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Phase 2: Reproduction, Nephrology and Urology > Lecture 11: Solid organ transplantation > Flashcards

Lecture 11: Solid organ transplantation Flashcards

1
Q

Define the term transplant?

A

Transfer (living tissue or organ) to another part of the body or to another body

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2
Q

Name the 4 different types of transplants?

A
  1. Autologous transplant
  2. Syngeneic transplant
  3. Allogeneic transplant
  4. Xenogenic transplant
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3
Q

Define autologous transplant?

A

When the donor and recipient of the transplant are the same individual

e.g. skin graft from another part of the body

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4
Q

Define syngeneic transplant?

A

When the donor and recipient of the transplant are gentically identical twins

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5
Q

Define allogeneic transplant?

A

When the donor and recipient of the transplant are not genetically identical but are from the same species

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6
Q

Define xenogenic transplant?

A

When the donor and recipient of the transplant are from different species

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7
Q

What are the two major types of allogeneic donors?

A

Living donor e.g. kidney, liver lobe, lung lobem haemopoietic stem cell

Deceased donors e.g. heart, pancreas, cornea

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8
Q

Name the two types of deceased allogeneic donor?

A

DBD: donation after brainstem death

DCD: donation after cardiac death

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9
Q

What is the survival outlook for donors and recipients of transplant?

A

Good survival rates for both living donor and recipient.

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10
Q

There is not sufficient number of donors to treat all recipients. Which organisation in the UK decides who should get a transplant?

A

NHS blood and transplant (NHSBT)

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11
Q

How does the NHS blood and transplant decide who gets a transplant?

A

Ensures that organs donated for transplant are matched and allocated to patients in a fair and unbaised way.

Ensures equity of access for all patients.

Allocates transplant using 3 criteria: clinical need, waiting time and compatibility

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12
Q

What are the 3 criteria the NHS blood and transplant use to determine who should get the donated organ?

A
  1. Clinical need
  2. Waiting time
  3. Compatibility
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13
Q

Name the two determinates that determine the compatibility between donor organs and recipients?

A

Blood group

MHC/HLA

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14
Q

Describe blood group compatibility?

A

4 main blood groups: A, B, AB, O

Blood A has A antigens on the RBCs- meaning that in the plasma they contain anti-B antibodies. This means if A blood got into contact with B blood, the anti-B antibodies will start attacking the RBCs- immune reaction can occur.

This may be overcome by using immunosupression, plasma exxchange and immunoadsorption

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15
Q

Fill in the blanks regarding blood group compatibility

A
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16
Q

Define the major histocompatibility complex?

A

This is a group of genes that code for cell surface proteins essential for the acquired immune system to recognise foreign molecules

MHC 1 and MHC 2

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17
Q

Which chromosome is the major histocompatibility complex located on?

A

Short arm of chromosome 6

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18
Q

The major histocompatability complex contains which genes?

A

HLA genes

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19
Q

Why are HLA alleles known as being polymorphic

A

Polymorphism: genetic variation resulting in the occurence of multiple members of a single species.

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20
Q

What are the 6 major loci of the HLA genes?

A

Loci: fixed position on a chromsome where a particular gene is located.

  1. HLA-A
  2. HLA-B
  3. HLA-C
  4. HLA-DR
  5. HLA-DQ
  6. HLA-DP
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21
Q

Which locus of the HLA genes are the most polymorphic?

A

HLA-B

Has the most variability i.e. multiple different variations of the same gene

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22
Q

What are the 2 classes of HLA molecules?

A

HLA class 1

HLA class 2

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23
Q

Which loci of the HLA genes encode for HLA class 1 molecules?

A

HLA-

A, B, C

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24
Q

Which loci of the HLA genes encode for HLA class 2 molecules?

A

HLA-D:

R, Q, P

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25
Q

Describe the activity of the HLA class 1 molecule?

