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IMM005 > Transplantation > Flashcards

Transplantation Flashcards

1
Q

Who is the father of transplantation?

A

Peter Medawar

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2
Q

Why does transplant rejection occur?

A

Consequence of a robust immune system that was never designed for transplantation

Rejects all that is non-self

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3
Q

When was the first transplant carried out?

A

1954

Peter Brent Birgham Hospital

Between two identical twins

Recipient lived another 10 years and donor until he was 70

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4
Q

Why is the number of donations from dead donors always larger than from live donors?

A

You can take two kidneys from dead donors

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5
Q

What are the two types of donors of organ transplants?

A

Deceased (cadaveric)

Live

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6
Q

What are the two types of deceased donors?

A

Donation after brain death

Donation after circulatory death

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7
Q

Why is the quality of organs after brain death better than after circulatory death?

A

During brain death, the heart is still beating so the perfusion of the organ continues

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8
Q

How many hours after circulatory death must one wait before retrieving organs from the donor?

A

3 hours

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9
Q

People involved in live donor transplants

A

Relative, spouse friend

Paired exchange

Altruistic

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10
Q

What is an autograft?

A

Transplants or grafts from one site of the body to another in the same individual

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11
Q

What is an isograft?

A

Transplant from one genetically identical individual to another

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12
Q

What is a xenograft?

A

Transplant from one species to another

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13
Q

What is self-tolerance?

A

Normal immune homeostasis

Characterised by tolerance to antigens expressed in the individual’s own cells

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14
Q

When does self-tolerance develop?

A

In the thymus during childhood

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15
Q

Examples of transplantation antigens

A

HLA

ABO

Minor histocompatibility antigens

MICA/MICB

Endothelial cell antigens

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16
Q

What is an alloimmune response?

A

Induction of adaptive immune response to an allograft

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17
Q

Which arm of the immune response primarily causes rejection?

A

Adaptive immune response

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18
Q

What is allorecognition?

A

The process through which APCs recognise the foreign antigen present on allografts

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19
Q

What is the normal pathway by which APCs present foreign antigens to T cells?

A

Indirect pathway

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20
Q

Which pathways do APCs act through following transplantation?

A

Indirect pathway

Direct pathway

Semi-direct pathway

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21
Q

Describe the indirect pathway

A

Recipient APCs present non-self antigens to CD4+ T cells

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22
Q

Descibe the direct pathway

A

Donor APCs present non-self antigens to recipient CD8+ and CD4+ T cells

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23
Q

Describe the semi-direct pathway

A

Recipient APCs fuse with donor MHC

Recipient APCs use donor MHCs to present the foreign antigens to CD4+ and CD8+ T cells

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24
Q

What are ABO antibodies?

A

Naturally occurring preformed antibodies to non-O, non-self antigens

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25
Q

Why is the rhesus factor not important in transplantation?

A

Rhesus is not express in the epithelium

So it won’t be expressed on the organ

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26
Q

What is special about A2 individuals?

A

Blood group A2 individuals (20%) express lower densities of blood group A antigen

Can be successful donor in patients with anti-A

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27
Q

Which chromosome code for the MHC proteins in mice?

A

Chromosome 17

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28
Q

Which chromosome code for the HLA proteins in humans?

A

Chromosome 6

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29
Q

Features of MHC

A

Polygenic

Polymorphic

Codominantly expressed

Inherited from parents as a linked set of alleles = haplotypes

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30
Q

How many base pairs code for MHC

A

4 million

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31
Q

How many genes code for MHC

A

More than 200 genes

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32
Q

What is the MHC expression profile of HLA-heterozygous individuals?

A

Express up to 6 class I isoforms

Express six or eight class II isoforms

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33
Q

HLA genes

A

A B and C for class I

DR DQ DP for class II

34
Q

How is the HLA used to determine suitability for transplantation?

A

Use HLA mismatch in HLA A, B and DR

All matches in the codominantly expressed genes = 0 (mismatches)

1 match in the codominantly expressed genes = 1

No matches in the codominantly expressed genes = 2

35
Q

Which HLA mismatch profile is linked to highest transplant survival?

A

0,0,0

36
Q

All HLA genes have the same influence in transplant survival

TRUE or FALSE

A

FALSE

DR genes have greater influence in gene survival compared to A

37
Q

What is pre transplant sensitisation?

A

Determines the % of viable donors which the patient’s serum reacts to

38
Q

How can antibodies against donor HLA develop?

A

Pregnancy

Transfusion

Prior graft

Infection

Vaccination

39
Q

How does vaccination increase the possibility of anti-HLA developing?

A

The vaccination agent might share epitopes that the organ is also expressing

40
Q

How is pre transplant sensitisation determined?

A

Using a panel of reactive antibody

Measures the amount of anti-HLA preformed antibodies

41
Q

How were PRAs carried out originally?

