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Immuno Exam 3 > Lecture 24 Transplantation Immunology > Flashcards

Lecture 24 Transplantation Immunology Flashcards

1
Q

autograft

A

transplant from one anatomical location to another on the same person

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2
Q

isograft

A

transplant from one individual who is syngeneic to the donor (identical twin) HISTOCOMPATIBLE

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3
Q

allograft

A

transplant from one individual to a genetically dissimilar individual HISTOINCOMPATIBLE

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4
Q

alloantigens

A

antigens that differ between members of the same species

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5
Q

xenograft

A

graft between donor and recipient from different species; HISTOINCOMPATIBLE

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6
Q

Bone Marrow and HSC transplantation

A

allogeneic and autologous

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7
Q

Which type of transplants would you expect to see rejection?

A

allograft and xenograft because they are HISTOINCOMPATIBLE

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8
Q

Allogeneic bone marrow transplant runs a risk for

A

graft vs host disease

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9
Q

Colony stimulating factors include

A

granulocyte-monocyte-CSF or IL-13

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10
Q

Autologous bone marrow transplant

A

HSC or bone marrow from same individual following CD34, cryopreservation, ablative therapy followed by reintroduction of frozen HSC

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11
Q

First-set rejection

A

first graft from a histoincompatible donor leads to rejection in 2 weeks

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12
Q

Second-set rejection (immunological memory)

A

second graft from the same donor will be completely rejected within a week

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13
Q

which type of individuals would not reject an allograft

A

athymic - T cell plays a large role in rejection

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14
Q

Hyperacute rejection

A

within hours, pre-formed antibodies to incompatible MHC or blood group antigens and activation of complement causes a reaction

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15
Q

Hyperacute rejection is mediated by

A

present antibodies binding to tissue inducing complement and recruitment of phagocytic cells, platelet activation -> thrombosis -> hemorrhage -> necrosis

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16
Q

Pre-formed antibodies may be present as a result of

A

ABO incompatibility, previous incompatible transfusion, pre void blood transfusion from related donor, pregnancy

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17
Q

Manifestations of hyperacute rejection

A

fever, leukocytosis, loss of function of organ

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18
Q

Therapy for hyperacute rejection

A

NONE

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19
Q

Acute rejection

A

within days, non-sensitized patients’ T cell-mediated immunity recognizes mismatch of HLA types

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20
Q

Acute rejection is complete by

A

14 days, may be shorter in sensitized patients

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21
Q

Acute rejection occurs when

A

there is a mismatch or incomplete match in HLA types

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22
Q

Histological definition of acute rejection

A

infiltration of lymphocytes and monocytic macrophages

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23
Q

destruction of cells in acute rejection occurs by

A

cytotoxic T cells, phagocytosis and presentation of transplant antigen to help T cells

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24
Q

Therapy for acute rejection

A

immunsuppressive therapy (antibodies against T lymphocytes, corticosteroids, or other drugs)

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25
Q

Histological definition of chronic rejection

A

lymphoid proliferation and formation of lymphoid follicles, fibrotic changes

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26
Q

Chronic rejection

A

over months or years, CD4+ cell activation along with macrophage activation, cytotoxic T cell activation, antibody produced against allograft antigens, classical complement, and ADCC cause loss of function of organ

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27
Q

Therapy for chronic rejection

A

none, damage has been done

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28
Q

Graft vs host disease

A

transplantation of donor lymphocytes or precursors genetically dissimilar can ATTACK RECIPIENT’s tissue

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29
Q

To avoid Graft vs host disease

A

immunocompetent lymphocytes from donor and recipient must be immune compromised

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30
Q

Manifestations of Graft vs host disease

A

rash, hepato-slpenomagaly, lymphadenopathy, diarrhea, anemia, weight loss, wasting

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31
Q

Graft-versus-leukemia effect

A

donor T cells recognize minor histocompatibility or tumor-specific antigens and attack and kill leukemic cells, reducing the reoccurrence

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32
Q

Major Histocompatibility Complex (MHC)

A

primary immunological importance in graft acceptance or rejection

33
Q

transplantation agents

A

MHC

34
Q

HLA

A

products of the MHC gene complex

35
Q

MHC class I is composed of

A

several closely linked genes or loci known as A, B, C

36
Q

MHC class II is composed of

A

several closely linked genes or loci known as DP, DQ, and DR

37
Q

HLA class I are expessed on

A

All nucleated cells

38
Q

HLA class II are expressed on

A

a subset of hematopoietic cells (dendritic cells) and thymocytes

39
Q

HLA class II can be induced by what cytokine

A

INF-gamma

40
Q

Haplotype of MHC

A

combination of 6 alleles (one for each A, B, C, DP, DQ, and DR

41
Q

Genotype of MHC

A

2 haplotypes, 1 from each parent = 12 alleles expressed

42
Q

Use of HLA alleles for

A

MHC genetic polymorphisms is the basics for forensics, paternity testing, DNA ancestry, tissue typing

