Transplantation immunology

Question 1

Graft

Answer 1

Tissue to be transplanted

Question 2

Autograft

Answer 2

Donor is recipient

Question 3

Isograft

Answer 3

Donor is genetically identical to recipient

Question 4

Allograft

Answer 4

Donor is same species as recipient

Question 5

Xenograft

Answer 5

Donor is of different species

Question 6

Orthotopic graft

Answer 6

Donor tissue mobilised into natural anatomical location

Question 7

Heterotopic graft

Answer 7

Donor tissue in unnatural anatomical location

Question 8

Tranaplantation immunology

Answer 8

Events that occur after allograft or xenograft is performed

Question 9

Ineligibility of tissue donation

Answer 9

• Active cancer
• HIV/hep C
• Ebola
• CJD

Question 10

What is a domino transplant?

Answer 10

• CF: heart and lungs from deceased donor to CF pt, heart from CF to another recipient
• Paired donor transplant: could be 3+ pairs

Question 11

Which grafts provoke immune response?

Answer 11

Allografts and xenografts

Question 12

Which transplant will be spared of rejection?

Answer 12

Cornea - avascular

Question 13

ABO blood groups

Answer 13

• Two glycolipid antigens - A and B
• Each person has 2 ABO alleles
• Lacking A or B antigens will have corresponding antibodies in serum
• These are anti-A and anti-B antibodies
• 0 blood will have no antigens - anti-A and anti-B antibodies will be present

Question 14

Rh blood group

Answer 14

• Found in rhesus monkey
• Alleles of 3 genes code for antigen
• Can be + or -

Question 15

Where are MHC I found?

Answer 15

Nucleated cells

Question 16

Where are MHC II found?

Answer 16

Antigen presenting cells - dendrites, macrophages, B-cells

Question 17

HLA associated with MHC I

Answer 17

A,B,C

Question 18

HLA associated with MHC II

Answer 18

HLA DR, DB, DQ, DP

Question 19

When will donor and recipient match?

Answer 19

MHC I and ii

6 antigen matches

Question 20

Hyperacute rejection

Answer 20

• Mediated by pre-formed antibodied (ABO incompatability)
• ABO line vascular endothelium
• Binding of antibodies mediates immune response
• Graft is inflamed and organ failure occurs
• Graft must be removed

Question 21

Acute rejection

Answer 21

• Incidence is high for 90 days
• Humoral or cell mediated
• Antibodies not pre-formed
• HLA incompatability
• T cells recognise cells as non-self

Question 22

Direct recognition

Answer 22

• Recognising intact MHC displayed by donor APC in graft
• T cell recognises structure of intact allogeneic MHC
• Involves CD8+ and CD4+

Question 23

Indirect recognition

Answer 23

• Donor MHC is processed and presented by recipient APC by class ii MHC molecules
• Donor MHC is handled like foreign antigen
• Involves just CD4+ cells

Question 24

Acute rejection

Answer 24

• Cytotoxic T cells kill targets
• NK cells trigger apoptosis
• T helper cells (T1 recruit macrophages/CD8 +ve TC, type 2 recruit B cells)
• Mononuclear infiltrate occurs leading to necrosis of arterial walls
• Signs include graft failure and tenderness
• Reversible

Question 25

Chronic rejection

Answer 25

- Low grade cell mediated immunity - MHC - Endovascular inflammation (mediated by T cells, alloantibodies, macrophages, cytokines) - Smooth muscle hyperplasia - vascular congestion - Fibrosis - Allograft vasculopathy - New graft required

Question 26

How to reduce rejection chances

Answer 26

- Donor/recipient matching - Cross matching, ABO matching and HLA matching - Immunosuppressive therapy

Question 27

Cross matching

Answer 27

- Test for pre-formed antibodies - Recipient previously expose to HLAs may be antibodies already present that would increase chances of rejection - Tested by cross matching - mixed donor blood with recipients serum - If cross-match is negative, transplant is likely to be successful

Question 28

Tissue typing

Answer 28

- Before graft, donor and recipient tissue typed for HLA - HLA must be matched as closely as possible by HLA subtype and type of transplant influence importance - HLA DR very important for renal transplant - Six antigen match is not always necessary as can use immunosuppressive drugs

Question 29

Immunosuppression

Answer 29

- Anti-proliferative - Glucocorticoid - Calcineurin inhibitor

Question 30

Anti-proliferative drugs

Answer 30

- Anti-metabolites - Overlap with chemotherapeutics - Alternatives include cyclophosphamide (alklyating agent) and methotrexate (dihydrofolate reductase inhibition) - Azathioprine (pro-drug) and 6-mercaptopurine - Interfere with purine synthesis - impair DNA/RNA replication - Reduced cell turnover - Azathioprine converted to 6-mercaptopurine

Question 31

Glucocorticoids

Answer 31

- Anti-inflammatory and immunosuppressent]Inhibits phospholipase A2 - Reduced eicosanoid synthesis, cytokine synthesis, adhesion molecules - Induces endonucleases that mediate apoptosis in white cells - Paradoxically, neutrophils frequently raised on initiation

Question 32

Calcineurin inhibitors

Answer 32

- Calcium dependent enzyme - Intracellular signalling in T cells - Inhibition produces IL-2 - IL-2 important for cell-mediated immunity - IL-2 normally increases TH1 and 2 formation - E.g. tacrolimus