transplantation Flashcards by Chase Thompson

autograft

graft between different sites on the same individual - autologous transplantation

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isograft

graft between the same inbred strain of animals or monozygotic twins - syngeneic transplantation

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allograft

between non-identical animal/humans of the same species - allogeneic transplantation

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MHC is called what in humans

HLA

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MHC is on what chromosome

6th chromosome

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MHC I receptors are present on what cells

presented on most nucleated cells in the body - therefore RBC do not have

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MHC II receptors are present on what cells

APC macrophages, dendritic cells, and B cells

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MHC II involved extracellular antigens/endogenous antigens

extracellular antigens

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MHC I involved extracellular antigens/endogenous antigens

endogenous antigens

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MHC I uses TAP/HLA-DM to form the receptor antigen molecule

TAP

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MHC II uses TAP/HLA-DM to form the receptor antigen molecule

HLA-DM

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allogeneic hematopoietic stem cell transplant (SCT)

healthy donors receive G-CSF - patient receives chemotherapy and radiotherapy - transplantation of donor cells

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G-CSF

cause homeopathic stem cells to leave the bone marrow and enter the peripheral blood

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purpose of chemotherapy and radiotherapy

called conditioning 1. kills turmor 2. kills recipients ability to make their own blood 3. immunosuppression to the patient so they do not reject graft

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graft versus leukemia (GVL) effect

effect of t -cell depleted allografts - efficacy of donor lymphocyte infusions - outcomes from synergistic transplants

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effect of t -cell depleted allografts

bad - people with grafts that receive t-cell depletion had 50% more relapse than those without

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efficacy of donor lymphocyte infusions

give donor lymphocytes to have patient go back into remission

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outcomes from synergistic transplants

have more relapses - almost the same as the outcome if you did a graft with depleted t-cells

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infusion of donor lymphocytes after leukemia had relapsed can cure/hurt leukemia patients who have undergone SCT

cure

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removing/adding T cells from a stem cell graft increases relapse risk 3 fold

removing

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using a genetically identical (synergeic) donor increases/decreases relapse risk 3 fold

increases

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using a genetically identical (synergeic) donor increases/decreases relapse risk 3 fold

increases

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Impact of HLA matching on overall survival

8/8 - best survival rate 7/8 - increased survival 6/8 - less survival too little matching = targeted everywhere

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the odds of any sibling being an HLA match

1/4

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parents and children of patients are almost always

half-matches

ethnicity does/does not influence HLA

does

the most common HLA type

HLA-A\*02:01

western europeans

HLA-A\*24:02

ASIA

HLA-B\*53:01

AFRICA

WHO HAS A HIGHER CHANCE OF FINDING A HLA MATCH AFRICAN AMERICANS OR CAUCASIANS?

CAUCASIANS

current goal is ____ HLA match

12/12

if a 12/12 match cannot be found

umbilical cord blood transplant

umbilical cord blood transplant has more/less tolerant T cells

more making

HLA mis-match transplant would/would not require some degree of T cell depletion

would

you do/do not have to match ABPO blood type in SCT

do not

solid organ transplant needs/does not need to match ABO blood type

need to

SCT can be performed across ABO incompatibilities because _______ will be provided by the donors stem cells

hematopoiesis

can/cannot deplete donor stem cell product to remove anti-A or anti-B antibodies if recipient is A+ or B+

can

can/cannot remove red blood cells from the donor stem cell product id patients plasma is expected to react with donor red cells

can

graft versus host disease (GVHD)

