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Immunology Block 2 > Transplantation > Flashcards

Transplantation Flashcards

1
Q

what is polymorphism?

A

the presence of multiple alleles at a given genetic locus within the species

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2
Q

an autograft is performed on the _____ individual

A

same

usually of skin

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3
Q

an isograft is performed on the ____ _____ individual

A

genetically identical

any organ

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4
Q

an allograft is performed on the _____ individual

A

different (same species)

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5
Q

a xenograft is performed on the _________ species

A

different

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6
Q

autografts and isografts are _____ while allografts and xenografts are ______

A

accepted

rejected

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7
Q

how does major and minor H antigen rejection compare?

A

…

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8
Q

what are minor H antigens?

A

peptides derived from polymorphic cellular proteins bound to self MHC molecules

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9
Q

what cells recognize the minor H antigens?

A

recipient’s T cells after processing

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10
Q

where are minor H antigens encoded?

A

male chromosome

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11
Q

What cells play a role in allograft rejection of a kidney?

A

both CD4 and CD8 cells may be activated by non-self MHC and kill transplanted cells directly

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12
Q

what are the two mechanisms for the recognition of alloantigens in grafted organs?

A

direct recognition and indirect recognition

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13
Q

what happens in direct recognition?

A

The host T cells are stimulated by donor dendritic cells (APCs) which express both the allogenic (donor) MHC molecule and foreign peptide

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14
Q

what happens in indirect recognition?

A

mediated by T cells whose receptors are specific for allogeneic (donor) peptides derived from the grafted organ. Proteins from the graft are processed by recipient dendritic cells and therefore presented by recipient MHC class 1 or class 2 molecules

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15
Q

how does the direct pathway for allorejection occur?

A

migration of passenger leukocytes from donor graft to present to recipient CD4 and CD8 T cells

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16
Q

what does the cellular tissue rejection immune response include?

A
  • type 4 mechanisms
  • both CD4 and CD8 cells triggered
  • IL2, INF gamma, TNF alpha and beta
  • cytotoxic T cells specific for graft
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17
Q

which MHC 2 gene is most important for tissue rejection?

A

DR

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18
Q

the humoral response to transplants is involved in which pathway?

A
  • indirect

- B lymphocytes encounter soluble alloantigens from graft and present peptides to Th cells

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19
Q

What does Ab sensitization induce in the humoral response to transplants?

A
  • ADCC
  • Complement-mediated lysis
  • histamine is released, neutrophils release hydrolytic enzymes; increase in blood vessel permeability
  • immune complexes deposited-blood clotting
  • infarction in organ
  • major mediator of CHRONIC and HYPERACUTE rejection
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20
Q

what are the two groups of Host v Graft histocompatibility?

A

non-specific and specific

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21
Q

where does the non-specific component occur?

A

in any graft regardless of outcome

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22
Q

what characterizes the non-specific component of HvG?

A
  • inflammatory

- invasion of PMNs and mononuclear cells

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23
Q

what characterizes the specific component of HvG? (3)

A
  • hyperacute: pre-existing anti-alloantigen antibodies (anti MHC or isohemagglutinins)
  • Acute: first set and second set rejection mediated by T cells
  • Chronic: minor H antigens - T cell and Antibody mediated
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24
Q

Acute rejection(first set) is common in which individuals?

