Transplant Flashcards
(114 cards)
1
Q
Allograft
A
Unrelated
2
Q
Syngraft
A
Monozygous twin
3
Q
Xenograft
A
Different species
4
Q
Autograft
A
Same person
5
Q
Are syngrafts rejected
A
No
6
Q
Allograft rejected
A
Yup
7
Q
Xenograft
A
Hyperactive rejection
8
Q
Xenograft
A
Foreign
9
Q
Hyperactute rejection
A
Preformed antibodies to HLA class I antigens or antigens of the ABO blood group.
10
Q
What causes acute or accelerated acute rejections
A
Cellular allorecognition of the graft
11
Q
GVHD
A
Transfer of immunocompetent allogenic cells into an immune depressed individual leads to these rejecting the recipient
12
Q
Good hla matching
A
Prolongs graft survival
Done for renal
13
Q
Why is hla matching not done for liver, heart and lungs
A
Short periods for which the latter organs maintain their function when explanted
14
Q
Presensitization
A
Presence of preformed antibodies to HLA class I or ABO antigens in the recipients blood, it tested for in renal but not others
15
Q
When rejected organs are biopsies, what do they contain?
A
Inflammatory infiltrate with mononuclear white blood cells(lymphocytes and macrophages, CD4, 8, macrophages, B cells and NK cells)
16
Q
When a virgin helper CD4 cell sees an alloantigen, presented by APC what two options can it become if there is costimulation
A
TH1 or TH2
17
Q
If the surrounding medium is rich in IL12, a macrophage derived cytokine, what will the virgin THCD4 become with antigen presentation
A
TH1
18
Q
What does TH1 do
A
Activate CD8 and macrophages through IL2 and IFNy
19
Q
If the surrounding is rich in IL-4 the virgin CD4 T cell will become what
A
TH2
20
Q
What does TH2 do
A
Secrete IL4 and IL10 and direct B cells and antibody production
21
Q
What CD4 predominates in rejection
A
TH1
22
Q
What does IFNy from TH1 do
A
Recruit and activate macrophages and enhance MHC expression on the graft, making it particularly susceptible to the cytotoxic action of CD8 cell
23
Q
What does IL2 do
A
Fav our the activation of cytotoxic T cells
24
Q
Alloantigen
A
Antigen recognized during rejection
25
What are the key allantigens
MHC-HLA molecules
26
Direct allorecognition
Recipients immune system can recognize an intact MHC
27
Indirect allorecognition
Peptide derived rom the foreign MHC could be presented on APC
28
Is direct or indirect allorecognition more common
Direct
29
Hyperacute rejection
Minutes
| Preformed antibodies
30
Accelerated rejection
1-5 days
| T cells
31
Acute rejection
From 2 week
| T cells
32
Chronic rejection
Months to years
| Antibodies, complement, adhesion molecules
33
Hyperacute rejection is mediated by ___ __ in the recipient that are directed against antigens of the donor organ
Preformed antibodies
34
Example of hyperacute rejection
```
ABO blood group barrier
Antibodies against HLA class I from previous transfusions, transplants or pregnancies
```
35
Where are ABO blood group antigens presented
Endothelial cells
36
How manage hyperacute rejection
Preventative
| Accommodation
37
Accommodation
Temporary depletion of natural antibodies may result in long term graft survival, despite the return of antibodies in the presence of their specific target antigens
38
Acute rejection is mediated by ____ and becomes apparent _ days post op
T cells
| 7
39
In acute rejection, how do T cells see alloantigen
Mainly direct
40
What cells infiltrate in acute rejection
Lymphocyte and monocyte
41
Accelerated acute rejection
1-5 days
| T cells that have been sensitized to alloantigen (pregnancy, transduction)
42
How treat acute rejection
Suppression
43
Chronic rejections appears _ or _ after successful transplantation
Moonthe years
44
Is cell infiltration a major feature of chronic rejection
No
45
in chronic rejection __ release IL1, 6 TNFa
Macrophages
46
How it is expected that chronic rejection occurs
Early damage to the vascular endothelium is predisposing
