Transplantation

Question 1

what is autografting?

Answer 1

transfer of graft from one part of the body to another

Question 2

what is allografting?

Answer 2

transfer of graft from one individual to another of the same species

Question 3

what is xenografting?

Answer 3

transfer of graft from one individual to another of different species

Question 4

what is isografting?

Answer 4

transfer of graft between identical twins

Question 5

what are allo-antigens?

Answer 5

all antigens that differ between individuals of the same species

Question 6

what do TCRs recognize?

Answer 6

foreign peptides in self-MHC molecules

Question 7

name 3 different allo-antigens

Answer 7

1. major histocompatibility complex (MHC) antigens/ HLA; cause fast and strong rejection because of differences in HLA
2. minor histocompatibility complex antigens (miHLA = non-MHC antigens); cause slow and weak graft rejection because of genetic differences in other proteins but same HLA
3. blood group antigens

Question 8

name the 3 characteristics of HLA class I

Answer 8

1. HLA-A/B/C
2. present on all nucleated cells of the body
3. recognized by CD8+ T cells

Question 9

name the 3 characteristics of HLA class II

Answer 9

1. HLA-DP/DQ/DR
2. present on APCs and activated CD4+ T cells
3. recognized by CD4+ T cells

Question 10

name 2 types of minor allo-antigens

Answer 10

1. all other proteins that differ in amino acid composition between donor and recipient because of genetic mutation/polymorphism, presented by recipient HLA to recipient T cells
2. proteins encoded by y-chromosome because of transplantation from man to woman, presented by recipient and donor HLA to recipient T cells

Question 11

what is direct allo-recognition?

Answer 11

recipient T cell recognizes intact donor HLA on donor APC, is the result of cross-reactivity of TCRs that recognize self MHC molecule + foreign peptide to a foreign MHC molecule + another foreign peptide

Question 12

what is indirect allo-recognition?

Answer 12

recipient T cells recognizes peptide of donor HLA presented in recipient HLA molecule on recipient APC

Question 13

what is semi-direct allo-recognition?

Answer 13

recipient APCs acquire intact donor HLA presenting peptides recognized by recipient T cell

Question 14

name 4 signs of kidney transplant rejection

Answer 14

1. rise in creatine
2. decreased urine production
3. fever, malaise, abdominal pain
4. reduced liver function

Question 15

name the 4 targets for rejection

Answer 15

1. ABO blood group system
2. HLA
3. minor antigens
4. injury

Question 16

what happens after a ABO-incompatible transplantation?

Answer 16

anti-ABO antibodies stick to red blood cells and organ graft resulting in hyperacute rejection (lysis of blood/organ cells)

Question 17

what are 3 reasons for having pre-existing antibodies against donor HLA (donor reactive antibodies)?

Answer 17

1. pregnancy
2. blood transfusions
3. earlier transplantation

Question 18

how can donor reactive antibodies be detected before transplantation?

Answer 18

cross-match (complement dependent cytotoxicity) test; expose donor cells to recipient serum and complement, in the presence of DSA donor cells will be lysed

Question 19

what are the 3 requirements of an organ transplantation?

Answer 19

1. ABO system compatible
2. negative cross match
3. HLA typing

Question 20

why is tissue injury not compatible for transplantation?

Answer 20

1. leads to inflammatory responses/ischemia reperfusion injury
2. cardiac death donor; disturbance of blood supply to donor organs
3. brain death donor; cytokine storm affecting donor organs

Question 21

how can ischemia reperfusion be reduced?

