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Immunology > Lecture 26: Immunology of Transplants and Transfusions > Flashcards

Lecture 26: Immunology of Transplants and Transfusions Flashcards

1
Q

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

A

MHC and blood group antigens

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2
Q

What is the determinate of an individuals tissue type

A

MHC

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3
Q

What mediates immunological rejection of incompatible tissue

A

MHC

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4
Q

Found on all nucleated cells and presents to CD8+

A

MHC I

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5
Q

Found on all pAPC’s and present to CD4+

A

MHC II

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6
Q

Found on complement proteins and other genes

A

MHC III

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7
Q

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

A

MHC polymorphism

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8
Q

Autograft

A

Transplantation of tissue between sites within on individual

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9
Q

What transplant type has no rejection

A

Autografts

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10
Q

Isografts

A

Transplantation of tissue from a genetically identification individual

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11
Q

Allograft

A

Transplantation of tissue from a member of the same species

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12
Q

When does rejection of allograft typically occur

A

Within 1-2 weeks

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13
Q

Xenograft

A

Transplantation of tissue from a member of different species

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14
Q

When does rejection of a xenograft typically occur

A

Within hours

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15
Q

Pathogen transfer is a big concern with which type of transplant

A

Xenograft

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16
Q

Without ___all grafts except autographs will eventually be destroyed

A

Immunosuppression

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17
Q

What are some basics of graft rejection

A

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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18
Q

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

A

Alloreactive B and T cells

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19
Q

Rejection within 48 hours

A

Hyperacute

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20
Q

Rejection within 7 days

A

Accelerated

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21
Q

Rejection after 7 days

A

Acute

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22
Q

Rejection after several months up to years

A

Chronic

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23
Q

What mediates rejection in Hyperacute rejection

A

Pre-existing antibodies

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24
Q

What mediates rejection in accelerated and acute rejection

A

Cell mediated

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25
Q

What mediates chronic rejection

A

Mostly antibodies but still cell mediated reactions present

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26
Q

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

A
  1. MHC incompatibility
  2. RBC antigen incompatibility
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27
Q

MHC incompatibility results in what type of response

A

T cell response

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28
Q

RBC antigen incompatibility results in what type of response

A

Antibody response

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29
Q

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

A

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

30
Q

What are the main mechanisms of acute rejection

A
  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
31
Q

DC cells present antigens to what cell during acute rejection

A

Th1

32
Q

Th1 secretes what during acute rejection

A

IL-2 and IFN-y

33
Q

What do NK cells produce during acute rejection

A

IFN-y and TNF-alpha

34
Q

TNF-alpha activates what effector cells

A

Macrophages and NK’s

35
Q

What is the direct pathway of rejection

A

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

36
Q

When does direct pathway occur in rejection timeline

A

Early/acute

37
Q

What is the indirect pathway of rejection

A

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

38
Q

When does indirect pathway of rejection occur in rejection timeline

A

Later/chronic

39
Q

What is the immunosuppression protocol to halt rejection in dogs

A

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

40
Q

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

A

50% 1 year survival

41
Q

What is the immunosuppression protocol for cats

A

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

42
Q

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

A

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

43
Q

Where are grafts taken from

A

Immune privileged sites

44
Q

What are some immune privileged sites

A

Eyes, thymus, testes, and brain

45
Q

Inflammation is controlled by grafts from immune privileged sites via

A

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

46
Q

What are the immunosuppressive moleculesto control graft rejection

A

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

47
Q

What is graft vs host disease

A

Cells from graft attack host

48
Q

What does MHC I mediated graft vs host disease result in

A

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

49
Q

How would you treat MHC I mediated graft vs host disease

A

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

50
Q

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

A

Autoantibodies, lupus like syndrome

51
Q

How would you treat MHC II mediated graft vs host disease

A

anti IL-4 antibody

52
Q

Why is a fetus considered a partial allograft

A

Paternal antigens are foreign to mother

53
Q

How do you prevent fetal allograft rejection

A

Maternal side: suppress cytotoxic T cells, and suppress T cell function

Placenta: immunosuppressive molecules and inhibition of complement

54
Q

What cells suppress Tc cells on maternal side

A

UNK cells, Tregs, and Fas L

55
Q

What molecules suppress T cell function on maternal side

A

HLA-E, FasL, IDO

56
Q

What are the immunosuppressive molecules in placenta

A

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

57
Q

What molecules inhibit complement activity in placenta

A

IDO, DAF, and MCP

58
Q

Equine endometrial cups survive 80 says although it expresses ___ antigen

A

Paternal MHC I

59
Q

What is the most antigenic canine erythrocyte

A

DEA 1 (includes 1.1, 1.2 and 1.3 subtypes)

60
Q

What is the universal canine donor

A

Negative for DEAs: 1.1, 1.2, 1.3, 3, 5, 7

Positive for DEA 4

61
Q

What are the feline blood types

A

A, B, AB

62
Q

What is the universal donor for cats

A

No universal donor, all cats must be typed

63
Q

How many blood cell antigens do horses have

A

> 30

64
Q

How many blood types do horses have

A

400,000

65
Q

What are most antigenic blood types in horses

A

Qa and Aa

66
Q

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

A

Negative for Qa and Aa

Quarter horse or standardbred gelding most likely Qa and Aa-

Gelding of same breed next best option

67
Q

What is major cross matching

A

Recipient serum and donor cells

68
Q

What is minor cross matching

A

Recipient cells, donor serum

69
Q

What are you looking for in cross matching test

A

Agglutination and hemolysis

70
Q

What is equine neonatal isoerythrolysis

A

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

71
Q

What is the antigen that causes neonatal isoerythrolysis in mule foals

A

Donkey factor antigen

Immunology (22 decks)

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