Lecture 26: Immunology of Transplants and Transfusions Flashcards
Response to transplantation and transfusions is based upon degree of similarity or dissimilarity of ___ and ___
MHC and blood group antigens
What is the determinate of an individuals tissue type
MHC
What mediates immunological rejection of incompatible tissue
MHC
Found on all nucleated cells and presents to CD8+
MHC I
Found on all pAPC’s and present to CD4+
MHC II
Found on complement proteins and other genes
MHC III
What is main reason why it is hard to find a suitable organ donor
MHC polymorphism
Autograft
Transplantation of tissue between sites within on individual
What transplant type has no rejection
Autografts
Isografts
Transplantation of tissue from a genetically identification individual
Allograft
Transplantation of tissue from a member of the same species
When does rejection of allograft typically occur
Within 1-2 weeks
Xenograft
Transplantation of tissue from a member of different species
When does rejection of a xenograft typically occur
Within hours
Pathogen transfer is a big concern with which type of transplant
Xenograft
Without ___all grafts except autographs will eventually be destroyed
Immunosuppression
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
What cells can cause ischemic necrosis and cytotoxic destruction of donor cells if activated
Alloreactive B and T cells
Rejection within 48 hours
Hyperacute
Rejection within 7 days
Accelerated
Rejection after 7 days
Acute
Rejection after several months up to years
Chronic
What mediates rejection in Hyperacute rejection
Pre-existing antibodies
What mediates rejection in accelerated and acute rejection
Cell mediated
What mediates chronic rejection
Mostly antibodies but still cell mediated reactions present
What are the two main players in the pathophysiology of acute rejection
- MHC incompatibility
- 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
- DC cells present antigen to Th1 cells, which secrete IL-2, IFN-y and activate Tc and NK cells
- Tc respond to foreign antigens
- NK produce INF-y and TNF-a
- 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
