Lecture 26: Immunology of Transplants and Transfusions Flashcards by Jen McGann

Response to transplantation and transfusions is based upon degree of similarity or dissimilarity of ___ and ___

MHC and blood group antigens

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What is the determinate of an individuals tissue type

MHC

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What mediates immunological rejection of incompatible tissue

MHC

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Found on all nucleated cells and presents to CD8+

MHC I

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Found on all pAPC’s and present to CD4+

MHC II

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Found on complement proteins and other genes

MHC III

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What is main reason why it is hard to find a suitable organ donor

MHC polymorphism

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Autograft

Transplantation of tissue between sites within on individual

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What transplant type has no rejection

Autografts

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Isografts

Transplantation of tissue from a genetically identification individual

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Allograft

Transplantation of tissue from a member of the same species

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When does rejection of allograft typically occur

Within 1-2 weeks

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Xenograft

Transplantation of tissue from a member of different species

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When does rejection of a xenograft typically occur

Within hours

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Pathogen transfer is a big concern with which type of transplant

Xenograft

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Without ___all grafts except autographs will eventually be destroyed

Immunosuppression

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What are some basics of graft rejection

Passenger leukocytes of donated tissue migrating out of cell, recipient APC’s take up donor antigen, active also reactive B and T cells that initiate graft rejection

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What cells can cause ischemic necrosis and cytotoxic destruction of donor cells if activated

Alloreactive B and T cells

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Rejection within 48 hours

Hyperacute

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Rejection within 7 days

Accelerated

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Rejection after 7 days

Acute

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Rejection after several months up to years

Chronic

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What mediates rejection in Hyperacute rejection

Pre-existing antibodies

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What mediates rejection in accelerated and acute rejection

Cell mediated

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What mediates chronic rejection

Mostly antibodies but still cell mediated reactions present

What are the two main players in the pathophysiology of acute rejection

1. MHC incompatibility 2. RBC antigen incompatibility

MHC incompatibility results in what type of response

T cell response

RBC antigen incompatibility results in what type of response

Antibody response

What are some other causes of acute rejection (besides MHC and RBC)

Tc cell infiltration, damage to endothelial cells, thrombosis of vessels, loss of blood supply to organ, surgical trauma

What are the main mechanisms of acute rejection

1. DC cells present antigen to Th1 cells, which secrete IL-2, IFN-y and activate Tc and NK cells 2. Tc respond to foreign antigens 3. NK produce INF-y and TNF-a 4. Blood group antigens stimulate Th2 cells and produce antibodies

DC cells present antigens to what cell during acute rejection

Th1

Th1 secretes what during acute rejection

IL-2 and IFN-y

What do NK cells produce during acute rejection

IFN-y and TNF-alpha

TNF-alpha activates what effector cells

Macrophages and NK’s

What is the direct pathway of rejection

Recipient T cells enter graft and respond to foreign MHC donor cells, T cells attack graft vascular endothelium resulting in vessel destruction and thrombosis

When does direct pathway occur in rejection timeline

Early/acute

What is the indirect pathway of rejection

Processing of graft antigens by host DC’s, generation of Tc cells

When does indirect pathway of rejection occur in rejection timeline

Later/chronic

What is the immunosuppression protocol to halt rejection in dogs

Azathioprine, prednisone, cyclosporine +/- bone marrow allograft from donor

What is the survival % for 1 year of dogs with renal allografts

50% 1 year survival

What is the immunosuppression protocol for cats

Prednisone, cyclosporine +/- ketaconazole to prolong 1/2 life of cyclosporine

What is the survival % to 6 months and 3 years in cats with renal allografts

6 months= 59-70% 3 years= 40-50%

Where are grafts taken from

Immune privileged sites

What are some immune privileged sites

Eyes, thymus, testes, and brain

Inflammation is controlled by grafts from immune privileged sites via

Impermeable tissue/blood barrier, no dendritic cells, low MHC expression, immunosuppressive molecules

What are the immunosuppressive moleculesto control graft rejection

IDO, TGF-B, neuropeptide, complement inhibitors, CD95L

What is graft vs host disease

Cells from graft attack host

What does MHC I mediated graft vs host disease result in

Bone marrow destruction, mucosal destruction (diarrhea, skin and oral ulcers), liver disease, Th1 cytokines

How would you treat MHC I mediated graft vs host disease

Antibodies against IFN-y and TNF-a to decrease Th1 cytokines

What is the result of MHC II mediated graft vs host disease

Autoantibodies, lupus like syndrome

How would you treat MHC II mediated graft vs host disease

anti IL-4 antibody

Why is a fetus considered a partial allograft

Paternal antigens are foreign to mother

How do you prevent fetal allograft rejection

Maternal side: suppress cytotoxic T cells, and suppress T cell function Placenta: immunosuppressive molecules and inhibition of complement

What cells suppress Tc cells on maternal side

UNK cells, Tregs, and Fas L

What molecules suppress T cell function on maternal side

HLA-E, FasL, IDO

What are the immunosuppressive molecules in placenta

Estradiol, progresterone, alpha-macroglobulin, alpha-fetoprotein, interferons, phospholipids

What molecules inhibit complement activity in placenta

IDO, DAF, and MCP

Equine endometrial cups survive 80 says although it expresses ___ antigen

Paternal MHC I

What is the most antigenic canine erythrocyte

DEA 1 (includes 1.1, 1.2 and 1.3 subtypes)

What is the universal canine donor

Negative for DEAs: 1.1, 1.2, 1.3, 3, 5, 7 Positive for DEA 4

What are the feline blood types

A, B, AB

What is the universal donor for cats

No universal donor, all cats must be typed

How many blood cell antigens do horses have

> 30

How many blood types do horses have

400,000

What are most antigenic blood types in horses

Qa and Aa

What are the most ideal horses for blood transfusions given no universal donor

Negative for Qa and Aa Quarter horse or standardbred gelding most likely Qa and Aa- Gelding of same breed next best option

What is major cross matching

Recipient serum and donor cells

What is minor cross matching

Recipient cells, donor serum

What are you looking for in cross matching test

Agglutination and hemolysis

What is equine neonatal isoerythrolysis

Occurs when foal is Aa (+), Aa RBC’s Mare is Aa (-) producing Anti Aa antibodies in milk resulting in hemolytic disease of mare

What is the antigen that causes neonatal isoerythrolysis in mule foals

Donkey factor antigen

Lecture 26: Immunology of Transplants and Transfusions Flashcards

(71 cards)