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Mandal > Transplantation Immunology > Flashcards

Transplantation Immunology Flashcards

1
Q

When are transplants needed?

A
  1. Irreversible organ damage
  2. No other treatments work
  3. End-stage organ failure
  4. Can w/ genetically different people (allogeneic)
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2
Q

Issues with Transplantaion

(transplant rejection)

A
  • allogeneic differences
  • Differences in HLA Antigens
  • Host t cells attack graft by recognizing HLA Ag
    *
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3
Q

Graft Versus host disease

(GvHD)

A
  • donor lymphocytes attack the graft recipient causing graft versus host disease
  • obsereved in bone marrow transplantaton
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4
Q

what do you need for a succesful skin graft?

A

remove all T cells from graft

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5
Q

Allograft rejection

A
  • genetic relationship between donor and recipient determines if rejection will occur
  • Host vs graft immune response causes rejection
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6
Q

which grafts are accepted and which are not?

A

Accepted

  • Autografts- from one part of the body to the other
  • Isografts- btwn twins

Rejected

  • allografts- btwn two people (same species)
  • Xenografts- btwn differnt species, animal +human
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7
Q

Hyperacute Recognition

A
  • occurs within minutes to hours
  • Ab-mediated
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8
Q

Acute Rejection

A
  • occurs days-weeks
  • initiated by alloreactive T cells
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9
Q

chronic rejection

A

observed months to years following transplantation

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10
Q

Donor-recipient compatibility requirements

A
  • ABO compatible
  • recipeient can’t have anti- donor HLA Abs
  • Donor should be a close HLA match
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11
Q

two major methods for prevention of Allograft Rejection

A
  1. careful matching of the donor & recipient
  2. use immunosuppressive drugs
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12
Q

careful matching of the donor and recipient

via

A
  1. ABO blood typing
  2. HLA matching: Tissue Typing
  3. Tissue cross-matching
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13
Q

ABO Blood typing

A
  • Donor organ must be ABO blood group Ag compatible with recipient
  • RhD matching in unimportant
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14
Q

HLA Matching

A
  • determine HLA alleles by tissue typing
  • HLA subclass I- HLA-A, HLA-B, HLA-C
  • HLA subclass II- HLA-DQ, HLA-DR, HLA-DP
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15
Q

Tissue cross-matching

A
  • determines if patient has Abs that will react with donor WBCs
  • Recipient’s serum is mixed with donor leukocyte
    • positive reaction trasplantation is contra indicated
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16
Q

Immunosuppressive drugs used in transplantation ?

A
  • Drugs affect
    • T-Lymphocyte function
    • both T and B lymphocyte function
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17
Q

Consequences of immunosuppression

A

increased risk of infections especially opportunistic

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18
Q

opportunistic diseases

A
  • Fungal: candia
  • viral: EBV, CMV
  • listeria, mycobacterial
  • increased risk of cancer
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19
Q

Drugs that affect T-Lymphocyte Function

A
  • calcineurin inhibitors
  • inhibitors of T lymphocyte activation and proliferation
  • anti-T cell immunoglobulins
  • IL-2 receptor antagonists
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20
Q

calcineurin inhibitors mechanism

A
  • inhibits
    • transcription of IL-2 gene & IL-2 production
    • calcineurin enzymes
    • activation of transcription factor NFAT (in T cell)
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21
Q

calcineurin inhibitor drugs

A
  • Cyclosporine( Sandimmune)
  • Tacrolimus/ FK-506 (Prograf)

supress inflammation in oral inflammation

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22
Q

what do cyclosporine and tacrolimus do?

A
  • inhibit calcineurin enzyme
  • block T cell activation by inhibiting activation of NFAT

immunosuppressive drugs

23
Q

calcineurin enzyme function

A

activates T cell

24
Q

MTOR (mammalian target of rapamycin) inhibitor

mechanism

A
  • Inhibition of IL -2 driven profliferation of T lymphocytes
25
Q

what does IL-2 stimulates

A

T lymphocytes

26
Q

differnece btwn calcineurin inhibitors and MOTR ?

