Lecture 13 - Immunological memory Flashcards
Primary vs secondary to infections: what is the time taken roughly for the adaptive immune system to respond?
~7-10 days
~3 days
Memory B cells: what causes their formation, where are they generated, where are they typically found, do they have any specific cell surface markers, what antibodies do they most frequently express, what process have they already undergone, how long do they live, and how are their numbers maintained?
Mechanism not fully understood, activation of B cells causes differentiation into memory cells as well as proliferation
Generated in germinal centres
Secondary lymphoid organs and circulation
CD27
High affinity class switching Abs - IgA, IgE, IgG
Already undergone a round of clonal selection and somatic hypermutation - better at generating a strong immune response than most underdeveloped naive t-cells
Very long
Potentially proliferation may be due to cytokines made by memory cells or other immune cells
CD27: what is it, where is it found, and what medical potential is there for it?
Cluster of differentiation 27 - costimulatory molecule
Found in memory B cells
Cancer immunotherapy - checkpoint inhibitor (ER)
Initial response vs secondary response: what are the differences in frequency of antigen-specific B cells, isotype of antibody produced, and affinity of antibody?
Primary vs Secondary:
* 1:10⁴-1:10⁵ vs 1:10²-1:10³ (higher in secondary)
* IgM>IgG vs IgA, IgG
* Low vs high
Memory B cells: why do they trigger quicker responses than normal B cells?
- High surface immunoglobulin (BCR) expression
- High affinity surface BCR
- High MHC II expression
- High co-stimulatory molecule expression
These mean they have an increased ability to interact with Th cells and so can respond at lower antigen doses and also have already undergone class switching and affinity maturation
Plasma cells: how long do they live and where do they exist?
Two types:
* Short-lived - red pulp of spleen/medullary chords of lymph nodes
* Long-lived - resides in the bone marrow and just produces antibodies
Memory cell differentiation: transcription factors involved
Plasma cell - BLIMP-1
Memory cell - BCL-6
Short-lived plasma cells may migrate to the bone marrow where they become long-lived plasma cells
What is the difference between long-lived plasma cells and memory cells?
Memory cells - move through the body in secondary lymph nodes and through the circulation and react strongly to its antigens and mount a quicker and stronger immune response against it
LLPCs - live in the bone marrow and constitutively produce antibodies to cause high levels of Abs in the blood
BLIMP-1
Causes plasma cell differentiation
BCL-6
Causes memory cell differentiation
Memory t-cells: how many are produced after an immune response roughly, what do they need for their survival, what are their differences with naive and effector cells, and what surface molecules do they each express?
~1:10²-1:10³ of naive t-cell pool (1/100-1000)
IL-7 and IL-15 for survival as well as self-MHC antigen to continue proliferation
Hard to distinguish, often requires the use of multiple markers to differentiate:
* Naive - ie CCR7/CD62L/CD45RA
* Effector - CD69/Granzyme B/FasL
* Memory - Bcl-2/CD45RA/CD44/IFN-γ
Blurred lines between central and effector t-cells
B and T cell differences: class switching, affinity maturation, and identification
- No class switch in t-cells
- No affinity maturation in t-cells
- T-cells are harder to identify due to lacking the prior two features
Memory T-cell formation
Long-lived memory cell differentiation:
* IL-7 and IL-15 directly for survival
* Interactions with self-antigen to maintain proliferation
IL-7
Required for progression into a memory T-cell
IL-13
Required for progression into a memory T-cell