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IMIN 371 > T cell Differentiation and Function > Flashcards

T cell Differentiation and Function Flashcards

1
Q

What are the different types of T cells a naive CD4+ T cell can differentiate into?

A

Treg cells, Th17 cells, Th2 cells, Th9 cells, Tfh cells, Th1 cells, and Th22 cells

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2
Q

Effector function Th2 Cells

A

These cells combat infections against helminths and activates eosinophils

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3
Q

Polarizing Cytokines

A

Cytokines that naive T cells are exposed to that stimulate the differentiation into a specific T cell type

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4
Q

Polarizing cytokine of Th2 cells

A

IL-4

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5
Q

What is the master transcriptional regulator of Th2 cells?

A

GATA3

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6
Q

What are the effector cytokines released by Th2 cells?

A

IL-4, IL-5, and IL-13

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7
Q

What is the Th2 cells role in disease?

A

Causes allergic reactions

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8
Q

Effector function Th1 Cells

A

Combats intracellular pathogens and activates macrophages (viral infections)

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9
Q

Polarizing cytokine of Th1 cells

A

IL-12, IFN-gamma, and IL-18

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10
Q

What is the master transcriptional regulator of Th1 cells?

A

T-Bet

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11
Q

What are the effector cytokines released by Th1 cells?

A

IFN-gamma, and TNF

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12
Q

What is the Th1 cells role in disease?

A

Causes inflammatory response in infected tissue

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13
Q

Describe the process of how a naive CD4+ T cells differentiates into Th1 cells.

A
  1. The TCR of the naive T cell binds the Ag bound to MHC II (Ag will be from a intracellular pathogen)
  2. The costimulatory signal occurs between the CD28 on the T cell and the CD80/86 on the APC
  3. The APC produces IL-12 (or other Th1 polarizing factors) which is the 3rd and final signal for Th1 differentiation
  4. The IL-12 signal activates the T-Bet transcription factor which starts the differentiation into a Th1 cells
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14
Q

What do Th1 cells do to dendritic cells and how?

A

The activate dendritic cells.

  1. They license DCs to present to naive CD8+ T cells via CD40 on DC and CD40L on TH1 cells
  2. They secrete more chemokines that recruit more inflammatory cells to the site of infection (such as CXCL6 and CXCL3)
  3. They secrete proinflammatory cytokines (such as IFN-gamma) that activate more inflammatory cells
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15
Q

What do Th1 cells do to macrophages and how?

A

They activate macrophages. Th1 ae very important for clearing bacteria that replicate inside macrophages (ex, TB).

The signaling through CD40/CD40L and IFN-gamma promote the fusion of endosomes with lysosomes to increase the killing of bacteria

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16
Q

Describe the process of how a naive CD4+ T cells differentiates into Th2 cells.

A
  1. The TCR of the naive T cell binds the Ag bound to MHC II (Ag will be from a extracellular pathogen; typically a helminth)
  2. The costimulatory signal occurs between the CD28 on the T cell and the CD80/86 on the APC
  3. The APC or other innate cells produces IL-4 which is the 3rd and final signal for Th2 differentiation
  4. The IL-4 signal activates the GATA-3 transcription factor which starts the differentiation into a Th2 cells
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17
Q

What do Th2 cells do to macrophages?

A
  • the increase of IL-13 causes macrophages to increase Ag presentation and co-stimulation
  • there is an increase of scavenger receptors on macrophages for fungal Ag (mannose R and dectin R)
  • there is an increase in chitinases to degrade fungal and insect chitin
  • There is an increase in anti-inflammatory cytokines such as IL-10 and factors that promote “wound healing” such as TGF-beta
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18
Q

How do Th1 and Th2 cells cross-regulate each other?

A

The expression of the 1 master transcriptional regulator blocks the expression of the other (encodes for the production of the specific cytokines for the corresponding response and those cytokines block the interaction of the other transcriptional regulator).

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19
Q

Effector function Treg Cells

A

Functions to suppress the immune response

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20
Q

Polarizing cytokine of Treg cells

A

IL-2 and TGF-beta

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21
Q

What is the master transcriptional regulator of Treg cells?

A

FoxP3

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22
Q

What are the effector cytokines released by Treg cells?

A

IL-10 and TGF-beta

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23
Q

What is the Treg cells role in disease?

A

They inhibit the antitumor response

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24
Q

Effector function Treg Cells

A

They combat extracellular pathogens (bacteria and fungi) in barrier tissues

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25
Q

Polarizing cytokine of Treg cells

A

IL-6, IL-23, and TGF-beta

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26
Q

What is the master transcriptional regulator of Treg cells?

A

RORgammat

27
Q

What are the effector cytokines released by Treg cells?

A

IL-17A, IL-17F, IL-22

28
Q

What is the Treg cells role in disease?

A

They are involved in autoimmunity tissue inflammation

29
Q

Describe how Th17 and peripheral Treg cross-regulate each other.

