Transplantation Flashcards
List the 4 transplantation types.
For each type, give an example.
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.
List 5 sources of transplants.
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).
List 3 factors which influence the quality of a graft for transplantation.
1 - Cell numbers / size of the graft.
2 - Possibility of infection or cancer from the graft.
3 - Life span of the graft.
List 2 factors which must be matched to ensure graft rejection doesn’t occur.
1 - Match for ABO blood group antigens.
2 - For bone marrow stem cell transplants, match for HLA genes (difficult due to polymorphisms).
List the human leukocyte antigens which are synonymous with MHC class I and II.
- MHC class I is synonymous with HLA A, B and C.
- MHC class II is synonymous with HLA DP, DQ and DR.
On which chromosome are human leukocyte antigen genes found?
Chromosome 6.
Which type of molecules are processed by the protein encoded by the ABO gene?
Where are these target molecules found?
- Carbohydrates.
- On the surface of erythrocytes.
Which protein is encoded by the ABO gene if the phenotype is blood group A?
N-acetylgalactosaminyl transferase.
Which protein is encoded by the ABO gene if the phenotype is blood group B?
D-galactosyl transferase.
What is the specific function of the product of the blood group A ABO gene?
It adds a GalNAc group to the carbohydrate found on the surface of erythrocytes.
What is the specific function of the product of the blood group B ABO gene?
It adds galactose to the carbohydrate found on the surface of erythrocytes.
Which proteins are encoded by the ABO gene if the phenotype is blood group AB?
The products of both blood group A and blood group B.
Which proteins are encoded by the ABO gene if the phenotype is blood group O?
None.
What immunological advantage do people with blood group O have?
What about people with blood group A and blood group B?
- 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.
What type of antibodies are anti-A and anti-B antibodies?
IgM constant region.
List the blood groups in order of prevalence.
1 - Blood group A (42%).
2 - Blood group O (38%).
3 - Blood group B (14%).
4 - Blood group AB (6%).
Why is it advantageous that the anti-A and anti-B antibodies are IgM antibodies?
Because IgM doesn’t cross the placenta.
List 2 instances in which red cells might be transfused.
1 - In a patient with anaemia.
2 - After suffering trauma.
List 3 instances in which platelets might be transfused.
1 - In a patient with thrombocytopenia.
2 - After suffering trauma.
3 - Following stem cell transplantation.
List 3 instances in which plasma might be transfused.
1 - In a patient with coagulopathy.
2 - After suffering trauma.
3 - To replace blood factors, e.g. after suffering burns.
List 3 molecules that are often transfused in the blood.
1 - Factor 8.
2 - Immunoglobulin.
3 - Albumin.
Describe the process of platelet transfusion.
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.
What volume of platelets and plasma can be extracted from the blood in an apheresis?
250mls of platelets and plasma can be derived from 2L of blood.
List 3 causes of thrombocytopenia which might require platelet transfusion.
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.
What platelet count is considered to be very low?
What is the risk of having such a platelet count?
- <10*10^9/L.
- There is a risk of spontaneous bleeding.
Give an example of an alternative use of apheresis.
To harvest mobilised stem cells.
What is the Rhesus D antigen?
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.
Which type of antibodies are able to cross the placenta?
IgG antibodies.
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?
Anti-D immunoglobulin is administered routinely during the third trimester, when the anti-D antibodies would usually cross the placenta.
Define polymorphism.
The variability of a gene.
Why are corneas particularly easy to transplant?
Because they are avascular.
List the phases of rejection.
1 - Hyperacute rejection.
2 - Acute rejection.
3 - Chronic rejection.
What causes hyperacute rejection?
ABO mismatch.
Where is ABO expressed other than in erythrocytes?
In endothelial cells.
Via which mechanism do IgM antibodies mediate attack?
Why does this mean that hyperacute rejection often causes clotting?
- Complement activation.
- Hyperacute rejection due to ABO mismatch will cause clotting as complement will expose collagen underlying the endothelium.
What is the treatment for hyperacute rejection?
Immediate removal of the rejected organ.
How does hyperacute rejection differ immunologically from acute rejection?
- 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.
Define allorecognition.
The ability of an individual’s immune system to distinguish its own tissues from those of another.
What is the difference between direct and indirect allorecognition?
- 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.
Which mechanisms underlie chronic rejection?
Chronic rejection is part CD8+ T cell mediated and part antibody mediated.
*Currently not well understood.
How does chronic rejection cause damage to the host?
Chronic rejection causes smooth muscle cell proliferation leading to vessel occlusion.
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).
1 - Leukaemia.
2 - Immunodeficiency.
Give an example of a risk of using haematopoietic stem cell transplants from an identical twin.
The risk of leukaemia relapsing is greater in transplants from identical twins than in other donors.
What is graft vs host disease?
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.
List 5 properties of a graft that predispose a recipient towards graft vs host-disease.
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.
How is damage caused to the graft in graft vs host disease?
T cells deplete the graft.
What is the treatment for graft vs host disease?
Immunosuppressants:
1 - Cyclosporine A.
2 - Methotrexate.
3 - Azathioprine.
4 - Prednisolone.
Describe the mechanism of action of cyclosporine A.
- It inhibits intracellular signalling by selectively targeting a phosphatase known as calcineurin.
- This blocks T cell activation.
Describe the mechanism of action of azathioprine.
- 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.
Describe the mechanism of action of prednisolone.
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.
How important is HLA match in kidney transplantation?
How important is blood group match?
- HLA match is important.
- Blood group match is important.
How important is HLA match in liver transplantation?
How important is blood group match?
- HLA match is not important.
- Blood group match is not important.
How important is HLA match in lung and cardiac transplantation?
How important is blood group match?
- HLA match is important.
- Blood group match is important.
How important is HLA match in haematopoietic stem cell transplantation (HSCT)?
How important is blood group match?
- HLA match is critical.
- Blood group match is not important.
Describe the nature of immunosuppressive therapy that is required of patients that have undergone kidney transplantation.
Immunosuppression is life-long and moderate.
Describe the nature of immunosuppressive therapy that is required of patients that have undergone liver transplantation.
Immunosuppression is life-long and mild.
Describe the nature of immunosuppressive therapy that is required of patients that have undergone lung / cardiac transplantation.
Immunosuppression is life-long and moderate.
Describe the nature of immunosuppressive therapy that is required of patients that have undergone haematopoietic stem cell transplantation (HSCT).
Immunosuppression is severe but only lasts 1 year after transplantation.
How does autologous transplantation work?
Embryonic stem cells are grown using gametes, which are then stimulated to grow into the required tissues and transplanted back into the patient.
