
- 5-10 day lag, smaller peak, usually IgM>IgG, lower average affinity, more variable
SECONDARY - 1-3 day lag, larger peak, IgG (some situation where IgA/IgE due to heavy chain class switching), higher average affinity
