Transplantation Immunology
1. Indicate by reference to the genetic mapping of the human HLA system,
the probability of finding HLA identical siblings versus parents and
unrelated individuals.
HLA
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Human leukocyte antigen
Also known as the human MHC (major histocompatibility complex)
Antigen on the surface of the cell that enables the leukocyte cells of a different person to
know that it is non self. E.g. The recipients leukocytes will recognise a donor’s tissue as
foreign based on the HLA
Until 1999 there were about 1000 HLA alleles discovered
The main target of cellular immune response in organ donation and cause rejection of tissue
in unrelated people.
Two classes
o Class I – presents antigens to CD8 (cytotoxic) T cells
o Class II – presents antigens to CD4 (helper) T cells
Three Class I HLA genes – A – B – C
Three Class II HLA genes – DP – DQ – DR
Each person inherits 2 copies of each gene locus therefore will have 6 Class I and 6 Class 2
loci
In the human population there are multiple alleles for each gene locus. E.g 151 known HLA A
alleles, 301 known HLA B alleles. This is known as polymorphism
A typical person is likely to inherit 2 different alleles of many of the MHC loci which is
beneficial as it increases the likelihood the person can present a range of different antigenic
peptides that can be presented to the T cells.
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Mendelian inheritance says that there is a 25% chance offspring will inherit the same HLA
type.
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Polymorphism of the HLA gene means that there can be much variation so there is a higher
chance of finding a matched sibling to a parent to an unrelated person.
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The HLA alleles found on one chromosome is termed a haplotype
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Testing for HLA typing involves using serum that contains HLA antigens. If the donor’s serum
reacts with the patient’s cells, the individuals are incompatible.
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Crossmatching is used to detect if a donor’s antibodies will react with the recipient’s
antigens and therefore reject the transplant
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In heart transplants it is impractical to distribute based on HLA typing due to limited
availability of the organ
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Prevention of rejection
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HLA typing
Immunosuppression
Autologous transplantation – using own tissue. E.g. cultivating own bone marrow
and then transplanting
Tissue engineering
Immunomodulation – a substance that alters the immune response by augmenting
or reducing the ability of the immune system to produce antibodies against the
antigen. E.g. corticosteroids, cytotoxic agents, immunoglobulins