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Im+Haem yien > Transplantation > Flashcards

Transplantation Flashcards

1
Q

What is rejection?

A

Rejection = damage done by immune system to a transplanted organ

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2
Q

What are the different kinds of transplant?

A
  • Autologous transplant
    • Tissue returning to the same individual after a period outside the body, usually in a frozen state
  • Syngeneic transplant
    • Transplant between identical twins
  • Allogeneic transplant
    • Between genetically non-identical members of the same species
  • Cadaveric transplantation
    • Uses organs from dead donor
  • Xenogeneic transplant
    • Between two different species
    • Carries highest risk of rejection
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3
Q

What can transplants be seperated into?

A
  • Solid organ transplantation
  • Stem cell transplantation
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4
Q

What are exampels of solid organs that can be transplanted?

A
  • Heart
  • Lung
  • Liver
  • Pancreas
  • Cornea
  • Trachea
  • Kidney
    • Most common
  • Skin
  • Vascular tissue
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5
Q

What is the most common kind of transplant?

A

Kidney

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6
Q

What criteria must be met before transplantation?

A
  • Good evidence damage is irreversible
  • Alternative treatments not applicable
  • Disease must not recur
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7
Q

What is the main risk of transplantation?

A

Rejection

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8
Q

How can the risk of rejection be minimised?

A
  • Donor and recipient must have compatible ABO
  • Recipient mist not have anti-donor human leukocyte antigen (HLA) antibodies
  • Donor should be selected with as close as possible HLA match to recipient
  • Patient must take immunosuppressive treatment
    • Varies depending on organ
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9
Q

What are the different kinds of rejection?

A
  • Hyperacute rejection
  • Acute rejection
  • Chronic rejection
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10
Q

Describe the timing of hyperacute rejection?

A
  • Within hours
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11
Q

Describe the mechanism of hyperacute rejection?

A
  • Preformed antibodies binding to either ABO blood group or HLA class I antigens on graft
  • Antibody binding triggers a type II hypersensitive reaction, and graft destroyed by vascular thrombosis
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12
Q

What hypersensitivity is involved in hyperacute rejection?

A

Type II

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13
Q

How can hyperacute rejection be prevented?

A
  • Careful ABO and HLA cross-matching
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14
Q

Describe the timing of acute rejection?

A
  • Within few days or weeks of transplantation
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15
Q

Describe the mechanism of acute rejection?

A
  • Type IV (cell-mediated delayed hypersensitive reaction
  • Donor dendritic cells stimulate an allogeneic response in local lymph node and T cells proliferate and migrate to donor kidney
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16
Q

What hypersensitivity is acute rejection?

A

Type IV

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17
Q

What is the main cause of acute rejection?

A
  • HLA incompatibility
    • Main cause
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18
Q

Describe the timing of chronic rejection?

A
  • Months or years after transplant
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19
Q

What are the causes of chronic rejection?

A
  • Recurrence of pre-existing autoimmune disease
  • Recurrence of acute attacks
20
Q

Describe the mechanism of chronic rejection?

A
  • Element of allogenic rejection, often mediated by T cells, which can result in repeated acute rejection
21
Q

What are the different phases of graft rejection and what happens?

A
  • Afferent phase
    • Donor MHC molecules on ‘passenger leucocytes’ (dendritic cells) within graft are recognised by recipients CD4+ T cells
  • Effector phase
    • CD4+ T cells recruit effector cells responsible for the tissue damage of rejection
      • Macrophages, CD8+ T cells, NK cells and B cells
22
Q

What does tolerance in the context of transplantation mean?

A

In the context of transplantation, means no response to alloantigen’s present on transplanted tissue but responses to pathogens not affected

23
Q

How is tolerance achieved in transplantation?

A

Achieved with immunosuppressant drugs:

  • Prevent rejection if given at the time of transplantation
    • Once stopped, rejection still takes place
  • Lacks specificity of true tolerance and thus also prevents immune response to infectious agents
    • Opportunist infections are major limit to use of potent immunosuppressive drugs
24
Q

What is tissue typing?

A

Tissue typing = procedure in which tissues of prospective donor and recipient are tested for compatibility

25
Q

What are the 2 different steps in tissue typing?

A
  • HLA typing
    • Typed at the A, B and DR loci
  • HLA cross matching
    • Information put into registry of donors and compared
    • If identify match, further typing occurs
    • Matching test done to confirm as typing rarely perfect match
      • B cells from donor taken (as expressed class 1 and 2 of HLA), then mixed with serum from recipient (has antibodies), looking for no reaction
26
Q

What is stem cell transplantation?

A

Haematopoietic stem cells used to restore myeloid and lymphoid cells

27
Q

What does SCT stand for?

