Transplantation Immunity Flashcards

1
Q

what needs to match b/w donor and recipient to have it last

A

MHC

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2
Q

tissue compatibility testing

A

need to test tissue to determine if it is compatible with recipient

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3
Q

GVHD stands for

A

graph vs host disease

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4
Q

what is GVHD

A

the transplant rejects the donor

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5
Q

what is definition of transplantation

A

Transfer of living cells, tissues, and organs (a graft) from one part of the body to another or from one individual (donor) to another (recipient or host).

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6
Q

what is definition of transfusion

A

is a special case of transplantation and the most frequent.

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7
Q

examples of live transplant organs

A

skin
bone marrow
kidney
blood

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8
Q

what is autogenic or autograft

A

from one part of your own body to another

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9
Q

will autogenic graft be accepted without immunotherapy

A

yes - it is yourself

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10
Q

examles of autogenic grafts

A

skin
stem cell
vein
blood

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11
Q

syngeneic or isograft describe

A

identical twins - one idential person to another

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12
Q

syngeneic accepted without immunotherapy

A

yes

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13
Q

another name for syngeneic

A

isograft

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14
Q

another name for autogeneic

A

autograft

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15
Q

allogeneic or alograft

A

one individual in species to another individual in species

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16
Q

most common form of transplant

A

allogeneic

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17
Q

another name for allogeneic

A

allograft

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18
Q

allogeneic accepted without immunotherapy?

A

no - rejected

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19
Q

xenogeneic transplant

A

from a member of a different species

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20
Q

another name for xenogeneic

A

xenograft

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21
Q

xenogeneic accepted without immunotherapy?

A

no

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22
Q

ex of xenogenic transplant

A

heart valve - like pig

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23
Q

exampel of allogeneic transplant

A

blood, cornea, heart, lung, liver, kidney, bone marrow

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24
Q

to prolong transplant survival, what needs to happen

A

they are screened and matched at MHC and test that recipient does not have pre-existing antibodies that would recognize the tissue

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25
Q

if the donor has antibodies against the tissue when does rejection happen

A

before the transplant is even finished

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26
Q

what leads to most rapid form of transplant rejection

A

blood group different

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27
Q

need to match blood for

A

successful transplant

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28
Q

what are the three targets of alograft rejection

A

Blood group (ABO) antigens

MHC I and MHC II

Minor histocompatibility antigens

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29
Q

what is universal donor

A

O-

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30
Q

what is universal recipient

A

AB+

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31
Q

what are the two different ways MHC I and II can be recognized during transplant rejection

A

direct and indirect mechanism

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32
Q

we can never get rid of TCR that have receptors that bind to

A

somebody else’s MHC cells

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33
Q

direct mechanism

A

being directly recognized

donor APC migrate to secondary lymphoid tissue and stimulate alloreactive recipient T cells

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34
Q

indirect mechanism

A

MHC molecules taken up like foreign antigen by receipient APC, processed, and presented on recipient MHC to recipient T cells

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35
Q

direct allorecognition

A

APC carried over in the transplanted tissue that are directly recognized by CD4 or CD8 T cells
T cell activation

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36
Q

indirect allorecognition

A

shedding of MHC from donor DC, aquired by recipient APC, processed, prseented on recipient MHC to the alloreactive T cell

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37
Q

indirect allorecognition allows for production of

A

antibodies against foriegn MHC molecule

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38
Q

how are antibodies against foreign MHC possible in indirect

A

alloreactive CD4, B cells may have receptor specific, if the b cell is specific, i will be taken up and processed and b cell will recruit help from CD4 T cell to generate antibody against the alloreactive MHC molecule

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39
Q

is it possible to perfectly match MHC

A

no - there are so many possible polymorphisms

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40
Q

where is it most important to get MHC match

A

class II

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41
Q

most importnat MHC to match for

A

class II -especially MLH -DR

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42
Q

what do you want to match in order of importatnce for MHC for transplant

A

DR
A
B

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43
Q

why isn’t it 100% acceptance for transplant with completely MHC match

A

there will always be a minor mismatch, it won’t be profound rejection reaction but can still give rise to rejection

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44
Q

what are minor histocompatibility antigens

A

polymorphic proteins - AA sequence from particular proteins may differ

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45
Q

examples of proteins that make minor histocompatiility issues

A

stress induced proteins

Y chromosome proteins

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46
Q

describe Y chromosome proteins

A

female could reject male tissue even if they are HLA identical, female doesn’t have any male protein so she can’t handle

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47
Q

review pg 18

A

pg 18

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48
Q

if individual has antibodies aginast ABO blood groups you can use their serum to ____ the mismatched RBC

A

agglutinate

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49
Q

what technique do you use tot test for ABO blood type

A

agglutination

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50
Q

what is agglutinate

A

RBC clump together

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51
Q

assay used to detect difference in MHC class II is

A

mixed lymphocyte reaction

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52
Q

describe mixed lymphocyte reaction

A

mix donor and recipient, if they are mismatched at MHC class II then alloreactive cells in recipient will proliferate - extent of proliferation. differences detected are usually HLA-DR

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53
Q

to tell if recipient have attack of donor, have to stop them proliferating so you know if it is donor vs. recipient, how do you do this?