Endothelium further damaged by antibodies to alloantigen, deposition of immune complexes, activation of complement , exposure of collagen and activation of the clotting cascade
FAVORING ENDOTHELIAL CELL PROLIFERATION and narrowing of the vascular lumen
47
GVH
Grafts have immunocompetent cells recognize alloantigen of the recipient
48
GVH is common after transplantation of __ ___
Bone marrow
49
What happens when GVH becomes symptomatic
It is GVHD
50
GVHD divided into two entities
```
Acute disease (1-2 months)
Chronic disease(develops 2-3 months)
```
51
What does GVHD effect in humans
Skin, liver, intestinal tract, immune system
52
How long does GVHD happen after bone transplant
Days weeks
53
Characterization of GVH
Erythema on palms and soles and ears
Hyperbilirubinaemia
Diarrhea
54
Characterization of severe GVHD
Jaundice, increased Alkaline phosphatase, which denotes cholestasis, and of transaminases, a ding of liver damage
Diarrhea abdominal pain
55
What causes the symptoms of GVHD
Epithelial cell injury
56
Chronic GVHD shares certain clinical characteristics with __ __
Systemic sclerosis
57
Prophylaxis for acute GVHD
Combination of methotrexate and ciclosporin
58
Treatment of established GVHD
Methylprednisolone, ciclosporin/tacrolimus
| Anti-CD52 monoclonal antibody campath1
59
Tissue typing
Kidneys bc robust-can bee 48 hours cold
60
HLA types kidneys have a graft survival in 1st year os ___% while nonmatched have __%
88 79
61
How test for presenstization
Incubating the serum of the recipient and the lymphocytes of the donor. Binding of antibodies in the recipient serum is analyzed by flow cytometry
62
Presensitization is an absolute ___ in renal transplant
Contradiction
63
Is presensitization evaluated in cardiac and liver transplantation
No
64
Immunosuppressive drugs
Dampening down the immune system
65
Azathioprine
Inhibits purine synthesis
66
Corticosteroids
Block cytokine gene expression
67
Ciclosporin A; tacrolimus
Block Ca2+ dependent T cell activation pathway
68
Sirolimus
Blocks il2 triggered proliferation and CD28/CTLA4 mediated co stimulators signals
69
Azathioprine
Purine antagonist and functions as an effective antiproliferative agent.
70
Corticosteroids have multiple effects on the immune system
Decrease B cells and inhibit monocyte trafficking , T cell proliferation and cytokine gene expression
71
Side effects of corticosteroids
Skin, bones, and other tissues continue to present problems in clinical
72
Glucorticoid:prednisone
Given immediately before or at the time of transplantation
73
Methylprednisone
Administered immediately upon diagnosis of beginning rejection and continued once daily for 3 days
74
Do prednisone and azathioprine act non specifically on the immune system
Yup
75
Ciclosporin a
Calcineurin inhibitor
Small fungal cyclic peptide
Reduce GVHD following bone marrow transplant
76
Major effects of ciclosporin a
T cells-inhibit il2 secretion
| Stimulate production of cell growth inhibitory cytokines, such as TGFb
77
What does TGFb do
Inhibits both T cell proliferationa nd the generation of cytotoxic lymphocytes , a heightened production of tgfb may contribute to the immune suppressive activity of ciclosporin A
78
Ciclosporin a side effect
Nephrotoxicity
79
Tacrolimus
Macro life antibiotic isolated from a Japanese soil fungus, streptomyces T
Similar effects and side effects of ciclosporin
80
Side effects tacrolimus
Renal
81
Ciclosporin and tacrolimus are what
Calcineurin inhibitors
82
Sirolimus
Rapamycin , macrocyclic lactose that inhibits biochemical pathways that are required for cell progression through the late G1 phase or entry into the S phase of the cell cycle and is labeled as an antiproliferatice
83
Side effects sirolimus
Hypertriglyceridaemia
84
Antibodies can be used to target specific immune cells thought to be involved in rejection
Target cells are abolished or lessened through antibody directed cell lysis or modulation of surface molecules
85
Monoclonal antibody
