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Winter course I > Transplantation > Flashcards

Transplantation Flashcards

1
Q

what is autografting?

A

transfer of graft from one part of the body to another

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2
Q

what is allografting?

A

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

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3
Q

what is xenografting?

A

transfer of graft from one individual to another of different species

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4
Q

what is isografting?

A

transfer of graft between identical twins

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5
Q

what are allo-antigens?

A

all antigens that differ between individuals of the same species

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6
Q

what do TCRs recognize?

A

foreign peptides in self-MHC molecules

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7
Q

name 3 different allo-antigens

A
  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
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8
Q

name the 3 characteristics of HLA class I

A
  1. HLA-A/B/C
  2. present on all nucleated cells of the body
  3. recognized by CD8+ T cells
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9
Q

name the 3 characteristics of HLA class II

A
  1. HLA-DP/DQ/DR
  2. present on APCs and activated CD4+ T cells
  3. recognized by CD4+ T cells
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10
Q

name 2 types of minor allo-antigens

A
  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
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11
Q

what is direct allo-recognition?

A

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

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12
Q

what is indirect allo-recognition?

A

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

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13
Q

what is semi-direct allo-recognition?

A

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

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14
Q

name 4 signs of kidney transplant rejection

A
  1. rise in creatine
  2. decreased urine production
  3. fever, malaise, abdominal pain
  4. reduced liver function
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15
Q

name the 4 targets for rejection

A
  1. ABO blood group system
  2. HLA
  3. minor antigens
  4. injury
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16
Q

what happens after a ABO-incompatible transplantation?

A

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

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17
Q

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

A
  1. pregnancy
  2. blood transfusions
  3. earlier transplantation
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18
Q

how can donor reactive antibodies be detected before transplantation?

A

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

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19
Q

what are the 3 requirements of an organ transplantation?

A
  1. ABO system compatible
  2. negative cross match
  3. HLA typing
20
Q

why is tissue injury not compatible for transplantation?

A
  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
21
Q

how can ischemia reperfusion be reduced?

A

machine preservation; oxygen, nutrient, temperature control

22
Q

name the 4 types of graft rejection

A
  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
23
Q

name 2 treatments for acute cellular rejection

A
  1. high doses of methylpredisolone (corticosteroids)
  2. ATG; anti-thymocyte globulin, depletion of T cells
24
Q

name 3 treatments for antibody mediated rejection

A
  1. plasmapheresis
  2. IVIg; depleting antibodies
  3. rituximab; anti-CD20, depleting B cells
25
Q

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

A
  1. T cells
  2. tubulointerstitial
  3. vascular rejection
26
Q

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

A
  1. antibody; monocytes and NK cells
  2. microvascular inflammation
  3. C4d+
  4. donor specific antigen (DSA)
27
Q

name the 3 stages of immunosuppression

A
  1. induction therapy
  2. maintenance therapy
  3. anti-rejection therapy
28
Q

what is the standard induction therapy for kidney transplantation?

A

basiliximab, signal 3 blocking antibody and anti-CD25

29
Q

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

A
  1. infections
  2. malignancies (cancer)
  3. cardiovascular disease
30
Q

name 3 immunosuppressive drugs used in maintenance therapy

A
  1. tacrolimus
  2. mycophenolate mofetil
  3. prednisolon
31
Q

how does prednisolon work?

A

inhibit mRNA expression

32
Q

how can infections be prevented before use of immunosuppressives?

A
  1. vaccinations before transplantation
  2. anti-bacterial/viral prophylaxis
  3. tapering immunosuppression
  4. life style advice
33
Q

how can malignancies be prevented before use of immunosuppressives?

A
  1. population screening
  2. tapering immunosuppression
34
Q

how can cardiovascular disease be prevented before use of immunosuppressives?

A
  1. steroid-free regimen
  2. tapering tacrolimus
35
Q

why does tacrolimus need therapeutic drug monitoring?

A

small therapeutic window and prone to infections with other drugs

36
Q

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

A

belatacept, iscalimab, mTOR inhibitors

37
Q

name 3 advantages of cellular therapies

A
  1. less side effects
  2. long term effects
  3. more specific (antigen-specific)
38
Q

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

A
  1. myeloid lineage (MDSC, M2, tolerogenic DC)
  2. mesenchymal stem cells (MSC)
  3. lymphoid lineage (CD4/8, T/B cells)
39
Q

what is the function of myeloid regulatory cells?

A

play a role in tissue homeostasis

40
Q

what is the function of regulatory macrophages (M2)?

A

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

41
Q

name 3 subtypes of mesenchymal stem cells

A
  1. osteoblasts
  2. adipocytes
  3. chrondrocytes
    peri-capillary localisation
42
Q

what is the function of MSC?

A

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

43
Q

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

A

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

44
Q

what is the function of belatacept?

A

co-stimulation blockade

45
Q

name 3 new forms of immunosuppression

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

Winter course I (15 decks)

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