Lecture 5 Flashcards

(55 cards)

1
Q

What is the CMI?

A

Cell mediated immunity

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2
Q

What are the functions of CD4+ and CD8+ cells in CMI?

A

CD4s recruit and activate phagocytes to kill ingested and some extracellular microbes
CD8s kill cells harboring microbes in cytosol, eliminating reservoirs of infection.

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3
Q

What do Th1s secrete?

What do Th2s secrete?

A

IFNgamma

IL-4, 5, and 13

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4
Q

What are the three signals required for T cell activation/differentiation?

A

Ag presentation, co-stimulatory molecules, and cytokines.

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5
Q

What do each of the three required signals for T cell activation do for the T cell?

A

Ag presentation activates the T cell
Co-stimulation allows the T cell to survive
Cytokines allow the T cell to differentiate into what’s req’d

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6
Q

Which T cell can respond to their target without co-stimulation?

A

Effector T cells

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7
Q

Which T cell homing receptors are on naive T cells?

A

L-selectin, LFA-1, and CCR7

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8
Q

Which T cell homing receptors are on activated effector and memory T cells?

A

E- and P- selectin ligand, LFA-1, VLA-4, and CXCR3, etc.

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9
Q

What does LFA-1 and its receptor ______ do for the T cells?

A

LFA-1 and ICAM-1 allows the stable arrest on high endothelial venules - allows T cell to stop in lymph node

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10
Q

What does L-selectin and its receptor _______ do for the T cells?

A

L-selectin and L-selectin ligand allow adhesion of T cells in high endothelial venules in lymph node

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11
Q

Which two receptors allow T cells to stick to HEVs in lymph nodes to be activated?

A

LFA-1 and L-selectin

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12
Q

Through what do naive T cells migrate to enter lymph nodes?

What do naive T cells express that mediate their selective migration into lymph nodes?

A

High endothelial venules

They express L-selectin (CD62L) and the chemokine receptor CCR7

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13
Q

Why do effector T cells migrate to the sites of infection?

A

They express adhesion molecules and chemokine receptors that bind to ligands expressed/displayed on vascular endothelim in response to inate immune responses to microbes.

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14
Q

Describe in brief the homing of effector T cells to a site of infection.

A

CTLs have adhesion molecules/chemokine receptors that bind to ligands in site of infection. Their homing is independent of Ag recognition but those that do recognize the Ag are preferentially retained/activated at infection site.

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15
Q

What is S1P?

A

S1P is phospholipid sphingosine 1-phosphate which regulates entry /exit of T cells through lymph nodes

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16
Q

Describe how S1P regulates T cell migration.

A

Levels of S1P are higher in the blood/lymph than inside lymph nodes.
Before T cells are activated (w/o Ag stim) they have a high expression of S1P receptor so exit LN.
If Ag stim present they suppress their S1P expression for clonal expansion inside LN.

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17
Q

How do T cells exit the LN after Ag stim?

A

They lose expression of L-selectin, CCR7, and re-express S1P to leave the LN.

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18
Q

What allows T cells to travel to the LN?

A

CCL5 is expressed higher in the LN and attracts T cells

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19
Q

What are the secondary lymphoid tissues?

A

Lymph node
Spleen
Peyer’s patch

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20
Q

Where are most DCs located?

A

In secondary lymphoid tissues - resident DCs

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21
Q

How do DCs migrate from secondary tissues to the lymph nodes?

A

They activate their CCR7 receptor and travel to the LN in tandem with the T cells

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22
Q

How do DCs mature to become APCs in peripheral tissues?

A

DCs encounter MAMPs and are activated
TLR signaling induces expression of CCR7 and enhances processing of pathogen antigens
CCR7 directs DCs to migrate to LN and ups their co-stim molecules & MHC molecules
Activated DCs in T cells zones prime naive T cells

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23
Q

What are CTLs specialized for?

A

The killing of cells infected in INTRAcellular pathogens

24
Q

How do CD4 and CD8s interact?
How does this work?
Which receptor/molecule is used?

