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Flashcards in Transplantation Deck (30)
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1

What are the 3 stages of transplant rejection?

1) Recognition
2) Activation
3) Effector function

2

What is recognised following a transplantation?

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

3

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

1) Direct
2) Indirect

4

What is Direct Transplant Recognition?

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

5

What is Indirect Transplant Recognition?

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

6

Hyperacute Transplant Rejection - Time frame?

Mins-Hrs

7

Hyperacute Transplant Rejection - Mechanism?

Preformed Ab which activates Complement

8

Hyperacute Transplant Rejection - Pathology?

Thrombosis and Necrosis

9

Hyperacute Transplant Rejection - Treatment?

Prevention - Crossmatching

10

Acute Cellular Transplant Rejection - Time frame?

Weeks-Months

11

Acute Cellular Transplant Rejection - Mechanism?

CD4 activating a Type IV reaction

12

Acute Cellular Transplant Rejection - Pathology?

Cellular Infiltrate

13

Acute Cellular Transplant Rejection - Treatment?

T-cell Immunosuppression

14

Acute Antibody Mediated Transplant Rejection - Time frame?

Weeks - Months

15

Acute Antibody Mediated Transplant Rejection - Mechanism?

B-cell activation - antibody attacks vessels

16

Acute Antibody Mediated Transplant Rejection - Pathology?

Vasculitis, C4d

17

Acute Antibody Mediated Transplant Rejection - Treatment?

Ab removal and B-cell Immunosuppression

18

Chronic Transplant Rejection - Time frame?

Months - Years

19

Chronic Transplant Rejection - Mechanism?

Immune and non-immune mechanism

20

Chronic Transplant Rejection - Pathology?

Fibrosis

21

Chronic Transplant Rejection - Treatment?

Minimise Organ Damage

22

Graft v Host Disease - Time frame?

Days - weeks

23

Graft v Host Disease - Mechanism?

Donor cells attack Host

24

Graft v Host Disease - Pathology?

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

25

Graft v Host Disease - Treatment?

Prevention/ Immunosuppression - corticosteroids

26

Immune Recognition

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

27

Tissue Matching for Transplant

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

28

Pre-transplant induction agents?

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

29

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

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

30

3 Other post transplantation complications?

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)