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SMP - MIM Part 1 > Lecture 9 - T Cell Immunity > Flashcards

Lecture 9 - T Cell Immunity Flashcards

1
Q

Antigen uptake mechanism?

  1. DCs
  2. Macrophages
  3. B cells
A
  1. Macropinocytosis and phagocytosis
  2. Macropinocytosis and phagocytosis
  3. Antigen-specific receptor (Ig)
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2
Q

Location?

  1. DCs
  2. Macrophages
  3. B cells
A
  1. Ubiquitous throughout body
  2. Lymphoid tissue, connective tissue, and body cavities
  3. Lymphoid tissue and peripheral blood
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3
Q

Effects?

  1. DCs
  2. Macrophages
  3. B cells
A
  1. Activation of naive T cells
  2. Activation of macrophages and effector T cells in secondary lymphoid tissues
  3. Delivery of help to B cells and activation of effector T cells in secondary lymphoid tissues
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4
Q

Do most infections utimately engage both T- and B-cell-mediated adaptive immunity?

A

YUP

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5
Q

What is an immune module? What are the 3 types?

A

Each immune module contains sensor cells, ILCs, effector T cells and antibody isotypes:

  1. Module 1: ILC1, TH1 cells, IgG1 and IgG3, MO
  2. Module 2: ILC2, TH2 cells, IgE, mast cells, eosinophils and basophils
  3. Module 3: ILC3, TH17 cells, opsonizing IgG, neutrophils
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6
Q

Purpose of macropinocytosis by APCs?

A

Take up soluble antigens

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7
Q

Can macrophages express MHC? How?

A

Yes, MHC expression is inducible by bacteria and cytokines

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8
Q

Can B cells express MHC? How?

A

Yes, constitutively and the expression increases on activation

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9
Q

Can the APC deliver co-stimulation?

  1. DCs
  2. Macrophages
  3. B cells
A
  1. Constitutively by mature nonphagocytic lymphoid DCs
  2. Inducible
  3. Inducible
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10
Q

What are the 5 different routes by which DCs can take up, process and present antigens?

A
  1. Receptor-mediated phagocytosis
  2. Macropinocytosis
  3. Viral infection
  4. Cross-presentation after phagocytic or macropinocytic uptake
  5. Transfer from incoming DC to resident DC
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11
Q

DC using receptor-mediated phagocytosis:

  1. Type of pathogen presented?
  2. MHC loaded?
  3. Type of naive T cell activated?
A
  1. Extracellular bacteria
  2. MHC II
  3. CD4 T cells
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12
Q

DC using macro-pinocytosis:

  1. Type of pathogen presented?
  2. MHC loaded?
  3. Type of naive T cell activated?
A
  1. Extracellular bacteria, soluble antigens, virus particles
  2. MHC II
  3. CD4 T cells
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13
Q

DC presenting viral infection:

  1. Type of pathogen presented?
  2. MHC loaded?
  3. Type of naive T cell activated?
A
  1. Viruses
  2. MHC I
  3. CD8 T cells
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14
Q

DC conducting cross-presentation after phagocytic or macropinocytic uptake:

  1. Type of pathogen presented?
  2. MHC loaded?
  3. Type of naive T cell activated?
A
  1. Viruses
  2. MHC I
  3. CD8 T cells
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15
Q

Transfer from incoming DC to resident DC:

  1. Type of pathogen presented?
  2. MHC loaded?
  3. Type of naive T cell activated?
A
  1. Viruses
  2. MHC I
  3. CD8 T cells
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16
Q

What happens if there is a viral infection but the DC cannot get infected by it? Purpose?

A
  1. Cross-presentation after phagocytic or macropinocytic uptake
    OR
  2. Transfer from incoming DC to resident DC

Allows DCs to take up exogenous viruses via the endocytic pathway, and then transfer that virus to the cytosolic pathway where it is broken down into peptides that are loaded onto MHC class I molecules to present to naïve CD8+ T cells

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17
Q

What is autophagy? Purpose for DCs?

A

Cross-presentation mechanism to recycle damaged/used proteins/organelles in the cytosol: endosome formation => fusion with lysosome => recycling by breaking them down => loaded onto MHC II

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18
Q

Role of innate lymphoid cells with regards to APCs?

