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Renal system > Transplantation immunology > Flashcards

Transplantation immunology Flashcards

(50 cards)

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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.

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A

biprosthetic valve

22
Q

what mediates immune reactions to transplants

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A

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

23
Q

what are the patterns of rejection?

Study These Flashcards
A

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

24
Q

hyperacute rejection

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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
acute rejection
``` 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
cells involved in acute rejection
cytotoxic T cells kill targets NKs trigger apoptosis T helper cells recruit other cells signs may include graft failure and tenderness
27
what cells due T helper cells recruit?
type 1 = macrophages and cytotoxic cells | type 2 = B cells
28
chronic rejection
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
what causes endovascular inflammation?
mediated by T cells alloantibodies macrophages cytokines
30
how to reduce rejection?
most important is donor/ recipient matching | immunosuppressants
31
donor/ recipient matching
ABO matching | HLA matching
32
HLA matching
``` ABC = MHC 1 - interact with cytotoxic cells D = MHC II = interact with T helper cells ```
33
most important HLA matching
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
HLA DR
very important for renal transplant
35
rejection in young children
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
immunosuppressants
usually 3 agents given
37
what are the 3 immunosuppressant agents?
anti-proliferative glucocorticoid calcineurin inhibitor to target all aspects of immune system
38
anti-proliferative
overlap with chemotherapeutics | usually anti-metabolites, some are cyclophosphamide and methotrexate
39
what anti-proliferative drugs are usually used?
azathioprine (pro drug) - converted to 6-mercaptopurine non-enzymatically in tissues
40
azathioprine
interferes with purine synthesis/ handling impairs DNA/RNA replication results in reduced cell turnover
41
prescribing azathioprine
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
contraindication of azathiprine
allopurinol for gout inhibits the enzyme xanthine oxidase which breaks down azathioprine so the drug will accumulate and is life threatening
43
calcineurin
calcineurin is a calcium dependent enzyme | which is involved in intracellular signalling within T cells
44
calcineurin inhibitors
inhibits production of IL-2 | e.g. tacrolimus
45
IL-2
important for enhancement of cell mediated immunity
46
glucocorticoids
anti-inflammatory and immunosuppressant
47
how do glucocorticoids work?
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
arachidonic acid derivatives
prostaglandins thromboxanes prostacyclins
49
why are neutrophils raised?
increased circulating neutrophils due to loss of adhesion molecules because they removed from cells
50
what can immunosuppressants not do?
prevent chronic rejection

Renal system (17 decks)

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