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75 Cards in this Set

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inbred strain
product of repeat brother sister matings; homozygous at all loci
syngenic
genetically identical at all loci
congenic
mice are genetically identical except for a small genomic region
MHC restriction
APCs used for re-stimulation must have the same MHC as the original strain
MHC
major histocompatibility locus; complex locus encoding many genes related to antigen presentation
MHC class I and II genes of humans
Class I: A, B, and C
Class II: DP, DQ, Dr
MHC class I and II genes of mice
Class I: K, D, L
Class II: I-A, I-E
Genetic polymorphism
many alternative forms of the same gene or alleles are present in a population "normal variants"
mutation
an alteration in the sequence of a gene as compared to the sequence of the predominant allele in a population
haplotype
the set of genes within a complex locus which are inherited as a group because they are linked on a chromosome
HLA
human leukocyte antigens; can test a person's HLA type by testing their white blood cells for reactivity to a panel of anti-leukocyte antibodies
Endogenous pathway
antigens from the cytosol are presented on MHC I molecules to CD8 T-cells
exogenous pathway
antigens internalized through endocytosis or phagocytosis are presented on MHC II molecules to CD4 T-cells
Process for finding which gene is mutated in RMA-S cells?
1. Take RMA cells and isolate mRNA
2. Make cDNA library
3. transfect RMA-S with pools of cDNA
4. check for rescued MHC I
TAP
transporters associated with antigen processing
which cells are considered the professional antigen presenting cells?
1. B-cells
2. macrophages
3. dendritic cells
how do viruses interfere with Class I MHC expression in order to escape killing by CTLs?
1. herpes simplex virus protein ICP47 can selectively bind to TAP and inhibit the transfer of peptides into the ER
2. human cytomegalovirus (HCMV) encodes proteins that retain MHC I molecules in the ER preventing presentation on the cell surface
invariant chain
binds MHC II molecules in the ER; blocks the binding of peptides; cleaved in the endosome leaving CLIP still bound to the MHC II
HLA-DM (H-2M in mice)
binds to and stabilizes empty Class II molecules; releases CLIP and allows other peptides to bind allowing MHC II molecule to travel to the cell surface
how do pathogens evade MHC II?
1. adenovirus interferes with Class II upregulation in APCs
2. HIV interferes with Class II processing
3. intracellular leishmania and mycobacteria manipulate phagosomes to prevent antigen presentation
MIIC
compartment for MHC II
cross-priming
the loading of antigenic peptides derived from exogenous proteins onto MHC I molecules
alloreactivity
non-specific T-cell response to mismatched MHC (1-5% of all T-cells are reactive to a given MHC allele)
SH2 domain
src homology domain; binds to specific phosphotyrosine containing motifs in signaling molecules such as ITAMs and helps PTKs find targets and scaffolds assemble signaling complexes
Lck and Fyn
Src family kinases that phoshporylate ITAMS and ZAP-70 once it is recruited
Zap-70
binds to phosphorylated ITAMs on CD3 zeta chains and activates downstream signaling events
LAT
part of the complex that recruits PLC-gamma
SLP-76
part of the complex that recruits PLC-gamma
GADS
part of the complex that recruits PLC-gamma
NFAT
transcription factor in the Ca+2 release pathway
cyclosporin
immunosuppressant drug that blocks the activity of calcineurin
FK506
immunosuppressant drug that blocks the activity of calcineurin
What is ras?
a small G-protein
what are nude mice defective in?
transcription factor required for terminal epithelial differentiation - leads to no thymus
what are scid mice deficient in?
DNA PK (DNA protein kinase) -> no gene rearrangement
which cells mediate positive selection?
cortical epithelial cells
which cells mediate negative selection?
medullary epithelial cells and dendritic cells
pre T-alpha
common chain that pairs with TCRbeta
when does TCR alpha rearrangement begin?
at the double positive stage
where does positive selection take place?
occurs on cortical epithelial cells (thymic cortex)
where does negative selection take place?
at the cortico-medullary junction
AND thymus mutation
see no single positive CD8 T-cells in either the spleen or the thymus; recognizes pigeon cytochrome c
OT-1 thymus mutation
see no single positive CD4 T-cells in either the spleen or the thymus; recognizes ovalbumin
how does a T-cell "decide" whether to express CD4 or CD8
Depends on the MHC it has affinity for -> if it binds to MHC I becomes single positive CD8 T-cell; if it binds to MHC II, becomes single positive CD4 T-cell
Aire
a transcription factor who job is to drive expression of genes in the thymus so you can eliminate self-reactive peptides
Low affinity for peptide-MHC
Positive selection
high affinity for peptide-MHC
negative selection
What happens after T-cells leave the thymus?
Naive T-cells exit the thymus and enter the bloodstream. If they remain in the bloodstream, they will pass through the spleen. They can also enter lymph nodes by crossing the high endothelial venules. If the T-cells are not activated, they re-enter the bloodstream and start all over again
Why are dendritic cells such good APC's?
1. they express both MHC I and II
2. They start in the right place (tissues)
3. they end up in the right place (lymph node)
4. immature DCs are highly efficient at taking up antigens in the tissues
5. After maturation and migration, mature DCs present these antigens to T-cells in the lymph node.
6. They express co-stimulatory molecules
Signal 1 without signal 2 leads to what?
anergy
Tregs
regulatory T-cells (a 3rd mechanism of tolerance); CD4+CD25+ T-cells (express TCRalphabeta, produced in the thymus, necessary for maintenance of tolerance)
FoxP3
transcription factor required for Treg development
TLR4
recognizes LPS
TL9
CpG unmethylated DNA
TLR5
flagellin
TLR1
lipoproteins, peptidoglycan
Th1
produces IFN-gamma and IL-2
Th2
produces IL-4, IL-5, and IL-13
Th17
produces IL-17, IL-21, and IL-22
cytokines
small proteins (<30 kDA) that signal between cells
autocrine
cytokine acts back on the producing cell (ex. IL-2)
paracrine
cytokine acts on neighboring cell or cells (ex. IFN-gamma)
endocrine
cytokine acts on distant cells (IL-5)
cytokine signal transduction
1. activation of JAK family tyrosine kinases, phosphorylation of receptor (tyrosine phosphorylation of STAT by JAK kinase)
2. Dimerization of STAT
3. Specific gene transcription
function of IFN-gamma
1. activates macrophages
2. induces B-cells to class switch to IgG2
3. Helps CTL differentiation
function of IL-4, IL-5, and IL-13
1. induces B-cells to class switch to IgE
2. induces eosinophil differentiation and activation
function of IL-17 and IL-21
1. important at mucosal surfaces
2. induces neutrophil recruitment
3. specific role in B-cell class switching unclear
intracellular bacteria and viruses mediate the following immune responses:
1. cell-mediated immunity
2. activated macrophages
3. opsonization
4. CTL production
extracellular bacteria and fungi mediate the following immune responses:
1. tissue inflammation
2. recruitment of neutrophils
3. activates macrophages
4. opsonization
worms and large parasites mediate the following immune responses:
1. humoral immunity
2. IgE production
3. degranulation of mast cells
4. eosinophils
which B-cells isotypes are good at neutralization?
IgG1, IgG2, IgG3, IgG4, IgA
which B-cell isotypes are good at opsonization?
IgG1, IgG3
which B-cell isotypes are good at sensitization for killing by NK cells
IgG1, IgG3
which B-cell isotypes are good at sensitization of mast cells
IgE
which B-cell isotypes are good at activating complement?
IgM, IgG1, IgG3