Lectures 14 & 15: Antigen Uptake, Processing & Presentation Flashcards
what is the infectious non-self model that was developed in 1989?
APC have self-non-self discrimination system (the ability to detect foreign is no longer limited to T cells)
APCs bridge the ____ and ___ immune systems to help instruct ___ cells
innate and adaptive; T cells
do APC typically requires activation to enable antigen presentation?
yes
what are PAMPs? What detects them?
pathogen-associated molecular patterns and are detected by TLReceptors
what 2 things do the APC activation of DC, macrophages and B cells have in common?
- acquisition/enhancement of Class 2 MHC
2. CD80/86
does MHC restriction impact Tcell activation?
yes
t/f T cells ONLY recognize antigen that is presented by a self-MHC molecule
t
antigen recognition by CD4+ T cells is restricted by class __ MHC
2
t/f T helper cells can only become activated by cells with self class 2 MHC
t
CD8+ cytotoxic T cells can only recognize cells with __ class MHC
1
in order for cytotoxic T cells to kill a target cell, what other cell must have the same antigen in its class 1 MHC?
APC and target cells must both have same antigen in their self MHC1
give 2 examples of cells that have few to no MHC1
fibroblasts and liver cells have few and some neurons have none
what is the function of CD80/86 in APC activation?
they are upregulated to act as costimulatory activity with the MHC
what is the co-stimulatory molecule on Naive CD4+ T cells?
CD28
what has to happen to antigens in order for them to be immunogenic?
need to be processed (degraded); proteins are NOT presented intact
when does fixing need to occur in order for cells to be able to present antigen?
Can happen:
- after the cell has the Ag
- fixing and then exposing to antigen
what is the effect of fixing APC?
freezes the proteins in native conformation so they cannot be processed and they will fail to be presented
Does antigen processing and presentation differ between MHC1&2 loading? What is the significance?
- yes
2. allows the immune system to deal with extracellular and intracellular pathogens
The endogenous pathway processes ___ antigens and presents them to class __MHC
intracellular; 1
the exogenous pathway processes ___ antigens and presents them to class __ mHC
extracellular; 2
in the endogenous pathway, what is the function of Ubiquitin?
binds to cytoplasmic proteins ex: viral or tumor antigens) and targets them for proteolysis by proteosomes (the “intestines of cells’)
upon activation of the endogenous pathway, certain proteins in the ____ are replaced, resulting in the ____ which has increase proteolytic activity favouring production of class __ MHC binding peptides
constitutive proteasome; immunoproteasome; 1
what is the function of TAP in the endogenous pathway?
Transporter associated with antigen processing; carries peptides across the RER for class 1 loading
does TAP transport require energy?
yes
TAP has a high affinity for ___ peptides and favours what types of peptides?
high affinity for peptides with 8-13 AA and favours those with with complimentary AA positions to their AA anchor residues
how can enzymes in the RER of the endogenous pathway help peptides fit into MHC1?
by trimming longer peptides so they can fit in the groove
in the endogenous pathway, in the RER, ___proteins assist with the loading and processing of peptide fragments as they bind to MHC1 and stabilizes this interaction and helps loaded MHC1 to move out of the RER to the cell surface
chaperone
in the exogenous pathway, what is the method macrophages, DC and B cells use to take up antigen?
macrophages: phagocytosis and/or endocytosis
DC: phagocytosis and/or endocytosis
B cells: endocytosis
in the exogenous pathway, phagocytosis of Ag by APC causes the Ag to go through a series of ____. What is the role of this?
protease-containing vessicles, each with a lower pH than the last; this degrades the peptides into peptide fragments that can be loaded into MHC2
in the exogenous pathway, peptide fragments meet up with class __MHC that are arriving from vessicles from the ___
2; RER
in the exogenous pathway, where are Class 2 MHC synthesized?
on polysomes within the RER
when class 2 MHC are in the RER, they associate with ____
the invariant chain (aka CD74)
what are the functions of the invariant chain in the exogenous pathway? (2)
interacts with the peptide-binding cleft of MHC2 to prevent binding of endogenous peptides and ensures the a and B chains fold properly, exit the RER and are routed through the endocytic processing pathway
the invariant chain is degraded in the ___ compartment, leaving behind a fragment called the ___ in the MCH groove to prevent premature peptide binding
endocytic; CLIP
what is the CLIP?
class 2 associated invariant chain peptide
the peptide binding cleft of MHC2 has an open conformation to allow the CLIP to be replaced by the ___
antigenic peptide
in humans, the exchange of the CLIP for antigenic peptide is catalysed by a ____ molecule
nonclassical class 2 MHC (HLA-DM)
____ (also a nonclassical class 2 MHC), modulates the activity of HLA-DM and plays a role in presentation of self-peptides and self-tolerance
HLA-DO
when class 2 MHC–peptide complex is transported to the plasma membrane, the pH is ___, which causes it to assume a ___ form
neutral; stable
dendritic cells have the ability to present ___ antigen to CD8+ and CTL (cross presentation)
exogenous
dendritic cells activate CD4+ T cells through class __ MHC, which then license the DC by activated cells using _____, enabling ____ of exogenous Ag
2, CD40L; cross presentation
what explains how dendritic cells are able to activate CTL even when they are not infected by a virus?
cross-presentation
Is the processing and peptide loading of class 1 and 2 MHC the same?
no; they have different processes
exogenous nonpeptide antigens such as lipids and glycolipids are presented by ___ molecules
CD1
CD1 molecules structurally resemble ___ and associate with ____
class 1 MHC alpha chain; B2 microglobulin and exogenous antigen
CD1 molecules associate with exogenous antigens in the ___ compartment
endosomal
CD1 is inducible and expressed by multiple ____ cell type
APC
what types of cells recognize CD1 presentation of lipids and glycolipids?
NKT cells and certain T cells
