Transplant

Question 1

What are the three phases of the immune response transplanted graft?

Answer 1

• Phase 1: recognition of foreign antigens
• Phase 2: activation of antigen-specific lymphocytes
• Phase 3: effector phase of graft rejection

Question 2

What are the most relevant protein variations in transplants?

Answer 2

ABO blood. group

HLA

Question 3

Where is HLA coded fo?

Answer 3

Chromosome 6 on MHC

Question 4

What are the two main immune components for rejection?

Answer 4

T cell mediated rejection

antibody (B cell) mediated rejection

Question 5

What are the three types of HLA class I?

Answer 5

A, B, C

Question 6

What are the three types of HLA class II?

Answer 6

DR, DQ, DP

Question 7

What cells is HLA I presented on?

Answer 7

ALL cells

Question 8

What cells in HLA II presented on?

Answer 8

APCs

Question 9

Why has the high variability (polymorphism) evolved in HLA?

Answer 9

So that HLA molecules can present a wide variety off antigens

Question 10

What are the three most polymorphic/immunogenetics class subtypes for HLA?

Answer 10

A, B, DR

Question 11

Explain T cell mediated rejection broadly

Answer 11

1. APC presents donor HLA to recepient HLA
2. T cell activates > inflammatory cell recruitment
3. Effector phase > organ damage

Question 12

What are the 3 key signals required for T cell activation?

Answer 12

1. APC - T cell receptor interaction
2. Co-stimulatory signal
3. Amplification > activation via cytokine production

Question 13

What are the actions. of activated T cells?

Answer 13

Proliferation 
Produce cytokines 
Provide help to CD8 cells 
Provide help to antibody production 
Recruit phagocytic cells

Question 14

Whose APCs work in rejection, the recipient or the donor’s?

Answer 14

BOTH

Because if you transplant in an organ, that organ will contain APCs from the donor

Question 15

Where does APC- T cell interaction occur?

Answer 15

In the lymph nodes

Question 16

Which two cell types are activated in the effector phase ?

Answer 16

Cytotoxic T cells > granzyme, perforin, Fas ligand

Macrophages > phagocytosis, release of proteolytic enzymes, cytokine and free radical production

Question 17

What do T cells do / how do they interact with endothelium in the effector phase?

Answer 17

They tether, roll and arrest on endothelial surface

They then crawl through interstitial and start attacking the tubular epithelium

Question 18

What are typical histological features of T cell mediated rejection?

Answer 18

Lymphocytic interstitial infiltration
ruptured tubular basement membrane
Tubulitis (inflame cells within the tubular endothelium)

Question 19

What can a fail in kidney transplant function be due to?

Answer 19

Rejection
Nephrotoxic drugs
Viral infection (from immunosuppressioN) 
vascular disease 
lymphoma (viral)

Question 20

Explain the two types of antibodies you need to be weary of in transplants?

Answer 20

Anti-A and Anti-B antibodies (naturally occurring)

Anti-HLA antibodies (form following exposure)

Question 21

How do antibodies act in a transplant?

Answer 21

• Antibodies bind to HLA antigens on endothelium of blood vessel in transplanted organ
  Antibodies then fix complement which assembles to form MAC > ENDOTHELIAL CELL LYSIS
• Binding of complement also recruits monophages, NK, neutrophils
• Inflammatory cells within kidney capillaries (CAPILLARITIS) also cause endothelial injury

Question 22

What is the end product of antibodies acting against a transplant?

Answer 22

GRAFT FIBROSIS

Question 23

What are the two key ways we prevent graft rejection?

Answer 23

Tissue typing (AB/HLA typing)
Immunosuppression

Question 24

When do we screen for anti-HLA antibodies=?

Answer 24

BEFORE transplant 
AT time of transplant (once organ assigned )
AFTER transplant (repeat measurement to check for new antibody formation)

Question 25

What three techniques can be used for anti-HLA antibody screening?

Answer 25

Cytotoxicity assay Flow cytometry Solid phase assay

Question 26

What are key drug types given for immunosuppression in T cell mediated rejection?

Answer 26

``` Steroids Calcineurin inhibitors Cell cycle inhibitors TCR inhibitors Monoclonal antibodies ```

Question 27

What are key drug types given for immunosuppression in B cell mediated rejection?

Answer 27

``` anti CD20 (rituximab) BAFF inhibitors (target cytokines that promote B cell activation and growth) Proteasome inhibitors (block antibody production by plasma cells) Complement inhibitors ```

Question 28

What categories is the general immunosuppression treatment made up of?

Answer 28

Induction agent Baseline immune suppression treatment of episodes of acute rejection

Question 29

What is given for baseline immune suppression

Answer 29

TRIAD: - Calcineurin inhibitor - cell cycle inhib ( mycofenolat mofetil OR azathioprine) - steroids

Question 30

How do you treat episodes of acute rejection?

Answer 30

Cellular: steroids, OKT3/ATG | Antibody-mediated: IVIG, plasma exchange, antiC5, antiCD20

Question 31

Name some calcineurin inhibitors

Answer 31

tacrolismus | Ciclosporin

Question 32

Name some cell cycle inhibitors

Answer 32

mycofenolate mofetil | azathioprine

Question 33

Name some TCR inhibitors

Answer 33

OKT3 | ATG (Anti-Thymocyte globulin)

Question 34

What can you give for GvHD prophylaxis?

Answer 34

methotrexate/cyclosporin

Question 35

How do you treat GvHD'

Answer 35

steroids

Question 36

What are common viral associated malignancies?

Answer 36

HHV8 | EBV