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IIH > Transplantation > Flashcards

Transplantation Flashcards

1
Q

List the 4 transplantation types.

For each type, give an example.

A

1 - Cell transplantation, e.g. blood transfusion.

2 - Stem cell transfusion, e.g. bone marrow transfusion.

3 - Tissue transplantation, e.g. corneal transplantation.

4 - Organ transplantation, e.g. lung transplant.

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2
Q

List 5 sources of transplants.

A

1 - Autologous (from self).

2 - Syngeneic (from genetically identical twins).

3 - Haploidentical (from parent to child).

4 - Allogeneic (from different members of the same species).

5 - Xenogeneic (from another species).

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3
Q

List 3 factors which influence the quality of a graft for transplantation.

A

1 - Cell numbers / size of the graft.

2 - Possibility of infection or cancer from the graft.

3 - Life span of the graft.

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4
Q

List 2 factors which must be matched to ensure graft rejection doesn’t occur.

A

1 - Match for ABO blood group antigens.

2 - For bone marrow stem cell transplants, match for HLA genes (difficult due to polymorphisms).

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5
Q

List the human leukocyte antigens which are synonymous with MHC class I and II.

A
  • MHC class I is synonymous with HLA A, B and C.

- MHC class II is synonymous with HLA DP, DQ and DR.

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6
Q

On which chromosome are human leukocyte antigen genes found?

A

Chromosome 6.

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7
Q

Which type of molecules are processed by the protein encoded by the ABO gene?

Where are these target molecules found?

A
  • Carbohydrates.

- On the surface of erythrocytes.

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8
Q

Which protein is encoded by the ABO gene if the phenotype is blood group A?

A

N-acetylgalactosaminyl transferase.

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9
Q

Which protein is encoded by the ABO gene if the phenotype is blood group B?

A

D-galactosyl transferase.

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10
Q

What is the specific function of the product of the blood group A ABO gene?

A

It adds a GalNAc group to the carbohydrate found on the surface of erythrocytes.

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11
Q

What is the specific function of the product of the blood group B ABO gene?

A

It adds galactose to the carbohydrate found on the surface of erythrocytes.

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12
Q

Which proteins are encoded by the ABO gene if the phenotype is blood group AB?

A

The products of both blood group A and blood group B.

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13
Q

Which proteins are encoded by the ABO gene if the phenotype is blood group O?

A

None.

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14
Q

What immunological advantage do people with blood group O have?

What about people with blood group A and blood group B?

A
  • Bacteria have similar enzymes to those produced by the ABO gene.
  • People with blood group O have antibodies against the sugar groups processed by these enzymes as part of their immune response to bacteria.
  • People with blood group A have anti-B antibodies, and people with blood group B have anti-A antibodies.
  • People with blood group AB lack both anti-A and anti-B antibodies.
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15
Q

What type of antibodies are anti-A and anti-B antibodies?

A

IgM constant region.

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16
Q

List the blood groups in order of prevalence.

A

1 - Blood group A (42%).

2 - Blood group O (38%).

3 - Blood group B (14%).

4 - Blood group AB (6%).

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17
Q

Why is it advantageous that the anti-A and anti-B antibodies are IgM antibodies?

A

Because IgM doesn’t cross the placenta.

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18
Q

List 2 instances in which red cells might be transfused.

A

1 - In a patient with anaemia.

2 - After suffering trauma.

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19
Q

List 3 instances in which platelets might be transfused.

A

1 - In a patient with thrombocytopenia.

2 - After suffering trauma.

3 - Following stem cell transplantation.

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20
Q

List 3 instances in which plasma might be transfused.

A

1 - In a patient with coagulopathy.

2 - After suffering trauma.

3 - To replace blood factors, e.g. after suffering burns.

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21
Q

List 3 molecules that are often transfused in the blood.

A

1 - Factor 8.

2 - Immunoglobulin.

3 - Albumin.

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22
Q

Describe the process of platelet transfusion.

A

By a process known as apheresis:

1 - Blood is transported from the donor to a machine that separates the blood components by centrifugation.

2 - Plasma and platelets are isolated from the blood and the remaining blood is returned to the donor.

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23
Q

What volume of platelets and plasma can be extracted from the blood in an apheresis?

A

250mls of platelets and plasma can be derived from 2L of blood.

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24
Q

List 3 causes of thrombocytopenia which might require platelet transfusion.

A

1 - Autoimmune diseases such as immune thrombocytopenic purpura (ITP), where autoantibodies destroy platelets.

2 - Blood cancers affecting platelet production.

3 - Chemotherapy destroying platelets / other haematopoietic cells.

25
Q

What platelet count is considered to be very low?

What is the risk of having such a platelet count?

A
  • <10*10^9/L.

- There is a risk of spontaneous bleeding.

26
Q

Give an example of an alternative use of apheresis.

A

To harvest mobilised stem cells.

27
Q

What is the Rhesus D antigen?

A

A highly immunogenic protein antigen found on erythrocytes that induces an IgG immune response.

*The presence of the Rhesus D antigen is indicated by the ‘positive’ or ‘negative’ stated on a person’s blood type.

28
Q

Which type of antibodies are able to cross the placenta?

A

IgG antibodies.

29
Q

How are anti-D antibodies (antibodies against Rhesus D antigen) produced by a RhD negative mother prevented from crossing the placenta and causing lysis of a RhD positive child?

