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Lecture 11 - Antigens & APC 2
Antigens & APC 2
48
Immunology
Undergraduate 4
04/04/2015

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Term
What are the 3 main types of true APCs?
Definition
DCs
macrophages
B cells
Term
Which APCs are most efficient? Why? (2)
Definition
Dendritic Cells

-lots of adhesion & co-stimulatory molecules on surface
-no antimicrobial enzymes or ROS = can load more undegraded antigen onto MHC molecules
Term
What makes B cells unique in terms of their APC ability?
Definition
have BCRs (antigen receptors)
Term
What do BCRs do?
Definition
allows B cells to respond to specific antigens
Term
How do B cells handle T-dependent antigens?
Definition
-rapidly process & present to antigen-specific T cell
Term
How do B cells handle T-independent antigens?
Definition
B cells are immediately activated, differentiate into plasma cells which secrete antibody
Term
Are B cells more important during a primary or secondary immune response?
Definition
secondary (due to development of memory B cells, Ig class switching, affinity maturation)
Term
Do DCs have a role in regulating the immune response?
Definition
yes
Term
What are the precursors for DCs?
Definition
lymphoid cells
myeloid precursor cells
Term
Myeloid precursor cells can differentiate into ________ , _________ , or _______ depending on ________
Definition
myeloid DCs (MDC)
FDC
Langerhangs cells (LC)

cytokines present in the area & interaction with surrounding cells
Term
What do FDCs do? (2)
Definition
-secrete BAFF important for memory B cell survival
-Ig class switching within GCs of 2ndary lymphoid tissue
Term
MDCs are able to induce differentiation of regulatory T cells in the presence of _____ and ____
Definition
IL-10 and TGF-beta
Term
Which myeloid sub-population is important for maintaining tolerance to self-antigens & commensal microbes in peripheral tissue?
Definition
myeloid DCs (MDCs)
Term
Which myeloid sub-population traps epidermal antigens?
Definition
LCs
Term
Lympoid DC precursors differentiate into _____ and then _____
Definition
plasmacytic cells and then plasmacytoid DCs (PDCs)
Term
What do PDCs in the thymus do?
Definition
present self-antigens to T cells during positive & negative T-cell selection
Term
Where does positive selection of T cells occur? Which cells are selected? Why is this important?
Definition
in the thymic cortex

CD4+CD8+

ensures the surviving T cells can recognize MHC class I or class II molecules
Term
What happens after CD4+CD8+ T cells have been selected?
Definition
differentiate into CD4+ OR CD8+

negative selection in thymic medulla to remove T cells which bind strongly to self-peptide
Term
Where does negative selection take place?
Definition
thymic medulla
Term
What happens to T cells which don't succeed in positive/negative selection?
Definition
apoptosis
Term
Peripheral PDCs are an important source of _____ and _____
Definition
IFN-alpha and IFN-beta
Term
Peripheral PDCs are involved in activating _____ cells which indicate they are involved in triggering the immune response to a viral infection
Definition
Natural killer
Term
Why are immature DCs not effective in carrying out antigen presentation?
Definition
cell membrane doesn't have the key signaling & adhesion molecules
Term
Immature DCs are very good at.....
Definition
trapping & phagocytising particles & microbes
Term
When do DCs mature?
Definition
as they travel from their resident tissue to secondary lymphoid tissues, drawn by CCL19 and CCL21
Term
Mature DCs express ______ which acts as an adhesion molecule with ______ an naive T-cells
Definition
DC-SIGN

ICAM-3
Term
As DCs mature they secrete _____ which attracts T cells
Definition
CCL22
Term
What are the 3 signals DCs provide to T cells
Definition
1. MHC-restrcted antigen presentation to TCR

2. Co-stimulatory signaling through DC CD40 and CD80/86 to T cell

3. Cytokine or receptor-mediated signaling to drive T cell polarization
Term
DC1 cells secrete _____ which drive(s) Th1 cell differentiation favouring ____
Definition
IL-12

CMIR
Term
DC2 cells secrete _____ which drive(s) Th2 cell differentiation favouring ____
Definition

IL-1, IL-4, IL-6, IL-10

AbMIR

Term
What do pigs and ruminants have instead of IL-4?
Definition
IL-13
Term
DC IL-23 supports differentiation of....
Definition
Th17 cells
Term
What determines DC 1 / 2 differentiation?
Definition
PAMP & DAMP ligands and the cytokine mileau in surrounding tissue
Term
TLR ___, ____, ___ and ___ promote DC1 cell differentiation
Definition
3, 4, 5 and 9
Term
DCs are mucosal surfaces preferentially secrete...
Definition
IL-4 and IL-10
Term
Why are thymic PDCs unable to provide signals 2 & 3 to T cells?
Definition
they are perpetually immature
Term
What is required in order for phagocytic cells to be able to present exogenous antigens to activate Th-cells?
Definition
must express MHC class II
Term
Where are MHC Class II synthesized?
Definition
in the RER
Term
What stabilizes the alpha and beta chains of the MHC while the molecule is being packaged?
Definition
invariant chain
Term
What is a CLIP?
Definition
small peptide fragment remaining after the invariant chain of a lysosome is degraded
Term
What happens when a lysosome molecule phagocytizes a particle? (3)
Definition
-CLIP is displaced by antigenic peptides
-phagolysosome is directed to cell surface
-MHC Class II molecules are expressed on cell mmb
Term
What mediates the exchange of CLIP for an antigenic peptide? What regulates its activity?
Definition
non-classical MHC Class II molecule DM

DM is regulated by DO
Term
What class of MHC is required to process endogenous antigens?
Definition
MHC Class I
Term
Describe the processing that takes place for endogenous antigens
Definition
1. Ubiquitination
2. Processing within proteosome
3. Degradation & recycling of most peptides
3. Remaining peptides transported to ER via TAP1 & TAP2
4. Peptides loaded onto MHC class I
5. MHC class I released from ER, directed to cell surface to interat with Tc cell TCRs
Term
What transporter proteins carry endogenous peptide fragments from the cytoplasm to the ER & load them onto MHC class I?
Definition
TAP1 & TAP2
Term
How are MHC class I molecules assembled?
Definition
1. alpha chain & B2-microglobulin produced & assembled in RER & ER
2. Calnexin associates with alpha chain until it is replaced by B2 microgobulin
3. Celreticulun, tapasin, ERp57 associate in peptide-binding grove to increase stability
Term
What is cross-priming?
Definition
when exogenous viral proteins are not completely degraded in phagoendosome, so end up being processed in proteosome & loaded onto Class I rather than Class II molecules
Term
Are MHC molecule antigen-binding sites specific or non-specific?
Definition
non-specific (degenerate)
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