A

CD4 cells help drive CD8 T cell responses
CD4+ cells can activate APCs further so they can better activate CD8+ cells
4-1BBL is a ligand on APCs that further activates CTLs

25
What molecules do CTLs use to kill infected cells?
Perforin Granzymes Granulysin Fas ligands
26
What happens to CTL cells to allow efficient cytotoxic killing?
T cells become cellularly polarized during specific Ag recognition to allow the cytotoxic granules to focus on the infected cell.
27
What is the function of perforin?
Makes holes in target cells to allow granzymes in to cytoplasm
28
What is the function of Granzymes?
They are serine proteases which activate apoptosis once in the cytoplasm of the cell
29
What is the function of granulysin?
Has antimicrobial actions and can induce apoptosis
30
Describe in more detail how granzymes work.
Granzymes are serine proteases which cleaves pro-caspase3 allowing caspase 3 to act on CAD. CAD is cleaved by caspase 3 which destroys DNA causing apoptosis.
31
What is FasL?
FasL is a ligand expressed by CTLs on the membrane which can bind to Fas (aka CD95) on target cells inducing apoptosis by caspases.
32
How prevalent is Fas-FasL mediated apoptosis? Why? What does Fas-FasL not require? How long does Fas-FasL take?
Not very prevalent - usually used for killing of tumours/macrophage infected cells. Only 20% of apoptosis attributed to Fas-FasL It does not require granule exocytosis as it is a surface molecule. Much longer than CD8/NK killing
33
What is the function of Th1 cells? | What do they use to function?
Macrophage activating effectors | IFNgamma, TNFalpha, CD40L, FasL
34
What is the function of Th2 cells? | What do they use to function?
Barrier immunity activation | IL4, 5, 13, and CD40L
35
What is the function of Th17 cells? | What do they use to function?
Barrier immunity activation and neutrophil recruitment | IL-17A, IL-17F, IL22, CD40L
36
What is the function of Treg cells? | What do they use to function?
Suppressive cytokines IL-10 TGFbeta
37
What are the two major apoptotic pathways? | How prevalent are each and which is fastest?
Perforin/granzyme - quick - used 80% of time | Fas-FasL - slower than CD8/NK killing - used 20%
38
What are the major cytokines produced by Th1 cells? What are the immune cell types targeted by Th1 cytokines? What microbes are targeted by Th1 cells?
IFN gamma on macrophages Macrophages enhace intracellular bacterial killing Microbes in macrophage vesicles like bacteria
39
What are the major cytokines produced by Th2 cells? What are the immune cell types targeted by Th2 cytokines? What microbes are targeted by Th2 cells?
IL4, 5, and 13 Eosinophils, mast cells, and basophils Helminth parasites
40
What are the major cytokines produced by Th17 cells? What are the immune cell types targeted by Th17 cytokines? What microbes are targeted by Th17 cells?
IL-17 and 22 Neutrophils Extracellular bacteria and fungi
41
What are the major cytokines produced by Tfh cells? What are the immune cell types targeted by Tfh cytokines? What microbes are targeted by Tfh cells?
IL-21 B cell differentiation All types
42
What are the major cytokines produced by Treg cells? What are the immune cell types targeted by Treg cytokines? What microbes are targeted by Treg cells?
Tregs produce IL-10 They inhibit DCs from activating T cells None
43
What cytokines push naive T cells into becoming Th1 cells?
IFNgamma and IL-12
44
What cytokines push naive T cells into becoming Th2 cells?
IL-4
45
What cytokines push naive T cells into becoming Th17 cells?
TGFbeta, IL-6, and IL-23
46
What cytokines push naive T cells into becoming Tfh cells?
IL-6
47
What cytokines push naive T cells into becoming Treg cells?
TGFbeta and IL-2
48
Which STAT pathway is used in Th1 production? | What does that pathway activate?
STAT1 and 4 | T-bet
49
Which STAT pathway is used in Th2 production? | What does that pathway activate?
STAT6 | GATA-3
50
Which STAT pathway is used in Th17 production? | What does that pathway activate?
STAT3 | RORgammaT
51
Which STAT pathway is used in Tfh production? | What does that pathway activate?
STAT3 | Bcl-6
52
Which STAT pathway is used in Treg production? | What does that pathway activate?
STAT5 | FoxP3
53
TGFbeta primes which two T cell subsets? | What does this imply?
Tregs and Th17s | Reflects their complementary roles in promoting mutualism with microbiota
54
What does it mean to "prime" a T cell?
The first transcription factor that begins to act upon the differentiation of T cells is said to prime it. Full activation comes upon the receipt of all transcription factors.
55
How does the activation of one subset of T cells affect the proliferation of other subsets?
Cytokines can negatively regulate the development of effector activity of other subsets. SLIDE30