L9 - Dendritic Cells + Antigen Processing

How is adaptive immunity triggered?

The capturing and presenting of foreign materials

3 Major APCs

1. Dendritic Cells

2. Macrophages

3. B Cells

When are APCs attracted/activated?

Attracted to… microbial products + tissue damage

Activated by… inflammation triggers

MHCs

Major Histocompatibility Complexes

Antigen-presenting receptors → APCs capture foreign microbes, break them up and present them on their surfaces (MHCs)

MHC act as the “spoon” that presents the antigen (peptide) to the T cells

Dendritic Cells

An APC that presents antigen to a naive T cell (has never seen its self-antigen before)

• Essential in intiating primary immune response

B Cells

APC → presents antigen to memory T_H cell

Macrophages

APC → present antigen to memory T_H cell

What are T_H cells?

T Helper cells → activate other immune cells

Where are DCs typically present?

Epithelial tissues and lymphoid organs

Why do dendritic cells have adhesion molecules on its dendrites?

Adhesion molecules (ICAM, B7, LFA etc.) allows for prolonged interaction with T cells → makes it the only one that can activate naive T cells and trigger a primary immune response

What are the major functions of the dendritic cells?

1. Sentinel cells → activate innate defense

2. APCs → process antigens and initiate adaptive immune system

3. Regulates adaptive immunity

• Tells cells what kind of pathogen they’re dealing with

Which are more efficient: APCs or DCs?

DCs 100x more efficient → has dendrites with MHCs that can harbor many different antigens for T cells to find

Immature dendritic cells

• Found: Skin/mucosa

• Antigen uptake (sentinel cells)

• Lots of FcR → “receptor for antibody legs” → can take in opsonized (tagged) pathogens

• No processing (low surface MHC)

• Low IL-12

Mature Dendritic cell

• Found: Lymphoid Organs

• Antigen Presentation

• High surface MHC → processing

• Low FcR

What is Fc and FcR?

• Fc: “legs” of antigen

• FcR: receptor for antigen “legs”

Langerhans Cell

Dendritic cells present in skin → first line of defense

Process antigens and migrate to lymph nodes to activate immune responses

Follicular DCs

• Don’t migrate!

• Located: lymphoid follicles

• Lack MHC II on surface

• Complement and Fc receptors → attaches to antigen:antibody complexes

• Do NOT process antigens → keeps it for weeks

• Function: present antigens to B cells

• Beaded dendrites (which are antigen-antibody complexes)

Iccosomes

1. Antigen packages on follicular dendrites → break off and attach to B cells

2. B cells ingest iccosomes (if they have right BCR)

3. Antigen processed

4. B cell presents antigen on MHC II to T_H cell

Macropinocytosis

DCs take in ECF to test for signs of pathogens

How to dendritic cells respond to infection?

1. Sense pathogen via macropinocytosis → activated

2. DCs stop phagocytosis → go to interstitial space → go to lymph node

3. Only go to lymph node when infection present → stimulated by TNF-a

How are T cells deactivated?

No pathogens → will bind to own self-antigens → get eliminated

DC migration

1. Activated DC upregulate MHC II and co-stimulatory molecule B7

2. Phagolysosome fuses with endosomes w/ MHC II molecules

3. Peptides loaded onto MHC II → go to cell surface

4. Present to T-cells in lymph nodes

What are the 3 signals DCs provide when they stimulate T helper cells?

1. T-cell antigen receptors bind antigen fragments on MHC

2. Co-stimulatory molecules like CD40 and CD80/86

3. Cytokine secreted by DCs in response to pathogen

Are macrophages good APCs?

No → don’t express enough MHC II or co-stimulatory molecules

• Can function as APC if INFy cytokine activates them and allows them to express more

Are B cells good APCs?

No → naive B cells don’t express enough co-stimulatory B7 molecules or MHC for T cell activation

• Can become better if activated by T_H

• Play a bigger role in secondary immune response