A
  • Present peptides from inside the cell
  • Binds to proteins derived from intracellular proteins including peptides derived from viruses.
  • Peptides derived from proteolytic degradation are transported via transporter associated with antigen processing (TAP) from the cytoplasm to the lumen of the ER.
  • The HLA class 1 associates with the TAP on the luminal side- causing the assembly of the MHC peptide complex
  • Once assembled, the MHC complex is transported via the golgi, to the cell surface where it interacts with the receptors on the surface of CD8 T cells
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26
Q

What does HLA stand for?

A

Human leukocyte antigen

27
Q

What is the difference between MHC and HLA?

A

MHC is found in verebrates

HLA is only found in humans

Similar function

28
Q

The HLA class 1 presents the peptides to which T cell?

A

CD8 (cytotoxic) T cells

29
Q

The HLA class 2 presents the peptides to which T cell?

A

CD4 (Helper) T cells

30
Q

Describe the structure of the HLA class 1?

A

Heterodimers

Consists of two polypeptide chains: α and β2 chain.

Two chains are linked noncovalently between the β2 and α3

31
Q

Describe the structure of the HLA class 2?

A

Heterodimers

Composed of an α and β chain.

β1​ -> α1

β2​ -> α2

32
Q

HLA class 1, the polymorphism is located in axons?

A

2 and 3

33
Q

HLA class 2, the polypmorphism is located in axons?

A

Axon 2

34
Q

Describe the activity of the HLA class 2 molecule?

A
  • Present peptides from outside the cell
  • Binds to proteins derived from extracellular and cell surface proteins including peptides derived from bacteria.
  • HLA class 2 are partially assembled within the ER and is then transported via the golgi to MIIC vesicles
35
Q

Which cells express HLA class 1 molecules?

A

Expressed on the cell surface of all nucleated cells

36
Q

Which cells express HLA class 2 molecules?

A

Expressed on the cell surface of antigen presenting cells e.g. dendritic cells, B cells and macrophages, and activated T cells

37
Q

How many HLA molecules can an antigen binding cell have on its cell surface?

A

Can express 1000’s of different HLA molecules at the cell surface

Various types e.g. HLA-A, HLA-DQ

38
Q

Which type of peptide does HLA class 1 bind to?

A

Viral peptides

39
Q

Which type of peptide does HLA class 2 bind to?

A

Bacterial peptides

40
Q

Which type of T cell does the HLA class 1 present the antigen to?

A

CD8 T cell

41
Q

Which type of T cell does the HLA class 2 present the antigen to?

A

CD4 (T helper) cell

42
Q

HLA class 1 binds peptides derived from:

A) Intracellular proteins

B) Extracellular proteins

A

A) Intracellular proteins

43
Q

HLA class 2 binds peptides derived from:

A) Intracellular proteins

B) Extracellular proteins

A

B) Extracellular proteins

44
Q

What is an advantage and disadvantage of HLA Polymorphism

A
  • Advantage to the species for protection against different pathogens
  • Disadvantage for transplantation of tissue and organs between HLA incompatible individuals
45
Q

Describe the immune response that occurs when bone marrow is transplanted?

A

When bone marrow is transplanted, it replaces the immune system of the recipient and can generate an immune response against the recipient as the recipient’s tissue and organs are recognised as “non-self” resulting in graft versus host disease.

46
Q

What Is Direct Allorecognition?

A

The process by which donor-derived major histocompatibility complex (MHC)-peptide complexes, typically presented by donor-derived ‘passenger’ dendritic cells, are recognised directly by recipient T cells.

i.e. T-cells respond vigorously to non-self HLA molecules

47
Q

HLA matching is associated with better outcome for transplant but mismatch are accepted. Why?

A

Large diversity in HLA

Low possibility that donor and recipient will have exact HLA.

Accepts mismatch- but kept to a minimum.

Immunosuppresion to prevent rejection

48
Q

Describe what would occur if a kidney was transplanted and the recipient was not immunosuppressed?

A

The immune system of the recipient will mount an immune response against the “non-self” kidney resulting in rejection of the kidney

49
Q

Which organ doesnt seem to suffer acute rejection and hence HLA matching isnt necessary?

