4) Antigen Presentation and MHC Flashcards
ALL nucleated cells express which MHC molecule?
Class 1
What cells express MHC class II?
antigen-presenting cells (APCs)
1) dendritic cells
2) macrophages
3) B cells
Do APCs express MHC class I?
yes because they are nucleated as well
Do RBCs express MHC molecules?
NO, they are NOT nucleated
MHC proteins in humans are called…
HLA (human leukocyted antigens)
Total set of MHC genes on each chromosome
MHC haplotype (one from each parent)
refers to different genes within each person
polygenic
refers to wide variety of genes in the human genome pool
polymorphic
A, B, C genes are encoded for which MHC proteins?
MHC Class I
DP, DQ, DR genes are encoded for which MHC proteins?
MHC Class II
Which characteristics (3) virtually guarantees that two randomly selected individuals will not be identical matches (not related individuals such as siblings)?
1) polygenic
2) polymorphic
3) codominant
How many MHC proteins do each individual express?
theoretically 6 different Class I and 6 different Class II (3 different of each from each parent)
True or False. Peptides are covalently bound to MHC proteins on cell surface.
FALSE. they are non-covalently bound
Which HLA allele is found in patients with narcolepsy? Which class of MHC is this?
HLA-DR2, class II
Which HLA allele is found in patients with ankylosing spondylitis? Which class of MHC is this? (possible boards topic)
HLA-B27, class I
True or False. Paternity tests are 100% definitive.
No, they can only exclude the alleged father, but cannot 100% definitively determine who the actual father is.
Why is matching so difficult for organ transplantation?
patient will reject non-self MHC protein and recognize it as foreign, inducing an immune response to the transplanted organ
Which MHC proteins have one big alpha chain and one small beta chain?
MHC class I
True or False. The microglobulin beta chain in MHC class I is NOT important for the actual binding of antigens
True. But it is important for getting the MHC molecule to the cell surface
What are the three regions of a Class I MHC molecule?
1) peptide-binding
2) transmembrane
3) cytoplasmic
Why do infections by Plasmodium go undetected by cytotoxic T cells?
RBCs are not nucleated, thus also lack MHC Class I proteins
Which MHC proteins presents antigens to CD8+ T cells (cytotoxic T cells)?
MHC Class I
Which MHC proteins presents antigens to CD4+ T cells (T-helper cells)?
MHC Class II
The binding region of MHC Class I proteins are for peptides of which size?
small fragments of 9-11 amino acids long
Describe the molecular structure of MHC class II proteins
two non-covalently-linked polypeptide chains (same as MHC Class I, but beta chain in class II is just as big as the alpha chain)
MHC Class II molecules can bind to longer peptides, why is this possible?
MHC class II have peptide-binding regions for larger peptides (10-30 amino acids long). the ends of the binding regions are open-ended (long hot dog for a regular-sized hot dog bun)
CD4+ T cells are also known as…
T helper cells
CD8+ T cells are also known as …
cytotoxic T cells
CD8+ binds to this MHC class proteins
class I
CD4+ binds to this MHC class proteins
class II
True or False. T cells can recognize and bind to all kinds of molecules such as peptides, polysaccharides, and lipids.
FALSE. T cells can ONLY bind to peptides presented on MHC molcules
Dendritic cells are important in which type of immune response?
primary
Macrophages and B cells are important for which type of immune response?
secondary
Which of the three APCs is the most potent APC and the best at their job?
dendritic cells are the most professional APCs
True or False. dendritic cells are in nearly all organs of the body.
True
Where are dendritic cells produced?
bone marrow
Where do dendritic cells (DCs) go after they are produced?
circulate in blood then migrate into tissues where they reside as immature DCs and constantly sample the environment through phagocytosis and macropinocytosis
What is the most potent activator of macrophages?
IFN-gamma
Describe how antigen processing can lead to upregulation of MHC molecules on APCs
1) APC presents antigens to CD4+ and NK cells thus activating them
2) CD4+ and NK cells produce and release IFN-gamma
3) IFN-gamma activates APCs
4) IFN-gamma causes APCs to upregulate MHC class II expression
What effects do upregulation of MHC class II have?
high level of MHC class II expression on APCs –> more T cells being presented to by APCs –> more IFN-gamma released –> better and faster immune response
What happens when dendritic cells capture antigens?
they become activated, travel to lymph nodes and present antigens to T-helper cells (CD4+)
Which pathway do MHC class I molecules process antigens?
endogenously
What occurs inside uninfected cells during endogenous antigen processing? Why is this important?
Class I MHC proteins bind to self peptides. It’s a sign to NK cells that they are fine and not infected. This is why cancer cells down-regulate Class I MHC
Describe the steps of endogenous antigen processing in response to viral infection
1) virus within the cytoplasm synthesizes viral proteins
2) viral protein is broken down by proteasome into small peptide fragments (9-11 a.a.’s)
3) the peptide fragments are transported to ER where MHC class I is being assembled
4) peptide fragment is attached to MHC class I in the ER
5) the MHC complex is packaged and shipped to the cell surface
6) APC then presents the antigen to CD8+ (cytotoxic T cells)
Which pathway do MHC class II molecules process antigens
exogenously
How are exogenous antigens obtained?
they are internalized by phagocytosis, receptor-mediated endocytosis or gluid phase pinocytosis
Describe the steps of exogenous antigen processing in response to viral infection
1) virus particle is internalized and enters cell as an endosome
2) endosome binds with lysosome and the virus is broken down to peptide fragments
3) Class II MHC (with clip protein) is packaged into exocytic vesicle by the Golgi
4) the vesicle then docks with the phagolysosome (containing peptide fragments of virus)
5) Clip protein falls off class II MHC and peptide binds instead
6) the vesicle is then brought to cell surface where class II MHC presents the antigen to CD4+ (T helper cells)
What does the invariant chain, clip protein, do?
it binds to the peptide-binding region to prevent self peptides from binding to it (which would elicit an auto-immune response)
Some DCs are even more awesome and can present antigens via BOTH endo- and exogenous pathways. Why is this important?
viral infections can stimulate cytotoxic T cells (CD8+) instead of just T helper cells (CD4+). This leads to a much faster immune response (cells are getting killed faster)
Describe how DCs are shunted to endogenous pathway instead of the other route
once the antigen has been captured within phagosome, the vesicle fuses with the ER, where DCs are being assembled.
