Transplant Immunology Flashcards
(88 cards)
1
Q
(blank) has evolved as the treatment of choice for end-stage organ failure resulting from a wide variety of causes
A
transpant
2
Q
Transplant of which organs are commonplace?
A
kidney, liver, pancreas, intestine, heart and lung
3
Q
The main problem facing the field today is not surgical technique, or management of rejection or complications, but rather (blank)
A
supply of organs
4
Q
The number of transplants has not kept pace with the steadily growing waiting list due to (blank)
A
(ethical dilemmas)
5
Q
What does allogenic mean?
A
genetically different within the same species
6
Q
What makes me different from you?
A
alloantigens
7
Q
Transplanted tissues (grafts) between genetically different (allogeneic) individuals are attacked by the (blank)
A
immune response (like pathogens)
8
Q
Antigenic differences between individuals (alloantigens) induce (blank) immune responses
A
alloreactive
9
Q
The most important alloantigens are (blank) protens
A
MHC (has a major number of alleles)
10
Q
Which of the MHC molecules would be more problematic in tissue transplant?
A
MHC class I (because they are found on all cells)
11
Q
The MHC gene complex in humans is called (blank)
A
human leukocyte antigen (HLA)
12
Q
What someones HLAs are, are called (blank)
A
HLA typing
13
Q
HLA MHC class I are found at what loci?
A
A B C
14
Q
HLA MHC class II are found at what loci?
A
DR, DQ, DP
15
Q
The HLA complex is located at chromosome (blank)
A
6
16
Q
Every human expresses (blank) MHC class I alleles (one allele of HLA-A, -B, and -C from each parent) and at least six MHC class II alleles (one allele of HLA-DQ and -DP and one or two of -DR from each parent
A
6
17
Q
WHat principle is this:
several MHC genes in the genome
A
polygenic
18
Q
What priniciple is this:
each gene has a large number of aleles
A
polymorphic
19
Q
(blank) have the most allels of any loci in the human genome
A
MHC
20
Q
(blank) means that both alleles on matching chromosomes will be expressed on the cell surface
A
co-domnance
21
Q
T or F
It is unlikely that two individuals would have the same MHC haplotype (alleles on a chromosome), except in the case of monozygotic (identical) twins
A
T
22
Q
How can you get a successfull transplant?
A
If you transplant tissue from one part of your body to another part of your body (autograft) or between genetically identical humans (syngeneic graft)
23
Q
What is syngeneic graft?
A
getting tissue from a genetically identical human
24
Q
Allogenic transplants (allografts i.e transplant from someone else) are rejected in about (blank) days after grafting
A
10-13 days
25
Transplans b/w individuals of different species (xenogeneic) are also rejected rapidly. What are thes grafts called?
xenografts
26
In allografts and xenografts the rapid death of the transplanted tissue is called (Blank)
acute rejection
27
If you differ in just one MHC allele can you transplant the organ?
nope it still will cause rejection
28
What was the earliest tissue transplant and most common?
Blood transfusion
29
Why are RBC and Platelets pretty easy to transplant?
because they have a very small amoutn of MHC and usually are not targets of T cells
30
What must you match on blood cells to transfuse?
Blood must be matched for ABO and Rh blood group antiges to avoid rapid destruction by antibodies in the recipient
31
Grafts between MHC allogeneic mice are rejected in 10-13 days. What happens if you put a second graft in the same animal? What does this tell us?
it is rejected even faster
| Second-set rejection reveals immunological memory.
32
IF you take a sensitized animal (i.e one that already had been given a tissue and rejected it) and take the animals T cells out of it and then transfer it to a naive animal what will happen?
it will have immunological memory and respond super bad to a tissue transplant, as if the first mouse was give a second transplant
33
Matching MHC types between donor and recipient prolongs but does not (blank) graft rejection
eliminate
34
Do MHC-matched human siblings have successful transplantation? WHy?
Cuz there are still other differences that will still elicit an immune response
35
What is direct allorecognition?
activated APC from donor graft migrate to lymphoid organ. APC presents a donor peptide to recipient T cell along with co-stimulation (CD80/86) which will elicit immune response and rejection
36
What cell will cause graft destruction first?
