Dendritic Cells and Antigen Processing (9)

ONLY ___ can activate naïve T cells.

DCs

Three Major APCs ____: special APCs that are especially important in activating a naïve T cell and triggering a primary response

Dendritic cells

Three major APCs are: ...

Dendritic cells (DCs) Macrophages B-cells

* List three professional antigen presenting cells and give brief description of how/when they present antigen

Dendritic cells (DCs) Macrophages B-cells 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).

Can retain antigen for many weeks. ____ do not process antigens. Their primary function is to present antigen to B-cells. (Always in the B cell area of the lymph bind to Ag/ AB complex on there dendrite Break off from dendrites & present to B cells)

FDCs

B-cells as APCs Once activated by T-helper cells, B-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. Thus, B-cells play much more significant role as APCs in the ____ immune response than in the ___ response.

secondary primary

When DCs stimulate T-helper cells, they provide three signals:

First signal: T cell antigen receptors bind antigen fragments attached to MHC molecules. Second signal: Co-stimulatory molecules like CD40 and CD80/86. Third signal: Provided by cytokine secreted by DCs in response to microbial stimulus.

* Differentiate between follicular dendritic cells and dendritic cells (their origin, antigen presentation, and locations).

Follicular Dendritic Cells in the B cell area where dendritic cells in the T cell area Follicular Dendritic Cells have to give Ag to B cells where Dendritic cells can present to T cells Capture Ag, B cells don't need processed Ag T cells do need processed Ag

* Explain the differences between immature and mature dendritic cells

Immature ( in the tissue) - The point of it being in tissue is it is a sentinel cell constant sampling the environment to see if there is anything foreign there - Ag uptake & processing -Low surface MHC 2 -High intracellular MHC2 -High FcR -Low CD40,80,86 -Low IL-12 ( the job of IL-12 is to tell T cell which way to go in immue response ) Mature Dendritic Cells ( in the lymphoid organ) - Ag presentation -High surface MHC 2 -Low intracellular MHC2 -Low FcR (Low FcR why is because it doesn't care about binding to the pathogen AB complex) -High CD40,80,86 -High IL-12 -DC sign

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). - MHC are inside the cell

Migration of Activated DCs During the journey, activated DCs upregulate their expression of MHC II molecules and of the co-stimulatory molecule B7. This leads to ...

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.

Exogenous = ...

something that has come from outside - They take up a pathogen that has come from outside as opposed to some inside I.e viral infection

Dendritic Cells (DCs) Major functions:

Serve as sentinel cells - activate innate defenses Process exogenous antigens - initiate adaptive immune system (Exogenous = something that has come from outside) Regulate adaptive immunity (Tells T cells to go into a direction of immune response ( TH1 or TH2 T cell))

The point of it being in tissue is it is a sentinel cell constant sampling the environment to see if there is anything foreign there Low IL-12 when immature, the job of IL-12 is to ...

tell T cell which way to go in immune response (T cells which direction to go TH1 or TH2)

DCs are present primarily in ... Many arms to have many receptors molecules - Capture pathogen, process it & present it to T cells why it has so many arms

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

*Define Langerhans cell

These are present in the skin along with dendric cells When they mature & encounters Ag they will go to the lymph node Long arms to capture Ag

MHC class I Pathway

Virus infects the cell Our cells have a mechanism to sample what is produced in the cell to make sure all parts are normal Every cell add a molecule to every any protien made in the cell, chop it up Load MHC & present on the surface & let T cells make sure to check it to see if it is bad or not bad T cells will scan to make sure there is no foreign peptide is self leave it on Make sure that our body is not taken over If it is self Ag they will leave it alone Present endogenous Will recognize & kill that cell by ctotoxic T cell

DCs process once it gets an Ag then what happens

When dendritic encounter a pathogen, chop it up & present it on MHC molecules they go to draining lymph nodes & there are T cells areas to go to present their Ag Dendritic cells make a cytokin called CCL22 - This tells T cells that this dendrite cell has foreign peptides on it so see if it has your Ag on it Present Ag on its MHC molecule but T cell are not there so needs to go to the lymphnode where there is a high amount of T cells and a higher chance of finding the right T cell -All T cells scan to see of that MHC has its Ag

Macrophages are NOT efficient antigen presenters. In resting stage, they are not good APCs because ... However, when activated by cytokines, such as INFγ, their expression of MHC II and co-stimulatory molecules are up-regulated, and they can function as APC.

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

FDC looks like an octopus with a large number of tentacles! The "tentacles" are beaded dendrites. The 'beads' are ...

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

Only ____ can activate naïve T ( mature T cells that have not see their Ag yet) cells and trigger a primary immune response.

dendritic cells - macrophages & B cells cannot activate naïve T cells

B-cells as APCs 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.

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

do not migrate are located in lymphoid follicles (B-cell area) lack MHC II molecules on their surface carry many complement and Fc receptors

Job of a _____ Sits in the lymph nodes in B cell area & holds the Ag until B cell comes & responds

follicular DC

Follicular Dendritic Cells The immune complexes form spherical bodies on the dendrites called __ The _____ break off from the dendrites and subsequently attach to B-cells.

iccosomes

The ____ 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.

iccosomes

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. They only move to the lymph node when an ...

infection in underway, stimulated by inflammatory cytokine TNF-⍺.

In the epithelium, DCs are constantly taking in extracellular fluid by a process called ____ to sample for signs of pathogens and their products.

macropinocytosis

MHC____ molecules are present on all APC MHC ____ are presented on all nucleated cells including APC because viruses can infect all cells

2 1 APC have both MHC 1 & 2

When the activated DCs arrive in the lymph node, TH cells scan the large array to 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 ____ T-cells.

3000

APCs are attracted by ...

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

____ immunity is triggered by capturing and presenting of foreign materials to cells that can recognize it. This is done by Antigen-Processing Cells, also known as Antigen-Presenting Cells (APCs).

Adaptive

MHC class II Pathway

Ag presenting cells present process Ag on T cells APC takes up Ag breaks it into small peptides, becomes phagosomes then fuses with lysosome = Phagosome then chop off into simple peptides, MHC is produced in ER Peptide loaded onto MHC & transported MHC2 molecules in this pathway This is how an Ag is taken up, broken down, & loaded onto the MHC moleucle

Origin of Dendritic Cells

All 4 come from bone marrow 2 linages Lymphoid precursor (DC2) & myloid precursor (DC1) DC2 -When activated produce Interferon Alpha & Beta ( create antiviral environment) (innate part)

T cell cannot recognize Ag unless it is ...

processed by Ag presenting cells catcher, to chop up the Ag & present it on there surface MHC receptors to present it to T cells - T cell will not load an Ag unless processed and on MHC

Three Major APCs _____: Present antigen to memory TH cells - T helper cells

B cells & Macrophages