Theme 2 Lecture 11: MHC and Transplant rejection Flashcards

1
Q

What is MHC?

A
  • The genetic complex that creates the proteins that result in the expression of antigens
  • MHC is the DNA that generates HLA proteins in humans
  • human MHC = HLA
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2
Q

What does MHC and HLA stand for?

A

MHC - Major histocompatibility complex

HLA - Human leukocyte antigens

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3
Q

What is isograft?

A

genetically identical e.g in humans this can only happen in identical twins

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4
Q

What is an allograft?

A

non identical, same species

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5
Q

What is a xenograft?

A

a tissue or organ transplant from a donor of a different species from the recipient

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6
Q

How was HLA discovered?

A

-looked at sera of multiparous women and patients who had multiple transfusions

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7
Q

Which antigen on cell surface is responsible for the reaction between leukocytes and antibodies?

A

Anti-MAC (HLA-A2)

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8
Q

What are the 2 types of HLA antigens?

A
class I: more ubiquitous, expressed on all cells with a nucleus, not RCBs
class II: expressed mainly on APCs
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9
Q

Which chromosome codes for HLA antigens?

A

short arm of chromosome 6

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10
Q

Which class of HLA antigens present cells to effector CD8 T cells?

A

MHC Class I

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11
Q

Which class of HLA antigens present cells to effector CD4 T cells?

A

MHC Class II

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12
Q

Which type of cells do HLA Class I and II pick up?

A

HLA Class I tend to pick up peptides from cytosolic proteins e.g viruses
HLA Class II tend to pick up ingested, external proteins

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13
Q

Give a key feature of HLA molecules?

A

they are highly polymorphic - lots of variability so each molecule can bind to very different peptides

There is much more polymorphism in class I HLA than class II

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14
Q

What is positive selection of T cells?

A
  • cells in the thymus present peptides on their own MHC Class I and II molecules, allowing immature T cells to bind
  • If a T cells TCR binds to MHC complexes on thymic cells, it will be positively selected
  • if not, apoptosis will occur
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15
Q

What is negative selection of T cells?

A
  • TCRs bind to MHC complexes in thymus leading to cell death
  • to prevent recognising and attacking our own cells
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16
Q

What is MHC restriction?

A

A T cell can interact with a self MHC molecule and a foreign peptide bound to it, but will only respond to the antigen when it is bound to a particular MHC molecule

17
Q

What are people with HLA-B53 protected agaisnt?

A

cerebral malaria

18
Q

What is the immunological synapse?

A

when the recipient T cell meets the APC cell of donor - this is primary signalling by receptor and MHC molecule

19
Q

What is the direct pathway?

A

recipient T cell directly recognises donor APCs

20
Q

What is indirect pathway?

A

method by which APCs are usually presented

21
Q

Once the cells from the recipient have recognised the APC, what types of response can they generate?

A
  1. can generate B cells that generate anti donor antibodies
  2. can generate cytotoxic CD8 cells which cause cytolysis of class I HLA antigens
    - CD4 cells can set up hypersensitivity reactions
22
Q

What is HLA typing?

A

genetic test used to identify certain individual variations in a person’s immune system.

23
Q

Why do we do HLA typing?

A
  • less rejection episodes if donor tissue is well-matched to recipient
  • better graft survival
  • less sensitisation - will develop less antibodies so they can have another transplant in the future
24
Q

What is tissue typing?

A

“test sample” of skin graft before organ transplantation

25
Q

Explain the renal transplant pathway

A
  1. medically fit for listing
  2. HLA typing
  3. details on waiting list / regular serum screening for antibodies
  4. organ offer
  5. real or virtual crossmatch
  6. renal transplant
  7. post op monitoring
26
Q

Why do we need to check patient dosen’t have antibodies before transplant?

A

prevents hyperacute rejection

27
Q

What is the complement dependent cytotoxicity test (CDC)?

A
  • test for antibodies
  • detects complement fixing IgG/ IgM HLA and non-HLAs
  • developed in 1970s
  • you take serum from the recipient and add in cells from donor
  • cells from donor will express HLA on surface
  • if recipient has antibodies against HLA antibodies then they will stick to the cells when the serum is added
28
Q

What is flow cytometry?

A
  • take donor serum and add to cells - use flourescent dye to show if antibodies are adherent after washing
  • this technique is more sensitive than CDC
  • it is now more common to use beads (luminex screening)
29
Q

What are the 3 types of rejection?

A
  1. acute antibody mediated rejection - most severe, occurs in first day, will only occur if recipient has pre-formed antibodies
  2. acute cellular rejection - occurs in first week
  3. chronic antibody mediated rejection - occurs in 6 months
30
Q

What is HAR?

A
  • hyperacute rejection

- if patient has pre formed antibodies

31
Q

Why would we perform pre transplant cross match?

A

involves taking cells from recipient and cells from the spleen of the donor to see if there is any reactivity - if there is reactivity we do not go ahead due to the chance of rejection

32
Q

What is acute cellular rejection?

A
  • t cell dependant
  • t cell immunosuppression directed against foreign HLA molecules
  • effect of HLA mismatch
  • typically 7-10 days after transplant
33
Q

what is the long term effect of anti-HLA antibodies?

A

developing antibodies against the HLA molecules of your donor will cause the graft survival time to decrease so you will develop chronic antibody mediated rejection