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Flashcards in T cells Deck (51)
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1
Q

Name the 2 effector T cell classes and what they do:

A
  • CD4 T cells: help other cells (B cells) to respond to extracellular sources of infx.
  • CD8 T cells: kill cells that are infected w virus or other intracellular pathogens (CYTOTOXIC).
2
Q

What interaction determines whether a T cell and B cell of the same Ag specificity will result in B cell activation (via CD40 expression + cytokines)?

A

Cognate interaction.

3
Q

T cells activate infected macrophages to kill intravesicular bacteria/pathogens. What 2 signals are required for this?

A
  • IFN-gamma (produced by TH1)

- CD40 ligand on T cell must bind CD40 receptor on macrophage

4
Q

What to classes of T cell receptors (TCR) are there?

A
  • a:B (alpha: beta)–> CD4 and CD8, common circulating T cell
  • y:d (gamma: delta): funx not understood
5
Q

Where does TCR rearrangement and selection occur?

A

Thymus. (precursor T cells travel here from the BM)

6
Q

Epitopes are presented to TCR in the context of what?

A

An MHC (self) molecule.

This is a specialized Ag-presenting glycoprotein.

7
Q

What does MHC restriction mean?

A

TCRs can only bing to a particular peptide bound to a particular MHC molecule.

8
Q

What are the two classes of MHC molecules and where are they found?

A
  • MHC class I: HLA A,B,C; found on most NUCLEATED cells

- MHC class II: HLA DP, DQ, DR; found only on APCs.

9
Q

What MHC do CD8 and CD4 T cells recognize?

A

CD8: MHC I (intracellular infx ex. viruses)

CD4: MHC II (extracellular infx ex. bacteria)

10
Q

How are do antigens get processed and presented by MHC I and MHC II?

A

intracellular antigen–> proteosome–> ER–> peptide binds MHCI–> presented on cell surface (to CD8 cells)

extracellular antigen–> endocytosed in vesicle–> phagolysozome–> peptide binds MHC II–> presented on cell surface ( to CD4 cells)

11
Q

Where are each of the following found within the thymus:

cortical epithelial cell
dendritic cell
thymocyte
macrophage
medullary epithelial cell
Hassall's corpuscle
A

cortical epithelial cell (thymic origin): cortex

thymocyte (BM origin): throughout the thymus as it develops

medullary epithelial cell (thymic origin): cortico-medullary jnx/medullar

dendritic cell (BM origin): medulla

macrophage (BM origin): medullar

Hassall’s corpuscle: medullar

12
Q

Where does gene rearrangement of T cells (thymocytes) occur?

A

cortex of thymus.

13
Q

What is:

Positive selection

Negative selection

A
  • positive selection: selecting for T cells that are restricted by ‘self’ MHC
  • negative selection: eliminating T cells that recognize Ags of self tissue (autoreactive)
14
Q

Where does positive selection take place?

A

cortex of the thymus (cortical epithelial cells present MHC+peptide to TCR)

15
Q

During positive selection, what happens to the co-receptor that is not involved in the epithelial APC-TCR interaction?

A

The co-receptor (either CD8 or CD4) not involved in the interaction ceases being expressed.

16
Q

Self-restrcited CD4 or CD8 cells are tested for their reactivity to self-peptide in what process?

A

negative selection

17
Q

What cells present self-peptide to CD4/CD8 cells during negative selection?

A

dendritic cells and macrophages

18
Q

What TF extends negative selection to proteins that are specific to one or a few cell types (self)?

A

AIRE: autoimmune regulator

ex. transcription of insulin which is usually made only by beta cells in the pancreas

19
Q

Where is AIRE active?

A

AIRE is active in a sub-population of epithelial cells in the thymic medulla.

20
Q

Where does central T cell tolerance happen?

A

thymic medulla

21
Q

Where are naive T lymphocytes activated by their specific Ag?

A

secondary lymphoid tissue

22
Q

What chemokines do CCR7 receptors expressed by T cells bind to? Where are these secreted?

A

CCL21
CCL19

secreted in the lymph node cortex.

23
Q

What happens when T cells interact with their specific Ag in the lymph node?

A

They complete differentiation and proliferate (become effector cells).

24
Q

What ‘professional’ APCs are required to provide the necessary ‘co-stimulation’ to activate T cells?

A

dendritic cells
macrophages
B cells

25
Q

What ligand and receptor form the costimulation signal (signal 2)?

A
CD80 ligand (APC)
CD28 receptor (T cell)
26
Q

How do T cells become ‘anergic’ (unable to be activated)?

A

When there only a specific signal (MHC-Ag + TCR) with no co-stimulation signal occurring.

27
Q

the NFAT transcription factor requires what other complex of TF’s to transcribe IL-1? What upstream interaction allows for this?

