8- Antigen Presentation and the MHC Flashcards
APCs have what 2 types of molecules on their cell surface?
Both class I and class II
What are the 3 types of APCs? Which are phagocytic? Which have class II molecules?
(1) Mononuclear phagocyte (macrophages) – phagocytic, class II
(2) Dendritic cells– phagocytic, class II
(3) B Lymphocytes– class II, NOT PHAGOCYTIC
What is the name for macrophages in the liver? In the brain?
Liver- Kupffer cells
Brain- Microglial cells
What are dendritic cells called in the skin?
Langerhans’ cells
The two types of dendritic cells.
PLASMA CYTOID DENDRITIC CELLS: protection from viruses. produce huge amounts of interferon
CONVENTIONAL DENDRITIC CELLS: Phagocytizes pathogen (activating the cell) and presents antigen to T-cells via MHC class II molecules.
Class I molecules are loaded where?
In the cytoplasm. A viral protein is degraded and then the peptide fragments are bound by MHC class I in the ER and then transported to the cell surface where they present to CD8 T-cells.
Class II molecule loading? How does this differ with B-cells?
(1) Foreign peptide taken in via vesicle
(2) Acidification activates proteases which degrade antigen into peptide fragments
(3) Vesicles containing peptide fuse with vesicles containing MHC class II molecules which then go to cell surface and present to CD4 T-lymphocytes
In B cells, antigen first binds to B cell receptor on B- cell surface, before it is pulled in and degraded.
Function of TAP1/TAP2?
To take proteins which have been brought in and broken down by the proteasome, and push them into the ER to be bound to Class I molecule.
Where are MHC Class I molecules synthesized?
ER
Are peptides normally being presented by the MHC class I molecule?
YES! The normal “self” proteins are presented in regular homeostatic functioning. When a virus is present, these proteasomes grind up viral protein and present that instead (mostly) AND increases the amount of MHC molecules on the surface.
Function of HLA-DM
MHC Class II molecules have a peptide called CLIP bound to them which keeps proteins from binding. HLA-DM is responsible for removing CLIP in the presence of foreign proteins, allowing them to bond.
Major differences between class I and II loading
I: loaded with INTRACELLULAR antigen in the ER
II: loaded with EXTRACELLULAR antigen in a vesicle
Th1 vs. Th2 CD4+ T cells
Th1: Host immunity effectors against intracellular bacteria and protozoa. Produce cytokines that activate macrophages to increase phagocytic activity.
Th2: Host immunity effectors against extracellular parasites including helminths. Produce cytokines which allow for growth and differentiation of plasma cells (from B cell to plasma cell)
What must occur in order for a T-cell to be activated?
2 signals:
Engagement of TCR with foreign peptide and ligation of CD28 by B7 (which is on the surface of the APC only if a microorganism has been engulfed).
How is a T-cell activated if there is no microorganism which has been engulfed, but there are simply foreign peptides?
After TCR is signaled by MHC II, it brings CD40L to the surface. This signals the CD40 of the APC to present B7 on the surface, which interacts with CD28, fully activating the T-cell.
