Transplantation

Question 1

What are the 3 stages of transplant rejection?

Answer 1

1) Recognition
2) Activation
3) Effector function

Question 2

What is recognised following a transplantation?

Answer 2

HLA - A, B, DR = these are the most important
Minor HLA - other polymathic self peptides
ABO Blood Antigens

Question 3

What are the two types of recognition that occur in transplantation?

Answer 3

1) Direct

2) Indirect

Question 4

What is Direct Transplant Recognition?

Answer 4

Donor APC presenting antigen and/or MHC to recipient T-cells. Acute rejection mainly involves direct presentation

Question 5

What is Indirect Transplant Recognition?

Answer 5

Recipient APC presenting donor antigen to recipient T-cells - i.e. the immune system working normally, as it would for an infection. Chronic rejection mainly involves indirect presentation

Question 6

Hyperacute Transplant Rejection - Time frame?

Answer 6

Mins-Hrs

Question 7

Hyperacute Transplant Rejection - Mechanism?

Answer 7

Preformed Ab which activates Complement

Question 8

Hyperacute Transplant Rejection - Pathology?

Answer 8

Thrombosis and Necrosis

Question 9

Hyperacute Transplant Rejection - Treatment?

Answer 9

Prevention - Crossmatching

Question 10

Acute Cellular Transplant Rejection - Time frame?

Answer 10

Weeks-Months

Question 11

Acute Cellular Transplant Rejection - Mechanism?

Answer 11

CD4 activating a Type IV reaction

Question 12

Acute Cellular Transplant Rejection - Pathology?

Answer 12

Cellular Infiltrate

Question 13

Acute Cellular Transplant Rejection - Treatment?

Answer 13

T-cell Immunosuppression

Question 14

Acute Antibody Mediated Transplant Rejection - Time frame?

Answer 14

Weeks - Months

Question 15

Acute Antibody Mediated Transplant Rejection - Mechanism?

Answer 15

B-cell activation - antibody attacks vessels

Question 16

Acute Antibody Mediated Transplant Rejection - Pathology?

Answer 16

Vasculitis, C4d

Question 17

Acute Antibody Mediated Transplant Rejection - Treatment?

Answer 17

Ab removal and B-cell Immunosuppression

Question 18

Chronic Transplant Rejection - Time frame?

Answer 18

Months - Years

Question 19

Chronic Transplant Rejection - Mechanism?

Answer 19

Immune and non-immune mechanism

Question 20

Chronic Transplant Rejection - Pathology?

Answer 20

Fibrosis

Question 21

Chronic Transplant Rejection - Treatment?

Answer 21

Minimise Organ Damage

Question 22

Graft v Host Disease - Time frame?

Answer 22

Days - weeks

Question 23

Graft v Host Disease - Mechanism?

Answer 23

Donor cells attack Host

Question 24

Graft v Host Disease - Pathology?

Answer 24

Skin (rash), Gut (D+V, bloody stool) and liver (jaundice) involvement

Question 25

Graft v Host Disease - Treatment?

Answer 25

Prevention/ Immunosuppression - corticosteroids

Question 26

Immune Recognition

Answer 26

T cells recognise antigen with MHCs, B cells can recognise just antigen APCs present antigen to T cells (dendritic cells, Macrophages, B cells)

Question 27

Tissue Matching for Transplant

Answer 27

Important to reduce Antigen differences and therefore recognition and rejection 1) determine donor and recipient blood group and HLA type - PCR. Maximise similarity 2) Check recipients pre-formed Ab against ABO and HLA - via CDC (complement Dependent Cytotoxicity), FACS (flow cytometry) and Luminex (like solid phase FACS- can pick up abs to individual HLAs) 3) Cross Match- via CDC and FACS. test if serum from recipient is able to bind/kill donor lymphocytes - positive crossmatch is contraindicated for transplantation 4) after transplant check again for new antibodies vs the graft

Question 28

Pre-transplant induction agents?

Answer 28

Suppress T cell responses e.g. anti CD52 Alemtuzumab or anti-CD25 Basiliximab

Question 29

What can you use to treat repeat episodes of acute rejection?

Answer 29

Cellular - Steroids, IVIG | Ab-mediated - IVIG, plasma exchange, anti-c5

Question 30

3 Other post transplantation complications?

Answer 30

1) Infections 2) Malignancy - Viral associated (x100) Kaposi's (HHV8) and Lymphoproliferative Diseases (EBV) - Skin Cancer (x20) - other - lung, colon (x2-3) 3) Atherosclerosis - Hypertension and hyperlipidaemia (x20)