Histocompatibility & Transplantation Immunology - 1 Flashcards
what are MHC antigens and their functions?
- group of glycoproteins
- hold + position antigenic peptides and present them to T lymphocytes
- play a critical role in regulation of humoral + cell mediated response
- determine compatability of tissue for graft transpantation
MHC molecules in humans are called…
human leukocyte antigens - HLA
MHC class 1
where are they found?
what do they present antigens to?
3 main types?
- found on all nucleated cells
- present Ag to cytotoxic CD8+ T cells
- 3 main types : HLA-A, HLA-B, HLA-C
MHC class 2
where are they found?
what do they present antigens to?
3 main types?
- found only on APC
- present Ag to helper CD4+ T cells
- 3 main types : HLA-DP, HLA-DQ, HLA-DR
MHC restriction
- property of T cells to recognise self antigens
- antigens need to be presented to them or they’re non-responsive
- T cell education of self Ag and their selection take place in the thymus
- restriction of non-self antigens alerts T cells to respond
structure of MHC class 1
- made up of 2 polypeptide chains (α + β2-microglobulin)
- α - organised into 3 extracellular domains (α1-α3), transmembrane region, cytoplasmic tail
- α1 +α2 domains fold together - forms peptide binding groove
- β2-microglobulin made of β-pleated shetts
- β2 interacts w α chain + provides molecular stability
- β2 increases affinity of peptide binding by groove
- β2 does not have a transmembrane region
structure of MHC class 2
- 2 homologous poly peptide chains α & β
- α1 + β1 domains fold together - peptide binding groove
- α2 + β2 domains : conserved region
- β2 domain interacts with CD4+ receptors on Th cells
- both chains have transmembrane regions + cytoplasmic tails
- class 2 presents larger peptides than class 1
MHC class 2 presentation (extracellular)
- bind peptides from antigens internalised by APCs
- inside cell, antigen is digested by enzymes within phagolysosomes into peptides
- MHC class 2 synthesised on ER, carried into endosome
- phagolysosome containing antigenic peptides fuse with endosome containing MHC class 2
- MHC + peptide join up via peptide binding groove
- complex transported to and inserted in cell membrane for presentation
- complex recognised by Th cells
MHC class 1 presentation (intracellular)
- binds peptides dervied from antigens sythesised within the cell
- antigens digested into small peptides
- peptides transported into ER
- peptides bind the cleft of MHC class 1 in lumen of ER
- complex packaged into vesicle by golgi body + inserted into cell membrane for presentation
- class I molecules take a survey of every protein made inside the cell by presenting its fragments to T cells
what is a transplant?
the transfer of biological materia from one person to another
autologous transplantation
transplantation of self tissue from one part of body to another
syngenic
transplantation between two genetically identical persons (twins)
allogenic transplantation
transplantation between two genetically different people
xenogenic transplantation
transplantation between two different species (i.e. pig to human)
no immune responses generated for what kind of transplantations?
autologous & syngenic ( genetically indetical )