Answer 21

machine preservation; oxygen, nutrient, temperature control

Question 22

name the 4 types of graft rejection

Answer 22

1. hyperacute rejection; immediate lysis of donor cells, presence of ABO or donor HLA specific antibodies
2. acute rejection; cellular rejection, T cell mediated (rapid rise in creatinine, fluid retention, infiltration of recipient immune cells in graft)
3. acute antibody mediated rejection; humoral rejection, B cell mediated (anti-donor HLA antibodies bind to donor cells, activate complement system, lysis of target cells and phagocytosed by macrophages)
4. chronic rejection; slow deterioration of kidney function, continuous low level of inflammation and chronic calcineurin inhibitory (CNI) nephrotoxicity, fibrosis in the graft

Question 23

name 2 treatments for acute cellular rejection

Answer 23

1. high doses of methylpredisolone (corticosteroids)
2. ATG; anti-thymocyte globulin, depletion of T cells

Question 24

name 3 treatments for antibody mediated rejection

Answer 24

1. plasmapheresis
2. IVIg; depleting antibodies
3. rituximab; anti-CD20, depleting B cells

Question 25

what are the 3 histological aspects of a kidney T cell mediated rejection (TCMR)?

Answer 25

1. T cells 2. tubulointerstitial 3. vascular rejection

Question 26

what are the histological aspects of a kidney antibody mediated rejection?

Answer 26

1. antibody; monocytes and NK cells 2. microvascular inflammation 3. C4d+ 4. donor specific antigen (DSA)

Question 27

name the 3 stages of immunosuppression

Answer 27

1. induction therapy 2. maintenance therapy 3. anti-rejection therapy

Question 28

what is the standard induction therapy for kidney transplantation?

Answer 28

basiliximab, signal 3 blocking antibody and anti-CD25

Question 29

what are the 3 most important side-effects of immunosuppressive drugs?

Answer 29

1. infections 2. malignancies (cancer) 3. cardiovascular disease

Question 30

name 3 immunosuppressive drugs used in maintenance therapy

Answer 30

1. tacrolimus 2. mycophenolate mofetil 3. prednisolon

Question 31

how does prednisolon work?

Answer 31

inhibit mRNA expression

Question 32

how can infections be prevented before use of immunosuppressives?

Answer 32

1. vaccinations before transplantation 2. anti-bacterial/viral prophylaxis 3. tapering immunosuppression 4. life style advice

Question 33

how can malignancies be prevented before use of immunosuppressives?

Answer 33

1. population screening 2. tapering immunosuppression

Question 34

how can cardiovascular disease be prevented before use of immunosuppressives?

Answer 34

1. steroid-free regimen 2. tapering tacrolimus

Question 35

why does tacrolimus need therapeutic drug monitoring?

Answer 35

small therapeutic window and prone to infections with other drugs

Question 36

what are alternative immunosuppressive agents for a CNI-free regimen?

Answer 36

belatacept, iscalimab, mTOR inhibitors

Question 37

name 3 advantages of cellular therapies

Answer 37

1. less side effects 2. long term effects 3. more specific (antigen-specific)

Question 38

name 3 immune cell types that can be used for cellular therapy

Answer 38

1. myeloid lineage (MDSC, M2, tolerogenic DC) 2. mesenchymal stem cells (MSC) 3. lymphoid lineage (CD4/8, T/B cells)

Question 39

what is the function of myeloid regulatory cells?

Answer 39

play a role in tissue homeostasis

Question 40

what is the function of regulatory macrophages (M2)?

Answer 40

induced by co-stimulation of activated macrophages, produce IL-10

Question 41

name 3 subtypes of mesenchymal stem cells

Answer 41

1. osteoblasts 2. adipocytes 3. chrondrocytes peri-capillary localisation

Question 42

what is the function of MSC?

Answer 42

expression of immunomodulatory factors (IDO; depletion of L-tryptophan to inhibit lymphocyte proliferation and PD-L1; provide inhibitory signal to T cells)

Question 43

what is the mechanism of regulating immune responses by CD4+ Tregs?

Answer 43

central tolerance; to delete responses to self-antigens peripheral tolerance; to limit responses to antigens

Question 44

what is the function of belatacept?

Answer 44

co-stimulation blockade

Question 45

name 3 new forms of immunosuppression

Answer 45

1. anti-IL6 2. Imlifidase; eliminates anti-HLA IgG 3. CAR T cells