Transplantation Immunology Flashcards
(53 cards)
1
Q
When are transplants needed?
A
- Irreversible organ damage
- No other treatments work
- End-stage organ failure
- Can w/ genetically different people (allogeneic)
2
Q
Issues with Transplantaion
(transplant rejection)
A
- allogeneic differences
- Differences in HLA Antigens
- Host t cells attack graft by recognizing HLA Ag
*
3
Q
Graft Versus host disease
(GvHD)
A
- donor lymphocytes attack the graft recipient causing graft versus host disease
- obsereved in bone marrow transplantaton
4
Q
what do you need for a succesful skin graft?
A
remove all T cells from graft
5
Q
Allograft rejection
A
- genetic relationship between donor and recipient determines if rejection will occur
- Host vs graft immune response causes rejection
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
7
Q
Hyperacute Recognition
A
- occurs within minutes to hours
- Ab-mediated
8
Q
Acute Rejection
A
- occurs days-weeks
- initiated by alloreactive T cells
9
Q
chronic rejection
A
observed months to years following transplantation
10
Q
Donor-recipient compatibility requirements
A
- ABO compatible
- recipeient can’t have anti- donor HLA Abs
- Donor should be a close HLA match
11
Q
two major methods for prevention of Allograft Rejection
A
- careful matching of the donor & recipient
- use immunosuppressive drugs
12
Q
careful matching of the donor and recipient
via
A
- ABO blood typing
- HLA matching: Tissue Typing
- Tissue cross-matching
13
Q
ABO Blood typing
A
- Donor organ must be ABO blood group Ag compatible with recipient
- RhD matching in unimportant
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
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
16
Q
Immunosuppressive drugs used in transplantation ?
A
- Drugs affect
- T-Lymphocyte function
- both T and B lymphocyte function
17
Q
Consequences of immunosuppression
A
increased risk of infections especially opportunistic
18
Q
opportunistic diseases
A
- Fungal: candia
- viral: EBV, CMV
- listeria, mycobacterial
- increased risk of cancer
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
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)
21
Q
calcineurin inhibitor drugs
A
- Cyclosporine( Sandimmune)
- Tacrolimus/ FK-506 (Prograf)
supress inflammation in oral inflammation
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
what does IL-2 stimulates
T lymphocytes
26
differnece btwn calcineurin inhibitors and MOTR ?
Calcineurin inhibitors-
* No IL-2
MTOR
* IL-2 present but inhibited
27
MTOR drugs
* Sirolimus(Rapamune) or Rapamycin
28
Sirolimus(Rapamune) or Rapamycin function?
* MTOR
* IL-2 driven proliferation inhibited ( IL-2 still present)
29
Anti T-cell immunoglobins mechanism
antibodies bind to T lymphocytes
30
Anti T-cell immunoglobins drugs
* Antithymocytes Globulin (Atgam)
* Murononab, alpha-CD3 (OKT3)
31
Antithymocytes Globulin (Atgam)
mechanism
* non-specific (wide specifity)
* Bind T cells & B cells, platelets, and other leukocytes
(Anti T cell immunoglobins)
32
Anti-CD3 monoclonal Ab
function and drug
* depletes T cells by binding to CD3 and promoting phagocytosis or complement-mediated lysis
* Drug: Murononab
33
Murononab drug
* Anti-CD3 monoclonal Ab
* depletes T cells by binding to CD3 and promoting phagocytosis or complement-mediated lysis
34
Anti-IL-2 receptor (CD25) Ab
mechanism
* Inhibits T cell proliferation by blocking IL-2 binding and depletes activated T cells
* Anti-IL-2 receptor (CD25) Ab
35
Anti-IL-2 recptor (CD25) Ab
drugs
Daclizumab (Zenapax)
Basiliximab (simulect)
-mab
36
Daclizumab(Zenapax)
Basiliximab (simulect)
* Anti-IL-2 recptor (CD25) Ab drugs
* IL-2 can't bind to IL-2 receptor
* No T cell proliferation
37
Antimetabolites
mechanism
* inhibition of purine synthesis in lymphocytes blocking proliferation
* block cell division
38
Antimetabolite drugs
Azathioprine (Imuran)
Mycophenolate mofetil (cellcept)
39
Azathioprine (Imuran)
Mycophenolate mofetil (cellcept)
drugs
antimetabolites
40
corticosteroid drugs
* Prednisone (orasone, deltasone)
* methylprednisolone ( Methylpred, solumedrol)
41
Prednisone (orasone, deltasone)
methylprednisolone ( Methylpred, solumedrol)
drugs
corticosteroids
42
cyclosporine and FK-506
mechainism
block t cell cytokine production by inhibiting activation of the NFAT transcription factor
43
Azathioprine
blocks proliferation of lymphocyte precursors
44
mycophenolate mofetil mechanism
blocks lymphocyte proliferation by inhibiting guanine nucleotide synthesis in lymphocytes
45
rapamycin
blocks lymphocyte proliferation by inhibiting IL-2 signaling
46
corticosteroids mechanism
reduce inflammation by inhibiting macrophage cytokinw secretion
47
manifestation of chronic oral graft versus host diease
(GVHD)
* transplant does hve oral mannifestation
* lechenoid changes
* mucosal atrophy
* ulcerations
* taste disturbances
* salivary gland hypofunction
48
treatment for oral GVHD
* Cyclosporine & corticosteroids
49
tacrolimus
sirolimus
* tacrolimus-can use rather than cyclosporine if disease is in the liver
* sirolimus-used in renal transplant patients
50
hydroxychloroquine
antimalarial drug used to treat lupus
antiflammatory
decrease TNF alpha IL-1
51
thalidomaide
anti-inflammatory effect
decrease in TNF-alpha activity
52
methotrexate
anti-metabolite
immunomodulatory and anti-inflammatory effects
53
topical and local therapy for oral cGVHD
drugs
* topical corticosteriod
* topical cyclosporine
* local phototherapy (UV)
* Topical azathioprine
* topical tacrolimus