CD8 T cells
37
WHat is indirect allorecognition?
Your own APC cells present the graft peptide as a foreigner and elicits T cell response
38
What are the clincal manifestations of hyperacute graft rejection?
Why does this happen?
occurs w/in minutes of transplant and has thrombosis of graft vessels and ischemic necrosis of graft
Recipient antibodies attack RBCs in the grafted tissue via complement and clottign system. (this is rare cuz now we test for blood type and for antibodies against the cells of potential donor)
39
What does a graft need to be successful?
needs a blood supply
40
What is this:
normal kidney grafted into patient with defective kidney and preexisitng antibodies aganst donor antigens. Antibodies against donor antigens bind vascular endothelim of graft initiating an inflammatory reponse which occludes blood vessels and graft becomes engorged and purple colored because of hemorrhage.
Antibody-mediated hyperacute graft rejection
41
What is acute graft rejection?
| How do you avoid this?
happens within days/weeks after transplant, principle cause of early graft failure, mediated by CD8 T cells (MAJOR), complement and antibodies
Immunosuppresive therapy,,
42
In acute graft rejection, recipient (blank) cells attack alloantigenic MHC peptides in the graft
CD8 T
43
What is chronic graft rejection?
Insidious (slowly but hurtfully) form of graft damage that occurs over months to years, leads to loss of graft function.
44
How does chronic graft rejection present?
as graft fibrosis and narrowing of graft blood vessels (graft arteriosclerosis) caused by CD4 T cells that are perpetually releasing mediators
45
In chronic graft rejection, (bank) react with graft alloantigens and secrete cytokines that stimulate the proliferation and activities of fibroblasts and vascular smooth muscle cells
CD 4 T cells
46
What is the principal cause of graft failure?
Chronic graft rejection
47
Where do you see the fibrosis and scarring of chronic graft rejection?
- Heart (accelerated coronary artery atherosclerosis)
- Lung (bronchiolitis obliterans)
- Liver (vanishing bile duct syndrome)
- Kidney (chronic allograft nephropathy)
48
What factors increase risk of chronic rejection?
previous episode of acute rejection
inadequate immunosuppression
Donor-related factors (e.g old age, hypertension)
Long cold ischemia time; reperfusion injury to organ
Recipient-related factors (e.g, diabetes, hypertension, hyperlipidemia)
Post-transplant infection (e.g. CMV)
49
(blank) is used to correct hematopoietic defects or to restore bone marrow cells damaged by irradiation or cancer chemotherapy
Hematopoietic stem cell transplantation
50
Is bone marrow easy to transplant?
no, Allogeneic bone marrow cells are very immunogenic, so that successful transplantation requires careful HLA matching of donor and recipient
51
Mature allogeneic T cells in the graft can attack the recipient’s tissues, resulting in a serious clinical reaction called (blank)
graft-versus-host disease
52
WHy do peope use myeloablative therapy (kills patients bone marrow)?
to destroy messed up bone marrow or make room for donor bone marrow to fit
53
What is super scary about bone marrow transplants?
mature donor T cells attack recipient tissues causing graft versus host disease due to alloantigens on the bone marrow :(
54
Can you give a scid kid a bone marrow transplant?
yes!!! because skid kids dont have functioning T cells so nothing will attack the donor bone marrow
55
When you have graft vs host disease what are the symptoms?
| How do you control this?
you see a rash on the face and diarrhea, pneumonitis and liver damage :(
immunosuppressive drugs
56
What is the graft vs leukemia effect?
the donor T cells attack the cancerous cells in leukemia
57
What doesnt the trophoblast have? WHat does this mean?
