Immunogenetics Flashcards
How conserved is the ability to recognise self from non self? Define autographs, allographs and xenograft.
Very conserved - ability seen even in the lowest of organisms.
Autograft - same individual (always accept)
Allograft - same species (sometiems reject)
Xenograft - different species (always reject)
What is transitive acceptance vs non transitive acceptans?
A + B accept and B + C accept so A + C accepts
Non transitive = A + C does not accept.
How do we know that histocompatibility molecules exist?
The fact that the same species can reject each other grafts means there must be a histocompatability molecules that differ within species and receptors recognising them. There must also be a mechanism for learning and tolerance.
How were the MHC molecules discovered?
Graft acceptance in inbred mice segregated with hyper variable region of the genome. This was a group of genes in strict LD
What are the characteristics of an adaptive immune system?
Responds to foreign antigens Retains memory Improves with experience Specific for antigens Mediated by cellular and soluble factors
What happens if you cross two inbred strains different MHC mice then give an allograft of one or other of the MHC types?
Crossed mice will accept both but neither of the original can accept new crossed mouse.
Describe the human MHC molecules
These are encoded by 6 HLA genes. They are highly polymorphic with most changes in the antigen binding site. The HLA proteins bind and present cut of peptides (antigens) to T-cells.
These peptides are created by a multicatalytic protease called an immunoprotease. Normally this only processes self proteins. Both self and non self are presented by the HLA.
How do T cell receptors recognise antigens?
HLA proteins present peptide antigens on the outside surface of the cell. When this is a non self antigen the T cell receptors bind to it recognising the antigen in the context of the HLA molecules it is bound to. The T cell then triggers an immune response
What conflict is there between HLA, T cell receptors and self vs non self recognition.
TCR diversity, self tolerance and MHC recognition creates a conflict. Large diversity in TCR is good for recognising pathogens but also means you might reject self proteins.
An immature repertoire of TcRs will include:
Harmful - recognise self antigens
Useless - no MHC recognition
Useful - recognises non self and has a little interaction with self MHC molecules.
How does the body select/reject the useful and dangerous T cells?
Occurs at a young age whilst the T cell mature in the thymus. Thymus made up of lobules including outer cortex and inner medulla both filled with bone marrow derived immature T cells. Positive and negative selection occurs here.
Negative: Medullary thymic epithelial cells have disordered gene regulation and can create every single self proteins. Any TcR that binds is marked for removal (98% of cells).
Positive: Cortical thymic epithelial cells produce only partial agonists in their HLA molecules so do not activate for destruction but do mark all the T cells to be maintained if they interact with the HLA molecule.
Why are there 6 HLA genes?
Polygenism and also very large alleilic variation. This gives a very large scope for protection and reaction with non self pathogens. Which allows the human race to survive.
Link to HIV
