Dendritic Cells (DCs) and Antigen Processing

APCs

Antigen-Processing Cells

Antigen-Processing Cells (APCs) are also known as

Antigen Presenting Cells (APCs)

Adaptive immunity is triggered by

capturing and presenting of foreign materials to cells that can recognize it this is done by APCs

Three major APCs are:

1. Dendritic cells (DCs)

2. Macrophages

3. B-cells

APCs are attracted by

microbial products and tissue damage and are activated by the triggers of inflammation

Dendritic cells and macrophages are also

sentinel cells, so the antigen processing can be rapidly initiated as body is responding to the microbial insult.

APCs capture

foreign microbes or their products and process large proteins by breaking them into peptides and presenting on their surfaces attached to specialized antigen-presenting structures, called Major Histocompatibility Complex (MHCs)

ONLY dendritic cells

can activate naïve T cells and trigger a primary immune response.

Dendritic cells

special APCs that are especially important in 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 present primarily

in the epithelial tissues (skin, mucosa) and in lymphoid organs (lymph nodes, spleen, thymus).

Major functions of DCs

1. Serve as sentinel cells - activate innate defenses

2. Process exogenous antigens - initiate adaptive immune system

3. Regulate adaptive immunity

DCs are __ times more efficient APCs

100

DCs can take up:

dead microorganisms, soluble antigens, antigen released by dead cells, etc.

Immature dendritic cell

• Tissues

• Antigen uptake/ processing

Mature Dendritic cells

• Lymphoid organs

• Antigen presentation

FDCs

Follicular Dendritic Cells

Follicular dendritic cells (FDCs) are different from other DCs in that they:

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

FDCs can retain

antigen for many weeks

FDCs do not

process antigens.

Primary function of FDCs is to

present antigen to B-cells

FDC looks like

an octopus with a large number of tentacles! The “tentacles” are beaded dendrites.

Iccosomes

Immune complexes form spherical bodies on the dendrites

Beads on FDC structure

are antigen:antibody complexes that have attached to the dendrites via complement and Fc receptors

Iccosomes break off

from the dendrites and subsequently attach to B-cells.

Iccosomes are ingested

by activated B-cells with BCRs specific for the antigen. The antigen is processed, and the B-cell presents the antigen on MHC II molecules to activated T-helper (TH) cells.

macropinocytosis

Process by which DCs in the epithelium are constantly taking in extracellular fluid to sample for signs of pathogens and their prodcust

DCs pickup antigens

from site of infection and take them to an environment that is full of immune cells.

The activated DCs

stop phagocytosis, move into the interstitial space, and are carried by lymph flow to the nearest lymph node

activated DCs upregulate

their expression of MHC II molecules and of the co-stimulatory molecule B7.

Phagolysosome

containing digested antigens will fuse with endosomes containing MHC II molecules.

Peptides

are loaded on to the MHC II molecules and eventually reach the cell surface where the loaded peptides can be presented to T-cells

When the activated DCs arrive in the lymph node,

TH cells scan the large array of loaded peptides for their cognate antigen.

Activated DCs in lymph nodes express

100 times more MHC II molecules than any other APC, and one activated DC can activate up to 3000 T cells

When DCs stimulate T-helper cells,

they provide three signals

1st signal

T cell antigen receptors bind antigen fragments attached to MHC molecules.

2nd signal

Co-stimulatory molecules like CD40 and CD80/86.

3rd signal

Provided by cytokine secreted by DCs in response to microbial stimulus

Macrophages are __ efficient antigen presenters.

NOT

In resting stage, Macrophages are

not good APCs because they do not express adequate levels of MHC II and/or co-stimulatory molecules

When macrophages are activated by cytokines such as INFγ,

their expression of MHC II and co-stimulatory molecules are up-regulated, and they can function as APC

Naïve B-cells are

not good antigen presenters because they do not express the co-stimulatory B7 molecule needed for T-cell activation and also express low levels of MHC II molecules.

Naïve B-cells activated by T-helper cells

become efficient APCs

Activated B-cells upregulate

the expression of MHC II and of co-stimulatory B7 molecules, and become a very potent activator of T-helper cells

B-cells play much more significant role as APCs

in the secondary immune response than in the primary response