Lecture 28: Immune Memory Flashcards
What is the basis of vaccination (and the reason why vaccines work)?
immunological memory
How do naive and memory cells differ?
differences in frequency (10^4 - 10^5 in the naive repertoire and 10^2 - 10^3 in the memory repertoire)
differences in their function / phenotype
Which antibodies do memory B cells produce?
IgG and IgA
What are the fate decisions of B cells?
low affinity IgM secretion
isotype switch, low affinity IgG
IgG secretion, high affinity
memory B cell
What are memory B cells generated in response to?
T-dependent antigens
generated during germinal centre reaction
What is the role of long lived plasma cells?
direct protection
antibody production is antigen independent
Where do long lived plasma cells migrate to?
the bone-marrow
Where do memory B cells migrate to?
the spleen / LN
What is the role of memory B cells?
required for immune protection when serum antibody not present at high enough concentration
Why are memory B cells better than naive B cells?
present in higher numbers than naive B cells
respond to reactivation faster
have undergone affinity maturation -> produce higher quality antibody
How do almost all clinically effective vaccines act?
via antibody-mediated immunity
How do pathogens such as HIV, influenza and TB escape humoral immunity?
by the rapid variation of antigens and / or intracellular localisation (T cell-mediated immunity required for control)
What are the characteristics of memory T cells?
increased precursor frequency (1000x) compared to naive cells
different phenotype
rapid effector function
long-lived
What do naive T cells require for survival?
need self-MHC molecules and IL-7
What do memory T cells require for survival?
do not need MHC expression
need IL-15 for survival (+IL-7)
What are the different types of memory T cells?
effector memory T cells, central memory T cells and resident memory T cells
What are the different models by which memory T cells are generated?
separate precursor model, asymmetric fate model, decreasing potential model and signal strength model
What does T-bet influence?
the formation of short-lived effector cells (90%)
What does eomes influence?
the formation of memory precursor cells (10%)
What do long-lived memory cells express?
IL-7R+ KLRG1-
What do memory T cells depend on?
IL-15
What are CD4 T cells required for?
generation of CD8 T cell memory
Why are CD4 T cells required for CD8 T cell memory?
involved in dendritic cell licencing / activation -> co-stimulation, cytokines
provision of IL-2 signals
Why is CD4+ T cell memory more complex?
because of the diversity of effector cells formed
numbers decline faster than CD8+ T cells post infection
What is the localisation of central memory T cells?
blood and lymphoid tissues e.g. lymph nodes, spleen, bone marrow
What are the functional properties of central memory T cells?
increased proliferative potential, increased IL-2, increased recirculation and decreased effector function
Where are effector memory T cells localised?
blood and nonlymphoid tissues e.g. gut, liver, skin, lungs
What are the functional properties of effector memory T cells?
decreased proliferative potential, decreased IL-2, increased recirculation and increased effector function
Which T cells are lost over time?
effector memory T cells
What is the localisation of tissue-resident memory T cells?
mainly tissues: gut, skin, lung, glands, brain, thymus, lymph nodes
high frequency at sites of previous infection
What are the functional properties of tissue-resident memory T cells?
decreased IL-2, no recirculation and increased effector function
What is the evidence of tissue-resident memory T cells being non-recirculating cells?
tissue-transplantation and cell depletion
How were tissue-resident memory T cells missed?
studies often limited to human blood
previously thought memory T cells in the tissues and blood were the same
What does location of memory T cell dictate?
rapidity of memory T cell protection
What do high numbers of T resident memory cells correlate with?
subclinical herpes virus reactivation
patients that control HIV infection
What do T resident memory cells provide?
immunity against re-infection
are present at sites of previous infection
What do patients with more T resident memory cells have?
better outcomes against cancer
force cancer into a state of dormancy
