03/06c T Cells Flashcards

1
Q

What four events are required for T cell priming?

A

1) Antigen capture by dendritic cells
2) Activation of dendritic cells
3) Co-localization of dendritic cells and naive T cells at lymphoid tissues
4) Cross-talk and activation signals between dendritic cells and T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the three components of activating cross-talk between DCs and T cells?

A

Antigen presentation (signal 1)
Co-stimulatory molecules (signal 2)
Cytokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How are newly-activated T cells retained in the lymph node?

A

Activated T cell downregulate expression of S1P receptors
S1P is a chemotactic lipid that normally promote T cell egress from the lymph node
It takes several days for the trapped antigen-specific T cell to proliferate, differentiate, and re-express S1P receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What molecules mediate initial binding of a T cell with an APC? What is their mechanism of action?

A

T cell adhesion molecules LFA-1 and CD2
Form an initial low-affinity binding, long enough for TCRs to interact with peptide-MHC complexes
When TCRs become activated, this signals a conformational change in LFA-1 and promotes a longer binding
If the TCR is NOT activated, the T cell will let go and continue sampling other APCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the Immunologic Synapse?

A

Interaction between LFA-1 and ICAM-1, and TCRs with MHC-peptide complexes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is Signal 1?

A

Binding of TCRs to MHC-peptide complexes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is Signal 2?

A

Stimulation of CD28 on T cells by B7-1 and B7-2, which promotes T cell activation, proliferation, and survival via IL-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is IL-2?

A

Major T cell growth factor - necessary for growth, proliferation, and differentiation of T cells to become effector cells
Produced mainly by CD4 T cells
Also used therapeutically in chemotherapeutics and immunosuppressive drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the effects of Signals 1 and 2?

A

Stimulate the expression of IL-2 and IL-2 receptors

Stimulate the survival, proliferation, and differentiation of T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What happens if a naive T cell sees Signal 1, but not Signal 2?

A

Leads to tolerance induction or anergy - important for maintaining peripheral tolerance of the host

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the function of CTLA-4?

A

Induced on activated T cells and binds to B7 more avidly than CD28
Delivers inhibitory signals to activated T cells to help terminate the T cell response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

In what applications is CTLA-4 used therapeutically?

A

Treatment of rheumatoid arthritis
To extend graft survival
Treatment of melanoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the helper activities of CD4 cells?

A

Express cytokines that allow them to activate other cells
Major example - CD40 ligand binds CD40 on APCs - makes them more potent by increasing their expression of B7 molecules, cytokines, and other activators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the effector functions of Th1 cells?

A

Stimulate macrophages through production of IFN to make them more efficient at phagocytosis and destruction of virus-infected cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the effector functions of Th2 cells?

A

Drive IgE production and mobilize eosinophils from the bone marrow to destroy helminths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the effector functions of Th17 cells?

A

Secrete IL-17 and recruit lots of neutrophils to clear extracellular bacteria and fungal infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What diseases are associated with Th1 cell responses?

A

Autoimmune disorders

Tissue damage due to cytokine storm

18
Q

What diseases are associated with Th2 cells?

A

Allergic diseases (e.g. asthma)

19
Q

What diseases are associated with Th17 cells?

A

Organ-specific autoimmune disorders such as rheumatoid arthritis and multiple sclerosis

20
Q

What is Signal 3?

A

Cytokines provided by APCs
Specific cytokines dictate what type of effector T cell will result from differentiation
Cytokines produced by polarized T cells can also promote further polarization of the same cell type, and inhibit polarization of other cell types (positive and negative feedback)

21
Q

Which cytokines are associated with Th1 cell differentiation?

A

IL-12

IFN gamma

22
Q

Which cytokine is associated with Th2 cell differentiation?

A

IL-4

23
Q

Which cytokines are associated with Th17 cell differentiation?

A

TGF-beta

IL-6

24
Q

How long do T cells remain polarized? What is the function of this?

