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Advanced Immunology and Cell Biology > T-cell priming > Flashcards

T-cell priming Flashcards

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1
Q

What could be a reason for individuals showing immune reactivity to SARS-CoV-2 before being infected by the virus itself?

A

Individuals who have been infected with other sorts of common cold coronaviruses (CCC) are more reactive to the coronavirus.

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2
Q

What is the concept of immune cross-reactivity based on?

A

It is based on the concept that there are pre-existing memory T-cells that can react to a new pathogen.
These pre-existing memory cells may have been made when an individual was infected with a different, homologous, pathogen.

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3
Q

Where are naive T-cells activated and by what?

A

CD4+ and CD8+ are activated in the secondary lymphoid organs by dendritic cells.

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4
Q

What is another name for CD80 and 86?

A

B7.1 and B7.2 respectively.

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5
Q

How many cells respond, when a dendritic cell presents an antigen?

A

Roughly 1 in 100 000

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6
Q

What receptors and molecules are involved in which of the 3 steps of T-cell activation?

A

Signal 1: MHC loaded with antigen binds to TCR.
Signal 2: Co-stimulation between CD80/86 (B7.1/B7.2) on the dendritic cell and CD28 on the T-cell
Signal 3: Cytokines released by the dendritic cell determine effector cell subset

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7
Q

Name five examples of T-helper subsets and the cytokines which lead to their induction.

A
  1. Th1 : IL-12 and INF-y
  2. Th2 : IL-4
  3. Th17 : IL-6, TGF-b and IL-23
  4. Tfh : IL-6. IL-21
    5 Treg : TGF-b
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8
Q

What is the function of CD40L and CD40?

A

CD4+ T-helper cells activate CD8+ and B-cells. They do so through CD40L (on the Th cell) and CD40 (on B-cells and CD8+) mediated activation.

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9
Q

What are CD62L and CCR7 characteristics of?

A

Naive T-cells and some memory T-cells

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10
Q

Which molecules are both important for entering the lymph nodes?

A

CCL19 and CCL21

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11
Q

What are the characteristics of Central Memory T-cells?

A
  1. L-selectin (CD62L) positive
  2. CCR7-positive
  3. Circulate the lymphoid organs
  4. Stem-cells-like, can be activated by antigen and cytokines
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12
Q

What are the characteristics of Effector memory T-cells?

A
  1. L-selectin (CD62L) negatice
  2. CCR7-negative
  3. Circulate lymphoid and non-lymphoid tissues
  4. Already differentiated and have high levels of effector molecules
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13
Q

What is the role of Resident Memory T-cells?

A

They are found only in tissues and are responsible for the response to local infections.

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14
Q

What are the CD8 and CD4 receptors on T-cells doing?

A

CD8 and CD4 are both co-receptors of TCR. CD8 is on cytotoxic T-cells and CD4 is on T-helpers.

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15
Q

What cells can present extracellular antigen on their MHC-I?

A

Dendritic cells.

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16
Q

What is cross-presentation important for?

A

It is important for inducting a viral and tumor immune response.

17
Q

How many MHC-I/II variants are out there?

A

3 MHC-I and 3 MHC-II

18
Q

What part of the MHC molecule is the most affected in terms of polymorphism?

A

The peptide groove

19
Q

What is the main difference between different MHC forms?

A

Each MHC can then bind different peptide sets.

20
Q

What techniques can be used to study the proliferation of T-cells?

A
  1. CFSE / CTV dilution
21
Q

What techniques can be used to study the proliferation of T-cells?

A
  1. CFSE / CTV dilution
  2. 3H-thymidine incorporation
  3. Ki67 staining (not used much anymore)
22
Q

What is the concept of CFSE/CTV (cell trace violet) dilution?

A

Cells stained with the dye inherit 50% of the staining intensity. By measuring the stain color intensity, one could measure how many divisions/generations of cells have happened.

23
Q

How can one measure cytokine production in T-cells?

A
  1. ELISA
  2. Elispot
  3. Intracellular cytokine staining
24
Q

Briefly explain how Elispot works.

A

Elispot is a measuring method in which a well is coated with cytokine-specific antibodies. T-cells are then thrown into the well and they release cytokines. The cytokines then form precipitates which are visible as dots.
Quantification of T-cells that produce a specific cytokine is based on the number of dots produced after stimulation.

25
Q

Briefly explain how Intracellular cytokine staining works.

A

Activated T-cells are blocked from releasing cytokines, thus those accumulate in the ER. The cells are then made permeable. Antibodies specific to a specific type of cytokine are used, which bind to cytokines in the lysed ER.
This is used to quantify how many cells produce a specific cytokine, using flow cytometry.

26
Q

How can polymorphisms of the MHC molecules specifically influence an immune reaction?

A

Polymorphisms influence the peptide binding groove of the MHC molecule. As a consequence, those will find a different peptide chain from the virus proteome, which means that those MHC molecules may activate a slightly different immune response pathway.

27
Q

Can you get a CD8+ response without MHC-II?

A

No, because MHC-II activates CD4+ T-helpers, which in turn stimulate CD8+ cells.

28
Q

What technique can be used to measure an antigen-specific T-cell response?

A

MHC/Ag-tetramers

29
Q

What kind of MHC is the MHC-peptide tetramer made of?

A

MHC-I

30
Q

Briefly describe MHC tetramer staining.

A

Four recombinant MHC-I molecules are loaded with a specific peptide and are then bound to streptavidin (carrier molecule). The MHCs then bind to T-cells which express their respective receptors. Amount of cells that react is then counted using flow cytometry.

31
Q

Why is an MHC-I tetramer needed and not a monomer?

A

Monomers may have a low affinity to the TCR and thus antigen-specific T-cells cannot be detected.

32
Q

Does a vaccine or infection lead to the highest immunological memory?

A

A hybrid between infection and vaccination leads to the highest immunological memory.

33
Q

What kind of T-cells correlates with milder COVID-19 cases in patients?

A

CD8+ T-cells that can recognize conserved coronavirus epitopes.
The conserved epitopes may stay the same between all coronaviruses, so CD8+ T-cells can recognize those, even if a patient has never had COVID-19 before.

33
Q

What kind of T-cells correlates with milder COVID-19 cases in patients?

A

CD8+ T-cells that can recognize conserved coronavirus epitopes.
The conserved epitopes may stay the same between all coronaviruses, so CD8+ T-cells can recognize those, even if a patient has never had COVID-19 before.

Advanced Immunology and Cell Biology (8 decks)

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