A

Stem cell transplantation

28
Q

What are the different kinds of stem cell transplantation?

A
  • Autologous SCT
    • Marrow removed, frozen and reinfused after potent chemotherapy given
    • Minimal immunologic risk
  • Allogenic SCT
    • Much riskier procedure than most solid organ transplants
      • Mortality rate of 20% even with well-matched donors
    • Only carried out in
      • Hematologic malignancy with no alternative treatment
      • Cases when myeloid cell production is reduced, such as aplastic anaemic
      • Primary immunodeficiency’s such as severe combined immunodeficiency
29
Q

When is allogenic SCT carried out?

A
  • Hematologic malignancy with no alternative treatment
  • Cases when myeloid cell production is reduced, such as aplastic anaemic
  • Primary immunodeficiency’s such as severe combined immunodeficiency
30
Q

Where are different sources of stem cells?

A
  • Bone marrow
    • Aspiration of considerable amount of donor marrow under GA
  • Peripheral blood
    • Harvested after treating the donor with colony-stimulating factors to increase number of circulating stem cells
  • Cord blood
    • Contains large numbers of stem cells, which can be frozen before use
    • Immature lymphocytes less likely to cause graft versus host disease
    • Can only be used for child or small adult
31
Q

What is done to destroy recipients own stem cells to allow engraftment of donor cells?

A

Conditioning is done to destroy recipients stem cells and allow engraftment of donor cells, achieved by:

  • High dose chemotherapy
  • High dose radiotherapy
32
Q

What is graft versus host disease?

A

Occurs when donor T cells respond to allogeneic recipient antigens:

  • Mismatch in major or minor histocompatibility antigens
33
Q

How is graft versus host disease prevented?

A
  • All patients given SCT are given immunosuppressive drugs, even if donor and recipient are HLA identical
34
Q

What does GVHD stand for?

A

Graft versus host disease

35
Q

When does acute GVHD become chronic?

A

>4 weeks after stem cell transplant

36
Q

What organs are involved in GVHD?

A
  • Acute GVHD (occurs up to 4 weeks after SCT)
    • Skin, gut, liver and lungs
  • Chronic GVHD
    • Skin and liver
37
Q

Describe the prognosis of GVHD?

A
  • When severe, 70% mortality risk
38
Q

What are the side effects of cyclosporine?

A
  • Increased risk of infection
  • Increased risk of certain cancers
  • Nephrotoxic properties
  • Diabetes
  • Hypertension
39
Q

What are the side effects of rapamycin?

A
  • Raised lipid and cholesterol levels
  • Hypertension
  • Anaemia
  • Diarrhoea
  • Rash
  • Acne
  • Thrombocytopenia
  • Decreases in platelets and haemoglobin
40
Q

What are problems with xenotransplantation?

A
  • Primates assemble different sugar side chains from other species
    • Galactose-a1, 3-galactose is sugar present in all cells of most non-primate species
    • Immune system recognises this as all human possess antibodies against it following exposure to gut bacteria
    • These antibodies bind onto xenotransplanted organs, activating complement and triggering hyperacute rejection
  • Complement inhibitors from other species do not inhibit human complement, so xenotransplanted organs activate complement
41
Q

What are different classes of immunosuppresive drugs?

A
  • Corticosteroids
    • At low doses – act on antigen-presenting cells preventing some of early stages of graft rejection
    • Higher doses – direct effect on T cells and can treat episodes of rejection
  • T-cell signalling blockade
    • Drugs – cyclosporine, tacrolimus
    • Mechanism – interacts with proteins in the intracellular T-cell signalling cascade
  • IL-2 blockade
    • Monoclonal antibodies against IL-2 receptor
      • Drugs – basiliximab, daclizumab
      • Mechanism – completely block IL-2 having potent immune suppression effects
      • Indication – only used to treat episodes of acute graft rejection
    • Rapamycin
      • Administration – orally
      • Mechanism – interacts with signalling events downstream of IL-2 receptor
      • Indication – less potent than monoclonal antibodies so used to prevent graft rejection
  • Antiproliferatives
    • Drugs – azathioprine, mycophenolate mofetil and methotrexate
    • Mechanism – inhibit DNA production, prevention lymphocyte proliferation
    • Side effects – myelotoxicity (bone marrow suppression)
42
Q

For T cell signalling blockade drugs:

  • drug names
  • mechanism
A
43
Q

For IL-2 blockade drugs:

  • names
  • mechanism
  • indication
A
44
Q

For rapamycin:

  • administration
  • mechanism
  • indication
A
45
Q

For antiproliferatives:

  • names
  • mechanism
  • side effects
A
46
Q

What is myelotoxicity?

A

Bone marrow suppression

Im+Haem yien (23 decks)

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