Immunology (Final) Chpt 14: Cell-Mediated Cytotoxicity: Tc Cells, Nk Cells, & Nkt Cells

Front 1

What are the soluble effector molecules produced by CTL t-cells?

Back 1

1. Cytotoxins (perforins and granzymes)

2. IFN-gamma

3. TNF-beta

Front 2

What are the membrane-bound effector molecules produced by CTL t-cells?

Back 2

Fas ligand (FASL)

Front 3

What are the soluble effector molecules produced by Th1 t-cells?

Back 3

1. IL-2

2. IL-3

3. TNF-beta

4. IFN-gamma

5. GM-CSF (high)

Front 4

What are the membrane-bound effector molecules produced by Th1 t-cells?

Back 4

Tumor necrosis factor beta (TNF-beta)

Front 5

What are the soluble effector molecules produced by Th2 t-cells?

Back 5

1. IL-3

2. IL-4

3. IL-5

4. IL-6

5. IL-10

6. IL-13

7. GM-CSF (low)

Front 6

What are the membrane-bound effectors produced by Th2 effector T-cells?

Back 6

CD40 ligand

Front 7

What are CTLs aka?

Back 7

Cytotoxic T-Lymphocytes

Front 8

What are CTLs generated by?

Back 8

CTLs are generated by immune activation of Tc cells.

Front 9

What are the two phases of response that CTLs are involved in?

Back 9

1. Tc cells undergo activation and differentiate into active CTLs.

2. Effector CTLs recognize Ag-class I MHC complexes.

Front 10

List 4 properties of CTLs.

Back 10

1. Lytic

2. Recognize and eliminate alter non-self cells

3. CD8+

4. MHC I restricted

Front 11

What are CTL-Ps aka?

Back 11

CTL Precursors. They are naive Tc cells that are not capable of killing.

Front 12

The threshold to activate CTL-Ps to become CTLs is ? and requires ? signals.

Back 12

The threshold to activate CTL-Ps to become CTLs is high and requires 3 signals.

Front 13

List the 3 signals required to activate CTL-Ps.

Back 13

1. An Ag-specific signal transmitted by TCR complex upon recognition of MHC I complexed to a "licensed" APC (usually a dendritic cell).

2. Costimulatory signal transmitted by CD28-B7

3. Signal induced by IL-2 binding to IL-2R resulting in proliferation and differentiation of the Ag-activated CTL-P into effector CTLs.

Front 14

In the generation of effector CTLs what gives dendritic cells a "license"? What becomes expressed?

Back 14

Th1 and costimulation with CD40-CD40L gives dendritic cells a "license". IL-2R becomes expressed.

Front 15

The proliferation of memory CTL-Ps is not dependent upon what?

Back 15

The proliferation of memory CTL-Ps is not dependent on Th cells.

Front 16

The proliferation of memory CTL-Ps is not dependent upon Th cells and may also not require what else?

Back 16

CD28-B7 interactions may also not be required.

Front 17

Ag-activated memory CTL-Ps appear to secrete sufficient amounts of IL-2 to do what?

Back 17

They secrete sufficient amounts of IL-2 to stimulate their own proliferation and differentiation into CTLs.

Front 18

The increase in Ag-specific CD8+ cells is measurable. Describe how this can be observed in mice.

Back 18

Mice were infected with VSV (vesicular stomatitis virus). The distribution of VSV-specific CD8+ cells is not uniform. There is a greater percentage in these organs in this order: kidney>lungs>liver.

Front 19

The killing of target cells occurs in ?.

Back 19

The killing of target cells occurs in stages.

Front 20

What is the primary event in CTL-mediated killing?

Back 20

The primary event in CTL-mediated killing is conjugate formation.

Front 21

Conjugate formation is the primary event in CTL-mediated killing. Describe the process.

Back 21

The process begins with TCR-CD3 on the CTL recognizing Ag-MHC I complex. The integrin receptor (LFA-1) on CTL binds to ICAMS on target cell forming the conjugate. Once complete the CTL cell goes back for recycling.

Front 22

Pore formation (caused by ?)in target cell membranes mediates what?

Back 22

Pore formation (caused by perforin) mediates granzyme entry into target cell.

Front 23

What is Ca++ required for?

Back 23

Exocytosis, insertion of perforin monomers into the membrane, and polymerization to form cylindrical pores.

Front 24

Give a basic step by step breakdown of pore formation in target cells.

Back 24

1. Increased Ca++

2. Granule fuses with plasma membrane of CTL

3. Opens and perforin monomers expel

4. Perforin assembly poymerizes

5. Pore forms and fluid rushes in

6. The cell burst (apoptosis)

Front 25

CTL-stimulated target cell apoptosis occurs by how many pathways?

Back 25

Two

1. Fas pathway

2. Perforin-Granzyme pathway

Front 26

The Fas pathway involves the association of ? and ?.

Back 26

It involves the assoc. of Fas and FADD

It is one of the pathways for CTL-stimulated target cell apoptosis.

Front 27

Describe the Perforin-Granzyme Pathway that mediates CTL-stimulated target cell apoptosis?

Back 27

1. Exocytosis releases both perforin and granzyme

2. Granzyme B enters target cell in two ways
(By perforin pores AND binding mannose-6-phosphate)

Front 28

What kind of cytotoxicity do NK cells have?

Back 28

Non-specific cytotoxicity

Front 29

What percentage of circulating lymphocytes are NK cells?

Back 29

5-10% of circulating lymphocytes are NK cells.

