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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
Q

Acute rejection (second set) is common when?

A

recipient is previously sensitized to HLA differences on graft

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26
Q

what is the major reason fro lack of success of transplant?

A

chronic rejection

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27
Q

during chronic rejection what cells invade the organ and induce scarring?

A

macrophages

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28
Q

what happens in the type 4 like inflammatory response in chronic rejection?

A

thickening of elastic lamina over time

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29
Q

T/F: human T cell responses to xenogeneic antigens are not as strong as allogeneic responses

A

TRUE

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30
Q

Preformed antibodies against xenogeneic antigens cause ______ rejection

A

hyperacute

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31
Q

Pigs expression Gal-alpha (1-3)-Gal is clinincally similar to _______ in humans

A

ABO

32
Q

summary of effector mechanisms for transplantion

A

…

33
Q

HLA and ABO matching is optimal for which organ?

A

kidney

34
Q

most grafts are autologous for which organ?

A

skin

35
Q

HLA matching is desirable but not always possible for which organ?

A

heart

36
Q

HLA typing is NOT AS IMPORTANT; ABO matching only is associated with which organ?

A

liver

37
Q

transplant islet cells alone is sufficient is for which organ?

A

pancreas

38
Q

the removal of CD+3 T cells is important for which organ?

A

bone marrow

39
Q

what location is most important in the maternal fetal graft relationship?

A

anatomic

40
Q

what is vascular throphoblast?

A

placental fetal tissue in contact with the mother - exposed to maternal blood - nutrient exchange

41
Q

class ___ molecules are not found on trophoblast; cells express non-polymorphic class ___ molecules

A

2; 1

42
Q

uterine layer produces which ______ cytokines

A

inhibitory

TGF-beta, IL-4, IL-10, leading to TH2

43
Q

what is the major way in which kidney transplantation differs from bone marrow transplantation?

A

recipient T cells attack transplant in kidney v. T cells from donor attack recipients tissues in bone marrow transplant

44
Q

In bone marrow transplantation, what procedures occur to make the patient healthy?

A

irradiation and chemotherapy, hemaptopoeitic cell infusion

45
Q

what are some diseases treatable by bone marrow transplantation?

A

osteoporosis, ataxia telangiectasia, mucopolysaccharidosis, gaucher’s syndrome, thalassema, sickle cell anemia

46
Q

what is the mechanism of GvH?

A

T cells in graft recognize HLA on host cells

47
Q

symptoms of GVH

A
  • organ enlargement - spleen, liver, lymph nodes
  • skin rash
  • diarrhea and weight loss
  • ## death
48
Q

how to prevent symptoms of GVH?

A

remove donor T cells

  • add anti-CD3 antibody + complement
  • peanut agglutinin (PNA) will bind T cells allowing them to be removed
49
Q

tolerance to allogenic skin can be established in bone marrow _____ mice

A

chimeric

50
Q

what drugs are used as immunosuppressive agents?

A

corticosteroids

51
Q

what is the function of decreased IL-1,3,4,5, TNF alpha, GM-CSF, and CXCL8 in corticosteroid therapy?

A

decreased inflammation caused by cytokines

52
Q

what is the fxn of decreased NOS in corticosteroid therapy?

A

decreased NO

53
Q

what does a decrease in phospholipase A2 and cyclooxygenase type 2 and an increase in lipocortin-1 lead to?

A

decrease in prostaglandins and leukotrienes

54
Q

what does a decrease in adhesion molecules do in corticosteroid therapy?

A

reduced emigration of leukocytes from vessels

55
Q

what does an induction of endonucleases do in corticosteroid therapy?

A

induction of apoptosis in lymphocytes and eosinophils

56
Q

what are the 4 key fxns of corticosteroids in immunosuppression?

A
  • block cytokine gene transcription
  • reduce cytokine secretion
  • reduce phagocytosis and killing by PMNs and macrophages
  • reduce MHC 2 expression
57
Q

what does cyclosporine A and FK506 (tacrolimus) do?

A
  • inhibits gene transcription of : IL-2, IL-4, INF gamma, IL-2R
  • blocks calcineurin phosphatase activity
  • blocks NFAT
58
Q

immunological effects of cyclosporine A and tacrolimus on T lymphocytes?

A
  • 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
Q

immunological effects of cyclosporine A and tacrolimus on B lymphocytes?

A
  • inhibition of cell division because T-cell cytokines are absent
  • inhibition of antigen driven cell division
  • induction of apoptosis following B-cell activation
60
Q

Granulocyte

A

reduced Ca2+dependent exocytosis of granules

61
Q

what is rapamycin similar to?

A

FK506

62
Q

what does rapamycin do?

A
  • binds to an immunophilin

- blocks proliferation of activated Th cells in the G1 phase of the cell cycle

63
Q

what CD markers can general inhibitors be targeted against?

A

Anti-CD52

64
Q

total body irradiation

A

…

65
Q

mitotic inhibitors include

A
  • azathioprine and mercaptopurine
  • cyclophosphamide
  • methotrexate
66
Q

azathioprine and mercaptopurine mechanism

A

blocks inosinic acid production in S phase cells

  • blocks both T and B cell proliferation
  • usu given just before and after transplant
67
Q

cyclophosphamide

A

alkylates and cross-links DNA helix

- blocks mostly T cell proliferation

68
Q

metrotrexate

A

is a folic acid antagonis and blocks purine biosynthesis

69
Q

what are some specific immunosuppressive therapies?

A
  • belatacept
  • injection of anti-CD3 and anti-CD4
  • anti-IL2R
  • chimeric anti-CD3 diphteria toxin conjugates
  • anti-TNF; anti-IFNgamma
70
Q

what does injection of anti-CD3 and anti-CD4 cause?

A

the removal of the relevant cells from circulation

71
Q

what is belatacept?

A

a soluble chimera of Ig Fc region and CTLA4

72
Q

Belatacept mechanism

A

binds B7 and prevents engagement of CD28 and generation of signal 2

73
Q

serotyping the HLA

A

…

74
Q

what test can be use to detect histoincompatibility(MLR)?

A

mixed lymphocyte reaction

75
Q

How does the MLR work?

A
  • 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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