4. Adaptive Immunity 1 Flashcards
Lifespan on naive B cells
5 days, mature B cells have a much more longer lifespan
Positive selection of antigen receptors
identifies cells that can bind antigen (in the
case of T-cells, MHC-bound peptide) and signal through their receptor
-this signal promotes their survival
Negative Selection of antigen receptors
Binding of self-antigen to the B-cell receptor or T-cell
receptor, which results in deletion of the cell by apoptosis
T and B cells with high affinity for self antigen are destroyed
Types of B cell responses
1) T cell dependent
- Usually proteins
- make up more of the B cell antigens
2) T cell independent
- Polysaccharides, lipids, bacteria
How do T cell dependent antigens activate B cells?
2 signal model
- Engagement of antigen receptor (BCR, “signal 1”)
- Co-stimulatory signal (“signal 2”).
How do T-independent antigens activate B-cells ?
By direct BCR (B cell receptor) aggregation
T-cell dependent B-cell response
- Antigen binding to BCR provides “Signal 1” to B-cell.
- Antigen is internalised, processed, antigenic peptides are displayed on MHC for T-cell recognition.
- TH (helper T-cell) recognizes antigen-MHC complex via the T-cell antigen receptor (TCR): provides “Signal 1” to T-cell.
- CD80/CD86 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 bind to CD40 providing “Signal 2” to B-cell.
- Cytokine production by activated T-cell also help to activate B-cell.
- B-cell proliferates and differentiates into antibody secreting B cell (plasma cell).
Primary Antibody Response
Lag Time- 5-10 days
Peak Response
-Smaller than secondary
Antibody Isotope
-IgM>IgG
Antibody Affinity
-Lower average affinity, more variable
Secondary antibody response
Lag Time
1-3 days
Peak Response
Larger than primary
Antibody Isotype
Relative increase in IgG (and IgA pr IgE)
Antibody affinity
- Affinity maturation causes higher average affinity compared to primary response
Antigen recognition by B-cells vs T-cells
Both form antigen receptors by V(D)J recombination
Antigen binding
B cells- bind intact protein antigen in solution through specific binding
T-cells bind peptides displayed on APC
How are B cells recognised immunophenotypically?
CD19 and CD20
How are T cells recognised immunophenotypically?
CD3, CD4 or CD8
BCR structure
2 light and 2 heavy chains, secreted and membrane bound
TCR structure
alpha-beta heterodimer, only membrane bound
Describe the T cell independent B cell response
Simple, repetitive antigens (often carbohydrates)
Mostly IgM
Modest affinity
No memory
B cells activated by direct BCR crosslinking
B cells can also be activated via Toll-like receptors (TLRs)
Somatic hypermutation
Rapid single base mutations that occur in the variable region
Changes affinity of antibody
Antibody class switching
B cells only
Antibody class defined by heavy chain isotype
Occurs in constant region so variable region stays the same
Variable region
HC and LC
Constant region of antibody
HC only
What is the name of the enzyme that cuts the DNA in antibody class switching?
Cytidine deaminase