Monospecificity and can be purified to homogeneity
86
Since the 80s, ALG and ATG have been used by many transplant centers for the treatment of rejection episodes (antilymphocyte globulin and antimyocyte globulin)
These polyclonal antisera are composed of multiple antibodies specific for a variety of lymphocyte cell surface molecules
87
Monoclonal anti CD3
OKT3 monoclonal antibody sees human cd3
Treat recipients of allograft in clinical transplantation
Intravenous administration of OKT3 clears T cell from circulation by opsonization
88
Disadvantage of anticd3 molecule
Side effects and development of anti mouse antibodies in 75% of ppl
89
Monoclonal anti-cd4 and anti-cd8
Okt4
| In clinical trials
90
Monoclonal antibodies specific for activation antigens
When T cells respond to antigen and become activated, they express IL2 receptor. Targeting this receptor may allow more selective immunosuppressive therapy. This antibody is used in islet transplantation
91
Side effects of antibody therapy
Syndrome of fever and myalgia that is believed to be caused by systemic release of cytokines
Also develop lymphomas
92
Lymphomas occur in _% of all recipients of transplanted organs
1-2
93
Immunosuppressive regimen
Multiple immunosuppressive drugs acting at different levels of T cell activation
Standard:tacrolimus and corticosteroid
94
__ antibodies are used in some centers before transplantation to prevent the activation of anti graft immune response
Antilymphocyte
95
Antilymphocyte antibodies are effective but increase the incidence of what
Lymphoproliferatice disorders and possibly infections
96
The administration of murine anti cd3 OKT3 is associated with what
Fever, chills, hypotension, pulmonary edema, encephalopathy, nephropathy...CAPILLRARY LEAK SYNDROME
97
Complications of immunosuppressive regimen
Infections, malignancies, bacterial fungal viral
98
Frequent agents of infection after transplant
CMV, herpes virus, fungal organisms, Aspergillus, Nocardia, cryptococcal, pneumocystis, toxoplasmosis
99
What is the most frequent and pathologically important post transplant infection
CMV
100
Does cmv infection last for life
Ya latent
101
When does cmv deactivate
Impaired T cell immunity
102
Primary cmv infection
If in organ that was transplanted
103
In renal, cardiac, lung, liver and bone marrow transplant, CMV causes what
Fever, leukopenia, hepatitis, pneumonia is, oesophagitis, gastritis, colitis, 1month after surgery
104
CMV retinitis can appear later
Ok
105
How treat cmv infection
Ganciclovir, a guanosine derivative
106
What are the most common cancers seen after organ transplant
Lymphoma, skin cancer, Kaposi Sarcoma
107
The development of __ diseases is also dependent on immunosuppression, induced by drugs such as ciclosporin, tacrolimus, okt3
Lymphoproliferative
108
In the setting of allotransplatation , lymphoproliferative diseases are aggressive with a high incidence of what
Central nervous system and extranodal involvement ; they are mainly classified as B cell derived large cell non Hodgkin lymphomas and can be polyclonal or monoclonal
109
Outcome os lymphoproliferative disease
Poor unless immunosuppressive therapy can be stopped
110
Origin of these lymphoproliferative diseases has been ascribed to the effect of the oncogenic ___ over B cells constantly stimulated by the allograft. Immusuppression would be a catalyst
EBV
111
The use of immunosuppression controls rejection episodes
The introduction of ciclosporin a in the 1980s has dramatically improved the outcome of allotransplantation
112
Immunosuppressive regimens typically include and use multiple drugs acting at different levels of what
T cell activation
113
Episodes of rejection resistant to conventional immunosuppressive regimens are controlled by what
Use of high dose steroids, tacrolimus, and antilymphocyte antibodies
114
Side effects of immunosuppression
Opportunistic microorganisms and malignancies
