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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
Why is the rhesus factor not important in transplantation?
Rhesus is not express in the epithelium So it won't be expressed on the organ
26
What is special about A2 individuals?
Blood group A2 individuals (20%) express lower densities of blood group A antigen Can be successful donor in patients with anti-A
27
Which chromosome code for the MHC proteins in mice?
Chromosome 17
28
Which chromosome code for the HLA proteins in humans?
Chromosome 6
29
Features of MHC
Polygenic Polymorphic Codominantly expressed Inherited from parents as a linked set of alleles = haplotypes
30
How many base pairs code for MHC
4 million
31
How many genes code for MHC
More than 200 genes
32
What is the MHC expression profile of HLA-heterozygous individuals?
Express up to 6 class I isoforms Express six or eight class II isoforms
33
HLA genes
A B and C for class I DR DQ DP for class II
34
How is the HLA used to determine suitability for transplantation?
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
Which HLA mismatch profile is linked to highest transplant survival?
0,0,0
36
All HLA genes have the same influence in transplant survival TRUE or FALSE
FALSE DR genes have greater influence in gene survival compared to A
37
What is pre transplant sensitisation?
Determines the % of viable donors which the patient's serum reacts to
38
How can antibodies against donor HLA develop?
Pregnancy Transfusion Prior graft Infection Vaccination
39
How does vaccination increase the possibility of anti-HLA developing?
The vaccination agent might share epitopes that the organ is also expressing
40
How is pre transplant sensitisation determined?
Using a panel of reactive antibody Measures the amount of anti-HLA preformed antibodies
41
How were PRAs carried out originally?
T cell CDC assays
42
Describe the process behind T cell CDC assays
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
What percentage of individuals is a complement with a PRA <10% suitable for?
98% of individuals would not react negatively
44
What percentage of individuals is a complement with a PRA >80% suitable for?
5% of individuals would not react negatively Individual will have to wait a long time
45
How is PRA calculated now?
Solid phase testing Flow cytometry and luminex
46
What does solid phase testing determine?
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
Describe how solid phase testing is carried out
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
What is the difference between a PRA and a crossmatch test?
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
What is a positive crossmatch associated with?
Immediate graft failure
50
What is induction therapy?
The short term use of immunosuppressants
51
Drugs taken during induction therapy
Corticosteroids Polyclonal immune globulins/ monoclonol antibodies
52
What is maintenance?
Drugs given on a long-term since there is always a potential for an immune response
53
What drugs are taken during maintenance?
Calcineurin inhibitors mTOR inhibitors Anti-metabolites
54
What arms of the immune system are targeted through immunosuppression?
Anti-CD25 - IL-2 receptor required for cell proliferation Anti-metabolites - block enzymes involved in nucleotide synthesis (cell cycle)
55
When can rejection occur?
Any time after transplantation
56
What are the characteristics of transplant rejection?
Rise in serum markers of graft function
57
What are the the three types of transplant rejection?
Hyperacute Acute Chronic
58
When does hyperacute rejection occur?
On the table The kidneys turn blue High levels of antibodies
59
When does acute rejection occur?
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
Characteristics of chronic rejection
High creatine Low urine output
61
One reason why hyperacute rejection occurs
Recipient has pre-existing antigens
62
Which two mechanisms of rejection exist?
Cellular rejection Antibody-mediated rejection
63
Which cells mediate cellular rejection?
T lymphocytes
64
How is cellular rejection defined?
A decline in clinical function of the allograft
65
Characteristics of cellular rejection
Well-defined histological changes on allograft biopsy
66
Which cells mediate antibody-mediated rejection?
B cells
67
How is antibody-mediated rejection defined?
Histological evidence of tissue injury in the setting of detectable donor-specific antibodies
68
Characteristics of antibody-mediated rejection
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
What increases the chance of rejection?
Pre-formed antibodies present specific to HLA I
70
Why are infections common in transplant recipients?
Due to immunosuppression
71
What are the types of infection that arises in transplant recipients?
Viral Fungal Opportunistic Others
72
What is a way to reduce the chances of infection in transplant recipients?
Infection prophylaxis
73
What are medical complications of transplantation?
Cancer Infection
74
What additional precautions must transplant recipients make to prevent complications?
Avoidance of sun exposure and smoking Annual cervical smear test
75
What is graft versus host disease?
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
What are the two types of graft versus host disease?
Acute < 100 days post-transplant Chronic > 100 days post-transplant
77
What is the incidence of graft vs host disease?
1-2% incidence
78
What is transplant tolerance?
A well-functioning graft lacking histological signs of rejection, in the absence of any immunosuppressive drugs, in an immunocompetent host
79
What are proposed strategies to achieve central and peripheral transplant tolerance?
Bone marrow transplantation Cellular therapy
80
What are the barriers of xenotransplantation?
Immunological Ethical

IMM005 (17 decks)

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