A

A long time (indefinitely?); will express the same cytokine when restimulated
Allows cells to quickly start making cytokines and mount the appropriate immune response the next time it encounters the pathogen

25
Q

What are the main effector functions of Th1 cells?

A

Activate macrophages to ingest and destroy microbes

Produce mainly IFN gamma; also IFN and other chemokines to contribute to leukocyte recruitment and enhanced inflammation

26
Q

What are the major functions of IL-12?

A

Induce Th1 cell differentiation and T cell production of IFN and TNF
Inhibit differentiation of Th2 cells
Enhance cytotoxic activity of NK cells and CTLs

27
Q

What are the major functions of IFN-gamma?

A

Inhibits viral replication
Activates macrophages to kill phagocytosed microbes
Promote NK activity
Act on B cells to promote class switching between certain IgG subclasses
Promote antigen processing and MHC expression

28
Q

What cell types make IFN-gamma?

A

Th1 cells
CTLs
NK cells
NKT cells

29
Q

How do CD4 Th1 cells activate macrophages?

A

Upregulate CD40 ligand and secrete IFN
CD40 ligand binds CD40 on macrophages and upregulates expression of IFN receptor
IFN activates the macrophage to kill phagocytosed bacteria and stimulate inflammation

30
Q

What are the two general types of macrophages? What are their functions?

A

M1 macrophages kill phagocytosed bacteria (generated early in infection, stimulated by IFN)
M2 macrophages inhibit inflammation, clean up, and repair damaged tissue (generated as infection resolves)

31
Q

What are the major effector functions of Th2 cells?

A

Stimulate IgE- and eosinophil-mediated reactions against helminthic infections
Produce IL-4, IL-5, IL-13, and IL-10
Block entry and promote expulsion of microbes from mucosal organs
Stimulate alternative macrophage (M2) activation for tissue repair

32
Q

What are the main functions of IL-4? Name four

A

Stimulates production of IgE by B cells
Stimulates gut peristalsis to clear the parasites
Stimulates recruitment of eosinophils
Contributes to M2 macrophage activation

33
Q

What are the main functions of IL-13? Name three

A

Increases mucous secretion in the gut and airways
Stimulates recruitment of eosinophils
Contributes to M2 macrophage activation

34
Q

What is the main function of IL-5?

A

Activates eosinophils

35
Q

What is the main function of IL-10?

A

Major anti-inflammatory cytokine - suppresses immune responses at the site of infection, after the infection has resolved
Downregulates expression of Th1 cytokines

36
Q

What are the main effector functions of Th17 cells?

A

Induction of neutrophilic inflammation against acute extracellular bacteria and fungi
Produce IL-17, which induces neutrophil infiltration and the production of antimicrobial substances

37
Q

What are the main effector functions of CD8 T cells (CTLs)?

A

Eliminate intracellular microbes by destroying infected cells (stop the spread of virus by eliminating the reservoir of infection)
Recognize target cells through MHC I, and secrete cytotoxic proteins (perforin and granzyme) into an immunologic synapse so that they cannot diffuse to nearby cells (specific recognition)
Also produce Fas Ligand to induce apoptosis
Produce IFN and TNF to activate macrophages

38
Q

How do effector T cells differ from naïve T cells? List five general ways

A

Express different adhesion molecules - lose L-selectin
Express different chemokine receptors - gain inflammatory chemokine receptors
Circulate differently, and home to sites of inflammation rather than secondary lymphoid organs
Show increased sensitivity for antigen
Have less stringent activation requirements (Signal 1 only)

39
Q

What are the three phases of T cell response?

A

1) Initial expansion of effector cells as they search for antigen
2) Contraction and homeostasis as infection is controlled
3) Memory - increased number of antigen-specific T cells circulating

40
Q

What are the major defining properties of memory T cells?

A

Ability to survive in a quiescent state after antigen is eliminated
Ability to mount a larger and more rapid response to antigens than naive T cells