43
Q

MHC is inherited as

A

a block of genes from each parent, because they are so closely linked

44
Q

The most potent transplant antigen is

A

MHC Class II HLA-DR

45
Q

The key initiating event in allograft rejection is

A

direct activation of the recipient’s CD4+ T cells by NONSELF HLA Class II molecules from donor

46
Q

Direct recognition

A

recognition of nonself HLA molecules does not require processed foreign peptides, instead CD4 recognized non-self HLA alone

47
Q

In direct recognition, because CD4 TCR does not need HLA + peptide for recognition, the body mounts a

A

much broader immune response (5% of all T cells respond)

48
Q

indirect recognition

A

receipient’s APC processes donor antigens and presents them to T cells

49
Q

Which locus is associated with the longest graph survival

A

HLA-DR

50
Q

Activation of CD4+ cells via

A

recognition of foreign HLA class II (with or without peptide) occurs

51
Q

Activation of CD8+ T cells via

A

direct activation by nonself HLA class I UT require the assistance of CD4+ T cells via IL-2 production

52
Q

Important cytokines in allograft rejection are predominantly

A

Th1, hence graft rejection reflects a type 1 immune reponse

53
Q

IFN-gamma role in allograft rejection

A

accumulation and activation of macrophages and increased HLA Class II expression, cytolytic response

54
Q

IFN-gamma and IFN-alpha/beta and TNF-alpha and beta role in allograft rejection

A

increase HLA class I expression and result in cytolysis of transplanted cells

55
Q

TNF-beta role in allograft rejection

A

cytotoxic to graft cells

56
Q

Tissues that are highly dependent on HLA matching for survival

A

bone marrow and kidney

57
Q

Tissues that are moderately dependent on HLA matching for survival

A

heart and liver

58
Q

Tissues that are not dependent on HLA matching for survival

A

cornea

59
Q

What is the reason for graft rejection when 2 individuals are HLA-matched

A

Minor histocompatibility antigens

60
Q

reaction due to minor histocompatibility antigens is

A

not as rapid, but patients must still be under immunosuppressive therapy to prevent graft rejection

61
Q

Testing for histocompatibility

A

blood typing and cross-match (ABO mismatch = hyperacute rejection), genotyping HLA by PCR

62
Q

Genotpying HLA alleles by PCR

A

HLA sequence-based typing (HLA-SBT), PCR, DNA sequencing, comparison to known allele sequences

63
Q

Prevention of allograft rejection

A

all medications are not antigen-specific, but rather induce generalized immune suppression

64
Q

Tissue typing (lymphocytotoxicity)

A

antibodies against known HLA sequence-marker is added to cells, cells stained indicate +HLA marker

65
Q

Mixed Leukocyte Reaction (1 way)

A

known LIVING donor available, highly sensitivite for major and minor HC, mix recipient and donor cells together (inactivate 1) if T cell reconizes other as foreign then cells divide and incorporate thymidine in DNA. If not foreign, no proliferation and no uptake

66
Q

Corticosteroids

A

inhibit T cell cytokine production and HLA expression (-ones)

67
Q

Antimetabolites

A

azathioprine and mercaptopurine - inhiibit lymphocyte proliferation - purine agonist; cyclophosphamide and chlorambucil - DNA alkylating agents; methotrexate - folic acid antagonist

68
Q

azathioprine

A

inhibit lymphocyte proliferation - purine agonist

69
Q

mercaptopurine

A

inhibit lymphocyte proliferation - purine agonist

70
Q

cyclophosphamide

A

DNA alkylating agents

71
Q

chlorambucil

A

DNA alkylating agents

72
Q

methotrexate

A

folic acid antagonist

73
Q

Blocking agents

A

antibodies against CD-3, IL-2 receptor, B7 ligands

74
Q

Antibody against CD-3

A

blocks T cell activation

75
Q

Antibody against IL-2R

A

receptor on T cells

76
Q

Antibody against B7 ligands

A

blocks effects of co-stimulating molecules

77
Q

Cyclosporine

A

inhibits T cell cytokine production by interfering with gene transcription

78
Q

FK506 and rapamycin

A

similar to cyclosporine - inhibits T cell cytokine production by interfering with gene transcription

Immuno Exam 3 (6 decks)

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