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Prof.

Ileana Constantinescu
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Immunogenetics a part of genetics which studies the
complexity of immune processes, concerning defense
and integrity of the host.

MHC encodes a group of highly diverse cell surface
proteins. There are two types of MHC molecules: class
I and class II molecules.

Polymorphism each MHC locus can express any one
of hundreds of different molecules.

Its genes are codominantly expressed.
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The structure of HLA class I molecules
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The structure of HLA class II molecules
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HLA alleles set found on one chromosome represents a haplotype.

HLA Genetics
Each individual inherits two MHC haplotypes from each parent and
thus he has two alleles for each gene.

These alleles are codominantly expressed.

The inheritence of MHC genes follows the Mendel segregation rules.
Father Mother
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2 digits
HLA-DRB1*13
A group of alleles which encode the DR13 antigen, i.e. there 62
DRB1*13 alleles: 1301 to 1362
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4 digits
HLA-DRB1*1301
A specific allele
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8 digits
HLA-DRB1*13010102
An allele which contains a mutation outside the coding region
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4 digits
HLA-DRB1*1301N
A null allele N
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8 digits
HLA-DRB1*13010102N
A null allele N which contains a mutation outside the
coding region
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4 digits
HLA-DRB1*1301L
L indicated that the allele is low expressed at the cell surface
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4 digits
HLA-DRB1*1301S
S indicated that the alleles is secreted but not stable at the
cell surface, find at soluble form
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4 digits
HLA-DRB1*1301C
C indicated that the allele is present in the cytoplasm but not at the cell
surface
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Host immune response against allograft
Direct antigen presentation

The response of recipient T cells to intact MHC/peptide
complexes on APCs from a graft is called direct
allorecognition.

That is APCs in the graft directly present alloantigens (the
foreign MHC molecules) for recognition by alloreactive T cells.

A recipients T cells can also react to donor MHC peptides
presented on the recipients own APCs. This pathway is called
indirect allorecognition.
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Clinical signification
Successful transplantation relies upon the immunologic compatibility
of recipients and their organ donor.

This compatibility depends on both, the extent of matching of the
tissue types (HLA types) of donor and recipient and the absence of any
pre-existing antibody reactivity of the recipient with the donor.

Both these factors influence the degree of immunosuppression
required to prevent rejection of the graft by the recipient.

The key element to successful transplantation is the ability to correctly
identify the tissue types of recipients and donors and to predict
whether a graft is likely to be rejected ( host versus graft disease) or in
the case of a BMT whether the graft will attack the recipient ( graft
versus host disease GvHD)
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