A

Calcineurin inhibitors-

  • No IL-2

MTOR

  • IL-2 present but inhibited
27
Q

MTOR drugs

A
  • Sirolimus(Rapamune) or Rapamycin
28
Q

Sirolimus(Rapamune) or Rapamycin function?

A
  • MTOR
  • IL-2 driven proliferation inhibited ( IL-2 still present)
29
Q

Anti T-cell immunoglobins mechanism

A

antibodies bind to T lymphocytes

30
Q

Anti T-cell immunoglobins drugs

A
  • Antithymocytes Globulin (Atgam)
  • Murononab, alpha-CD3 (OKT3)
31
Q

Antithymocytes Globulin (Atgam)

mechanism

A
  • non-specific (wide specifity)
  • Bind T cells & B cells, platelets, and other leukocytes

(Anti T cell immunoglobins)

32
Q

Anti-CD3 monoclonal Ab

function and drug

A
  • depletes T cells by binding to CD3 and promoting phagocytosis or complement-mediated lysis
  • Drug: Murononab
33
Q

Murononab drug

A
  • Anti-CD3 monoclonal Ab
  • depletes T cells by binding to CD3 and promoting phagocytosis or complement-mediated lysis
34
Q

Anti-IL-2 receptor (CD25) Ab

mechanism

A
  • Inhibits T cell proliferation by blocking IL-2 binding and depletes activated T cells
  • Anti-IL-2 receptor (CD25) Ab
35
Q

Anti-IL-2 recptor (CD25) Ab

drugs

A

Daclizumab (Zenapax)

Basiliximab (simulect)

-mab

36
Q

Daclizumab(Zenapax)

Basiliximab (simulect)

A
  • Anti-IL-2 recptor (CD25) Ab drugs
  • IL-2 can’t bind to IL-2 receptor
  • No T cell proliferation
37
Q

Antimetabolites

mechanism

A
  • inhibition of purine synthesis in lymphocytes blocking proliferation
  • block cell division
38
Q

Antimetabolite drugs

A

Azathioprine (Imuran)

Mycophenolate mofetil (cellcept)

39
Q

Azathioprine (Imuran)

Mycophenolate mofetil (cellcept)

drugs

A

antimetabolites

40
Q

corticosteroid drugs

A
  • Prednisone (orasone, deltasone)
  • methylprednisolone ( Methylpred, solumedrol)
41
Q

Prednisone (orasone, deltasone)

methylprednisolone ( Methylpred, solumedrol)

drugs

A

corticosteroids

42
Q

cyclosporine and FK-506

mechainism

A

block t cell cytokine production by inhibiting activation of the NFAT transcription factor

43
Q

Azathioprine

A

blocks proliferation of lymphocyte precursors

44
Q

mycophenolate mofetil mechanism

A

blocks lymphocyte proliferation by inhibiting guanine nucleotide synthesis in lymphocytes

45
Q

rapamycin

A

blocks lymphocyte proliferation by inhibiting IL-2 signaling

46
Q

corticosteroids mechanism

A

reduce inflammation by inhibiting macrophage cytokinw secretion

47
Q

manifestation of chronic oral graft versus host diease

(GVHD)

A
  • transplant does hve oral mannifestation
    • lechenoid changes
    • mucosal atrophy
    • ulcerations
    • taste disturbances
    • salivary gland hypofunction
48
Q

treatment for oral GVHD

A
  • Cyclosporine & corticosteroids
49
Q

tacrolimus

sirolimus

A
  • tacrolimus-can use rather than cyclosporine if disease is in the liver
  • sirolimus-used in renal transplant patients
50
Q

hydroxychloroquine

A

antimalarial drug used to treat lupus

antiflammatory

decrease TNF alpha IL-1

51
Q

thalidomaide

A

anti-inflammatory effect

decrease in TNF-alpha activity

52
Q

methotrexate

A

anti-metabolite

immunomodulatory and anti-inflammatory effects

53
Q

topical and local therapy for oral cGVHD

drugs

A
  • topical corticosteriod
  • topical cyclosporine
  • local phototherapy (UV)
  • Topical azathioprine
  • topical tacrolimus

Mandal (7 decks)

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