A

irradiate the donor cells - so you make it so they can’t divide

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54
Q

when you add thymidine at end of MLR what will not encorporate the thymidine

A

donor cells b/c they were irradiated

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55
Q

if there are no differneces at MHC II (what we want), that means what happened in mixed lymphocyte reaction

A

no reaction - the recipient did not proliferate

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56
Q

when you add thymidine what happens if donor and recipient had same MHC II

A

no reaction so 0 cpm

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57
Q

if recipient and donor do not share same MHC II what happens

A

recipient clls not tolerized, so when they are incubated the recipient cells are going to react against donor cells and will proliferate

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58
Q

add thymidine to MLR when the MHCII doesn’t match, what hapesn

A

radioactivity DNA, lots of cpm (pg 22)

59
Q

what is major downside to MLR

A

takes a long time - several days

60
Q

what does MLR stand for

A

mixed lymphocyte reaction

61
Q

how is typing of MHC done usually

A

sequening or other molecular means, it’s much faster

62
Q

microcytotoxicity test, how do you do it

A

buy antibodies against all the HLA alleles, and add to donor and recipient cells (seperately), if they bind it indicates the cells express the HLA allele, you add complement and the cells are lysed.

63
Q

why can you do Microcytotoxicity test in class I but not II

A

if you take peripheral blood from tissue, all would express class I but just tiny bit would express class II

64
Q

do donor and recipient both express HLA A 2? explain how you do it

A

add antibody then add complement, the ones that take it up will be lysed, add dye, the cells that do not express allele wil not be lysed, so see which cells killed by adding stain and it will be taken up by lysed cells. so blue = dead cells

65
Q

what is advantage of Microcytotoxicity assay

A

it’s fast

66
Q

what is major disadvantage of Microcytotoxicity assay

A

don’t have enough antibodies to distinguish from al the HLA-A and HLA-B alleles

67
Q

difference in HLA - where is it?

A

AA that lie in peptide binding route

68
Q

describe HLA-A immobilized probe array typing system

A

primers for the alpha 1 and alpha 2 regions - have PCR products from potential donor and recipient.
PCR
see what alleles both have

69
Q

HLA-A identifies

A

HLA-A locus, it’s identifying the locus

70
Q

an asterisk (*) means

A

it has been defined by sequensing

71
Q

review pg 28

A

28

72
Q

tissue crossmatching - describe

A

detects if recipient has pre-existant antiodies capable of recognizing donor cells

73
Q

fastest rejection possible

A

tissue crossmatching- if recipient already has antibodies against donor

74
Q

how do you analyze for tissue crossmatching

A

peripheral blood cells from donor, add from recipient, i didn’t catch the rest read pg 29

75
Q

why would a person have pres-existing antibodies against donor cells?

A

pregnancy
blood transfusion
prior transplantation

76
Q

what is classical test to match MHC I

A

microcytotoxicity assay

77
Q

MHC II classical test to match

A

mixed lymphocyte reaction

78
Q

purpose of typing donor and recipient is to avoid

A

rejection

79
Q

hyperacute rejection, how quicly

A

minutes-hours

80
Q

what is the most rapid form of transplant rejection

A

hyperacute

81
Q

what is cause for hyperacute rejection

A

pre-formed anti-donor antibodies + complement

82
Q

accelerated rejection, how quickly

A

2-4 days

83
Q

what is cause for accelerated rejection

A

reactivation of sensitized t cells

84
Q

what is most common kind of rejection

A

acute rejection & chronic rejection

85
Q

acute rejection, timing

A

about a week (minimum, can be a month to siix months)

86
Q

what is cause for acute rejection

A

primary activation of t cells

87
Q

what is time frame from chronic rejection

A

months to years

88
Q

what is the cause of chronic rejection

A

antibody and cell mediated rejection. not well understood

89
Q

what kind of response from accelerated rejection

A

memory response

90
Q

if somebody is getting second transplant what kind of rejection do you really need to look out for

A

accelerated rejection

91
Q

hyperacute, what type of hypersensitivty response

A

type II HSR (IgG against cell surface)

92
Q

acute and accelerated what type of HSR

A

type IV

93
Q

chronic, what type of HSR

A

II, III, IV

94
Q

hyperacute graft rejection mediated by

A

antibody

95
Q

describe steps in hyperacute graft rejection - 4 steps

A

Pre-existing antibodies enter the donor organ cells.
C’ is activated.
PMNs are attracted and destroy endothelial cells
Platelets adhere to denuded areas, coagulation is activated,and vessels are occluded

96
Q

____ can participate in acute rejection, but require CD4 t cell help

A

antibody

97
Q

induction of antibodies in acute vascular rejection, that person is at risk for what in another transplant

