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Immunology > Transplant immunology > Flashcards

Transplant immunology Flashcards

1
Q

What type of response is responsible for transplant reactions?

A

adaptive immune response

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2
Q

What three major advances have been made thanks to transplantation?

A
  1. technical skills of surgeons
  2. transplantation networks that are HLA-typed so that the best matches can be made
  3. the availability of immunosuppressive drugs (ex. CYCLOSPORIN A, FRK-506 to inhibit T cell activation or blockade of IL-2 receptor signal with RAPAMYCIN)
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3
Q

What are the disadvantages of transplantation?

A
  1. availability of healthy donor organs
  2. the disease that killed the patient may destroy the graft
  3. immunosuppressive drugs increase the risk of cancer and infection
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4
Q

Define autograft

A

a transplant from one site to another on the same person

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5
Q

Define isograft

A

a transplant between genetically identical individuals (twins). aka syngeneic graft

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6
Q

Define allograft

A

a transpplant between two genetically different individuals

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7
Q

Define xenograft

A

a transplant between individuals of different species

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8
Q

In what case are allografts not rejected?

A

when there are only MHC antigens, like those encoded by the male Y chromosome that are not expressed in females

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9
Q

Which cells mediate graft rejection?

A

T cells

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10
Q

What is a second-set rejection?

A

an MHC-specific second response where the rejection occurs more quickly than the first exposure

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11
Q

What happens when a graft is rejected?

A

When there is revascularization, immune cells infiltrate the area and there is cell necrosis in the graft

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12
Q

What are the two functions of MHC molecules?

A 
bind peptide fragments of antigen derived from pathogens to class I or class II MHC to display on APC
genetic gene complex that influences the ability of an organism to accept or reject transplanted tissue from another member of the same species
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13
Q

Define MHC haplotype

A

the particular combination of MHC alleles found on a single chromosome

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14
Q

What is the mixed lymphocyte reaction?

A

T cells from one individual are mixed with lymphocytes from a second individual to test whether or not the T cells divide and proliferate.
This method is used to detect different levels of histocompatibility

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15
Q

Which cells are essential for MLR (mixed lymphocyte reaction)?

A

CD4+ T cells ad macrophages

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16
Q

Give an example of acute rejection

A

kidney graft rejection
donor dendritic cells get into the blood vessels and activate recipient T cells, which travel to the graft and elicit a response

17
Q

Which foreign antigens are present in a fetus?

A

MHC antigens from father, foreign minor antigens (Y chromosome, RBS antigens, etc)

18
Q

Describe the timeline of a first set skin allograft rejection

A
  1. graft is vascularized in 3-7 days
  2. lymphocytes, monocytes, and neutrophils infiltrate and cause inflammation
  3. decreasing vascularization at 7-10 days
  4. visible necrosis at day 10
  5. rejection at 12-14 days post-transplant
19
Q

When does rejection occur in a second set rejection of the same allograft?

A

after 5-6 days

20
Q

What is a nude mouse?

A

lacks a thymus gland, also happens to not have any fur

21
Q

What can nude mice be used for?

A

will not reject human or other species tissues, so tissues can be grown in them and harvested

22
Q

What does irradiation do?

A

kills the fastest growing cells, ie. immune cells

23
Q

name two experiments that prove that T cells are responsible for graft rejection?

A

irradiate mice and inject some with serum and some with lymphocytes
OR
inject syngeneic T cells into nude mice and see if they react

24
Q

Which T cells are specifically responsible for graft rejection?

A

both CD4+ and CD8+, but alone, CD4+ has a greater impact

25
Q

On which cells are ABO antigens found?

A

erythrocytes, endothelial cells, and epithelial cells

26
Q

Define microcytotoxicity assay

A

antibodies for the different class I and class II molecules (plus complement) are reacted individually with the donor and recipient WBC in media that contain trypan blue (a vital dye that does not enter and stain live cells)

27
Q

What is the mixed lymphocyte reaction?

A
  1. take the WBC of potential donor and irradiate the cells so they can’t proliferate
  2. mix them with functional recipient cells
  3. incubate for 2-3 days then add 3H-thymidine and measure its incorporation into recipient cells

if the cells do not have the same MHC class II, the recipient cells will proliferate and will take up 3H-thymidine

28
Q

What happens if the MHC II loci between a donor and recipient is different?

A

there is lymphocyte proliferation

29
Q

What happens if the MHC I loci between a donor and recipient is different?

A

there is killing of target cells

30
Q

If the MHC I and II genes match, can there still be rejection?

A

yes, due to minor histocompatibility genes of the donor. this creates a weak response and takes a very long time

31
Q

What are the phases of graft rejection?

A
  1. sensitization: alloantigens of the donor the CD4+ and CD8+ T cells of the recipient
  2. donor MHC class I molecules present endogenous antigens to the recipient’s CD8+ T cells
  3. donor class II molecules present alloantigens to the recipient’s CD4+ T cells

recipient APC can also take donor antigens and present them to CD4+ T cells

32
Q

Is T cell response higher in graft rejection or a regular infection?

A

in graft rejection

33
Q

Which cells mediate the effector stage of graft rejection?

A

delayed-type hypersensitivity (DTH) and cytotoxic T lymphocytes (CTL). Ab + complement and Ab-dependent cytotoxicity play a smaller role

34
Q

What role do cytokines play in graft rejection?

A
  1. CTLs and macrophages migrate to the graft, CD4+ T cells produce large amounts of IFN-gamma, IL-2 and TNF-beta, promoting macrophage infiltration
  2. IL-2 stimulates proliferation of lymphocytes
  3. IFN-gamma induces and maintains DTH & activates macrophages to be more destructive
  4. TNF-alpha & -beta with IFN-alpha, -beta, and -gamma upregulate class I molecules & IFN-gamma upregulates class II
    IFN-beta can be toxic to cells
35
Q

What is a hyperacute reaction?

A

occurs within the first 24h. If the recipient has pre-existing antibodies, the complement cascades will initiate with infiltration of neutrophils. causes an intense inflammatory response and clots to form, blocking blood flow and inhibiting re-vascularization

36
Q

What could happen if a recipient has had repeated blood transfusions?

A

WBC in the transfusions could stimulate Abs against MHC antigens, which could react to the graft

37
Q

What could happen if a woman has multiple pregnancies?

A

she can become sensitized to the father’s MHC antigens and develop antibodies to them

38
Q

Define chronic rejection

A

occurs months or years after transplant & involves Abs and DTH & CTLs. only a new transplant can help the situation

39
Q

immunosuppressive therapies are necessary for ALL allografts. What are the disadvantages?

A

increases the risk of caner, hypertension, and infections

Immunology (11 decks)

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