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Y2 Clinical Pathology > MHC and Transplantation > Flashcards

MHC and Transplantation Flashcards

1
Q

What actually is the MHC complex?

A

It is a gene complex on the short arm of chromosome 6

The proteins coded for by the MHC genes are HLA proteins

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2
Q

What are the different types of HLA antigens in humans?

A

Class I - A, B and C

Class II - DR, DQ and DP

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3
Q

Where are class I HLA antigens found?

A

They consist of 3 alpha helices and are a heterodimer

they are found on all nucleated cells

they are not present on red blood cells

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4
Q

WHat is meant by the HLA molecules being a heterodimer?

A

They are completed by something that is non-polymorphic (same in everyone)

This is B2u in humans

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5
Q

How are class II antigens different to class I?

A

They have 2 alpha helices and 2 beta pleat sheets

They are expressed more selectively on antigen presenting cells

This includes dendritic cells, langerhans cells and Kuppfer cells

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6
Q

Where are the MHC genes found?

A

On the short arm of chromosome 6

A = alpha chain

B = beta chain

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7
Q

What is meant by HLA molecules being highly polymorphic?

A

They vary between different people depending on their genetic backgrounds

Variation is around the peptide groove area as different peptides will fit in the grooves

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8
Q

How has the number of defined HLA alleles changed over time?

A

There has been a rapid increase in defined HLA alleles

This is because humans are genetically outbred - everyone is very genetically different so everyone has different HLA antigens

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9
Q

What is the chance that 2 siblings will have the same HLA antigens?

A

A sibling has a 1 in 4 chance of inheriting the same antigens from their parents

It can be hard to find a match for a bone marrow transplant if a parent or sibling is not a match, due to the extent of diversity

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10
Q

What is the difference in function between class I and class II MHC molecules?

A

Class I are important in handling intracellular foreign proteins

Class II are important in handling extracellular proteins that have been endocytosed

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11
Q

Complete the table for the roles of MHC I and II in different cell types

A
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12
Q

What is the relationship between HLA and infectious disease?

A

There are associations of protection

e.g. If you have HLA-B53, you are protected from contracting malaria

Genetic diversity prevents the whole population from dying out as some people will be able to develop an immune response and eradicate the infection

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13
Q

What is the association between autoimmune diseases and HLA?

A

Autoimmune diseases are associated with HLA polymorphisms

e.g. DR2 has an association with Goodpastures nephritis - you are 16x more likely to get the disease

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14
Q

What is the difference between positive and negative selection?

A

Positive selection:

  • involves selection of T cells with an affinity for self antigens

Negative selection:

  • involves selecting against T cells that have too much affinity for self-antigens
  • this would lead to autoimmune disease
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15
Q

What is meant by allorecognition?

A

Anyone with a different genetic background to you that appears foreign to your immune system

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16
Q

How is rejection mediated in an allogeneic transplantation?

A

Rejection is mediated by lymphocytes

This is against HLA molecules

17
Q

Why does rejection occur in allogeneic transplantation?

A

APC migration

Foreign cells from the donor migrate to the inguinal lymph nodes and are recognised by lymphocytes in the recipient as foreign

There is a reaction between APCs and CD4+ T cells

This excites a vigorous immune response

18
Q

What molecules are missing from the immunological synapse?

A

Costimulation is needed for full immunological activation

19
Q

What are the effector functions of the allogeneic APC?

A
  • CD4 T cell gets activated and generates B cells that generate antibodies
  • CD8 T cells will destroy any cells with a class I molecule on them
  • CD4 produce delayed type hypersensitivity reaction
20
Q
A
21
Q

What is the purpose of tissue typing?

What is meant by haplotype?

A

Matching HLA types avoids rejection

You receive one haplotype from the mother and one from the father

a haplotype is a copy of the short arm of chromosome 6

there is a possibility of 4 different combinations

22
Q

What are the 2 different types of HLA typing?

A

Serological:

  • cell based

Molecular:

  • extraction of DNA
  • amplification
  • detection of sequence polymorphisms
23
Q

Why do people do HLA typing?

A
  • Less rejection episodes
  • better graft survival
  • less sensitisation
  • to establish relationships - e.g. paternity testing as one haplotype must come from the father
24
Q

What are the missing stages in the renal transplant pathway?

A

Every 3 months on dialysis, the patient is screened to make sure they do not have HLA antibodies

25
Q

Why may someone acquire HLA antibodies whilst waiting for a transplant?

A
  1. If they have had a previous transplant
  2. In pregnancy as the women is exposed to the HLA antigens of the male so may generate antibodies
  3. In a blood transfusion as white cells contaminate blood and perform the sensitisation
26
Q

What will happen if the patient has HLA antibodies at the time of transfusion?

A

Hyperacute reaction

the transplant turns black and is rejected immediately

27
Q

Why is antibody detection important and carried out?

A
  1. Prevents hyperacute reaction

General antibody detection:

  • this is against many HLA types

Specific antibody detection:

  • this is against the donor
  • pretransplant cross match either living or cadaveric
  1. Avoids aborted transplant
28
Q

What is meant by complement dependent cytotoxicity test?

A

It detects complement fixing IgG/IgM HLA and non-HLAs

  1. Recipient serum is added to a Petri dish containing donor T cells (with class I antigens on the surface)
  2. If the recipient has antibodies, they will bind and complement is added
  3. There is cell lysis if antibodies are present
29
Q

What are the disadvantages of complement dependent cytotoxicity test?

A
  1. Limited sensitivity
  2. Subjective
  3. Non-complement fixing antibodies
  4. Non-HLA antibody interference
30
Q

What is a more modern way of performing CDC?

A

Luminex screening

Beads have recombinant HLA molecules on their surface

if there is fluorescence, this shows that the patient has antibodies to the HLA molecule

31
Q

What are the 3 types of rejection?

A
  1. Acute antibody mediated rejection
  2. Acute cellular rejection
  3. Chronic antibody mediated rejection
32
Q

When does hyperacute rejection occur?

A

It happens if you have pre-existing antibodies at the point the transplant goes in

blood flows in from the renal artery, antibodies bind and activate clotting cascade and complement

33
Q

What are the 3 important types of pre-formed antibodies?

A

Blood group:

  • if you have blood group A, you will have anti-blood group B antibodies

HLA molecules:

  • high levels can lead to immediate rejection
  • this comes from transfusion, pregnancy or previous transplant

Animals of lower species:

  • this prevents pseudotransplantation
  • all humans have antibodies against carbohydrates from lower mammals
34
Q

How does hyperacute rejection occur?

A

Anti-HLA antibodies bind to endothelial cells and activate them

they may bind the antigen and activate the complement cascade

any cell with Fc portion will bind and set off inflammation

35
Q

What are the properties of acute cellular rejection?

A

It is T cell dependent

It typically occurs 7-10 days after transplant

the reaction is directed against foreign HLA molecules as a result of HLA mismatch

36
Q

What is the treatment for acute cellular rejection?

A

Invasion of lymphocytes means that patients are kept on immunosuppressant drugs and steroids

a large dose of Methylprednisolone is used to treat rejection

37
Q

Why are antibody tests performed after transplant?

A

Antibodies are a bio marker of poor outcome

Y2 Clinical Pathology (76 decks)

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