A

API complex works with NFAT to induce IL-2 transcription

CD28-CD80 interaction (co-stimulation) must take place.

28
Q

What cytokine do activated T cells produce high-affinity receptors for? What does this cytokine drive?

A

IL-2

IL-2 drives proliferation and differentiation of T cells

29
Q

What T cell type needs a stronger signal to be activated? What cell type aids with this?

A

CD8 (CTL) - because they can cause damage to host cells (all cell expressing MHC I)

CD4 cells sometimes help to express additional IL-2 in order to activate CD8 cells.

30
Q

What effector molecules fo activated T cells release?

A

cytokines

cytotoxins

31
Q

Do ACTIVATED T cells require co-stimulation in addition to MHC-Ag in order to respond?

A

No. Only naive T cells require co-stimulation.

32
Q

What types of CD4 T cells are there and what do they do?

A

TH1, TH2, TFH, TH17: activate and help other cell types carry out immune defense. Key for eradicating pathogens.

iTreg: maintain self-tolerance in the periphery and modulate the immune response to infx

33
Q

How do CD8 cells (CTL) kill infected cells?

A
  • Lytic granules

- FasL-Fas interaction

34
Q

List the following for TH1 effector CD4 cells:

  • cytokines inducing diff’ion
  • defining TF
  • characteristic cytokine
  • function
A
  • IL-12, IFN-gamma
  • T-bet
  • IL-12, IFN-gamma
  • activate macrophages
35
Q

List the following for TFH effector CD4 cells:

  • cytokines inducing diff’ion
  • defining TF
  • characteristic cytokine
  • function
A
  • IL-16, TGF-B, IL-23
  • BcI6
  • IL-21, IL-4
  • Activate B cells, maturation of Ab response (germinal centre activity)
36
Q

List the following for TH2 effector CD4 cells:

  • cytokines inducing diff’ion
  • defining TF
  • characteristic cytokine
  • function
A
  • IL-4
  • GATA3
  • IL-4, IL-5
  • Activate cellular and Ab response to parasites
37
Q

List the following for TH17 effector CD4 cells:

  • cytokines inducing diff’ion
  • defining TF
  • characteristic cytokine
  • function
A
  • IL-6, IL-21
  • TOTgT
  • IL-17, IL-6
  • Enhance neutrophil response
38
Q

List the following for Treg effector CD4 cells:

  • cytokines inducing diff’ion
  • defining TF
  • characteristic cytokine
  • function
A
  • TGF-beta
  • FOxP3
  • TGF-beta, IL-10
  • Suppress other effector T cells
39
Q

What do TH1 cells do?

A
  • macrophage activation (cell mediated immunity)

* IFN-gamma (know this)

40
Q

What two signals do macrophages require in order to become activated and kill intravasicular (in addition to being bound to the TCR via MHC-Ag)?

A
  • IFN-gamma

- CD40 ligand (TC) + CD40 receptor on macrophage

41
Q

What do TH2 cells do? What are the key cytokines involved?

A
  • help B cells mount Ab response against parasite pathogens

- IL-4, IL-5

42
Q

What do TFH cells do?

A

these helper T cells cooperate with naive B cells to initiate Ab response to infx. The interaction bw the two results in CD40L expression on the TFH and IL secretion (stimulates B cell proliferation and Ab secretion).

43
Q

What do TH17 cells do?

A

defend against pathogens not covered by TH1 and TH2.

important in autoimmune disease

secrete IL-17

44
Q

What cytotoxins to CTL release?

A
  • perforin: make pores in target PM
  • granulysin: ‘’
  • granzymes- cleave cell proteins–> triggers apoptosis
45
Q

What does the FasL (CTL) - Fas (target cell) interaction result in?

A

apoptosis of the target cell

46
Q

What T cell type is responsible for 1. cell mediated immunity 2. humoral immunity ?

A
  1. TH1

2. TH2

47
Q

What is polarization of the immune response? What disease polarisation cause differing clinical presentations in?

A

When cytokines in the environment cause bias towards TH1 or TH2 response.

Leprosy (mycobacterium leprae)

48
Q

Describe a TH1 (cell-mediated) bias response to leprosy

A
  • infected macrophages can suppress bacterial growth
  • slow progression
  • damage to skin and peripheral nerves
49
Q

TH2 (humoral) biased response to leprosy is:

A
  • bacteria inaccessible to Abs inside macrophages
  • bacteria grows unchecked
  • severe tissue destruction–> death
50
Q

What TF doe Tregs express?

A

Foxp3 (suppressive funx)

51
Q

What are the two types of Tregs?

A
  • nTreg: natural Tregs, made in the thymus

- iTreg: inducible Treg, arise from peripheral naive conventional T cells