A

They amplify the ability of the APCs to signal to and activate naïve T cells by producing the appropriate cytokine environment needed to turn on naïve T cells

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19
Q

What determines what subset of T cell a naive CD4+ T cell becomes?

A

Local environment in the secondary lymphoid tissue due to cytokines released by DCs and ILCs

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20
Q

Is the differentiation of CD4+ T cells rigid? Explain.

A

NOPE - they display plasticity in that there is some ability to change phenotypes from one subtype to another

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21
Q

2 activation cytokines for TH1 cells?

A
  1. IL-12

2. IFN-γ

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22
Q

2 roles of TH1 cells?

A
  1. Production of pro-inflammatory cytokines to help macrophages become more efficient phagocytes (better at killing the pathogens they have taken up via the endocytic pathway)
  2. Cell-mediated immunity: help B cells make IgG1 and IgG3 ABs
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23
Q

2 activation cytokines for TH2 cells?

A
  1. IL-2

2. IL-4

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24
Q

2 roles of TH2 cells?

A
  1. Production of anti-inflammatory cytokines and help B cells make IgA in the mucosa-associated lymphoid tissues
  2. Promote allergic response by helping B cells make IgE ABs in secondary lymphoid tissues => arms mast cells and eosinophils to effectively handle parasitic infections
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25
Q

4 activation cytokines for TH17 cells?

A
  1. TGF-β
  2. IL-6
  3. IL-21
  4. IL-23
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26
Q

What cytokine to naive CD4+ T cells express?

A

IL-2

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27
Q

Which T cell subset is responsible for auto-immune diseases?

A

Th17

28
Q

2 activation cytokines for TFH cells?

A
  1. IL-6

2. IL-21

29
Q

2 activation cytokines for Treg cells?

A
  1. TGF-β

2. IL-2

30
Q

CDs of helper T cells?

A
  1. CD45+
  2. CD3+
  3. CD4+
31
Q

Pathogens targeted by CD8+ T cells?

A
  1. Viruses

2. Some intracellular bacteria

32
Q

Pathogens targeted by TH1 T cells?

A
  1. Microbes that persist in macrophages vesicles

2. Extracellular bacteria

33
Q

Pathogens targeted by TH2 T cells?

A

Helminth parasites

34
Q

Pathogens targeted by TH17 T cells?

A
  1. Klebsiella pneumoniae

2. Fungi (e.g. candida)

35
Q

Pathogens targeted by TFH cells?

A

ALL

36
Q

2 immune cells that repair barrier epithelia?

A
  1. γ:δ T cells

2. TH17 T cells

37
Q

3 surface proteins of Treg cells?

A
  1. CD4
  2. CD25
  3. Foxp3
38
Q

How do T cells enter the lymph node?

A

Same mechanism of diapedesis described with DCs on the endothelium

39
Q

2 fates of T cells activated by MHC II?

A
  1. Effector T cell

2. Memory T cell

40
Q

How do naive T cells and DCs bind in a stable manner?

A

Cell adhesion molecules: LFA-1 on T cell - ICAM 1 on DC

41
Q

What is the pseudodimer model of CD4+ T cell activation? Purpose?

A

It proposes that after a TCR has ligated with its MHC II/peptide complex, it recruits another TCR ligated to an MHC II/peptide complex that carries a self-peptide and binds via CD4-MHC => 5-member complex appears to enhance the stability of the interaction => stable enough to initiate activation through the tyrosine kinase Lck => phosphorylating one or both CD3 clusters

42
Q

Mechanism of T cell proliferation once the naive T cell has been activated?

A

Activation of naive T cells in the presence of co-stimulation through CD28 signaling induces:
1. Expression and secretion of IL-2

  1. Modification of IL-2 receptors to high-affinity IL-2 receptors

=> IL-2 binds to the high-affinity IL-2 receptors to promote T-cell growth and cell cycle in an autocrine fashion

43
Q

Do naive T cells express an IL-2 receptor?

A

Yes, but with moderate affinity only

44
Q

Other name for IL-2?

A

T cell growth factor

45
Q

How does the IL-2 receptor of naive T cells increase its affinity upon activation of the T cell?