MHC molecules
| That T cells from mom wont recognize MHC molecules from dad inside the fetus
58
Tryptophan is essential for (blank) function
T cell
59
What keeps moms T cells from attacking the placenta?
the placenta secretes indole amine dioxygenase that catabolizes tryptophan and starves T cells (tryptophan is essential for T cell function)
60
Placental secretion of (blank) causes immune deviation
cytokines
61
T or F
With the extremely rare exception of grafts between identical twins, all recipients of tissue transplants will require immunosuppressive drug treatment for life
T
62
T or F
| Too little immunosuppression, their grafts will be rejected; too much immunosuppression, they will die from infections
T
63
Tissue transplants are rejected by the immune system, and the major antigen targets of rejection are (blank)
MHC molecules
64
The mainstay of preventing and treating the rejection of organ transplants is (blank)
immunosuppression
65
The most useful immunosuppressive drug in clinical transplantation is (blanK). What does it do?
cyclosporin A
perfers to stop T cells from dividing via blocakage of T cell phosphatese calcineurin and prevents transcription factor NFAT from activating cytokine genes
66
What does corticosteroids do?
inhibit inflammation, shut off NFKb, inhibits cytokine production by macrophages.
67
What does Azathioprine, cyclophosphamide, mycophenolate do?
inhibit proliferation of lymphocytes by interfering with DNA synthesis
68
What does Cyclosporin A, tacrolimus (FK506) do?
inhibits calcineurin-dependent activation of NFAT; block IL-2 production and proliferation by T cells
69
What does rapamycin (sirolimus) do?
inhibits proliferation of effector T cells by blocking Rictor-dependent mTOR activation
70
What does Fingolimod do?
blocks lymphocyte trafficking out of lymphoid tissues by interfering with signaling by the sphingosine-1-phosphate receptor
71
Why dont you want to use long term corticosteroid?
because they have a lot of bad side effects
72
What crosses nuclear membrane to bin to NF-Kb promotor and inhibits its transcription to reduce cytokines?
corticosteroids
73
What down-regulates proinflammatory cytokines, NO, prostaglandins, leukotrienes, and adhesion molecules?
corticosteroids
74
What are the three most common cytotoxic drugs/immunosuppressive agents?
How do they work?
azathioprine, mycphenolate, cyclophosphamide
they block DNA syntehsis and kill dividing cells (includes tumor cells and lymphocytes)
****lots of bad side effects******
75
What can CD4 T cells do to mess someone up pretty bad?
releases cytokines that can cause inflammation and fibrosis
76
What is the effect of corticosteroids on cytokines?
| which cytokines in particular?
decreases them
| IL-1, TNF-alpha, GM-CSF, IL-3, IL-4, IL-5, CXCL8
77
What is corticosteroids effect on NOS?
decreases it so you have decreased NO
78
What is corticosteroids effect on phospholipase A2, Cyclooxygenase type 2, annexin-1?
What does this result in?
decreases phospholipase A2 and cyclooxygenase type 2
increases annexin-1
Decrease prostaglandins and leukotrienes
79
WHat wil be corcticosteroids effect on adhesion molecules? what will this result in?
decrease, reduced emigration of leukocytes from vessels
80
What will corticosteroids do to endonucleases? What wil this result in?
increase it
| induction of apoptosis in lymphocytes and eosinophils
81
Microbial inhibitors of T cell signaling are used to prevent (blank)
allograft rejection
82
What are the three most common microbial inhibitors of T cell signaling?
cyclosporin A, Tacrolimus, and Rapamycin
83
How does Cyclosporin A, Tacrolimus (FK506), and Rapamycin (Sirolimus)
work?
they bind to intracellular immunophilins to inhibit T and B cell proliferation and granulocyte function, but affect immune responses indiscriminately.
84
Explain in detail the mode of action of cyclosporin A?
A T cell internalize calcium whih will bin to calmoduling which will then activate calcineurin. Calcineurin is what causes activation NFATvia dephosphorylation to make IL-2 and have T Cells proliferate. Cyclosporin A will inhibit calcinerin and prevent the dephosphorylation of NFAT. This does not have a lot of side effects
85
What does RAPTOR and mTOR do and what can block this and work as an immunosuppressent?
it causes T cell proliferation
| Sirolimus (rapamycin)
86
(blank) can be used to prevent graft rejection
monoclonal antibodies
87
How does Muromomab (OKT3) work?
it is an anti-CD3 so blocks all T cell production
88
Ho does Daclizumab and Basiliximab work?
it is an anti-IL2 receptor that will inhibit the proliferation and differention of T cells
