MHC Antigen Processing and Presentation

Question 1

what are exogenous antigens?

Answer 1

antigens that originate external or outside of the cell

Question 2

why would MHC class II expressed for an exogenous antigen?

Answer 2

to ensure humoral and T helper cell response

Question 3

why are exogenous antigens excellent targets of innate and humoral immunity?

Answer 3

they are visible external to the cell

Question 4

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 ____

Answer 4

CD74

Question 5

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

Answer 5

chaperone peptide

Question 6

during its transport to the cell surface, CD74 is
proteolytically degraded into a smaller peptide sequence called ____

Answer 6

CLIP

Question 7

what happens when CLIP forms an MHC class II-CLIP complex?

Answer 7

it fuses with the endosome or lysosome containing the processed exogenous antigen peptides

Question 8

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?

Answer 8

HLA-DM

Question 9

what are the peptides called when they are bound to MHC class II molecules?

Answer 9

immunodominant

Question 10

what are the two pathways of exocytosis?

Answer 10

constitutively secretory pathway and the regulated secretory pathway

Question 11

describe the constitutively secretory pathway

Answer 11

vesicles continuously traffic both membrane bound (MHC molecules) and secretory proteins to the cell membrane surface for release

Question 12

describe the vesicles of regulated secretory pathway

Answer 12

contain secretory proteins, but transport vesicles retained in the cytoplasm and are only released when they receive an appropriate signal (neurotransmitter, hormones)

Question 13

what are endogenous antigens?

Answer 13

synthesized in cell

Question 14

what are the most common sources of endogenous antigens?

Answer 14

viruses, select bacteria and parasites

Question 15

what is the function of proteasomes?

Answer 15

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

Question 16

what are defective proteins tagged with that guides the protein to the proteasome for digestion?

Answer 16

ubiquitin

Question 17

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

Answer 17

proteasome

Question 18

following digestion through a proteasome, what are small peptides tagged with to be trafficked to the ER?

Answer 18

transport peptide (TP)

Question 19

true or false: Since all nucleated cells can express MHC class I molecules, virtually any nucleated cell can process and present endogenous antigens

Answer 19

true

Question 20

nature has created a pretty savvy mechanism to root out infected or neoplastic cells for target by _________________

Answer 20

CD8+ cytotoxic T cell

Question 21

what is the ultimate APC that can take up exogenous proteins from dying cells or viral-infected cells and process it?

Answer 21

dendrites

Question 22

Cross-presentation of endogenous antigen by MHC class II molecules has been suggested to
occur during what cell survival phase?

Answer 22

autophagy

Question 23

although MHC molecules can present
self-peptides, there are a minimal number of autoreactive T cells present as during central
tolerance, why is this?

Answer 23

these autoreactive cells are induced to die via apoptosis

Question 24

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?

Answer 24

APCs

Question 25

what is an adjuvant?

Answer 25

non specific immune signal enhancer to stabilize the structure of an antigen that degrades rapidly and whose peptides are too small for processing

Question 26

how can an antigen illicit poor immune response besides degrading too rapidly?

Answer 26

they are poor degraders (i.e. metals) and or express few antigen epitopes (i.e. plastic polymers)

Question 27

what do superantigens (SAGs) bypass?

Answer 27

bypass the classic TCR-peptide-MHC-
complex to non-specifically activate multiple CD4+ T cells (pan T cell activation)

Question 28

what are SAGs and what are they produced by?

Answer 28

exotoxins produced by pathogenic bacteria (i.e.
Staphylococcal enterotoxin (SE), food poisoning, toxic shock syndrome)

Question 29

superantigens __________ link the MHC class II molecule with the Vβ TCR chain region on the CD4+ T cell

Answer 29

externally

Question 30

what makes SAGs so dangerous to the host?

Answer 30

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

Question 31

what is located in the cell walls that are an effective barrier to host immune defense and can facilitate entry into cells?

Answer 31

lipids and glycolipids

Question 32

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 ___

Answer 32

CD1

Question 33

how are lipid components continuously transported to the surface?

Answer 33

constitutive secretory pathway

Question 34

why does the CD1 have a deep binding groove?

Answer 34

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

Question 35

where are γ δ T cells found?

Answer 35

minute quantities in the blood but localized in
higher concentrations in select tissues of the body (i.e. gut mucosa).

Question 36

true or false: γ δ T cells are trafficked through the thymus

Answer 36

false

Question 37

how do γ δ T cells have a role in autoimmune diseases?

Answer 37

assisting autoantibody production

Question 38

in the class I region, what are the genes that that code for MHC molecules that don’t present antigen?

Answer 38

HLA-E, HLA-F and HLA- G as well as MICA and
MICB

Question 39

in the class II region, what are the genes that that code for MHC molecules that don’t present antigen and why?

Answer 39

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

Question 40

what does class III region code for?

Answer 40

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

Question 40

what does class III region code for?

Answer 40

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

Question 41

what is codominant expression?

Answer 41

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.

Question 42

what is coordinate regulation?

Answer 42

he co-expression of these 2 classes of MHC can be enhanced at the same time, via external signals (IFNγ)