Lectures 14 & 15: Antigen Uptake, Processing & Presentation

Question 1

what is the infectious non-self model that was developed in 1989?

Answer 1

APC have self-non-self discrimination system (the ability to detect foreign is no longer limited to T cells)

Question 2

APCs bridge the ____ and ___ immune systems to help instruct ___ cells

Answer 2

innate and adaptive; T cells

Question 3

do APC typically requires activation to enable antigen presentation?

Answer 3

yes

Question 4

what are PAMPs? What detects them?

Answer 4

pathogen-associated molecular patterns and are detected by TLReceptors

Question 5

what 2 things do the APC activation of DC, macrophages and B cells have in common?

Answer 5

1. acquisition/enhancement of Class 2 MHC

2. CD80/86

Question 6

does MHC restriction impact Tcell activation?

Answer 6

yes

Question 7

t/f T cells ONLY recognize antigen that is presented by a self-MHC molecule

Answer 7

t

Question 8

antigen recognition by CD4+ T cells is restricted by class __ MHC

Answer 8

2

Question 9

t/f T helper cells can only become activated by cells with self class 2 MHC

Answer 9

t

Question 10

CD8+ cytotoxic T cells can only recognize cells with __ class MHC

Answer 10

1

Question 11

in order for cytotoxic T cells to kill a target cell, what other cell must have the same antigen in its class 1 MHC?

Answer 11

APC and target cells must both have same antigen in their self MHC1

Question 12

give 2 examples of cells that have few to no MHC1

Answer 12

fibroblasts and liver cells have few and some neurons have none

Question 13

what is the function of CD80/86 in APC activation?

Answer 13

they are upregulated to act as costimulatory activity with the MHC

Question 14

what is the co-stimulatory molecule on Naive CD4+ T cells?

Answer 14

CD28

Question 15

what has to happen to antigens in order for them to be immunogenic?

Answer 15

need to be processed (degraded); proteins are NOT presented intact

Question 16

when does fixing need to occur in order for cells to be able to present antigen?

Answer 16

Can happen:

1. after the cell has the Ag
2. fixing and then exposing to antigen

Question 17

what is the effect of fixing APC?

Answer 17

freezes the proteins in native conformation so they cannot be processed and they will fail to be presented

Question 18

Does antigen processing and presentation differ between MHC1&2 loading? What is the significance?

Answer 18

1. yes

2. allows the immune system to deal with extracellular and intracellular pathogens

Question 19

The endogenous pathway processes ___ antigens and presents them to class __MHC

Answer 19

intracellular; 1

Question 20

the exogenous pathway processes ___ antigens and presents them to class __ mHC

Answer 20

extracellular; 2

Question 21

in the endogenous pathway, what is the function of Ubiquitin?

Answer 21

binds to cytoplasmic proteins ex: viral or tumor antigens) and targets them for proteolysis by proteosomes (the “intestines of cells’)

Question 22

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

Answer 22

constitutive proteasome; immunoproteasome; 1

Question 23

what is the function of TAP in the endogenous pathway?

Answer 23

Transporter associated with antigen processing; carries peptides across the RER for class 1 loading

Question 24

does TAP transport require energy?

Answer 24

yes

Question 25

TAP has a high affinity for ___ peptides and favours what types of peptides?

Answer 25

high affinity for peptides with 8-13 AA and favours those with with complimentary AA positions to their AA anchor residues

Question 26

how can enzymes in the RER of the endogenous pathway help peptides fit into MHC1?

Answer 26

by trimming longer peptides so they can fit in the groove

Question 27

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

Answer 27

chaperone

Question 28

in the exogenous pathway, what is the method macrophages, DC and B cells use to take up antigen?

Answer 28

macrophages: phagocytosis and/or endocytosis
DC: phagocytosis and/or endocytosis
B cells: endocytosis

Question 29

in the exogenous pathway, phagocytosis of Ag by APC causes the Ag to go through a series of ____. What is the role of this?

Answer 29

protease-containing vessicles, each with a lower pH than the last; this degrades the peptides into peptide fragments that can be loaded into MHC2

Question 30

in the exogenous pathway, peptide fragments meet up with class __MHC that are arriving from vessicles from the ___

Answer 30

2; RER

Question 31

in the exogenous pathway, where are Class 2 MHC synthesized?

Answer 31

on polysomes within the RER

Question 32

when class 2 MHC are in the RER, they associate with ____

Answer 32

the invariant chain (aka CD74)

Question 33

what are the functions of the invariant chain in the exogenous pathway? (2)

Answer 33

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

Question 34

the invariant chain is degraded in the ___ compartment, leaving behind a fragment called the ___ in the MCH groove to prevent premature peptide binding

Answer 34

endocytic; CLIP

Question 35

what is the CLIP?

Answer 35

class 2 associated invariant chain peptide

Question 36

the peptide binding cleft of MHC2 has an open conformation to allow the CLIP to be replaced by the ___

Answer 36

antigenic peptide

Question 37

in humans, the exchange of the CLIP for antigenic peptide is catalysed by a ____ molecule

Answer 37

nonclassical class 2 MHC (HLA-DM)

Question 38

____ (also a nonclassical class 2 MHC), modulates the activity of HLA-DM and plays a role in presentation of self-peptides and self-tolerance

Answer 38

HLA-DO

Question 39

when class 2 MHC–peptide complex is transported to the plasma membrane, the pH is ___, which causes it to assume a ___ form

Answer 39

neutral; stable

Question 40

dendritic cells have the ability to present ___ antigen to CD8+ and CTL (cross presentation)

Answer 40

exogenous

Question 41

dendritic cells activate CD4+ T cells through class __ MHC, which then license the DC by activated cells using _____, enabling ____ of exogenous Ag

Answer 41

2, CD40L; cross presentation

Question 42

what explains how dendritic cells are able to activate CTL even when they are not infected by a virus?

Answer 42

cross-presentation

Question 43

Is the processing and peptide loading of class 1 and 2 MHC the same?

Answer 43

no; they have different processes

Question 44

exogenous nonpeptide antigens such as lipids and glycolipids are presented by ___ molecules

Answer 44

CD1

Question 45

CD1 molecules structurally resemble ___ and associate with ____

Answer 45

class 1 MHC alpha chain; B2 microglobulin and exogenous antigen

Question 46

CD1 molecules associate with exogenous antigens in the ___ compartment

Answer 46

endosomal

Question 47

CD1 is inducible and expressed by multiple ____ cell type

Answer 47

APC

Question 48

what types of cells recognize CD1 presentation of lipids and glycolipids?

Answer 48

NKT cells and certain T cells