A

Anti-D immunoglobulin is administered routinely during the third trimester, when the anti-D antibodies would usually cross the placenta.

30
Q

Define polymorphism.

A

The variability of a gene.

31
Q

Why are corneas particularly easy to transplant?

A

Because they are avascular.

32
Q

List the phases of rejection.

A

1 - Hyperacute rejection.

2 - Acute rejection.

3 - Chronic rejection.

33
Q

What causes hyperacute rejection?

A

ABO mismatch.

34
Q

Where is ABO expressed other than in erythrocytes?

A

In endothelial cells.

35
Q

Via which mechanism do IgM antibodies mediate attack?

Why does this mean that hyperacute rejection often causes clotting?

A
  • Complement activation.
  • Hyperacute rejection due to ABO mismatch will cause clotting as complement will expose collagen underlying the endothelium.
36
Q

What is the treatment for hyperacute rejection?

A

Immediate removal of the rejected organ.

37
Q

How does hyperacute rejection differ immunologically from acute rejection?

A
  • Hyperacute rejection involves IgM antibodies that are already present in the blood (e.g. an A blood group person will have anti-B antibodies).
  • Acute rejection involves the priming of T cells against the allograft, and subsequent attack. Antibodies are also implicated in acute rejection, but to a lesser extent than in hyperacute rejection.
38
Q

Define allorecognition.

A

The ability of an individual’s immune system to distinguish its own tissues from those of another.

39
Q

What is the difference between direct and indirect allorecognition?

A
  • In direct allorecognition, more highly immunogenic cells such as macrophages from the allograft directly stimulate alloreactive T cells that are specific for that intact alloantigen.
  • In indirect allorecognition, the cell from the allograft is first taken up and processed by a professional antigen-presenting cell, which presents the alloantigen to T cells that are specific for that processed alloantigen.
40
Q

Which mechanisms underlie chronic rejection?

A

Chronic rejection is part CD8+ T cell mediated and part antibody mediated.

*Currently not well understood.

41
Q

How does chronic rejection cause damage to the host?

A

Chronic rejection causes smooth muscle cell proliferation leading to vessel occlusion.

42
Q

List 2 clinical conditions which might necessitate a haematopoietic stem cell transplantation (to replace the haematopoietic system of the recipient with that of the donor).

A

1 - Leukaemia.

2 - Immunodeficiency.

43
Q

Give an example of a risk of using haematopoietic stem cell transplants from an identical twin.

A

The risk of leukaemia relapsing is greater in transplants from identical twins than in other donors.

44
Q

What is graft vs host disease?

A

An immune attack that occurs in the first few weeks of transplantation from a graft against the recipient that usually focuses on the gut, skin and liver.

45
Q

List 5 properties of a graft that predispose a recipient towards graft vs host-disease.

A

1 - Poor HLA match.

2 - Originating from a non-family donor.

3 - Originating from a non-sex-matched donor.

4 - Originating from a more elderly donor.

5 - Originating from a CMV-positive donor.

46
Q

How is damage caused to the graft in graft vs host disease?

A

T cells deplete the graft.

47
Q

What is the treatment for graft vs host disease?

A

Immunosuppressants:

1 - Cyclosporine A.

2 - Methotrexate.

3 - Azathioprine.

4 - Prednisolone.

48
Q

Describe the mechanism of action of cyclosporine A.

A
  • It inhibits intracellular signalling by selectively targeting a phosphatase known as calcineurin.
  • This blocks T cell activation.
49
Q

Describe the mechanism of action of azathioprine.

A
  • It targets metabolic purine (A and G) synthesis.
  • T and B cells are particularly sensitive to this mechanism.
  • It therefore directly inhibits T cell proliferation.
50
Q

Describe the mechanism of action of prednisolone.

A

1 - It affects signal transduction and induces a programme of gene activation.

2 - Effector lymphocytes are particularly sensitive to this drug and therefore undergo apoptosis.

51
Q

How important is HLA match in kidney transplantation?

How important is blood group match?

A
  • HLA match is important.

- Blood group match is important.

52
Q

How important is HLA match in liver transplantation?

How important is blood group match?

A
  • HLA match is not important.

- Blood group match is not important.

53
Q

How important is HLA match in lung and cardiac transplantation?

How important is blood group match?

A
  • HLA match is important.

- Blood group match is important.

54
Q

How important is HLA match in haematopoietic stem cell transplantation (HSCT)?

How important is blood group match?

A
  • HLA match is critical.

- Blood group match is not important.

55
Q

Describe the nature of immunosuppressive therapy that is required of patients that have undergone kidney transplantation.

A

Immunosuppression is life-long and moderate.

56
Q

Describe the nature of immunosuppressive therapy that is required of patients that have undergone liver transplantation.

A

Immunosuppression is life-long and mild.

57
Q

Describe the nature of immunosuppressive therapy that is required of patients that have undergone lung / cardiac transplantation.

A

Immunosuppression is life-long and moderate.

58
Q

Describe the nature of immunosuppressive therapy that is required of patients that have undergone haematopoietic stem cell transplantation (HSCT).

A

Immunosuppression is severe but only lasts 1 year after transplantation.

59
Q

How does autologous transplantation work?

A

Embryonic stem cells are grown using gametes, which are then stimulated to grow into the required tissues and transplanted back into the patient.

IIH (26 decks)

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