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TCR is made up of...
Antigen-binding site, constant and variable region, CDR regions
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How many polypeptide chains make up a TCR?
2
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What characteristics does a TCR have?
all the TCR on the same cell are the same. each cell expresses a different TCR
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Tc, TCL, CTL
cytotoxic t cell
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What are the differences between TCR and BCR
TCR only has one binding site, they do not bind to soluble antigens, they have no rearrangement after antigen engagement, Matures in thymus, only used for recognition, no secreted receptor
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How many CDR loops does a TCR have?
6 (3 on each chain)
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What does TCR bind?
MHC-peptide complex
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Calpha has how many options for rearrangment?
1
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Cbeta has how many options for rearrangment?
2
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what sections does the alpha chain have?
VJ
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What sections does the beta chain have?
VDJ
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Where does rearrangment occur?
thymus
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What is a RAG proteins?
recombination enzyme specific to T and B cells
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What two parts make up a transposon?
Transposase (RAG) and Inverted repeates (RSS)
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What are the functions of CD3 and zeta?
help transport the TCR to the cell surface and transmission of signal extracellular to intracellular
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SCID
Severe combined immunodeficiency disease. people with SCID are susceptible to infections. lymphocyte profile (T- B- NK+), bone marrow transplant cna cure
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Omenn syndrome
RAG proteins have reduced activity. patient is T+ but low, B- NK+
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CD3delta and CD3epsilon deficiency diseases
mutations in some CD3 genes. patient is either T+/TCR- or T- and B+ NK+
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alpha:beta T cells make up how much of the population?
95%
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gamma:delta T cells make up how much of the population and where do they occur?
5%, predominate in epithelial tissue; recognize more than MHC-peptide complex
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Which TCR genes are together on a locus and what does this mean?
delta and alpha chain genes share a locus meaning that if the alpha chain is rearranged then the delta chain cannot be made. This is the decision point for a t cell to become an alpha:beta or gamma:delta
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Antigen Processing-
antigen is broken up and brought to surface
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Antigen presentation
MHC=peptide complex is displayed on the cell surface
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Antigen Presenting Cell
cell with a surface MHC-peptide
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Professional APC
super presenters that are leukocytes
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What do t cells do after recognizing an antigen?
they induce changes in other cells
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What do CD4 helper t cells do?
help other cells
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What does Th1 do?
changes a macrophage
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What does TH2 do?
changes a b cell or dendritic cell
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What does CD8 CTL do?
kills other cells
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What are CD4 and CD8?
co receptors that help bind to MHC I and MHC II
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CD8 T CELL + virus infected cell =
dead virus infected cell
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CD4 T cell + macrophage =
activated macrophage
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CD4 T cell + B cell =
Plasma cell
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How does MHC I display an antigen?
the pathogen replicates in the cell and proteins are degraded in the cytoplasm of the cell. peptides are then transported into the ER and bind to MHC I and then transported to the cell surface. MHC I expressing cells present to CD8 T cells. CD8 T cells (CTLS) kills the host cell using perforin and granzymes... NO ANTIBODIES
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How does MHC II display an antigen?
Pathogen is recognized and internalized by a professional APC. Phagolysosomes degrade the protein into peptides. The peptide-MHC II complex is transported to the cell surface. Professional APC contacts CD4 T cells. CD$ Th cells secrete cytokines to signal B cell maturation...Antibodies needed (recognize pathogen on APC)
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Which MHC binds to larger peptides?
MHC II
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What is peptide binding groove?
the binding spot on MHC binds to many different peptides that have similar features
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What on MHC I does CD8 bind?
alpha 3
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What on MHC II does CD4 bind?
beta 2
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What cells express MHC I?
most human cells
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What cells express MHC II?
leukocytes and thymic stromal epithelial cells
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IFN-gamma
increases expression of MHC I and II
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Alleles
DIfferent forms of one gene
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Allotypes
different forms of one protein (isoforms)
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Polymorphic
Alternative forms of one gene (many alleles)
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Oligomorphic
A few forms of one gene (few alleles)
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Monomorphic
no polymorphism
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Homozygous
same allele on both inherited chromosomes
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Heterozygous
different allele on both inherited chromosomes
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HLA- A, B, C
present peptide antigens to CD8 t cells and interact with NK cells
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HLA- E, G
interact with NK cells
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HLA- DP, DQ, DR
present peptides to CD4 T cells
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IFN- alpha, beta, gamma
increase expression of HLA class I heavy chain, B2 microglobulin, TAP, and proteasome subunits
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IFN- gamma
increases expression of HLA class II
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Anchor residues
residues in the peptide that anchor it to the MHC
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MHC restriction
TCR recognizes the complex of both the peptide and MHC by interacting with exposed amino acid residues
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How many peptide chains of MHC class II contribute to plymorphism?
2
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How many peptide chains of MHC class I contribute to plymorphism?
1
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Peptide binding motif
combination of anchor residues
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Balancing selection
favors multiple alleles
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Directional selesction
favors a single allele
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Haplotype
the combination of alleles in a region of the chromosome
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why do heterozygous individuals have an advantage over homozygous individuals?
they can recognize more peptides
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