Linking Innate and Adaptive Immunity 5 Flashcards
what is cross-presentation by DCs?
exogenous antigens are redirected to the endogenous presentation pathway and presented on MHC I
what are the only type of APCs that have been found to do cross-presentation?
dendritic cells
describe the redirection mechanism of cross-presentation by DCs
unclear!
what do we know about the redirection mechanism of cross-presentation by DCs?
DCs need a license/permission to redirect the exogenous antigen
how does the license for DCs work?
if DC presents an exogenous antigen to CD4+ helper T cell, it gets “licensed” to redirect the antigen into the endogenous pathway
i.e. antigen binds CD4+ T cell to activate it then activates DC
what is the license signal? what does this allow for?
cytokines sent btwn DC and CD4+ helper T cell
allows for antigen presentation on MHC I molecules to prime CD8+ T cell responses
what is required before the DCs receive a license?
must have activated CD4+ T cell!
what type of cells can present endogenous/cytosolic peptides by MHC II molecules?
any professional APC (DCs, macrophages, B cells)
by which process do MHC II molecules present cytosolic peptides? how does it work?
autophagy
digestion and breakdown by a cell of its own organelles and proteins in lysosomes
what is an autophagosome?
specialized vesicles that contain cytoplasmic content and fuse with lysosomes
describe the process of autophagy for antigen presentation
- parts of cytoplasm taken into autophagosomes
- proteins get degraded
- joins MHC II for exogenous pathway
describe an example of the presentation of cytosolic peptides by MHC II
- virus infects macrophages and decreases expression of MHC I
- macrophages redirect peptides to CD4+ cells to help clear infection
T cell responses are ____ restricted
T cell responses are MHC restricted
describe the experiment of incubating virus-infected target cells with cytotoxic T lymphocytes (CD8+) of same or different MHC haplotype
A. Both cell types have same haplotype –> lysis occurred because everything T recognizes the self-MHC molecule
B. Cell types have diff haplotype –> no lysis occurred because T cell can only recognize self-MHC molecule
what is MHC restriction?
a T cell can only recognize a peptide if it is presented by a self-MHC molecule
what is the exception to MHC restriction called?
allorecognition
what is allorecognition?
recognition of non-self MHC by some T cells in the body
what percent of all T cells can do allorecognition?
1-10% of all T cells in an organism
what does allogeneic mean?
non-self
what are non-self MHC molecules called?
allo-MHC
what is the consequence of allorecognition? why?
rejection of transplanted organs because people are genetically different so MHC is non-self and T cells attack
what is an allele?
one specific form of a gene
what is a locus?
the specific chromosomal location of a gene
what type of gene is MHC coded by?
human leukocyte antigen (HLA)
where and how is HLA found?
found in a cluster of genes on chromosome 6
what are the 2 classes of MHC genes?
- MHC I genes
- MHC II genes
what do MHC I genes code for? why?
only code alpha portion
B microglobulin is constant on another chromosome
what are the 3 MHC I genes?
- HLA-A
- HLA-B
- HLA-C
Describe the polymorphisms of MHC genes
multiple forms / alleles exist for each gene
what is an allele in the context of polymorphisms?
2+ forms of a gene at a locus
how many alleles do MHC genes have?
> 100
what is the difference btwn HLA-A and HLA-A1?
HLA-A is a gene
HLA-A1 is an allele
what is a haplotype?
combination of MHC alleles on 1 chromosome
each individual inherits _____ haplotype from each parent
each individual inherits 1 haplotype from each parent
MHC alleles are _________ expressed
MHC alleles CODOMINANTLY expressed
what does it mean that MHC alleles are codominantly expressed?
both maternal and paternal MHC genes are expressed in offspring
why is it good that MHC alleles are codominantly expressed?
best chance of presenting all possible antigen peptides it counters
what is inherited from each parent for MHC I?
1 HLA-A, HLA-B, and HLA-C
are humans homozygous or heterozygous? what consequence does this have?
heterozygous
hard to find transplant match
describe the inheritance of many MHC I alleles and what this results in
inherit 3 different MHC I alleles from each parent (each have a similar function but different structure)
therefore 6 alleles can be expressed in 1 person
results in a high degree of variance in MHC expression
what does a difference in alleles cause in the protein? what does this allow for?
causes a difference in amino acid locations within the groove sites
allows for presentation of a variety of peptides
what would happen if the amino acids outside of the groove sites were to change?
could affect the structure conformation and folding of MHC molecule
a given MHC molecule can bind 1 or many peptides?
a given MHC molecule can bind numerous peptides
some peptides can bind 1 or many MHC molecules?
some peptides can bind many diff MHC molecules
where does the variation of peptide binding groove usually occur on MHC II molecules?
on B1 chain
what is polygeny?
many genes having same functions
what are the 6 MHC II genes?
- HLA-DR
- HLA-DQ
- HLA-DP
- HLA-DM
- HLA-DOA
- HLA-DOB
what is polymorphism?
multiple allelic variants of each gene in a population
a b/b mouse mates with a k/k mouse, their progeny is b/k. can you transplant skin from b/k to b/b?
NO!!!! there will be peptides on b AND k MHC so 1-10% of b/b T cells will detect non-self (k) MHC and react
can b/b donate to b/b or k/k parent or b/k progeny?
YES - b/b, b/k
NO - k/k
can k/k donate to b/b or k/k parent or b/k progeny?
YES - k/k, b/k
NO - k/k
can b/k donate to b/b or k/k parent or b/k?
YES - b/k
NO - b/b, k/k
