9. Immune memory Flashcards
Structure of the lecture
- Importance of the immune memory
- B-cell memory
- T-cell memory
- Comparing B- and T-cell memory
Define the immune memory
1.1
The immunological memory is a state that is gained after the primary immune response. It involves faster responses to previously experienced diseases. It is characterised by changes in repertoire, cellular state and activation requirements.
Why is understanding the immune memory so important?
1.2
Creating more effective vaccines that provide longer-lasting, stronger responses
Example: Understanding long-lasting, generational measles immmunity in the Faroe islands helped us to create better measles vaccines and strategies
Why is immune memory important at the cellular- and population- level?
1.3
Important at the population level for understanding changing receptor frequency, and how diseases spread through the population.
Important at the cellular level for understanding gene expression, migration, activation and signalling.
What are the two modes of B-memory cell activation?
2.1
T-dependent. T-independent.
Compare T-dependent and T-independent B-memory cell activation
2.2
T-dependent: High affinity IgG, clonal expansion, antibody class switching, HIGH memory
T-independent: Low affinity IgG, cross-linked receptors with repetitive epitopes, LOW/NO memory
How do CD4+ T-cells help B-memory cell activation?
2.3
CD4+ T-cells aid in class switching and affinity maturation to allow for antibody precision to be maintained over time.
How do B-memory cells change over time?
2.4
Affinity altering, which can occur due to repeated exposure/vaccinated. This can be seen in increasing class-switched immunoglobulin, and increased affinity from somatic hypermutation.
This is dependent on the activity of CD4+ T-cells within the GC to maintain specificity
How are T-cells activated?
3.1
Naive CD4+ and CD8+ T-cells migrate through the lymph nodes, and are stimulated by pAP dendritic cells at the immunological synpase.
Activation occurs via the 3 signal model. MHC binds to the TCR. Then, stimulation occurs by CD80 and CD86 binding to C28 on the naive cell, and then the release of cytokines causes the T-cell differentiation
CD4+ T-cells are activated by MHC Class II, and produce Th cells, Tfh, nTreg and iTreg
CD8+ T-cells are activated by MHC Class I, and produce cytotoxic mediators and inflammatory cytokines
How are T-cell pools constrained and regulated?
3.2
They are regulated at the three main levels.
Naive level: Fixed pool size, each TCR at low frequency
Activated level: Temporarily flexible pool size, diverse set of functions
Memory level: Intermediate frequency of receptors, easy re-activation and re-circulation
What is the key trade-off in regulation of the T-cell repertoire?
3.3
Specificity vs., repertoire. Broad specificity against many antigens may reduce the risk of immune escape, but having high levels of specificity allows better destruction of individual pathogens.
Many clones vs., having the best clones
How can we measure specificity and repertoire?
3.4
Specificity: Peptide based cellular assays, MHC tetramers, flow cytometry
Repertoire: Flow cytometry, immunoscopy, sequence-based approaches
How do CD4+ T-cells display flexibility in their memory?
3.5
The memory pool has a range of committment levels
Three main levels of committment are pre-committed, partially committed and totally committed. Allows a biased, but flexible response in a mosaic form.
How is T-cell memory development modulated?
3.6
Three main modes:
- Linear (Cells split neatly down the middle)
- Bifurcated (Assymetrical)
- Self-renewing (Effector/Central T-memory refreshes)
3 main comparisons between B- and T-cell memory
4
- B-cells are constantly being ‘updated’ to improve antigen specificity. However, T-cells have a fixed receptor that is not modified after initial formation
- CD4+ T-cells aid the specificity of B-cells
- B-cells prioritise specificity over time, whereas T-cells have a trade off between specificity/repertoire
