Exam 1 -- Ch.4 Antigen Presentation Flashcards
How do we know when specific pathogens are present?
we rely on MHC (HLA)
What does MHC stand for?
MHC = major histocompatibility complex HLA = the MHC of humans
- a place to show antigens to T-cells
What are APCs?
= Antigen presenting cells
- they present antigens
Name some APCs.
- dendritic cells
- macrophages
- experienced B cells
What are Proteasomes?
normal protein turnover machinery in cytoplasm (constantly chewing up cellular proteins)
What are the two types of T-cells?
- Helper T cells (Cd4+)
2. Cytotoxic T cells (CD8+)
What are MHCs?
molecules that bind to protein fragments created in the cell and bring them to the surface of the cell
- they present the Ag to lymphocytes
What are the two methods of antigen presentation?
MHC I
MHC II
What does MHC I do? Why is this important?
presents the proteins that are constantly broken down WITHIN the cell and presents them of the cell surface
allows us to see what is being made IN cells
What does MHC II do? Why is this important?
on special cells that eat protein (phagocytosis) OUTSIDE of the cell and break it down and present the fragments on the cell surface
allows us to see what is happening OUTSIDE the cell
What type of cells can use MHC I method? What type of cells can use the MHC II method?
MHC I = almost ALL cells
MHC II = ONLY APCs
Describe the structures of MHC I and MHC II.
MHC I = only one long chain of AAs, beta not embedded in cell
- beta and alpha subunits are NOT equal
MHC II = two chains of AAs, both beta and alpha embedded in cell
- beta and alpha subunits are equal
What cells are constantly inspecting the presented fragments one MHCs?
cytotoxic lymphocytes (Killer T cells)
What does MHC I present?
- ordinary cellular proteins (enzymes, structural proteins)
- proteins encoded by viruses
- parasite proteins
T/F. Only a few cells in the body express MHC I.
FALSE–almost EVERY cell in the body expresses MHC I molecules
How do the proteins expressed by MHC I get there?
- Proteasomes chew up cellular protein into peptides
- Some peptides are broken into AAs for reuse, others go to ER
- Peptides to ER are attached to MHC I molecules (TAPI and TAP2)
- the peptide-MHC I complex is transported to cell surface
How do the peptides get to/into the ER to attach to the MHC I?
specific transport proteins (TAP1 and TAP2)
How many different MHC genes are there for humans?
six (3 from mom, 3 from dad)
- HLA-A, HLA-B, and HLA-C
In order for each MHC I protein to form a complete MHC complex, what happens?
pairs with another protein (beta2- microgloblin)
How many varients for HLA-A, B, and C are there?
hundreds
Due to the high variety of MHC I molecules, what ability does this give us?
ability to bind many different kinds of peptides
What is characteristic of the peptides loaded onto MHC I molecules?
- groove in which a peptide must fit
- most are 8-11 AAs long
- peptide anchored at both ends
- larger peptide bulge in center
What are the cells that inspect the peptides displayed by MHC I molecules?
Killer T Cells
What type of proteins do MHC II present?
APC’s eat extracellular proteins and present those
What is the process of MHC II expressing extracellular proteins?
- APCs “eat” extracellular protein and put in phagosome
- MHC II molecules are made in cytsol and injected into ER
- Invariant Chain Protein protects MHC II binding area
- Invariant Chain-MHC II complex is released into endosome
- Phagosome and endosome fuse
- Protein and invariant chain are broken down by enzymes in endosome (MHC II Complex preserved)
- Load peptides onto MHC IIs
- Transport MHC II-peptide to cell surface
If MHC II and MHC I are BOTH in the ER, how does MHC II not end up binding intracellular proteins?
a special protein protects binding area of MHC II called the Invariant Chain Protein
What is the extracellular protein enclosed in in the cell?
a phagosome
What is the Invariant Chain-MHC II complex released from the ER in? What occurs after it is released?
endosome
the phagosome (with EC protein inside) and endosome(with MHC II) with fuse
What is characteristic about the MHC II molecules and the peptides on them?
- they are open at both ends
- most peptides bound are 13-25 AAs
- peptide is anchored in center
- ends of peptides are allowed to hang over
What are the three types of MHC II Antigen Presenting Cells?
- Activated Dendritic cells
- Activated Macrophages
- Activated B Cells
T/F.
- APCs are all WBCs.
- APCs are all made in bone marrow
- APCs must migrate out to various sites in the body
- APCs must be activated before they can function.
TRUEEEEEEEE
What are the two things APCs provide?
- Provide high levels of MHCs required for T cell activation
- Provide co-stimulatory molecules required for T cell activation
Between an APC and T helper cell what are the two signals?
- APC presents antigen and the T- cell has a TCR recognizing it
- (co-stimulator) APC has B7 protein that will bind with T-cells CD28 protein
Describe a Dendritic Cell in its resting state.
- in normal tissue can take in 4x their volume of ECF per hour (sampling it)
- Expresses some B7 (co-stimulator)
- not a very good APC
- sentinel cells all over body (hunting for bad stuff)
What are two things that activate a Dendritic cell?
- Chemical signals form cells engaged in battle (TNF from macrophages and neutrophils; dying cells giving off chemical signals)
- Recognition of pathogen using PRRs and PAMPs on pathogens
Once activated, how long does a dendritic cell stay in the tissue? What is occur during this time?
Where does it leave to?
about 6 hours
- eats more stuff and MHC IIs become loaded with antigens
leaves through lymphatic system to nearest lymph node (to meet T cells)
What three things does an activated dendritic cells express more of?
- MHC II
- MHC I (if inf. w/ virus)
- B7 co-stimulatory proteins
T/F. Dendritic cells do the killing.
False– They do NOT do the killing, they get others to do the killing
How long to Activated dendritic cells live?
short lived to allow new dendritic cells to present antigens to lymph nodes to the virgin T cells
T/F. Macrophages travel just like dendritic cells do.
False–macrophages do not travel
Where are Macrophages located?
areas of the body exposed to the outside world
What are three functions of macrophages?
- garbage collectors
- APCs
- Ferocious killers (if highly activated)
What two things are needed for an macrophage to express enough MHC and co-stimulatory molecules to function as APCs?
- activation by cytokines (IFN-y)
2. Recognizing patterns (Toll-like Receptor recognition)
What function to macrophages serve to T cells?
to re-stimulate them
(T cells were activated by activated dendritic cells in lymph nodes, but experienced T cells need continual re-stimulation)
What do activated dendritic cells do to T cells? What do activated macrophages do to T cells?
Activated dendritic cells activated virgin T cells
Activated macrophages re-stimulate experienced T cells
What do activated B cells serve as? How fast are they?
APCs
- BCR have very high affinity for their antigen
- collect a lot of antigen
- very fast–> 30 minutes for a B cell to capture antigen and present it on cell surface on MHC II complex
What do T cells need a threshold number of in order to be activated?
of cross-linked TCRs and MHC IIs
What presents peptides to CD8 cells? Where are these peptides from?
MHC I; intracellular (endogenous antigen)
(CD8 cells = Killer T cells/ cytotoxic T cells_
What presents peptides to CD4 cells? Where are these peptides from?
MHC II; extracellular (exogenous antigen)
CD4 = Helper T cells
What type of cells express MHC I? MHC II?
MHC I –> expressed in almost every kind of cell
MHC II –> expressed only on cells of immune system, APCs
What is cross-presentation in a APC?
when MHC I and MHC II share info???
How does MHC related to transplant biology?
MHC genes used for Ag presentation are the very same genes responsible for tissue rejection
hence there name “ major HISTOcompatability complex”