A
  • TGF-beta is the key polarizing cytokine for both sets of T cells but the IL-6 is the switch allowing for RORgammat to dominate and induce Th17 subset and not the pTreg
30
Q

Why does there need to be a balance between the Th17 and Treg cells?

A

Because Th17 causes an inflammatory state and Treg cells maintain a normal state (can stop an immune response when they do not need to be happening anymore). If the balance is broken it can be very bad for the persons health.

31
Q

What is the function of Treg cells?

A
  • tolerance
  • they express high levels of inhibitory CTLA-4 molecules
  • they remove surrounding IL-2
  • they secrete anti-inflammatory cytokines (IL-10 and TGF-beta)
32
Q

What do inhibitory CTLA-4 molecules do?

A
  • they decrease the expression of CD80/86 expression (prevents co-stimulatory signal)
  • they increase indoleamine dioxygenase (IDO)
  • decreases IL-6/TNF-alpha production
33
Q

What does indoleamine dioxygenase (IDO) do?

A

Collects and processes tryptophan which is important for APC function (no Tryp=no APC function)

34
Q

Describe the linked suppression of Treg cells?

A
  • a bystander suppression effect can occur from Treg cells
  • A Treg cell that interacts with an APC can suppress T cells that engage distinct Ag-MHC II complexes on the same APC surface (so if there are other T cells bound to the same APC as a Treg cell the Treg cell can suppress the action of those other T cells)
  • important function in the mucosal system
35
Q

Effector function Th9 Cells

A

They combat extracellular pathogens including worms

36
Q

Polarizing cytokine of Th9 cells

A

IL-4 + TGF-beta

37
Q

What is the master transcriptional regulator of Th9 cells?

A

PU.1

38
Q

What are the effector cytokines released by Th9 cells?

A

IL-9

39
Q

What is the Th9 cells role in disease?

A

Autoimmunity

40
Q

Effector function Th22 Cells

A

Combats extracellular pathogens, particularly in the skin

41
Q

Polarizing cytokine of Th22 cells

A

IL-6 and TNF-alpha

42
Q

What is the master transcriptional regulator of Th22 cells?

A

AHR

43
Q

What are the effector cytokines released by Th22 cells?

A

IL-22

44
Q

What is the Th22 cells role in disease?

A

Inflammatory skin disease

45
Q

Effector function Tfh Cells

A

Regulates the affinity maturation of germinal center B cells

46
Q

Polarizing cytokine of Tfh cells

A

IL-6 and IL-21

47
Q

What is the master transcriptional regulator of Tfh cells?

A

Bcl-6

48
Q

What are the effector cytokines released by Tfh cells?

A

IL-4 and IL-21

49
Q

What does the fh mean in Tfh?

A

follicular helper cell

50
Q

Where do all of the polarizing cytokines come from?

A

The APC being exposed to particular cytokines or from cross presentation

51
Q

Mycobacterium leprae

A
  • Bacteria that causes leprosy
  • the bacteria replicate inside the macrophage vacuoles and there are 2 observable forms: tuberculoid leprosy and lepromatous leprosy
52
Q

tuberculoid leprosy

A
  • mild form (patient usually survives)
  • granulomas form and damage is limited to skin and nerves
53
Q

lepromatous leprosy

A
  • fatal form if untreated
  • extensive replication of bacteria
54
Q

What drives the different phenotypes of the leprosy disease?

A

Th1 and Th2 responses are associated with different pathologies and outcomes in leprosy (this is an example of pathological consequences of the wrong T helper response)

55
Q

What cytokines do CTL’s make? What do they do?

A

IFN-gamma and TNF-alpha

These cytokines are antiviral, they induce MHC-I and they activate macrophages.

56
Q

What are the 3 ways that CTLs induce cell death?

A
  • Cytotoxins (perforins and granzymes)
  • TNF-alpha
  • and FASL-FAS interactions
57
Q

Explain how CTLs induce cell death.

A
  1. The CTL recodnizes the Ag bound to MHC-1
  2. The target cell and T cell form a conjugate and the ganules enter the target cell
  3. CTL cytoplasmic rearrangment occurs (everything moves twoard congunction site)
  4. The CTL granules exocytose from the CTL cell twoard the target cells
  5. Apoptosis of the target cell occurs and the TCL is recycled and the process can restart with a new target cell
58
Q

What is needed for a CTL to induce cell death?

A

CTL adherance to a target cell is needed for the signal to go through

59
Q

Perforin

A

polymerizes to form a pore in the traget cell membrane

60
Q

Granzymes

A

Serine proteases, which activate apoptosis once in the cytoplasm of the target cell

61
Q

Cathepsin B

A

membrane bound protease that gets to the cell surface during degranulation and it degrades perforin near the CTL membrane (protects itself from perforins)

62
Q

How does TNF-alpha induce cell death?

A

They trimerize and trigger the TRADD domain which interacts with death domains

causes a slow kill

63
Q

How does FAS activation induce cell death?

A

The Fas ligand on CTL interacts with Fas on the target cell. This activates the downstream killing signals through a series of caspases and induces apoptosis of the target cell

IMIN 371 (12 decks)

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