A

hyperacute rejection

98
Q

most important participate in acute graft rejection

A

CD8 T cells

99
Q

what form of rejection is controlled by immunosuppressive therapy

A

acute graft rejection

100
Q

acute graft rejection, describe steps

A

donor APC migrate out of transplant to lymph node
there they stiulate alloreactive t cells in recipient (esp CD8)
the t cells migrate to transplant and kill cells in transplant

101
Q

all transplants will eventually succumb to

A

chronic graft rejection

102
Q

chronic graft rejection occurs despite

A

immunosuppressive therapy

103
Q

what kind of transplanation can the transplant reject the recipient

A

bone marrow transplantation

104
Q

at least 50% of pts who get bone marrow translant have some form of

A

GVHD

105
Q

prior to bone marrow transplantation have to make space for bone marrow cells, have to do what

A

ablate the bone marrow

106
Q

conditioning regimen prior to bone marrow transplant includes

A

radiation, chemotherapy, immunosuppressants, antivirals

107
Q

where is inflammation due to the conditioning regiment for bone marrow transplant

A

GI, skin, liver

108
Q

where is GVHD likely to affect

A

GI, skin, liver (quickly dividing cells)

109
Q

describe GVHD

A

T cells in transplant attack recipients tissues

110
Q

symptoms of GVHD

A

rash, jaundice, diarrhea

111
Q

why can’t we get rid of t cells from bone marrow before transplant to prevent GVHD?

A

there is higher risk of transplant failing if you get rid of t cells from donor
higher risk of leukemia relapse
higher risk of fungal infections
higher risk of EBV lymphoproliferative disease

112
Q

why does it help get rid of leukemia to keep the t cells in bone marrow

A

the t cells in bone marrow will attack the leukemia

113
Q

how do you mobilize stem cells from bone marrow to prepare for bone transplant

A

inject chemotherapeutic drugs into bone marrow, so it puts stem cells into circulation

114
Q

vast majority of recipients have to immunosuppressed, why

A

you won’t be able to find the perfect match, there are way too many variants

115
Q

for immunosuppressive therapy, how do they prevent activation and proliferatin of t cells

A

Inhibitors of IL-2 production
Cyclosporin A, FK-506 (Tacrolimus)

Inhibitors of IL-2/IL-2R signal
IL-2 antagonist mAbs (anti-CD25 Abs)
Rapamycin (Sirolimus) inhibits IL-2R signaling

116
Q

blocking IL-2/IL-2R blocks

A

clonal expansion

117
Q

to remove actively dividing cells for immunosuppressive therapy use what

A

cytotoxic drugs

118
Q

to deplete peripheral t cells for immunosuppressive therapy what do you use

A

anti-CD3 mAb, anti-CD4, anti-CD2

119
Q

what do you use to inhibit inflammatory response for immunosuppressive therapy

A

corticosteroids

120
Q

why do neutrophil numbers seem to go up with corticosteroids

A

they are inhibiting the things that make WBC stick to the cell walls, so it seems like there is more when you draw blood

121
Q

what does CTLA4 bind to

A

CD80 or CD86

122
Q

review pg 44

A

44

123
Q

how does CTLA4-IG prevent delivery of signal 2 to naive t cells?

A

make fusion protein, it makes it a soluble protein you can inject into recipient
see page 45

124
Q

blocking what prolongs graft survival

A

CD28

CD40L

125
Q

what is the most probable source of xenotransplantation

A

pigs

126
Q

what is the downside to pig transplants

A

we have natural antibodies to them

127
Q

we do not get strong what kind of response against the pig MHC

A

TCR

128
Q

why do we have heterophilic antibodies against pig antigens?

A

we do not have Galactose-a-1,3-galactose so our b cells are not exposed to them so reactive ones are not deleted

129
Q

when enzyme do humans lack that most mammals have

A

Galactose-a-1,3-galactose

130
Q

how much of our IgG is reactive against Galactose-a-1,3-galactose

A

1%

131
Q

what has happened to pigs to decrease rejection

A

took out the gene to make the Galactose-a-1,3-galactose but they just an alternative pathway to make it. we now make triple transgenic pigs -

132
Q

what is hDAF, hMCP and hCD59

A

complement regulating proteins

133
Q

what is hDAF

A

decay accelerating factor

134
Q

hMCP

A

membrane complement protein

135
Q

what does hCD59

A

prevents insertion of MAC

136
Q

what is autograft

A

frm one part of individual to another

137
Q

what are syngeneic grafts

A

b/w twins

138
Q

most common form of transplant

A

allogeneic transplant

139
Q

what is allogeneic transplant

A

from one individual to another of same species

140
Q

review pg 49

A

49

141
Q

indirect

A

llows generation of alloantibody

142
Q

type IV HSR

A

cytotoxic T cell or macrophage activation

143
Q

review pg 50

A

50