Lecture 3 - Antigen Processing and Presentation (Stiner) Flashcards
Which cells are professional antigen presenting cells (APCs?
Dendritic cells
Macrophages
B cells
Which MHC do most nucleated cells in the body use to present antigen?
MHC 1
This is important in cancer b/c cytotoxic T-cells can see antigens presented in the context of MHC 1
What are the two pathways of Antigen presentation?
- EXOgenous
2. ENDOgenous
Which pathway involves MHC ii and T-helper cells?
EXOgenous
Which pathway involves MHC I and cytotoxic T- cells?
ENDOgenous
What are the two pathways for antigen PROCESSING?
- Cytoplasmic Pathway (for endogenous antigens, recognized by CD8+ T cells)
- Endocytic Pathway (for exogenous antigens, recognized by CD4+ T cells)
Which antigen processing pathway uses proteasomes to break down cytoplasmic proteins?
Cytoplasmic pathway (for endogenous antigens recognized by CD8+ T cells)
Which antigen processing pathway uses lysosomes to break down endocytic proteins?
Endocytic pathway (for exogenous antigens recognized by CD4+ T cells)
***How does an MHC molecule make it from the ER (site of synthesis) to the cell membrane?
- MHC is associated with an INVARIANT CHAIN that keeps it from binding to anything.
- It is carried in an endosome.
- Invariant chain is digested, and now CLIP hangs out in the binding site of MHC.
- HLA-DM reMoves CLIP from MHC binding site, and MHC moves to cell surface.
* **HLA-DO blOcks HLA-DM & therefore keeps CLIP in binding site & MHC off cell surface.
How are MHC I and MHC II different?
MHC I -small -made of one protein -antigen binds only to the END of MHC I MHC 2 -wider -made of two proteins -antigen binds ALONG LENGTH of MHC II
What can an MHC haplotype influence? (3)
- response to pathogens
- susceptibility to certain diseases
- transplant success
What is an MHC haplotype?
The set of MHC alleles on an individual chromosome
Do MHC molecules discriminate from self and non-self?
No, they have a broad specificity for peptides.
What is needed for a CD8+ T-cell to become activated? Two signals.
- Primary stimulus
- T-cell receptor bind to MHC I on APC
- Secondary stimulus
- CD28 on T cell binds to B7 on APC
Where is B7 located?
on an APC presenting to a CD8+ T cells
Where is CD28 located?
on a T-cell that is getting info from an APC. CD28 connected to APC’s B7
What are the adhesion molecules involved in the CD8+ activation?
ICAM-1 on APC binds to LFA-1 on T cell
Where is ICAM-1 found?
on APC presenting to CD8+ cell.
Adhesion molecule.
ICAM-1 binds to LFA-1
Where is LFA-1 found?
on CD8+ T cell getting info from an APC cell.
Adhesion molecule.
LFA-1 binds to ICAM-1
What is the order of events during CD8+ activation?
- Adhesion (LFA-1 binds to ICAM-1)
- Ag-specific activation (TCR binds to MGC I)
- Costimulation (CD28 binds to B7)
What type of proteins to CD8+ T cells recognize?
cytosolic proteins
What type of proteins to CD4+ T cells recognize?
extracellular and intravesicular proteins
What are the 3 components of TCR?
- TCR
- Zeta chains
- CD3
(CD3 and zeta chains are required for signaling.)
What costimulatory receptor binds to B7 on APCs during T-cell activation?
CD28 on T cell surface
What receptor replaces CD28 on T cell surface once in the infection has been taken care of? We need to downregulate T cell activity.
CTLA-4 is now on the surface of the T cell. It also binds with B7 on APC
***What is the primary cytokine that T cells produce?
IL-2
What does the T-cell produce when it is activated?
IL-2
How does IL-2 amplify the T-cell response?
Adds an alpha segment to IL-2R, and therefore increases its affinity by 1000-fold
What does IL-2 do, and why is it so potent?
- T cell clonal expansion, differentiation into effector and memory cells
- regulatory T cell development, survival, and function
- NK cell proliferation, increased cytotoxic activity
What is the costimulatory signal that B cells need from T cells to be activated?
CD40 (on B cell) binds to CD40L (on T-cell)
Where is CD40?
B cell
Where is CD40L?
T cell
Which interleukin drives the development of TH1 cells?
IL-12
What does IL-12 do?
drives development of TH1 cells
What does IL-4 do?
Drives the development of TH2 cells
Potent inhibitor of TH1 response.
What interleukin drives the development of TH2 cells?
IL-4
What do TH1 cells help with?
cell-mediated immune responses
- activate macrophages
- complement antibodies and produce antibodies
- activate neutrophils
What to TH2 cells help with?
humoral immun responses (antibody)
Which TH cell makes IFN-gamma?
TH1
What cytokine does TH1 make?
IFN-gamma
What does TH2 make?
IL-4
What TH cell makes IL-4?
TH2