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Immunology > Transplantation 1 > Flashcards

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
Q

what are used to determine HLA loci

how

A

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
Q

although can get DNA from buccal swabs/saliva, what does the system in NHS labs do for HLA typing

A

extracts genomic DNA from whole blood

27
Q

whats the first step in determining HLA type by a molecular method

A

Sequence-specific primer (SSP) PCR

28
Q

what do SSP tests consist of

A

multiple different PCR primers specific for
known HLA polymorphisms in a kit format

29
Q

what are produced in SSP PCR if primers are complementary to DNA sample

A

Specific amplicons

30
Q

what do Individuals who are HLA-B27 (around 8%) have an increased risk for and get screened

A

ankylosing
spondylitis and other inflammatory disorders

31
Q

what disorder is HLA-B57 associated with

A

drug-induced inflammatory disorder

32
Q

what patients in the UK are screened for HLA-B57 before beginning
Abacavir (reverse transcriptase inhibitor) treatment

A

all HIV positive patients

33
Q

what major risk factor for hyperacute rejection was recognised over 40 years ago

A

recipients having
antibodies to antigens expressed on donor cells

34
Q

what may the antibodies on donor cells causing hyperacute rejection be due to

A

pregnancy
blood transfusion
previous transplantation

35
Q

what assays seek to identify donor-specific HLA antibody-mediated responses for given recipient

A

CDC crossmatch assays

36
Q

2 main reasons for kidney transplant

A

diabetes
High blood pressure

37
Q

3 main reasons for heart transplant

A

ischaemic heart disease

idiopathic dilated cardiomyopathy

congenital HD

38
Q

2 types of transplant donors

A

living
cadaveric

39
Q

what are kidney transplants subject to

A

ABO/HLA compatibility

40
Q

what are cadaveric donors

A

Those which are deemed to be ‘brain stem dead’ following
appropriate testing

41
Q

whats transplant allocation based on for kidney and pancreas

A

blood group match and
HLA-A, B and DR

42
Q

what is performed for all transplants, prior to surgery

A

a crossmatch

For heart and lung, logistics may prevent the crossmatch, so a virtual crossmatch is
performed instead

43
Q

what type of graft rejection should never happen

A

hyperacute

44
Q

what graft rejection always happens to some degree with
solid organ

A

chronic

45
Q

what response mediates hyperacute rejection

A

humoral response

46
Q

what are 2 causes hyperacute rejection which is usually seen within minutes of transplantation

A

pre-existing donor-specific
antibodies in the recipient

accidental
ABO mismatch

47
Q

what cascade is initiated when ab’s activate the complement pathway in hyperacute rejection

A

the blood clotting cascade

48
Q

what timeframe does acute rejection occur over

A

several days

49
Q

what is acute rejection caused by

A

activation of t lymphocytes

50
Q

what attack happens to endothelial cells in acute rejection due to mismatched HLA

A

cytotoxic t cell attack

51
Q

end result of chronic rejection

A

vascular disease

52
Q

what bind to endothelial cells and recruit Fc-receptor
bearing monocytes/MQ in chronic rejection

A

alloantibodies

53
Q

what do Inflammatory components in the vessel wall in chronic rejection lead to

A

damage,
thickening of the vessel wall and narrowing of lumen, inadequate
blood supply and damage

54
Q

what does allogeneic transplantation require if the transplant is to survive

A

immunosuppression by drugs

Immunology (13 decks)

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