- donor derived, t-cell mediated reactivity against recipient tissues - primary cause of non-relapse mortality

acute graft versus host disease (GVHD) occurs _____ months after SCT

chronic graft versus host disease (GVHD) occurs _____ months after SCT

acute GVHD primarily affects

skin, colon, liver

chronic GVHD primarily affects

skin eyes GI tract liver

treatment of graft versus host disease (GVHD) with

1. prevention: - inhibitors of T-cell activation * calcineurin inhibitors: tacrolimus * mTOR inhibitors: sirolimus - inhibitors of T-cell proliferation * methotrexate - T-cell depleting antiboides - immunosuppressive drugs: steroids

acute GVHD ratings how to measure

Stages 0-4 Grade A-D liver bilirubin and gut/stool

HLA mismatching increases/decreased risk of GVHD

increases

GCHD with an HLA matched graft

can have minor histocompatibility this occurs with genetically disimilar people, could bind at a higher affinity

stem cell donnor selection

1. male becuase female has no antibodies to the Y 2. HLA match 3. ABO type - would like to match but does not have to 4. stem cell source- peripheral blood stem cells engraft faser than bone marrow dervied stem cells 5. cytomegalovirus status- negative 6. related source- sibling perfered

solid organ transplant

- long-term tolerance - chronic immunosuppression is essential - HLA disparities are almost univeral in solid organ transplant except related sibiling renal transplant - both humoal and cellular mediated rejection mechanisms exist

solid organ graft rejection is mediated by

peptide /HLA disparities

would you rather transplant a live/deceased organ

live

alloimmunization against foreign HLA

blood reansfusions and pregnancies can expose an indivdual to foreign HLA , which can induce an antibody response

monitoring anti-HLA antibodies is important becasue

as patients develop more anti-HLA antibodies the number of potential organs decreases

hyperacute graft rejection

- occurs within hours (antibodies must be preformed) - anti-A and anti-B blood gorup - anti-HLA

direct allorecogntion

- APC derived from donor graft likely mismatched HLA binds to T cell - fades out in time becuase the APC donor will die out - acute rejection 7-21 days

indirect allogrecogntion

- APC dervied from the recipeint uptakes and processes donor proteins which present to T cells - chronic recipient verus graft effect - chronic rejection \> 21 days

organ allocation

- far fewer available organs than donors - decided with in hours - assignemtn based on ranking factors: * hyperacute rejection (ABO incompatibilty and alloimmunization to HLA) * illness of patient * sizing * distance of organ from patient

rejection prevention for organ transplant

1. anti-inflammatories- corticosteroids 2. inhibitors of DNA replication- asathioprine, mycophenolate 3. inhibitors of T cell activation- cyclosporine, tacrolimus, sirlimus 4. lymphocyte depeleting antibodies- rituximab

the goal of SCT is recipiant/donor dervied T cell activation

donor

HLA mismatches are associated with increased/decreased GVHD risk

increased

even with HLA matching GVHD can occur through

miHA

hyperacute rejection must be avioded mainly by

anti-A. anti-B or anti-HLA antibodies

hyperacute organ rejection is primarily a humoral/cell mediated process

humoral

alloreactivty and graft rejection is primarily a cell-mediated/humoral response

CELL-MEDIATED

1. Which of the following donors would be best for a renal transplant? 1. The kidney donor is the identical twin of the kidney recipient 2. The kidney donor is an HLA-matched sibling to the kidney recipient 3. The kidney donor is a living HLA-matched unrelated donor to the kidney recipient. 4. The kidney is cadaveric but HLA-matched and unrelated to the recipient.

The kidney donor is the identical twin of the kidney recipient

1. Which of the following donors would be best for a stem cell transplant to treat high risk leukemia? 1. The stem cell donor is the identical twin of the stem cell recipient 2. The stem cell donor is an HLA-matched sibling to the stem cell recipient 3. The stem cell donor is an HLA-matched but unrelated to the stem cell recipient 4. The stem cell donor is a haplo-identical (HLA half-matched) sibling to the stem cell recipient.

The stem cell donor is an HLA-matched sibling to the stem cell recipient

1. For solid organ transplantation… 1. Donor grafts and the recipient must be HLA matched 2. Donor grafts and the recipient must be ABO matched 3. Donor grafts and the recipient must be ABO compatible 4. Donor grafts must come from a living donor

Donor grafts and the recipient must be ABO compatible

1. Post-transplant immunosuppression increases the risk of all of the following except? 1. Viral reactivation 2. Opportunistic infection 3. New cancers 4. GVHD

GVHD

transplantation Flashcards

(70 cards)