Lecture 13 - Immunological memory Flashcards

1
Q

Primary vs secondary to infections: what is the time taken roughly for the adaptive immune system to respond?

A

~7-10 days
~3 days

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2
Q

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?

A

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

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3
Q

CD27: what is it, where is it found, and what medical potential is there for it?

A

Cluster of differentiation 27 - costimulatory molecule

Found in memory B cells

Cancer immunotherapy - checkpoint inhibitor (ER)

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4
Q

Initial response vs secondary response: what are the differences in frequency of antigen-specific B cells, isotype of antibody produced, and affinity of antibody?

A

Primary vs Secondary:
* 1:10⁴-1:10⁵ vs 1:10²-1:10³ (higher in secondary)
* IgM>IgG vs IgA, IgG
* Low vs high

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5
Q

Memory B cells: why do they trigger quicker responses than normal B cells?

A
  • 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

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6
Q

Plasma cells: how long do they live and where do they exist?

A

Two types:
* Short-lived - red pulp of spleen/medullary chords of lymph nodes
* Long-lived - resides in the bone marrow and just produces antibodies

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7
Q

Memory cell differentiation: transcription factors involved

A

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

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8
Q

What is the difference between long-lived plasma cells and memory cells?

A

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

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9
Q

BLIMP-1

A

Causes plasma cell differentiation

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10
Q

BCL-6

A

Causes memory cell differentiation

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11
Q

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?

A

~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

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12
Q

B and T cell differences: class switching, affinity maturation, and identification

A
  • 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
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13
Q

Memory T-cell formation

A

Long-lived memory cell differentiation:
* IL-7 and IL-15 directly for survival
* Interactions with self-antigen to maintain proliferation

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14
Q

IL-7

A

Required for progression into a memory T-cell

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15
Q

IL-13

A

Required for progression into a memory T-cell

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16
Q

Memory t-cells: what are the types and what are their differing surface markers?

A

Central memory t-cells - hard to distinguish, use different CCR7
Effector memory t-cells - CCR3/5/45RO
Tissue-resident memory t-cells - CCR3/5/45RO

Crossover may occur between central/effector memory t-cells

17
Q

IL7-α: what is it, what can it be a marker for, and how does it exist in t-cells?

A

IL-7 receptor α

T-cells that progress to memory T-cells

Expressed in naive t-cells but downregulated in most activated cells - activated cells with it may progress to memory t-cells

18
Q

Central memory t-cells: what is their surface marker, where are they mostly located, what does their activation result in, and how fast does it activate in comparison to effector memory t-cells?

A

CCR7

Peripheral lymphoid organs

  • Quick increase in CD40L
  • Quickly relocate to areas where viral infection first enters the lymph nodes

Take longer to generate but lasts longer

19
Q

Effector memory t-cells: what is their surface marker, where are they mostly located, what does their activation result in, and how fast does it activate in comparison to central memory t-cells?

A

CCR3/5/45RO, β1 and β2 integrins

Peripheral tissues - don’t express CC7 so don’t home to lymph nodes but the above markers cause them to move into peripheral tissues but they can re-circulate through blood/lymph systems

  • Chemokines produced quickly after antigen interaction

Short life span, low proliferation

20
Q

Tissue-resident memory t-cells: what is their surface marker, where are they mostly located, what does their activation result in, and how fast does it activate in comparison to central memory t-cells?

A

CCR3/5/45RO, β1 and β2 integrins

Stuck in tissues - dedicated mechanisms that cause retention in tissues:
* Downregulation of molecules that promote movement out of tissues - S1PR1, etc
* Upregulation of molecules that promote retention in tissues - ie CD69, CD103, TGF-β, etc

Chemokines produced quickly after antigen interaction

Short life span, low proliferation

21
Q

CD8+ memory t-cell generation: what does it require and what are the mechanisms behind the process?

A

Requires CD4+ t-cells

Not completely understood but theorised to involve CD40L expression on CD4+ t-cells which results in CD4+ IL-2 production which supports proliferation into memory CD8+ t-cells

22
Q

Immunological memory: does it last forever?

A

Potentially decades? Not sure how long exactly