Transplant

Question 1

Twin to twin transplant

Answer 1

Isograft

Question 2

Non-identical human to human transplant

Answer 2

Allograft

Question 3

Self to self transplant

Answer 3

Autograft

Question 4

Inter-species transplant

Answer 4

Xenograft

Question 5

Most common organ transplant

Answer 5

Kidney

Question 6

Principle of HLA

Answer 6

Class I (A, B, C) on all cells, class II (DR, DQ, DP) on APCs
Each HLA has many variations (e.g. HLA-DQ4)
HLA matching is important for transplant - mismatch = rejection

Question 7

T-cell or antibody mediated rejection

Answer 7

Rejection due to HLA mismatch

hyperacute if pre-sensitised or acute

Question 8

Antibody mediated rejection only

Answer 8

Rejection due to ABO mismatch

hyperacute

Question 9

Antibodies against HLA vs. antibodies against ABO

Answer 9

ABO antibodies naturally occurring (e.g. if you are group A you automatically have anti-B)
HLA not naturally occurring (require exposure)

Question 10

Two types of immune rejection

Answer 10

T-cell mediated

Antibody mediated

Question 11

5 ways to prevent rejection

Answer 11

1. Matching (PCR)
2. Screen for antibodies in recipient (via CDC, FACS, Luminex)
3. Cross match recipient + donor blood
4. Immunosuppression of recipient
5. Re-check recipient for antibodies post-transplant

Question 12

3 forms of immunosuppression

Answer 12

1. Pre-transplant induction
2. Immunosuppressants post-transplant
3. Acute rejection treatment

Question 13

3 induction agents

Answer 13

Target T cells

Anti-CD52 (alemtuzumab) or anti-CD25(IL2R) (basiliximab) or OKT3/ATG

Question 14

3 post-transplant immunosuppressants

Answer 14

CNI + MMF/Aza +/- steroids

Question 15

Treat acute rejection (T cells)

Answer 15

Steroids + OKT3/ATG

Question 16

Treat acute rejection (antibody)

Answer 16

IVIG + plasma exchange + anti-CD2 + anti-CD20

Question 17

Recipient APC presents to recipient T cells

Answer 17

Indirect recognition
CHRONIC REJECTION
(More natural immune response)

Question 18

Donor APC presents to recipient T cells

Answer 18

Direct recognition

ACUTE REJECTION

Question 19

HLA most important to match

Answer 19

DR > B > A

Question 20

Preformed Ab activates complement
Minutes-hours after transplant
Thrombosis + necrosis
Rejection type + treatment?

Answer 20

Hyperacute

Should have crossmatched

Question 21

Cd4+ binds APC
Weeks-months after transplant
Cellular infiltrate
Treat by T cell immunosuppression
Rejection type?

Answer 21

Acute (cell mediated)

Question 22

Type IV hypersensitivity

Answer 22

Requires 2 exposures
1st exposure = APC to CD4+ cells to produce memory CD4+ (Th1) against antigen
2nd exposure = APC to memory CD4+ releases IFN-gamma, IL2 and IL3 - activates macrophages to produce TNF-alpha

Question 23

Produced by Th2 cells to dampen Th1 cells

Answer 23

IL10

Question 24

B cell activation + antibody production
Antibodies bind endothelium
Vasculitis
Weeks-months after transplant
Treat by Ab removal + B cell suppression
Rejection type?

Answer 24

Acute (antibody mediated)

Question 25

``` Months-years after transplant Smooth muscle growth + blockage of graft vessels -> ischaemia + fibrosis Bronchiolitis obliterans Treat by minimising organ damage Rejection type? ```

Answer 25

Chronic

Question 26

``` Feature of HSC transplant Recipient BM eliminated + replaced by donor BM Donor cells recipient tissues Skin rash, D+V, bloody stool, jaundice Treat with corticosteroids Rejection type? ```

Answer 26

GVHD

Question 27

5 types of rejection

Answer 27

``` Hyperacute Acute (cellular) Acute (antibody) Chronic GVHD ```

Question 28

GVHD prophylaxis

Answer 28

Methotrexate / Cyclosporine

Question 29

Poor prognostic factor for transplant

Answer 29

Hypertension

Question 30

2 post-transplant complications

Answer 30

Infection (conventional / opportunistic) | Malignancy (Kaposi's HHV8, skin cancer)

Question 31

T cell activated by: HLA-DR HLA-A

Answer 31

CD4+ | CD8+

Question 32

HLA expressed on: All cells APCs

Answer 32

``` Class I (A, B, C) Class II (DR, DQ, DP) Coded by MHC on chromosome 6 ```

Question 33

T-cell mediated rejection

Answer 33

1. Recognition - CD4+ cells recognise mismatched HLA, presented on APCs. This may be direct (donor APCs) or indirect (recipient APCs) 2. Activation - of CD4+ cells when they bind APCs 3. Effector - CD4+ cells activate CD8+, B cells, macrophages etc. to mount an immune response that destroys the transplant Occurs in acute cell-mediated rejection

Question 34

Antibody mediated rejection

Answer 34

Hyperacute rejection - pre-formed Abs floating in blood attack foreign ABO on RBCs or foreign HLA on graft endothelium, resulting in rejection Acute antibody-mediated - B cells bind foreign HLA - independently activated to form plasma and memory cells - produce antibodies against foreign HLA on graft endothelium resulting in rejection

Question 35

2 types of acute rejection

Answer 35

T cell-mediated | Antibody-mediated

Question 36

Antibodies against HLA attack...

Answer 36

Graft endothelium

Question 37

anti-ABO vs. anti-HLA antibodies

Answer 37

anti-ABO - naturally occurring; attack RBCs | anti-HLA - not naturally occurring - require previous exposure (prev. transplant, pregnancy, transfusion)

Question 38

5 types of transplant rejection

Answer 38

``` Hyperacute Acute cell-mediated Acute antibody-mediated Chronic GVHD ```

Question 39

3 risk factors for chronic rejection

Answer 39

Hypertension > Most important Multiple acute rejection Hyperlipidaemia