L14: Cell Mediated Cytotoxic Responses

Question 1

the primary agents of cell-mediated (TH1)immunity are the____ cells

Answer 1

T_c and NK

Question 2

Lymphoid cells developing in the thymus ___rearrange TCR genes

Answer 2

DO rearrange

Question 3

Lymphoid cells developing in the bone marrow ____ rearrange TCR genes

Answer 3

DO NOT

Question 4

Lymphoid cells that develop in the thymus:

Answer 4

T_H

T_C

γδ T cells

NKT cells

Question 5

Lymphoid cells that develop in the bone marrow:

Answer 5

B cells

NK cells

Question 6

T_H cells

Answer 6

T_H- signal to tailor and coordinate responses.

Question 7

T_C cells

Answer 7

T_C– attack and kill cells displaying specific antigens by disrupting membrane andlysing cell.

Question 8

γδ T cells

Answer 8

• patrol epithelia
• attack and kill pathogens and rogue-self using same mechanisms as NK and TC cells
• signal
• Some authors refer to these as“primitive” because their function seems less specialized.

Question 9

Two types of NKT cells

Answer 9

• NKT
• iNKT

Question 10

iNKT cells (type 1)

Answer 10

respond to lipid antigens,especially those characteristic of bacteria.

Question 11

NKT cells (type 2)

Answer 11

recognize a wider array of lipids and have more variation in the receptor

Question 12

____ cells perform functions native to T_H, T_C, NK, Treg, and γδ T cells

Answer 12

iNKT

Question 13

B Cells

Answer 13

• rearrange immunoglobulin genes, phagocytize, but do not seem to be aprimary killer of pathogens, and do not attack rogue self.
• The antibodies that they produce are often important in directing attack by other cells.

Question 14

NK cells

Answer 14

• do not rearrange any genes.
• They attack and kill cells withsuspicious surface displays by disrupting their membranes and lysing the cells.

Question 15

Myeloid cells

Answer 15

• macrophages
• neutrophils
• eosinophils

Question 16

Macrophages

Answer 16

macrophages – phagocytize, present antigen

Question 17

neutrophils

Answer 17

neutrophils – phagocytize, do not present antigen

Question 18

Eosinophils

Answer 18

eosinophils – coordinate attack on eukaryotic parasites, do not present antigen,weakly phagocytic

Question 19

Steps for activating T_C cells

Answer 19

1. The TC cell binds a foreign antigen on MHC I (TC cells that bind self-antigen have been killed off during negative selection.)
2. CD45R on TC and TH attaches to CD22 (sometimes called CD45L) on target cells.
3. TH cell activates the cell, turning it into a CTL.

Question 20

____ speeds T_C activation by making it easier for the Tc cells to encounter the foreign antigen.

Answer 20

Cross presentation

Question 21

Activation of T_C cells leads to:

Answer 21

a. Cell division
b. Up-regulation of cell adhesion molecules
c. Synthesis of the complete IL-2 receptor

Question 22

CTL cell attached to target will up-regulate ____, forming

conjugate.

Answer 22

cell adhesion molecules

Question 23

Steps for CTL attack on target cell membrane:

Answer 23

1. cytoskeleton rearranges, directing Golgi and storage granules (perforins and granzymes) to target cell
2. granule contents released by exocytosis (Ca2+ dependent)
3. Perforin monomers undergo conformational change and insert in the targetmembrane (sequence homology with C9 of the complement system).
4. Granzymes (serine proteases) enter through pores and activate apoptosis.

Question 24

Alternatively, CTLs can induce apoptosis by ____

Answer 24

Fas ligand binding to target Fas receptor on the target cells

Question 25

Cells from mice that are both perforin knock-out AND Fas knock-out _____ be killed by cytotoxic T cells.

Answer 25

CANNOT

Question 26

CTL-dissociation

Answer 26

* The integrin holding the cells together reverts to its less avid form after 5 to 10 minutes. * The CTL undocks and begins looking for another cell to hit.

Question 27

CTL destroyed cells are scavenged by \_\_

Answer 27

macrophages or neutrophils

Question 28

Characteristics of NK cells

Answer 28

* Large cells with lots of granular inclusions. * Lymphoid, sharing a common progenitor and surface markers with T cells,including the use of signaling peptides similar to those in the complete CD3complex * Develop in the bone marrow and do not rearrange genes * Also have TLRs and inflammatory cytokine receptors typical of those ofmacrophages and neutrophils * Do express the receptor of FC of IgG (CD 16) and the IL-2 receptor. This allowsthem to recognize and attack antibody-coated cells during ADCC * Have MHC I receptor, but it is inhibitory, and not used to recognize antigen, butrather viral down-regulation.

Question 29

NK mechanism of killing

Answer 29

* Granules containing perforins and granzymes directionally released at target cell * Constitutively cytotoxic; do not require activation * Do not require antigen or MHC recognition * Adhesion to target triggers release

Question 30

However virus that down-regulate MHC I production may fool \_\_\_, but they will activate ___ cells.

Answer 30

fool T_C cells, activate NK cells

Question 31

Stress receptors are possesed by ___ cells

Answer 31

NK cells -There are a variety of stress indications displayed by sick cells,and a variety of receptors used by NK cells to sense them. The interaction promotes attack.

Question 32

\_\_\_\_\_\_ not only lowers the cell’s MHC production, it attempts to fool the NK cells by producing a fake MHC.

Answer 32

Cytomegalovirus * The viral genome codes for a proteinresembling MHC I. * This does not activate TC cells as it does not display foreign antigen. * However, it is recognized as MHC I by NK cells of susceptible mice. * The fake MHC binds to the same NK inhibitory receptor that real MHC binds to.

Question 33

How does Antibody Dependent Cell Mediated Cytotoxicity (ADCC) work?

Answer 33

1. Targeting of cell harboring pathogens. 1. The cells display abnormal antigen. 2. B-cells produce antibodies to this antigen 3. The antibodies attach so that their FC portion stick out from the cell.

Question 34

Which cells are capable of ADCC?

Answer 34

1) Cells with Antibody (FC) Receptors a. NK b. macrophages c. neutrophils d. eosinophils

Question 35

NK cells recognize \_\_\_\_, attacking \_\_\_\_, resulting in \_\_\_\_

Answer 35

IgG and IgM, rogue self, apoptosis

Question 36

Macrophages recognize \_\_\_\_, attacking \_\_\_\_, resulting in \_\_\_\_

Answer 36

IgG and IgM, pathogen, phagocytosis

Question 37

neutrophils recognize \_\_\_\_, attacking \_\_\_\_, resulting in \_\_\_\_

Answer 37

IgG and IgM, pathogen, phagocytosis

Question 38

Eosinophils recognize \_\_\_\_, attacking \_\_\_\_, resulting in \_\_\_\_

Answer 38

IgE, parasites, surface attack

Question 39

Graft vs Host disease

Answer 39

* Supply immuno-incompetent individual with competent lymphocytes from another genetically different individual. * The Tc cells activate and begin to attack the host cells. * The B cells produce antibodies to the host cells surface antigen. * The patient experiences a cell-mediated attack from both NK and TC cells, withsome help from the macrophages, neutrophils and maybe even complement. * The cells under heaviest attack are GI epithelial (diarrhea), skin (which mayslough off in sheets), and spleen, (which may attack the red blood cells, resultingin jaundice). The whole response can kill a person.