A

T cell CDC assays

42
Q

Describe the process behind T cell CDC assays

A

Add serum and complement with antigen you are testing

If there was a reaction, a stain would show up

The number of individuals the serum reacted against the total number of individuals tested was calculated

Using this percentage, the probability of a negative preliminary crossmatch was determined

43
Q

What percentage of individuals is a complement with a PRA <10% suitable for?

A

98% of individuals would not react negatively

44
Q

What percentage of individuals is a complement with a PRA >80% suitable for?

A

5% of individuals would not react negatively

Individual will have to wait a long time

45
Q

How is PRA calculated now?

A

Solid phase testing

Flow cytometry and luminex

46
Q

What does solid phase testing determine?

A

Calculates the likelihood of transplantation

Determines the number of existing alloantibodies in the individual and correlates it with the frequency of relevant HLA alleles in the population

47
Q

Describe how solid phase testing is carried out

A

Patient serum is added to the luminex machine

The machine contains beads with specific antigens, so the matching antibodies in the patients’ serum will bind and form a complex

A fluorescently labelled antibody will bind to this complex

The combination of dyes will form a special colour

The dye is then used to determine the number of antibodies specific to antigens

48
Q

What is the difference between a PRA and a crossmatch test?

A

PRA looks at pre-transplantation on a population basis

The crossmatch test in done at the time of the transplant and looks at the reaction between the serum and the donor specifically

49
Q

What is a positive crossmatch associated with?

A

Immediate graft failure

50
Q

What is induction therapy?

A

The short term use of immunosuppressants

51
Q

Drugs taken during induction therapy

A

Corticosteroids

Polyclonal immune globulins/ monoclonol antibodies

52
Q

What is maintenance?

A

Drugs given on a long-term since there is always a potential for an immune response

53
Q

What drugs are taken during maintenance?

A

Calcineurin inhibitors

mTOR inhibitors

Anti-metabolites

54
Q

What arms of the immune system are targeted through immunosuppression?

A

Anti-CD25 - IL-2 receptor required for cell proliferation

Anti-metabolites - block enzymes involved in nucleotide synthesis (cell cycle)

55
Q

When can rejection occur?

A

Any time after transplantation

56
Q

What are the characteristics of transplant rejection?

A

Rise in serum markers of graft function

57
Q

What are the the three types of transplant rejection?

A

Hyperacute

Acute

Chronic

58
Q

When does hyperacute rejection occur?

A

On the table

The kidneys turn blue

High levels of antibodies

59
Q

When does acute rejection occur?

A

Not time-dependent

Measures how active the immune system is

Determined by the cellular arm of the immune system or B cells and their antibodies

60
Q

Characteristics of chronic rejection

A

High creatine

Low urine output

61
Q

One reason why hyperacute rejection occurs

A

Recipient has pre-existing antigens

62
Q

Which two mechanisms of rejection exist?

A

Cellular rejection

Antibody-mediated rejection

63
Q

Which cells mediate cellular rejection?

A

T lymphocytes

64
Q

How is cellular rejection defined?

A

A decline in clinical function of the allograft

65
Q

Characteristics of cellular rejection

A

Well-defined histological changes on allograft biopsy

66
Q

Which cells mediate antibody-mediated rejection?

A

B cells

67
Q

How is antibody-mediated rejection defined?

A

Histological evidence of tissue injury in the setting of detectable donor-specific antibodies

68
Q

Characteristics of antibody-mediated rejection

A

Current or recent antibody interaction with the vascular endothelium

Deposition of complement split product c4d => antibody has bound to the endothelium and complement has deposited

The presence of microvascular inflammation or accumulation of CD3 => accumulation of lymphocytes

69
Q

What increases the chance of rejection?

A

Pre-formed antibodies present specific to HLA I

70
Q

Why are infections common in transplant recipients?

A

Due to immunosuppression

71
Q

What are the types of infection that arises in transplant recipients?

A

Viral

Fungal

Opportunistic

Others

72
Q

What is a way to reduce the chances of infection in transplant recipients?

A

Infection prophylaxis

73
Q

What are medical complications of transplantation?

A

Cancer

Infection

74
Q

What additional precautions must transplant recipients make to prevent complications?

A

Avoidance of sun exposure and smoking

Annual cervical smear test

75
Q

What is graft versus host disease?

A

Occurs following transplant of immunologically competent T cells or T cell precursors into the immunocomprimised recipients

T cells recognise the non-self antigens of the recipient and start attacking healthy tissue

76
Q

What are the two types of graft versus host disease?

A

Acute < 100 days post-transplant

Chronic > 100 days post-transplant

77
Q

What is the incidence of graft vs host disease?

A

1-2% incidence

78
Q

What is transplant tolerance?

A

A well-functioning graft lacking histological signs of rejection, in the absence of any immunosuppressive drugs, in an immunocompetent host

79
Q

What are proposed strategies to achieve central and peripheral transplant tolerance?

A

Bone marrow transplantation

Cellular therapy

80
Q

What are the barriers of xenotransplantation?

A

Immunological

Ethical

IMM005 (17 decks)

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