Lecture 21: Transplantation Immunology I Flashcards

1
Q

Autografts

A

Grafts exchanged from one part of an individual to another part of the same individual

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2
Q

Isograft

A

Grafts exchanged between different individuals of identical genetic make up (identical twins)

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3
Q

Allografts

A

Grafts exchanged between non identical members of same species

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4
Q

Xenografts

A

Grafts exchanged between members of different species

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5
Q

HLA Ags are _______ expressed

A

Co-dominantly

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6
Q

What Ags are particularly strong barriers to transplantation

A

HLA-A
HLA-B
(Class I HLAs)

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7
Q

The three most important Class II HLAs in transplantation are

A

HLA-DR
HLA-DP
HLA-DQ

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8
Q

Direct pathway of allorecognition

A

T cell receptors on recipient T cells directly recognize donor MHC molecules

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9
Q

Indirect pathway of allorecognition

A

Recipient T cells recognize donor MHC molecules that have been processed into peptides by recipient APCs
This pathway is important during chronic rejection (when number of donor APCs is too low to stimulate direct immune response)

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10
Q

Onset and cause of hyperacute rejection

A

Immediate onset caused by accidental ABO blood type incompatibility. Presents while still in surgery
-Could also occur when the recipient has been sensitized to donor MHC by previous transplants, blood transfusions or pregnancy

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11
Q

Onset and cause of acute rejection

A

Weeks to months
T cell mediated response directed against the foreign MHC. (Donor DCs migrate to lymph nodes and stimulate primary recipient response) Leukocytes infiltrate graft vessels

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12
Q

Onset and cause of chronic rejection

A

Months to years
T cell mediated process resulting from the foreign MHC “looking like” a self MHC carrying an antigen. Occurs due to occlusion of blood vessels and ischemia of organ. Macrophages infiltrate and smooth muscle proliferation is often seen

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13
Q

Onset and cause of graft vs host disease

A

Variable onset

Donor T cells in the graft proliferate and attack the recipients tissues. Most common in bone marrow transplants

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14
Q

Main pathway of allorecognition in Acute vs chronic rejection

A

Acute- mainly direct, but indirect can also play role

Chronic- Mainly indirect (Abs can also be involved, depositing complement into graft tissues)

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15
Q

Non immunologic allograft rejection

A

Damaged graft tissues release mediators which trigger several cascades leading to immediate tissue damage

  • Clotting cascade generates fibrinopeptides, attracting neutrophils and macrophages
  • Kinin cascade makes bradykinin causing vasodilation, increased vascular permeability
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16
Q

First step in the donor-recipient match work-up

A

ABO blood group compatibility

17
Q

In which grafts/transplants is ABO compatibility not important

A

Corneal transplant
Heart valve transplant
Bone/tendon grafts
Stem cell transplants

18
Q

What is cross-matching used for

A

To test the recipient serum for preformed Abs against donors HLAs
-Needed to prevent hyperactive Ab dependent rejection of graft

19
Q

What is tissue typing used for

A

To identify class I HLA Ags and make sure they match

20
Q

What is class II HLA typing used for and what is another name for it

A
Mixed lymphocyte reaction (MLR) - used to determine if the donor cells stimulate proliferation of the recipients lymphocytes
-If class II MHC Ags are the same, no proliferation will occur
21
Q

What percent of the host T cells are capable of recognizing and responding to a single foreign MHC

A

Up to 2%

22
Q

What cytokine/Helper T cell levels would be increased in the case of a humoral host vs graft rejection

A

Th2

IL-4, IL-5, IL-10

23
Q

What cytokine/helper T cell levels would be increased in the case of a cellular host vs graft rejection

A

Th1

IL-2, IFN-y

24
Q

Acute graft vs host disease symptoms and cause

A

Epithelial cell death in the skin, liver and GI
Caused by reaction of grafted mature T cells in the tissue transplant with allo-ags of host
Reaction is directed against miHAs of recipient (HLA Ags are usually matched

25
Q

Chronic graft vs host disease causes

A

Fibrosis and atrophy of affected organ

May obliterate small airways

26
Q

Steps in evolution of GVHD

A

Donor APCs activate donor CD8+ T cells by cross presentation of MHC I molecules
-Or donor APCs activate donor CD4+ T cells through MHC II molecules
Donor APCs can also activate naïve donor CD8+ T cells against new, non hematopoietic Ags

27
Q

Two facts about patients on immunosuppressive drugs*NB

A

They are more prone to opportunistic infections and have a raised incidence of malignancy

28
Q

Cyclosporin A and Tacrolimus mechanism of action

A

Inhibits IL-2,3,4,5, IFN-y, TNF-a gene transcription by blocking NFAT translocation to nucleus

29
Q

Anti-CD3 MAB (OKT 3) action

A

T cell activation, opsonization and depletion

-Blocks function of CD3 molecule in membrane of human T cells

30
Q

Anti-CD25 MAB action

A

Inhibits IL-2 function

31
Q

Sirolimus action

A

Inhibits cytokine-mediated signaling

32
Q

Corticosteroid action

A

Inhibits T cell proliferation
Transcription inhibition of pro-inflammatory genes
Induction of lymphocyte apoptosis

33
Q

What cells play an important role in triggering acute rejection

A

Donor DCs, they migrate to lymph nodes draining the organ and stimulate primary recipient response

34
Q

Does chronic rejection respond to immunosuppressive therapy

A

No

35
Q

What is the microcytotoxicity test used for

A

To test for the presence of preformed Abs reactive with various allogenic HLA Ags, which can cause hyperactive graft rejection

36
Q

How does the microcytotoxicity test work

A

Recipients serum is mixed with cells of a donor- if there is no cell damage, then a potential donor is identified