14 – Linking innate & adaptive: Exceptions & MHC genetics Flashcards
(32 cards)
3 Exceptions
Cross-presentation
Presentation of cytosolic peptides by MHC class II molecules
-Peptides in cytosol
Allorecognition
Cross presentation by …
DC can cross-present antigens
Exogenous antigens are redirected to endogenous presentation pathway
DC are the only APCs to be able to do this
Cross presentation by DCs example:
Viruses phagocytosed by DC = exogenous antigens
Virally-infected cells phagocytosed & viral peptides are presented on MHC I molecules
Mechanisms & functions of cross presentation
DC need license – permission to redirect
DC can present foreign antigen to CD4+ helper T cell (exogenous pathway) & get licensed to redirect exogenous Ag into endogenous pathway from T cell
License = cytokine & ligand signal between APC/helper T cell
-Allow presentation on MHC class I molecules
-Priming CD8+ T cell responses
Need to have activated CD4+ T cell first to then license and then cross-present
Presentation of cytosolic peptides by MHC class II molecules occur via ..
autophagy:
Digestion & breakdown by a cell of its own organelles & proteins in lysosomes
Autophagosome
Specialized vesicles that contain cytoplasmic content & fuses with lysosomes
mechanism of Presentation of cytosolic peptides by MHC class II molecules
1.Parts of cytoplasm taken in autophagosomes
2.Proteins degraded
3.Links up to exogenous pathway –> MHC II
Presentation of cytosolic peptides by MHC class II molecules example:
Some pathogens adapted to resist intracellular killing & macrophages in which they live require stimulation by cytokines to kill pathogens
TCR : … restriction
MHC restriction
Cell responses are MHC restricted
MHC restriction = given T cell can recognize specific peptides only when bound to a specific self MHC molecule
TCR restriction Example
strain A animals only respond to Ag presented by strain A APCs but not by strain B APCs
TCR specific to
Peptides
MHC
Allorecognition
recognition of non-self MHC by some T cells in body
1-10% of all T cells in an organism, can react to non-self (allogenic) MHC molecules (allo-MHC)
allorecognition: main mechanism of…
rejection of transplanted organs between genetically different individuals of same species
Direct allorecognition
recipient T cell recognition of donor/transplant MHC molecules expressed on surface of donor cells
Self T-cells recognize donor MHC is non self –> proliferate & differentiate –> try to get rid of them
Indirect allorecognition
recognition of processed donor peptides presented onto recipients’ own APCs via self MHC
Self-APC can take up pieces of donor APC –> process –> Resent to T cell
Gene
segment of chromosome that controls specific characteristics
Encodes for protein
Allele
one specific form of a gene
Locus
specific chromosomal location of gene
MHC molecules coded by … genes
on which chromosome?
HLA genes – human leukocyte antigen
Found in cluster of genes on chromosome 6 in humans
MHC genes – divided in .. classes, what are they?
2 main class - POLYGENY
MHC Class I genes – code for α chain
HLA-A
HLA-B
HLA-C
MHC Class II genes – code for α & β chain
HLA-DR
HLA-DQ
HLA-DP
HLA-DM
HLA-DOA
HLA-DOB
Polymorphism
Multiple variations (forms)/alleles - exists for each gene
Multiple allelic variants of each of MHC Class I & II genes in population
HLA-A is example of
gene
HLA-A1 to HLA-A2041 is example of
allele
polymorphism: allele
2 or more alternative forms of a gene at a particular locus
