Lecture 9 - Dendritic Cells and Antigen Processing Flashcards
How is adaptive immunity triggered?
By capturing and presenting of foreign materials to cells that can recognize it
What cells trigger adaptive immuntiy
antigen presenting cells
3 major antigen presenting cells
- Dendritic cells
- Macrophages
- B-cells
What are APCs attracted by
microbial products and tissue damage and
are activated by the triggers of inflammation
What is an advantage of DCs and macrophages also being sentinel cells
antigen processing can be rapidly initiated as body is responding to the microbial insult
How do APCs capture foreign microbes and process them
process large proteins by breaking them into peptides and presenting on their surfaces attached to specialized antigen-presenting structures, called Major Histocompatibility Complex (MHCs)
What are the only cells that can trigger naive T cells and what response do they trigger
dendritic cells, primary immune response
Dendritic cells
special APCs that are especially important in activating a naïve T cell and triggering a primary response
B cells
Present antigen to memory TH cells
Macrophages
Present antigen to memory TH cells
DCs are primarily present in
epithelial tissues (skin, mucosa) and in lymphoid organs (lymph nodes, spleen, thymus
Major functions of dendritic cells
- Serve as sentinel cells - activate innate defenses
- Process exogenous antigens - initiate adaptive immune system
- Regulate adaptive immunity
How much more efficiient are DCs as APCs
100x
What can DCs take up
dead microorganisms, soluble antigens, antigen
released by dead cells, etc.
How are follicular dendritic cells different from other DCs
I. do not migrate
II. are located in lymphoid follicles (B-cell area)
III. lack MHC II molecules on their surface
IV. carry many complement and Fc receptors
How long can FDCs retain antigen
many weeks
T/F FDCs process antigens
FALSE
Primary function of FDCs
present antigen to B cells
What FDC look like
octopus with a large number of tentacles! The “tentacles” are beaded dendrites.
Beads on FDCs are …
antigen:antibody complexes that have attached to the dendrites via complement and Fc receptors
Immune complexes on FDCs form
spherical bodies called iccosomes
What happens when iccosomes break off from dendrites
attach to B cells
What happens after iccosomes attach to B cells
ingested by activated B cells with BCRs specific for antigen, antigen processed, B cell presents antigen on MHC II molecules to activated TH cell
Macropinocytosis
DCs in epithelium take in extracellular fluid to sample for signs of pathogens and their products
What do DCs do after they pickup antigens from site of infection
take them to environment full of immune cells
What happens after activated DCs stop phagocytosis
move into the interstitial space, and are carried by lymph flow to the nearest lymph node
When do DCs move to lymph node
when infection is underway, stimulated by inflammatory cytokine TNF-a
During migration of activated DCs, expression of ____ and ____ are upregulated
MHC II and B7
_____ containing digested antigens will fuse with endosomes containing _______ molecules
Phagolysosomes; MHC II
___ are loaded on to the MHC II molecules and eventually reach the cell surface where they can be presented to ______________
Peptides; T cells
When the activated DCs arrive in the lymph node, _____ cells scan the large array of loaded peptides for their _____.
TH, cognate antigen
Activated DCs in lymph nodes express ____ times more MHC II molecules than any other APC
100
One activated DC can activate up to ____ T cells
3000
When DCs stimulate T helper cells, they provide three signals:
- T cell antigen receptors bind antigen fragments attached to MHC molecules.
- Co-stimulatory molecules like CD40 and CD80/86.
- Provided by cytokine secreted by DCs in response to microbial stimulus
What are NOT efficient APCs
macrophages
Why are macrophages not good APCs in the resting stage
do not express adequate levels of MHC II and/or co-stimulatory molecules
When can macrophages function as APCs
when activated by cytokines, such as INFγ, their expression of MHC II and co-stimulatory molecules are up-regulated
Why are naive B cells not good APCs
do not express the co-stimulatory B7 molecule needed for T-cell activation and also express low levels of MHC II molecules
When do B cells become efficient APCs
once activated by T helper cells
Activated B cells upregulate ___ and ___, and become potent activators of ____
MHC II; co-stimulatory B7; T helper cells
What immune response do B cells play a more significant role as APCs
SECONDARY
What are the only cells that can effectively stimulate naive T cells
DC
Dendritic cells express a high level of what antigen receptors on their surface
MHC II
How do DCs help T cells recognize antigens
DC ingest, fragment antigens, present them to surface MHC, recognized by TH cells