A

Heterodimer to heterotrimer

46
Q

What is a mechanism to keep the T cell proliferation under control? Clinical relevance?

A

T cell upregulation of CTLA-4 which binds B7.1/2 on APC => high affinity interaction is a
negative signal for the T cell, telling it to shut the proliferative phase of the response

Clinical relevance: researchers have been designing monoclonal antibodies to target CTLA-4 as a way to upregulate the immune response against tumor cells

47
Q

What is the CTLA-4 molecule similar to? How so? Difference?

A

Similar to CD28 in that it also binds B7.1, B7.2 on the APC

Difference: CTLA-4/B7.1, B7.2 interaction is much higher affinity

48
Q

How do cytotoxic T cells kill target cells while sparing neighboring uninfected cells?

A

Activated CD8+ T cells kill any cell for which their TCR is specific ONLY

49
Q

How do cytotoxic T cells and NKCs kill target cells? What is this pathway called?

A
  1. Use perforin to punch holes in the cell membrane (akin to the MAC of the complement cascade)
  2. Once the integrity of the membrane is disrupted, the
    T cell delivers granzyme and granulysin molecules into the cytosol of the target cell, which cause its destruction

= Fas pathway

50
Q

What are granzymes?

A

Serine proteases which activate apoptosis

51
Q

What are granulysins?

A

Has antimicrobial actions and can induce apoptosis

52
Q

What do most cytotoxic T cell responses require? Why?

A

Naïve CD8+ T cells often require co-stimulation from a CD4+ helper T cell that binds the same APC as the naïve CD8+ T cell and provide it with IL-2 for proliferation, as well as additional co-stimulatory signals (e.g. 4-IBBL)

Reason: because CD8+ T cells can inflict a lot of damage, they often require extra co-stimulation to confirm we really want to unleash them

53
Q

What is an example of a macrophage that will need TH1 help to kill a pathogen?

A

Macrophages that have taken up mycobacterium tuberculosis as it has a mechanism to prevent phagosomes from maturing to a point where they can fuse with lysosomes => bacterium can then escape in the cytosol

If macrophage displays a mycobacterium peptide on MHC II, a TH1 can bind it and provide the macrophage with interferon γ, which binds to macrophage receptors => increases its microbicidal capacity and overcomes the inhibitory effects of the mycobacterium on phagosome maturation

54
Q

5 possible sources of IL-4 to differentiate TH2 cells? What to note?

A
  1. ILC2
  2. Eosinophils
  3. Basophils
  4. Mast cells
  5. DCs

Note: origin unclear because DCs do not express IL-4 and the other cells are not found in T-cell areas of secondary lymphoid tissues

55
Q

Cytokines released by Treg cells?

A
  1. TGF-β

2. IL-10

56
Q

Cytokines released by TFH cells?

A
  1. IL-21

2. ICOS

57
Q

Cytokines released by TH17 cells?

A
  1. IL-6

2. IL-17

58
Q

Cytokines released by TH2 cells?

A
  1. IL-4
  2. IL-5
  3. IL-13
59
Q

Cytokines released by TH1 cells?

A
  1. IL-2

2. IFN-γ

60
Q

Transcription factor upregulated in TFH cells?

A

Bcl6

61
Q

Transcription factor upregulated in TH17 cells?

A

RORγT

62
Q

Transcription factor upregulated in TH1 cells?

A

T-bet

63
Q

Transcription factor upregulated in TH2 cells?

A

GATA3

64
Q

What does it mean for the cytokines produced by different T cell subtypes to be cross-inhibitory? Example?

A

They will drive differentiation of the naïve T cell to become one specific subset and will shut down any potential deviation to other pathways

For example: IFN-γ will drive the polarization of TH1 cells, while simultaneously inhibiting the polarization of TH2 cells

65
Q

What causes the DC to secrete the activating cytokines for Treg differentiation?

A

Absence of pathogens

66
Q

Via what 3 receptors do TH1 cells bind macrophages?

A
  1. CD40
  2. IFN-γ
  3. MHC
67
Q

What is cross-presentation after phagocytic or macropinocytic uptake?

A

Exogenous antigens taken into the endocytic pathway are delivered into the cytosol

SMP - MIM Part 1 (14 decks)

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