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Renal system > Transplantation immunology > Flashcards

Transplantation immunology Flashcards

1
Q

tissue involved in transplant

A

graft or transplant

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2
Q

donations

A

can be organs or tissue

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3
Q

what is rejection

A

describes the immune response to the graft, this is separate to graft failure

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4
Q

graft failure

A

occurs due to non-immune reasons

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5
Q

types of graft

A

based on location or based on donor

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6
Q

types of graft based on location

A

orthotopic graft

heterotopic graft

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7
Q

orthotopic graft

A

donor tissue mobilised into natural anatomical location e.g. liver

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8
Q

heterotopic graft

A

donor tissue mobilised into unnatural anatomical location - e.g. kidney, own ones not removed

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9
Q

types of graft based on donor

A

autograft
isograft
allograft
xenograft

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10
Q

autograft

A

donor is the recipient

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11
Q

isograft

A

donor is genetically identical to recipient

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12
Q

allograft

A

donor is same species as recipient

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13
Q

xenograft

A

donor is of different species to recipient

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14
Q

another classification of grafts

A

living or cadaveric

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15
Q

what conditions cause ineligibility for tissue donation

A

active cancer
HIV/ hep C
ebola virus
CJD - mad cows disease

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16
Q

what is the most common transplant?

A

kidney

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17
Q

deceased donors

A

circulatory deceased or brain deceased

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18
Q

viability of grafts

A

more viable in brain deceased donors

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19
Q

immunology

A

isografts and autografts do not provoke an immune reaction but allografts and xenografts do
decellularised transplants don’t carry antigens
avascular transplants are largely spared of rejection

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20
Q

avascular transplant e.g.

A

cornea, has little blood supply and no lymphatic drainage

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21
Q

decellularised transplant e.g.

A

biprosthetic valve

22
Q

what mediates immune reactions to transplants

A

ABO incompatibility - crucial
HLA incompatibility - important
minor histocompatibility complexes -minor

23
Q

what are the patterns of rejection?

A

hyperacute rejection - mins/ hours on operating table
acute reaction - weeks to months
chronic rejection - years

24
Q

hyperacute rejection

A

mediated by pre-formed antibodies (ABO)
ABO antibodies line vascular endothelium in addition to RBCs
binding of antibodies mediates immune response to antigen on donor organ
graft becomes inflamed and organ failure
graft must be removed immediately to avoid overwhelming systemic inflammation
organ becomes thrombotic and ischaemic
can be fatal
graft will not survive

25
Q

acute rejection

A 
cell initiated - T cells 
humoral or cell mediated response 
antibodies are not pr-formed
due to HLA (human MHC) incompatibility
T cells recognise these cells or fragments of antigens as non-self 
immune response against HLA
26
Q

cells involved in acute rejection

A

cytotoxic T cells kill targets
NKs trigger apoptosis
T helper cells recruit other cells
signs may include graft failure and tenderness

27
Q

what cells due T helper cells recruit?

A

type 1 = macrophages and cytotoxic cells

type 2 = B cells

28
Q

chronic rejection

A

due to long-term low grade cell mediated immunity
may be related to minor histocompatibility complexes
endovascular inflammation
smooth muscle hyperplasia - vascular congestion due to constriction
fibrosis
reduced blood flow
aka allograft vasculopathy

29
Q

what causes endovascular inflammation?

A

mediated by T cells
alloantibodies
macrophages
cytokines

30
Q

how to reduce rejection?

A

most important is donor/ recipient matching

immunosuppressants

31
Q

donor/ recipient matching

A

ABO matching

HLA matching

32
Q

HLA matching

A 
ABC = MHC 1 - interact with cytotoxic cells
D = MHC II = interact with T helper cells
33
Q

most important HLA matching

A

HLAs must be matched as closely as possible, but the HLA subtype and type of transplant influence important
different aspects of the immune system are involved in rejection in different organs

34
Q

HLA DR

A

very important for renal transplant

35
Q

rejection in young children

A

younger than 1 they may be able to receive ABO incompatible grafts due to their immature immune systems with a similar outcome to matched ones

36
Q

immunosuppressants

A

usually 3 agents given

37
Q

what are the 3 immunosuppressant agents?

A

anti-proliferative
glucocorticoid
calcineurin inhibitor
to target all aspects of immune system

38
Q

anti-proliferative

A

overlap with chemotherapeutics

usually anti-metabolites, some are cyclophosphamide and methotrexate

39
Q

what anti-proliferative drugs are usually used?

A

azathioprine (pro drug) - converted to 6-mercaptopurine non-enzymatically in tissues

40
Q

azathioprine

A

interferes with purine synthesis/ handling
impairs DNA/RNA replication
results in reduced cell turnover

41
Q

prescribing azathioprine

A

can be deactivated by thipurine methyltransferase or xanthine oxidase
need to check TPMT levels before prescription as these are variable in level and so person may be unable to break down the drug

42
Q

contraindication of azathiprine

A

allopurinol for gout inhibits the enzyme xanthine oxidase which breaks down azathioprine so the drug will accumulate and is life threatening

43
Q

calcineurin

A

calcineurin is a calcium dependent enzyme

which is involved in intracellular signalling within T cells

44
Q

calcineurin inhibitors

A

inhibits production of IL-2

e.g. tacrolimus

45
Q

IL-2

A

important for enhancement of cell mediated immunity

46
Q

glucocorticoids

A

anti-inflammatory and immunosuppressant

47
Q

how do glucocorticoids work?

A

inhibit phospholipase A2 via lipocortin-1
reduced eicosanoid synthesis (arachidonic acid derivatives)
dampens inflammatory response
reduced cytokine secretion
reduced adhesion molecules
induces endonucleases that mediate apoptosis within white cells
neutrophils are raised

48
Q

arachidonic acid derivatives

A

prostaglandins
thromboxanes
prostacyclins

49
Q

why are neutrophils raised?

A

increased circulating neutrophils due to loss of adhesion molecules because they removed from cells

50
Q

what can immunosuppressants not do?

A

prevent chronic rejection

Renal system (17 decks)

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