MHC Antigen Processing and Presentation Flashcards
what are exogenous antigens?
antigens that originate external or outside of the cell
why would MHC class II expressed for an exogenous antigen?
to ensure humoral and T helper cell response
why are exogenous antigens excellent targets of innate and humoral immunity?
they are visible external to the cell
With regards to MHC class II molecule, similar to antibody synthesis, both the α and β chains of the MHC are synthesized independently and assembled in the rough ER along with a special invariant chain peptide called ____
CD74
what does CD74 function as when it is seated in the binding groove of the MHC class II molecule to prevent binding of endogenous antigens
chaperone peptide
during its transport to the cell surface, CD74 is
proteolytically degraded into a smaller peptide sequence called ____
CLIP
what happens when CLIP forms an MHC class II-CLIP complex?
it fuses with the endosome or lysosome containing the processed exogenous antigen peptides
In the presence of what molecule does the MHC Class II molecule exchanges the CLIP fragment for the one of the exogenous antigen peptides then migrates to and fuses with the cell membrane surface presenting the processed exogenous peptide to the extracellular domain?
HLA-DM
what are the peptides called when they are bound to MHC class II molecules?
immunodominant
what are the two pathways of exocytosis?
constitutively secretory pathway and the regulated secretory pathway
describe the constitutively secretory pathway
vesicles continuously traffic both membrane bound (MHC molecules) and secretory proteins to the cell membrane surface for release
describe the vesicles of regulated secretory pathway
contain secretory proteins, but transport vesicles retained in the cytoplasm and are only released when they receive an appropriate signal (neurotransmitter, hormones)
what are endogenous antigens?
synthesized in cell
what are the most common sources of endogenous antigens?
viruses, select bacteria and parasites
what is the function of proteasomes?
degrade waste, improperly folded proteins or defective proteins to small amino acid sequences or peptides (~ 8-15 amino acids in length) for amino acid recycling
what are defective proteins tagged with that guides the protein to the proteasome for digestion?
ubiquitin
One avenue of cancer therapy involves using _____________ inhibitors to block protein
recycling (i.e. Bortezomib, trade name Velcade) as method to induce cell death. In humans, this
type of drug has been used to treat multiple myeloma and mantle cell lymphoma
proteasome
following digestion through a proteasome, what are small peptides tagged with to be trafficked to the ER?
transport peptide (TP)
true or false: Since all nucleated cells can express MHC class I molecules, virtually any nucleated cell can process and present endogenous antigens
true
nature has created a pretty savvy mechanism to root out infected or neoplastic cells for target by _________________
CD8+ cytotoxic T cell
what is the ultimate APC that can take up exogenous proteins from dying cells or viral-infected cells and process it?
dendrites
Cross-presentation of endogenous antigen by MHC class II molecules has been suggested to
occur during what cell survival phase?
autophagy
although MHC molecules can present
self-peptides, there are a minimal number of autoreactive T cells present as during central
tolerance, why is this?
these autoreactive cells are induced to die via apoptosis
even if recognition of autoantigens were to take place, the co-stimulatory signals normally present to upregulate T cell activation during an immune response to foreign antigen, what is absent?
APCs
what is an adjuvant?
non specific immune signal enhancer to stabilize the structure of an antigen that degrades rapidly and whose peptides are too small for processing
how can an antigen illicit poor immune response besides degrading too rapidly?
they are poor degraders (i.e. metals) and or express few antigen epitopes (i.e. plastic polymers)
what do superantigens (SAGs) bypass?
bypass the classic TCR-peptide-MHC-
complex to non-specifically activate multiple CD4+ T cells (pan T cell activation)
what are SAGs and what are they produced by?
exotoxins produced by pathogenic bacteria (i.e.
Staphylococcal enterotoxin (SE), food poisoning, toxic shock syndrome)
superantigens __________ link the MHC class II molecule with the Vβ TCR chain region on the CD4+ T cell
externally
what makes SAGs so dangerous to the host?
it has a very liberal specificity for the Vβ TCR chain region allowing for, if in sufficient quantity, the simultaneous non-specific activation of a significant percentage of T helper cells. This surge in activated T helper cells leads to a significant production and release of cytokines (a cytokine storm) into circulation leading to massive organ failure and very likely death
what is located in the cell walls that are an effective barrier to host immune defense and can facilitate entry into cells?
lipids and glycolipids
Upon entry, pathogens are processed and the lipid components are bounds to a cell surface protein composed of a large chain complexed with a β2-microglobulin called ___
CD1
how are lipid components continuously transported to the surface?
constitutive secretory pathway
why does the CD1 have a deep binding groove?
to accommodate the non-polar end of the glycolipid allowing the polar end of the composed of the carbohydrate to be presented to the TCR
where are γ δ T cells found?
minute quantities in the blood but localized in
higher concentrations in select tissues of the body (i.e. gut mucosa).
true or false: γ δ T cells are trafficked through the thymus
false
how do γ δ T cells have a role in autoimmune diseases?
assisting autoantibody production
in the class I region, what are the genes that that code for MHC molecules that don’t present antigen?
HLA-E, HLA-F and HLA- G as well as MICA and
MICB
in the class II region, what are the genes that that code for MHC molecules that don’t present antigen and why?
TAP proteins (TAP-1 and TAP-2) as well as the HLA-DM protein involved in the exogenous Ag peptide exchange with the CLIP fragment on the MHC class II molecule
with 2 Ig chains, the genes can code numerous variations between these chains resulting a large number of phenotypic variants of these genes
what does class III region code for?
important proinflammatory proteins including
proteins of the complement system (C2, C4 and factor B), cytokines TNF-α and TNF-β
(lymphotoxin), heat shock proteins (hsp-71 and hsp-72) and a steroid metabolic enzyme (21-
hydroxylase
what does class III region code for?
important proinflammatory proteins including
proteins of the complement system (C2, C4 and factor B), cytokines TNF-α and TNF-β
(lymphotoxin), heat shock proteins (hsp-71 and hsp-72) and a steroid metabolic enzyme (21-
hydroxylase
what is codominant expression?
express up to 6 different MHC class I molecules on their surface and up to 6 different MHC class II molecules at the same time, but only the APCs express the MHC class II molecules that express linear Ag peptide.
what is coordinate regulation?
he co-expression of these 2 classes of MHC can be enhanced at the same time, via external signals (IFNγ)
