Transplantation and Tumor Immunology

Question 1

What is the highest expected survival rate at 5 years amongst solid organ transplants?

Answer 1

Kidney (90%)

Question 2

What are the 5 major classes of immunosuppressive drugs?

Answer 2

1-Calcineurin inhibitors
2-mTOR inhibitors
3-Antiproliferative agents
4-Antibodies
5-Corticosteroids

Question 3

What are the two stages of host versus graft reaction?

Answer 3

1-Sensitization stage (recognition of alloantigens with T cells)
2-Effector stage (inflammatory response by B cells and other inflammatory cells)

Question 4

What are the 3 post HSCT phases (factors for infection risk of transplant)?

Answer 4

1-Phase 1 (pre engraftment day 0-30, prolonged neutropenia/mucocutaneous damage)
2-Phase 2 (post engraftment day 31-100, impaired immunity,m GVHD)
3-Phase 3 (late day>100 immunosuppression)

Question 5

What is the most common infection complication of radiation/chemotherapy?

Answer 5

Fungal Candadiasis

Question 6

What is the most frequent complication of bone marrow transplant patients?

Answer 6

Mucositis

*nonkeratinized mucosal surfaces

Question 7

GVHD have oral manifestations in >______% of cases

Answer 7

50

Question 8

Peak immunosuppression takes place during what period of post-transplant care?

Answer 8

3-6 months

*elective procedures should be postponed to 6-12 months post transplant

Question 9

What condition is caused by use of cyclosporine, is worsened if used with calcium channel blockers?

Answer 9

Gingival hyperplasia

*develops 1-3 months after starting drugs, epithelium invaded by candida hyphae

Question 10

Induction of CD8 responses against tumors requires what?

Answer 10

Cross-priming antigen presentation

Question 11

What are 2 types of tumor vaccine mechanisms that have been tested in animal/human systems using dendritic cells?

Answer 11

1-Dendritic cell transfection
2-Dendritc cell pulsed with tumor antigen

*tumor cells have also been transfected to express B7 or secrete IL-2 to indue CD8 T cell activation

Question 12

Antibody therapy has been used to block what two proteins to maintain an active T cell response?

Answer 12

CTLA4 and PD1

*Also to block CD20 to eliminate transformed B cells

Question 13

The hypothesis of why we still have cancer in the presence of a functional immune system is called what?

Answer 13

Tumor immunoediting

Question 14

What are the three E’s of cancer immunoediting?

Answer 14

1-Elimination
2-Equilibrium
3-Escape

Question 15

What are the 4 phases of the elimination process?

Answer 15

1-tumor reaches detectible size and INFy is produced
2-IFNy causes tumor cell death and cytokine production
3-Tumor infiltrated by NK cells and macrophages, more tumor cells killed
4-Tumor specific CD4 and CD8 T cells destroy remaining antigen-bearing tumor cells

Question 16

Any tumor variant that has survived elimination may persist for years as part of what process?

Answer 16

Equilibrium

Question 17

Surviving tumor variants that have acquired insensitivity to immune detection and begin to expand in what process?

Answer 17

Escape process

*may lead to death of host

Question 18

What are 5 mechanisms tumors use to avoid immune recognition?

Answer 18

1-Low immunogenicity
2-Tumor treated as self
3-Antigenic modulation
4-Tumor induced immunosuppression
5-TUmor induced privileged site (physical barrier)

Question 19

What are MDSCs?

Answer 19

Myleoid derived suppressor cells that look like immature hematopoietic cells and shut off immune system