Transplantation 1 Flashcards

1
Q

what is transplantation

A

the act of transferring cells, tissues, or organs from one
site to another

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2
Q

when did joseph Murray perform his first successful kidney
transplant from living donor

A

1954

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3
Q

what did Dr Christian Barnard carry out in 1967

A

the 1st human heart
transplant

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4
Q

Autograft

A

Tissue is derived from ‘self’, and can be transplanted back
to the same place or another site (same one body)

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5
Q

isograft e.g. first human kidney transplant in 1954

A

tissue transplanted between genetically identical twins

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6
Q

whats the most common transplant type

A

Allograft e.g kidney, heart, pancreas, lung, liver, bowel, bone, skin

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7
Q

whats an allograft

A

Tissue transferred from one individual to another

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8
Q

Xenograft e.g.

A

Tissue transferred from one species to another (eg.
Heart valves)

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9
Q

why is whole organ xenografting limited

A

due to the potential for hyperacute rejection

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10
Q

what are immunologically privileged sites e.g.

A

sites where grafts aren’t rejected e.g cornea, brain, testis, uterus (fetus)

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11
Q

what do corneal allograft transplants not require as they are immunologically privileged sites

A

no assessment of HLA type and no administration of immunosuppressive drugs

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12
Q

what is the major barrier to overcome in transplantation

A

Human Leucocyte Antigens (HLA)

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13
Q

how many classical HLA loci are there, each encoded by seperate genes

name them

A

6

Class I (A,B,C)
Class II (DR, DQ,DP)

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14
Q

Why do HLA’s determine histocompatibility

A

as they allow tissue to be recognised as ‘self’ or ‘non-self’ by the host IS

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15
Q

what is the primary function of HLA’s, making them very polymorphic

A

to serve as
recognition molecules in the initiation of an immune
response

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16
Q

what do HLA’s present to effector cells of IS (T cells)

A

peptides from foreign substances

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17
Q

What cells are HLA class I expressed on

what pathogens do they recognise

A

on nearly all cells (nucleated)

pathogens that reside inside cells e.g. viruses

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18
Q

What cells are HLA class II expressed on

what pathogens do they recognise

A

immune cells - antigen presenting

pathogens that reside outside the cells e.g. bacteria

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19
Q

what do HLA-A define

A

the locus

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20
Q

what does HLA-A24 show

A

the serologically defined antigen

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21
Q

what does asterisk mean in HLA-A*24

A

that the allele has been defined by molecular methods (low resolution)

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22
Q

what resolution does HLA-A*24:01 show

where is this required

A

higher resolution, specific allele

required for haematopoietic stem cell transplant

23
Q

what do father and mother produce when looking at HLA inheritance

A

4 haplotypes (sets of DNA variants along single chm)

24
Q

what must be determined for all organ recipients and donors to minimise chance of rejection

A

major HLA loci

25
what are used to determine HLA loci how
terasaki trays plates with serum containing anti-HLA antibodies. patient cells and complement get added and death occurs in wells where antibody reacts with patient sample Dyes show live (green) and dead (red) cells
26
although can get DNA from buccal swabs/saliva, what does the system in NHS labs do for HLA typing
extracts genomic DNA from whole blood
27
whats the first step in determining HLA type by a molecular method
Sequence-specific primer (SSP) PCR
28
what do SSP tests consist of
multiple different PCR primers specific for known HLA polymorphisms in a kit format
29
what are produced in SSP PCR if primers are complementary to DNA sample
Specific amplicons
30
what do Individuals who are HLA-B27 (around 8%) have an increased risk for and get screened
ankylosing spondylitis and other inflammatory disorders
31
what disorder is HLA-B57 associated with
drug-induced inflammatory disorder
32
what patients in the UK are screened for HLA-B57 before beginning Abacavir (reverse transcriptase inhibitor) treatment
all HIV positive patients
33
what major risk factor for hyperacute rejection was recognised over 40 years ago
recipients having antibodies to antigens expressed on donor cells
34
what may the antibodies on donor cells causing hyperacute rejection be due to
pregnancy blood transfusion previous transplantation
35
what assays seek to identify donor-specific HLA antibody-mediated responses for given recipient
CDC crossmatch assays
36
2 main reasons for kidney transplant
diabetes High blood pressure
37
3 main reasons for heart transplant
ischaemic heart disease idiopathic dilated cardiomyopathy congenital HD
38
2 types of transplant donors
living cadaveric
39
what are kidney transplants subject to
ABO/HLA compatibility
40
what are cadaveric donors
Those which are deemed to be ‘brain stem dead’ following appropriate testing
41
whats transplant allocation based on for kidney and pancreas
blood group match and HLA-A, B and DR
42
what is performed for all transplants, prior to surgery
a crossmatch For heart and lung, logistics may prevent the crossmatch, so a virtual crossmatch is performed instead
43
what type of graft rejection should never happen
hyperacute
44
what graft rejection always happens to some degree with solid organ
chronic
45
what response mediates hyperacute rejection
humoral response
46
what are 2 causes hyperacute rejection which is usually seen within minutes of transplantation
pre-existing donor-specific antibodies in the recipient accidental ABO mismatch
47
what cascade is initiated when ab's activate the complement pathway in hyperacute rejection
the blood clotting cascade
48
what timeframe does acute rejection occur over
several days
49
what is acute rejection caused by
activation of t lymphocytes
50
what attack happens to endothelial cells in acute rejection due to mismatched HLA
cytotoxic t cell attack
51
end result of chronic rejection
vascular disease
52
what bind to endothelial cells and recruit Fc-receptor bearing monocytes/MQ in chronic rejection
alloantibodies
53
what do Inflammatory components in the vessel wall in chronic rejection lead to
damage, thickening of the vessel wall and narrowing of lumen, inadequate blood supply and damage
54
what does allogeneic transplantation require if the transplant is to survive
immunosuppression by drugs