5-Antigen Recognition by T cells Flashcards
What type of Ag can T-cell Receptors (TCR’s) bind to?
Peptides
When does TCR rearrangement occur?
Only during development
Why is rearrangement different in TCR’s than BCR’s (Ab’s)?
Because Ab’s can rearrange to form a tighter bond with an Ag whereas TCR’s cannot rearrange after development
What are the RAG genes?
They are recombination activating genes that rearrange genes of Ig’s and TCR’s.
What disease occurs if there is a defect in the RAG genes?
SCID (severe combined immunodeficiency disease)
What is the clinical manifestations of SCID?
No B or T cell production leads to infections because there is no adaptive immune system.
What is the cause of Omenn syndrome?
It’s a missense mutation in the RAG gene
What ara the clinical manifestations of Omenn syndrome?
Quickly die, chronic inflammation and a bright red rash on the face and shoulders.
What are the components of the TCR complex?
The T cell receptor (α and β subunits) and 3 proteins from the CD3 family
What are the 2 functions of the CD3’s?
They move the TCR to the cell surface and help signal the inside of the cell when an Ag is bound to the TCR
What % of the TCR population is the γδ type?
Only 1-5%
Where are the γδ TCR’s located?
On epithelial tissue to defend the epithelium, like gut epithelium
What is the other name of the CD4 cells?
Helper T cells
What are the functions of the helper T cells?
Help other cells (like macrophages) respond to an infection, stimulation of B cells to produce Ab’s, secrete cytokines, and responds to MHC-II molecules
What is the other name of the CD8 cells?
Cytotoxic T cells
What are the functions of the Cytotoxic T cells?
Kill cells that have been infected with a virus or intracellular agent, and responds to MHC-I molecules
What are the general functions of the TH1 cells?
They enter the blood to seek out infections and secrete IFN-γ and activate macrophages.
What are the general functions of the TH2 cells?
They remain in the secondary lymphatic tissues to drive the proliferation and differentiation of B cells
What type of organisms get presented by an MHC-I molecule to a Tc cell?
intracellular organisms
What type of organisms get presented by an MHC-II molecule to a Th cell?
extracellular organisms
What is the structure of the MHC-I molecule?
1 large 3-part alpha subunit coded by the MHC gene and a small beta2 subunit not coded by the MHC gene
What is the structure of the MHC-II molecule?
has 2 equal sized subunits, which are both coded by the MHC gene.
Why do people say that the TCR has degenerate binding when compared to the BCR?
Because the TCR can bind to a wide rage of peptide sequences whereas the BCR’s are very specific.
Why do the MHC-I molecules bind smaller peptides than MHC-II?
Because the binding pocket on the MHC-I molecule is smaller due to the weird 3 alpha chain thing.
When the proteins are taken up by a cell, what is that vesicle called?
Proteasome
How do the small peptides of the immunoproteasome get pumped into the ER?
TAP 1 and 2 (Transporter associated with Antigen Processing)
After the proteins are pumped in by TAP, what is then pumped into the ER?
the MHC-I alpha and beta subunits
What helps fold the alphas and beta chains of the MHC-I molecule in the ER?
Calnexin
After the MHC-I is folded to its correct form, what happens with the MHC molcule and the proteins from the immunoproteasome?
They bind and then leave in leave in a vesicle to the membrane
What is bound to MHC-I molecules in the absence of an infection?
self-peptides
What is the cause of the Bare Lymphocyte syndrome?
The TAP proteins don’t work so the peptides from the immunoproteasome cannot enter the ER
What type of infections do Bare Lymphocyte syndrome patients suffer from?
Intracellular infections like viruses because they have 1% of the normal MHC-I levels
What happens to the proteins of the extracellular pathogens when they enter the APC cell?
They are pwned by lysosomes.
What fuses with the phagosomes when the bacterial proteins are all broken up in an APC?
Vesicles from the golgi containing MHC-II
What is the function of the invariant chain?
It binds to the MHC-II binding site so that it doesnt bind to the normal proteins in the ER
When the MHC II compartment is being transported to the phagosome, what happens to the invariant chain?
It is cleaved to become CLIP, which are small chunks of the invariant chain.
What is the function of the HLA-DM?
It removes CLIP from the MHC II compartment and allows the target peptide to bind to the MHC-II molecule.
Which has more allotypes, MHC-I or MHC-II?
MHC-I
What is an allele?
Different form of a gene
What is an allotype?
encoded protein from an allele
What is an isoform?
any particular form of an MHC protein
Why is the highly polymorphic nature of the MHC important?
It allows it to be effective and adaptible to a large range of pathogens.
