3.3.1 Tumor and Transplant Immunity

Question 1

What are the three phases of immunoediting?

Answer 1

Elimination, equilibrium, escape

Question 2

What are three therapeutic usages of Ab’s in regards to tumor treatment?

Answer 2

Immunodepletion, Receptor blockade, Toxin/drug/radio-conjugated Ab’s

Question 3

What is Rituximab?

Answer 3

Anti-CD20

Question 4

What is T cell exhaustion?

Answer 4

Repeated stimulation of T cells results in anergy

Mediated, at least in part, by negative regulators of T cell signaling (CTLA-4 and PD-1)

Question 5

What is CTLA-4?

Answer 5

Inhibitory co-receptor on activated T cells .

Binds B7-1/2

Question 6

What does CTLA-4-Ig block?

Answer 6

Blcoks CD28 co-stimulation by binding B7-1/2 (Abatacept)

inhibitory signaling

Question 7

What is the drug name of CTLA-4-Ig? Does it enhance or diminish T cell activity?

Answer 7

Abatacept; Diminishes T cell activity by blocking CD28 binding

Question 8

What does ipilimumab bind? Does it enhance or diminish T cell activity? When would you use this drug?

Answer 8

CTLA-4. Enhances T cell activation. When trying to fight cancer.

Question 9

Other than CTLA-4, what is the inhibitory co-receptor on T cells? What is its binding partner?

Answer 9

PD-1; PD-L1 and PD-L2 on DCs

Question 10

What drug blocks tolerance through an anti-PD-1 mechanism?

Answer 10

Nivolumab, approved for melanoma and NSCLC

Question 11

What is the process of creating the Supleucel-T vaccination?

Answer 11

Isolate APCs from patient, incubate with PAP (prostatic acid phosphatase- the tumor Ag)/GM-CSF, reinfuse the cells back into the patient

Question 12

What is unique about synthetic Ab’s?

Answer 12

They can have have two different variable regions specific for different targets (tumor Ag and immune receptors on T and NK cells)

Question 13

What would be a successful target for B cell leukemias/lymphomas?

Answer 13

CD19

Question 14

What does scFv stand for?

Answer 14

Single chain Ab

Question 15

What do they use to fuse a scFv to a T cell?

Answer 15

A zeta chain

Question 16

Define syngenic.

Answer 16

Genetically identical

Question 17

Define congenic.

Answer 17

genetically identical except for a single locus (e.g. knock-out mouse line)

Question 18

Define allogenic.

Answer 18

different members of the same species

Question 19

Define Xenogeneic

Answer 19

Members of a different species

Question 20

What is autologous transplantation?

Answer 20

Transplantation within the same individual (e.g. Skin grafts)

Question 21

What are the two immunologic mechanisms of transplant rejection?

Answer 21

Ab’s and T cells especially CTLs

Question 22

Differentiate b/t direct and indirect allorecognition.

Answer 22

Direct: recipient T cells recognize donor cells

Indirect: recipient APCs present donor antigens via cross-presentation

Question 23

What is the mixed lymphocyte reaction used for? How does it work?

Answer 23

Tests T cell-mediated rejection.

Mixed recipient cells with irradiated donor cells. If recipient cells respond, they proliferate.

Question 24

What are the 3 different phases of allograft rejection. Describe the time frame and processes involved in each.

Answer 24

Hyperacute: pre-existing Ab, often occurs if not correctly blood matched, activates complement and clotting (within minutes to hours)

Acute: CTLs target graft or BVs within graft (days to weeks)

Chronic: Th1-mediated (CTL, macrophages), to lesser degree Ab and complement, progressive loss of graft function, fibrosis of graft and graft arteriosclerosis (months to years)

Question 25

Draw the mechanisms of the three types of rejection.

Answer 25

Question 26

What are some of the drugs used in rejection prevention?

Answer 26

Corticosteriods, Cyclosporine, Mycophenolate mofetil, Rapamycin, Thymoglobulin

Question 27

Where is the signaling pathway does cyclosporine work?

Answer 27

It blocks PLC(gamma)1 activation of calcineurin

Question 28

Where in the signaling pathway does rapamycin work?

Answer 28

It blocks signaling from PI3-K activating mTOR

Question 29

Describe HSC transplantation.

Answer 29

1. Isolate CD34+ cells from blood of G-CSF-treated donors, BM, or cord blood
2. Prior to injection space must be cleared in BM

Question 30

What are some adverse health outcomes in the post-HSCT period?

Answer 30

1. Graft Failure
2. Delayed engraftment: hemorrhage, anemia
3. Opportunistic infections (CMV, EBV, bacterial pneumonias, fungal infecitons)
4. GvHD
5. Tumor reccurence, secondary malignancy

Question 31

Describe the directionality of rejection and GvHD.

Answer 31

Rejection: Recipient -> Donor

GvHD: Recipient <- Donor

Question 32

What are billingham’s postulates?

Answer 32

Question 33

Describe the three phases of acute GvHD.

Answer 33

Question 34

What are the three categories of chronic GvHD?

Answer 34

Question 35

What are the mechanisms of chronic GvHD?

Answer 35

Question 36

What are some therapies for GvHD?

Answer 36

corticosteriods, methotrexate, cyclosporine, mycophenylate, Anti-CD25 (Daclizumab)