Front 30

What do NK cells attack?

Back 30

Attack viruses, other intracellular pathogens, and tumors.

Front 31

What do NK cells produce to influence commitment?

Back 31

NK cells produce INF-gamma to influence T-cell subtype commitment.

Front 32

NK cell activity is stimulated by what?

Back 32

INF-alpha, INF-beta, and IL-12

Front 33

NK cells are the ? against ? infections.

Back 33

NK cells are the 1st line of defense against viral infections.

Front 34

The presence of INF-gamma, INF-alpha, and INF-beta indicate what?

Back 34

They indicate the presence of viral infected cells. They are released by viral infected cells.

Front 35

Once INF-alpha,gamma, and beta are released by virus infected cells what happens to the NK cell pop?

Back 35

It increases

Front 36

Once INF-alpha, gamma, and beta are released and the NK cell pop increases what do CTLs do?

Back 36

CTLs take over and produce memory cells for that virus.

Front 37

The presence of what drops as the presence of virus titer increases?

Back 37

The presence of IFN-alpha, beta, and gamma as well as the presence of NK cells drop as the virus titer increases. (see slide on pg 6)

Front 38

What do NK cells and T-cells share?

Back 38

They share a common early progenitor cell.

Front 39

NK cells do not develop where?

Back 39

Do not develop in the thymus.

Front 40

NK cells do not undergo ? ?.

Back 40

They do not undergo gene rearrangement. Because they do not have Ag specificity. (they don't care what they 'kill')

Front 41

What do RAG-1 KO mice lack? What are they used to study?

Back 41

They lack adaptive immunity (so no T and B cells). They are used to study immune system rxns to different Ags.

Front 42

What will keep RAG-1 KO mice healthy?

Back 42

NK cells and intact innate immunity mxms will keep them healthy enough if housed in clean conditions. (Because they lack adaptive immunity, T and B cells)

Front 43

Do NK cells or CTL cells have FasL? For what?

Back 43

NK cells have FasL on their surface and can induce death (apoptosis) in Fas-bearing targets.

Front 44

What do NK cell granules contain?

Back 44

Perforin and granzymes

Front 45

Which cells have memory NK or CTLs?

Back 45

CTLs (NK has no memory)

Front 46

Which cells are not MHC restricted, NK cells or CTLs?

Back 46

NK cells are not MHC-restricted.

Front 47

Which cells do not express Ag-specific receptors, CTLs or NK cells?

Back 47

Nk cells do not express Ag-specific receptors.

Front 48

Which cells require activation, NK cells or CTL cells?

Back 48

CTLs require activation (and NK cells do not)

Front 49

NK cells do not req activation because they are always ? with large ? ?.

Back 49

They are always cytotoxic with large cytoplasmic granules.

Front 50

What does the 'Opposing Signals Model' state?

Back 50

Activation and inhibition receptors are found. This is involved in the ability of the NK cells to distinguish between healthy cells from infected or cancerous cells is balanced.

Front 51

How can NK activating signals be delivered?

Back 51

Delivered by cytokines:

INF-alpha, beta, and gamma

IL-12

IL-15

Front 52

NK cells have activation and inhibition receptors. Which are better characterized?

Back 52

Inhibitory receptors are better characterized.

Front 53

Most of the inhibitory receptors found on NK cells are ? molecules.

Back 53

Ig-like molecules

Front 54

What are the intracellular sequences involved with the inhibitory receptors of NK cells?

Back 54

ITIMs (not ITAMs) (immunoreceptor tyrosine phosphate inhibitory motifs)

Front 55

How do the inhibitory receptors of NK cells block the lysis of target cells by NK cells?

Back 55

1. Detect normal levels of MHC-I expression on potential target cells.

2. Also prevent NK cell proliferation and induction of cytokines like INF-gamma and INF-alpha.

Front 56

The opposing signals model of NK cells states that the engagement of inhibitory NK cell receptors by ? delivers and ? signal that counteracts the ? signal.

Back 56

The opposing signals model of NK cells states that the engagement of inhibitory NK cell receptors by MHC-I delivers and INHIBITORY signal that counteracts the STIMULATORY signal.

Front 57

List two NK cell inhibitory receptors?

Back 57

KIRs and CD94/NKG2

Front 58

If an NK cell comes into contact with a normal cell what happens to the inh and activating receptors?

Back 58

If MHC-I seems normal then the activating receptor does not activate and their is no killing.

Front 59

If an NK cell comes into contact with a virus-infected cell what happens to the inh and activating receptors?

Back 59

The inhibitory cell detects an abnormal level. There is then no counteropposition signal to the activating receptor and the cell is then free to kill.

Front 60

What cells are a recent discovery?

Back 60

NKT cells

Front 61

What cells do NKT cells have properties in common with?

Back 61

CTL and NK cells (hybrid)

Front 62

NKT cells have ? complexes but shares little else with the others.

Back 62

They have TCR complexes but share little else with the others. TCR does not recognize MHC-bound peptides and this is an exception to the norm for TCRs. It recognizes a glycolipid.

Front 63

NKT cells are part of the ? ? system.

Back 63

NKT cells are part of the innate immune system.

Front 64

NKT cells may play a part of ? immunity.

Back 64

NKT cells may play a part of antibacterial immunity.

Front 65

NKT cells have no ?.

Back 65

NKT cells have no memory.

Front 66

Where do NKT cells develop?

Back 66

They develop in the thymus. This is why they have TCRs.