Lecture 8 - Transplant Immunology

Question 1

what are the three Transplant immunology tests?

Answer 1

HLA typing, HLA antibody screen and HLA crossmatch

Question 2

what are the two types of transplants?

Answer 2

haematopoietic stem cells transplants and solid organ transplants

Question 3

where do HSCs come from?

Answer 3

bone marrow, peripheral blood stem cells, umbilical cord

Question 4

what complicates the use of composite tissue?

Answer 4

composite tissues contain intent donor immune effector cells which can cause GvH disease

Question 5

what is pharmacogenetics?

Answer 5

associations with the HLA system and its response to therapeutic drugs

Question 6

what is an example of pharmacogenetic associations?

Answer 6

HLA B57 disproportionally present with hypersensitivity to abacavir

Question 7

what is HLA antigen typing?

Answer 7

profiling of the HLA present on patient/donor cells

Question 8

what is HLA antibody screening?

Answer 8

detection and identification of anti-HLA formed in the patient

Question 9

what is HLA crossmatching?

Answer 9

testing compatibility of patient HLA antibody profile against the donor, use recipients serum against cells from the donor

Question 10

what is an autograft?

Answer 10

transplant on the same person

Question 11

what is an allograft?

Answer 11

transplant of tissue or organ between two genetically non-identical members of the same species

Question 12

what is an isograft?

Answer 12

transplant of tissue or organs between genetically identical members of the same species

Question 13

what is a xenograft?

Answer 13

transplant between two different species

Question 14

what are the issues in the process of transplantation?

Answer 14

complexity, preparation, conditioning, cost

Question 15

what are the issues in the patient aspect of transplantation?

Answer 15

has to be in optimum condition, disease needs to be controlled

Question 16

what are the complications of the transplant process?

Answer 16

infection due to immunosuppressants, rejection due to immune response, GVHS, relapse or a secondary disease

Question 17

what is an example of a secondary disease caused by a transplant?

Answer 17

aggressive treatment used to rid of one disease can lead to another, e.g. different types of leukaemia

Question 18

what are the challenges or transplants?

Answer 18

availability of an organ, donor selection process, immunosuppression can be fatal

Question 19

what is HLA in relation to MHC?

Answer 19

HLA are antigens of the MHC located on chromosome 6

Question 20

what is HLA class I?

Answer 20

HLA genes A, B and C

Question 21

what is the structure of HLA class I?

Answer 21

single transmembrane alpha chain, covalently linked to polymorphic beta 2 macroglobulin

Question 22

what is class II HLA?

Answer 22

HLA DR, DQ and DP

Question 23

what is the structure of HLA class II?

Answer 23

2 transmembrane chains

Question 24

what size peptides bind to class I?

Answer 24

8 or 9 amino acids

Question 25

where do peptides bind on class I?

Answer 25

in area between helices and beta sheet

Question 26

what does variation in beta sheet cause?

Answer 26

a more varied range in the peptides that can bind

Question 27

what does variation in helices cause?

Answer 27

this determines which T cell receptors can bind to the HLA

Question 28

what size peptides bind to class II HLA?

Answer 28

14-21 amino acids

Question 29

what differs between class I and I?

Answer 29

tissue distribution

Question 30

where is class I expressed?

Answer 30

on all somatic cells

Question 31

where is class I not expressed?

Answer 31

CNS neurones, corneal endothelium, exocrine portion of pancreas

Question 32

what does class I present peptides to?

Answer 32

CD8 T cells

Question 33

where is class II expressed?

Answer 33

B cells, monocytes, macrophages, dendritic cells

Question 34

what does class II present peptides to?

Answer 34

CD4 T cells

Question 35

why are HLA genes inherited as a group?

Answer 35

close together on chromosome 6 and so do not undergo genetic variation

Question 36

what fields are needed for HLA matching?

Answer 36

1 and 2

Question 37

why is HLA most important group in transplants?

Answer 37

highest polymorphism, primary non-self target of immune system, decreases rejection when matched

Question 38

how is hyperacute rejection caused?

Answer 38

by pre-existing anti-HLA antibodies in the host, leading to complement activation and IV coagulation

Question 39

how does hyper acute rejection cause loss of the graft?

Answer 39

complement activated, capillaries become blocked and inflammation causes necrosis leading to loss

Question 40

how is accelerated graft rejection caused?

Answer 40

by pre-sensitisation of the donor to HLA via a transfusion or pregnancy causing memory leading to humeral or cellular response

Question 41

how is acute graft rejection caused?

Answer 41

by HLA mismatches causing a cellular immune response

Question 42

which type of rejection is most common?

Answer 42

acute

Question 43

how long does hyper acute rejection take?

Answer 43

minutes or hours

Question 44

how long does accelerated rejection take?

Answer 44

within 3 days

Question 45

how long does acute rejection take?

Answer 45

1 to 3 weeks

Question 46

how is acute rejection prevented?

Answer 46

immunosuppression and plasmaphoresis

Question 47

how is chronic graft rejection caused?

Answer 47

either a prolonged series of acute rejection tasks or possible slow progressive inflammatory response

Question 48

how is chronic rejection characterised?

Answer 48

by graft arterial occlusions known as graft arteriosclerosis

Question 49

what does chronic rejection lead to?

Answer 49

ishcemia and cell death

Question 50

what is the major cause of allograft rejection?

Answer 50

antibody mediated rejection

Question 51

how is antibody mediated rejection caused?

Answer 51

pre-formed antibodies or de-novo antibodies formed due to transplant

Question 52

how does antibody mediated rejection lead to loss of graft?

Answer 52

complement activated, leucocytes recruited and NK/monocyte mediated cytotoxicity occurs leading to endothelial damage and loss of vascular integrity

Question 53

how is antibody mediated rejection diagnosed?

Answer 53

impaired renal function, histological evidence of Ab activity such as C4d deposition, detection of HLA antibodies

Question 54

what is the treatment of antibody mediated rejection?

Answer 54

removal of antibodies via plasmapheresis, immunoadsorption or IV IgG

Question 55

how does IV IgG suppress an immune response?

Answer 55

inhibits T cell proliferation, cytokines and complement