A

The liver

50
Q

When would you not transplant donor into recipient in relation to HLA?

A

Mismatching of HLA molecules between donor and recipient is acceptable.

Transplant would not occur in the presence of ‘Donor specific antibody’ i.e. the recipient has been previously exposed to some of HLA molecules located in the donor (doesnt have to be previous expose to the donor- would be due to any other blood) and has formed antibodies against it.

51
Q

Name the routes in which patient may make antibodies against non-self HLA?

A
  1. Pregnancy
  2. Blood transfusion
  3. Previous transplant
52
Q

Describe how patients may make antibodies against non-self HLA when they are pregnancy?

A

The HLA molecules are inherited from the mother and father (50:50)

During pregnancy, the mother is exposed to the fathers half of the fetus HLA. In response, her body starts to form antibodies against these specific HLA molecules.

53
Q

Describe hyperacute rejection?

A
  • Rejection occurs immediately against the transplanted organ
  • Occurs a few minutes after the transplant when the antigens are completely unmatched
  • Occurs minutes / hours after transplant
  • Rare- as crossmatching of blood type and recipient HLA sensitivity is assessed prior to transplant
  • Initially it starts with complement activation leading to inflammation and then thrombosis. Causing damage to the endothelium
54
Q

The status of the donor and recipient must be attained before transplant.

What status are we testing for?

A
  1. Blood type
  2. HLA matching
  3. Recipient HLA sensitivity
55
Q

Define the term “HLA sensitivity”?

A

This is the status of the recipient for transplant.

HLA senstivity refers to the HLA antibody status of the recipient. If the recipient has previously been exposed to tissue with mismatch of HLA, the body will now have antibodies against these HLA molecules. If so, the donor transplant HLA status must be determined to make sure the antibodies will not form an attack on the new tissue.

56
Q

Name the three types of transplant rejection?

A
  1. Hyperacute rejection
  2. Acute rejection
  3. Chronic rejection
57
Q

All recipients have some amount of ___ rejection.

A

acute

58
Q

Describe acute transplant rejection?

A
  • May occur any time from the first week after the transplant to 3 months afterward.
  • Immune mediated (T-cells (cellular) and B-cells (antibodies)).
  • Treatment with immunosuppressors.
59
Q

Describe chronic transplant rejection?

A
  • Can take place over many years.
  • The body’s constant immune response against the new organ slowly damages the transplanted tissues or organ.
60
Q

The aim is to match graft life expectancy with patient life expectancy. Why?

A

Multiple transplants may be required for a recipient throughout their lifetime.

Often organs are damaged to some extent e.g. for descended donors- damage done during the death.

By trying to match graft life expectancy with patient life expectancy you are getting the most bang for buck.

61
Q

Describe the tier system used to allocate donors to recipients in the UK?

A

Two tiers: A and B.

Tier A is offered transplants first and if not useful, it is offered to tier B

62
Q

Describe the tier A group of transplant allocation

A

These are patients that are looked at first when an organ becomes available. Usually these patients are hard to match so when a match is found it is desirable to give it to these patients.

These patients are either have a:

  • Matchability score =10 (HLA match donor is hard) or
  • They have 100% calculated reaction frequency (lots of antibodies against foreign HLA molecules) or
  • Patients that have accrued 7 years of waiting time
63
Q

Describe the tier B group of transplant allocation

A

These are all other eligible recipients.

This individuals in this group are prioritised according to a points-based system- using 8 elements e.g. matchability, total HLA mismatch etc

64
Q

What are the 4 important tests to perform prior to transplant

A
  1. HLA type patient
  2. HLA type donor
  3. Screen patient for presence of preformed HLA alloantibodies (every three months when patient is on transplant list)
  4. Crossmatch patient and donor prior to transplant to ensure negative result i.e. no reactions

Phase 2: Reproduction, Nephrology and Urology (25 decks)

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