Transplant Immunology - Bailey

Question 1

In regards to transplants, what is the primary reason for morbidity and mortality?

Answer 1

Immune response

Question 2

________ means transplanting cell or tissue to the same anatomical site.

Answer 2

Orthotopic

Question 3

_______ means transplanting cell or tissue to a different anatomical site.

Answer 3

Heterotopic

Question 4

______ means transfer of circulating cells.

Answer 4

transfusion

Question 5

_____ is graft transplanted from one individual to the same individual.

Answer 5

Autologous graft

Question 6

______ is graft transplanted between two genetically identical (or very similar) individuals.

Answer 6

Syngeneic graft

Question 7

______ is graft transplanted between two genetically identical (or very similar) individuals.

Answer 7

Syngeneic graft (Twins or siblings)

Question 8

_______ is graft between two genetically diverse individuals.

Answer 8

Allogeneic graft

Question 9

Rejection of Graft is due to ________ mismatch.

Answer 9

MHC mismatch

Question 10

How are T cells activated?

Answer 10

T cells recognize antigen that is presented to them in the context of MHC.

Question 11

______ require antigen + MHC2 to be activated.

Answer 11

CD4+

Question 12

______ require antigen + MHC1 to be activated.

Answer 12

CD8+

Question 13

If a T cell has high avidity binding to self peptide and MHC, what happens?

Answer 13

Apoptosis of the T cell.

* this is how the body prevents the full development of auto reactive T cells.

Question 14

Can Alloreactive T cells recognize Allogeneic MHC + Self Peptide?

Answer 14

Some can.

Question 15

______ T cells will kill the target.

Answer 15

CD8+

Question 16

____ T cells will produce cytokines to help propagate the immune response.

Answer 16

CD4+

Question 17

What is direct Alloantigen recognition?

Answer 17

When T cells recognize allogeneic MHC directly

Question 18

What is indirect Alloantigen recognition?

Answer 18

When APC is used to present antigen to T cell.

Question 19

What are the 3 ways Allogeneic T cells lead to Graft Rejection?

Answer 19

1. Hyperacute rejection
2. Acute Rejection
3. Chronic Rejection

Question 20

What is Hyper acute Rejection?

Answer 20

Characterized by thrombosis (Blood clot) formation that begins within minutes to hours and graft dies.
*Antibodies lead to activation of complement cascade.

Question 21

What is Acute Reaction?

Answer 21

Alloreactive T cells become activated (after about a week) produce cytokines to:

1. Activate CD8+ T cells
2. Activate B cells to produce antibodies
3. Inflammation damages blood endothelial cells.
4. Inflammation leads to thrombosis (clot) formation.
5. Parenchymal cells can also be affected by CD8+ cells.

Question 22

What is Chronic Rejection?

Answer 22

Grafts that survive for 6 months or more can eventually develop blood vessel thickening due to intimal smooth muscle formation.
*Growth factors induce intimal thickening

Question 23

What ultimately leads to the death of a graft?

Answer 23

Loss of vascularization

Question 24

What is the mechanism of action for Rapamycin?

Answer 24

Blocks lymphocyte proliferation by inhibiting IL-2 signaling.

Question 25

What is the mechanism of action for Anti-CD3 monoclonal antibody?

Answer 25

depletes T cells by binding to CD3 and promoting phagocytosis or complement mediated lysis.

Question 26

What is the Mechanism of action for Anti-IL-2 receptor?

Answer 26

Inhibits T cell proliferation by blocking IL-2 binding and depletes activated T cells that express CD25

Question 27

What is the Mechanism of action for CTLA-4lg?

Answer 27

Inhibits T cell activation by blocking B7 costimulator binding to T cell.

Question 28

_________ Is a treatment for hematological disease.

Answer 28

Bone marrow transplant.

Question 29

What is one of the additional risks to bone marrow transplant?

Answer 29

Graft can attack the host. (Graft Versus Host disease)

Question 30

_____ can produce IFN-gamma.

Answer 30

Natural killer cells

Question 31

Some cancers can down regulate the expression of ________. Why is this important?

Answer 31

MHC1 | *Important because NK cells become activated in the absence of MHC1 and will then kill infected cells.

Question 32

_____ can produce IFN-gamma (cytokine). Why is this important?

Answer 32

Natural killer cells | * Important b/c helps to activate macrophages that can engulf tumor cells.

Question 33

Function of tumor macrophages depends upon ___________.

Answer 33

The Microenvironment

Question 34

______ macrophages can suppress tumors/kill tumor cells.

Answer 34

M1

Question 35

______ macrophages can enhance tumors.

Answer 35

M2

Question 36

____ can induce apoptosis in cancer cells.

Answer 36

T cells

Question 37

Antigen specific T cells are activated where?

Answer 37

In the lymph nodes

Question 38

______ induces apoptosis in target cell.

Answer 38

Granzyme

Question 39

_____ helps granzyme enter the target cell.

Answer 39

Perforin

Question 40

______ may be necessary for CTL activation.

Answer 40

Cross-priming

Question 41

What is the 2 important roles of Cd4+ cells?

Answer 41

1. Help to activate CD8+ cells | 2. Produce Th1 cytokines to lead classical (M1) macrophage activation

Question 42

Can immune system activity lead to the development of cancer? Explain.

Answer 42

Yes, 1. Cytokines can lead to hyperplasia (Increased cell proliferation) 2. Hyperplaisia can lead to dysplaisa (abnormal cell development) 3. Free radicals damage nucleic acids. * People with chronic inflammation diseases are at increased risk of developing cancer.