A

those with mismatch or insufficient immunosuppression

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25
Acute rejection (second set) is common when?
recipient is previously sensitized to HLA differences on graft
26
what is the major reason fro lack of success of transplant?
chronic rejection
27
during chronic rejection what cells invade the organ and induce scarring?
macrophages
28
what happens in the type 4 like inflammatory response in chronic rejection?
thickening of elastic lamina over time
29
T/F: human T cell responses to xenogeneic antigens are not as strong as allogeneic responses
TRUE
30
Preformed antibodies against xenogeneic antigens cause ______ rejection
hyperacute
31
Pigs expression Gal-alpha (1-3)-Gal is clinincally similar to _______ in humans
ABO
32
summary of effector mechanisms for transplantion
...
33
HLA and ABO matching is optimal for which organ?
kidney
34
most grafts are autologous for which organ?
skin
35
HLA matching is desirable but not always possible for which organ?
heart
36
HLA typing is NOT AS IMPORTANT; ABO matching only is associated with which organ?
liver
37
transplant islet cells alone is sufficient is for which organ?
pancreas
38
the removal of CD+3 T cells is important for which organ?
bone marrow
39
what location is most important in the maternal fetal graft relationship?
anatomic
40
what is vascular throphoblast?
placental fetal tissue in contact with the mother - exposed to maternal blood - nutrient exchange
41
class ___ molecules are not found on trophoblast; cells express non-polymorphic class ___ molecules
2; 1
42
uterine layer produces which ______ cytokines
inhibitory | TGF-beta, IL-4, IL-10, leading to TH2
43
what is the major way in which kidney transplantation differs from bone marrow transplantation?
recipient T cells attack transplant in kidney v. T cells from donor attack recipients tissues in bone marrow transplant
44
In bone marrow transplantation, what procedures occur to make the patient healthy?
irradiation and chemotherapy, hemaptopoeitic cell infusion
45
what are some diseases treatable by bone marrow transplantation?
osteoporosis, ataxia telangiectasia, mucopolysaccharidosis, gaucher's syndrome, thalassema, sickle cell anemia
46
what is the mechanism of GvH?
T cells in graft recognize HLA on host cells
47
symptoms of GVH
- organ enlargement - spleen, liver, lymph nodes - skin rash - diarrhea and weight loss - death -
48
how to prevent symptoms of GVH?
remove donor T cells - add anti-CD3 antibody + complement - peanut agglutinin (PNA) will bind T cells allowing them to be removed
49
tolerance to allogenic skin can be established in bone marrow _____ mice
chimeric
50
what drugs are used as immunosuppressive agents?
corticosteroids
51
what is the function of decreased IL-1,3,4,5, TNF alpha, GM-CSF, and CXCL8 in corticosteroid therapy?
decreased inflammation caused by cytokines
52
what is the fxn of decreased NOS in corticosteroid therapy?
decreased NO
53
what does a decrease in phospholipase A2 and cyclooxygenase type 2 and an increase in lipocortin-1 lead to?
decrease in prostaglandins and leukotrienes
54
what does a decrease in adhesion molecules do in corticosteroid therapy?
reduced emigration of leukocytes from vessels
55
what does an induction of endonucleases do in corticosteroid therapy?
induction of apoptosis in lymphocytes and eosinophils
56
what are the 4 key fxns of corticosteroids in immunosuppression?
- block cytokine gene transcription - reduce cytokine secretion - reduce phagocytosis and killing by PMNs and macrophages - reduce MHC 2 expression
57
what does cyclosporine A and FK506 (tacrolimus) do?
- inhibits gene transcription of : IL-2, IL-4, INF gamma, IL-2R - blocks calcineurin phosphatase activity - blocks NFAT
58
immunological effects of cyclosporine A and tacrolimus on T lymphocytes?
- reduced expression of IL-2,3,4, GM-CSF, TNF-alpha - reduced cell division because of decreased IL-2 - Reduced Ca2+dependent exocytosis of cytotoxic granules - inhibition of antigen-driven apoptosis
59
immunological effects of cyclosporine A and tacrolimus on B lymphocytes?
- inhibition of cell division because T-cell cytokines are absent - inhibition of antigen driven cell division - induction of apoptosis following B-cell activation
60
Granulocyte
reduced Ca2+dependent exocytosis of granules
61
what is rapamycin similar to?
FK506
62
what does rapamycin do?
- binds to an immunophilin | - blocks proliferation of activated Th cells in the G1 phase of the cell cycle
63
what CD markers can general inhibitors be targeted against?
Anti-CD52
64
total body irradiation
...
65
mitotic inhibitors include
- azathioprine and mercaptopurine - cyclophosphamide - methotrexate
66
azathioprine and mercaptopurine mechanism
blocks inosinic acid production in S phase cells - blocks both T and B cell proliferation - usu given just before and after transplant
67
cyclophosphamide
alkylates and cross-links DNA helix | - blocks mostly T cell proliferation
68
metrotrexate
is a folic acid antagonis and blocks purine biosynthesis
69
what are some specific immunosuppressive therapies?
- belatacept - injection of anti-CD3 and anti-CD4 - anti-IL2R - chimeric anti-CD3 diphteria toxin conjugates - anti-TNF; anti-IFNgamma
70
what does injection of anti-CD3 and anti-CD4 cause?
the removal of the relevant cells from circulation
71
what is belatacept?
a soluble chimera of Ig Fc region and CTLA4
72
Belatacept mechanism
binds B7 and prevents engagement of CD28 and generation of signal 2
73
serotyping the HLA
...
74
what test can be use to detect histoincompatibility(MLR)?
mixed lymphocyte reaction
75
How does the MLR work?
- detects differences in class 2 MHC | - response is mostly by CD4+ T cells responding to differences in class 2 MHC on stimulator cells

Immunology Block 2 (12 decks)

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