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Renal > Transplantation immunology > Flashcards

Transplantation immunology Flashcards

1
Q

Graft

A

Tissue to be transplanted

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2
Q

Autograft

A

Donor is recipient

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3
Q

Isograft

A

Donor is genetically identical to recipient

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4
Q

Allograft

A

Donor is same species as recipient

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5
Q

Xenograft

A

Donor is of different species

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6
Q

Orthotopic graft

A

Donor tissue mobilised into natural anatomical location

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7
Q

Heterotopic graft

A

Donor tissue in unnatural anatomical location

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8
Q

Tranaplantation immunology

A

Events that occur after allograft or xenograft is performed

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9
Q

Ineligibility of tissue donation

A
  • Active cancer
  • HIV/hep C
  • Ebola
  • CJD
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10
Q

What is a domino transplant?

A
  • CF: heart and lungs from deceased donor to CF pt, heart from CF to another recipient
  • Paired donor transplant: could be 3+ pairs
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11
Q

Which grafts provoke immune response?

A

Allografts and xenografts

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12
Q

Which transplant will be spared of rejection?

A

Cornea - avascular

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13
Q

ABO blood groups

A
  • 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
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14
Q

Rh blood group

A
  • Found in rhesus monkey
  • Alleles of 3 genes code for antigen
  • Can be + or -
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15
Q

Where are MHC I found?

A

Nucleated cells

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16
Q

Where are MHC II found?

A

Antigen presenting cells - dendrites, macrophages, B-cells

17
Q

HLA associated with MHC I

A

A,B,C

18
Q

HLA associated with MHC II

A

HLA DR, DB, DQ, DP

19
Q

When will donor and recipient match?

A

MHC I and ii

6 antigen matches

20
Q

Hyperacute rejection

A
  • 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
21
Q

Acute rejection

A
  • Incidence is high for 90 days
  • Humoral or cell mediated
  • Antibodies not pre-formed
  • HLA incompatability
  • T cells recognise cells as non-self
22
Q

Direct recognition

A
  • Recognising intact MHC displayed by donor APC in graft
  • T cell recognises structure of intact allogeneic MHC
  • Involves CD8+ and CD4+
23
Q

Indirect recognition

A
  • 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
24
Q

Acute rejection

A
  • 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
25
Q

Chronic rejection

A
  • 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
26
Q

How to reduce rejection chances

A
  • Donor/recipient matching
  • Cross matching, ABO matching and HLA matching
  • Immunosuppressive therapy
27
Q

Cross matching

A
  • 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
28
Q

Tissue typing

A
  • 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
29
Q

Immunosuppression

A
  • Anti-proliferative
  • Glucocorticoid
  • Calcineurin inhibitor
30
Q

Anti-proliferative drugs

A
  • 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
31
Q

Glucocorticoids

A
  • 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
32
Q

Calcineurin inhibitors

A
  • 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

Renal (26 decks)

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