Lecture 7 - Innate Adaptive Bridge

What transition does the "innate-adaptive bridge" refer to, and what cells are required to make it possible?

It refers to the transition between the innate and adaptive immune responses, which is only possible through the action of Antigen-Presenting Cells (APCs).

How is an adaptive immune response initiated once a foreign antigen enters the body?

The antigen must be transferred from its site of entry to lymphoid tissue, a process best mediated by Antigen-Presenting Cells (APCs).

What are the three types of Antigen-Presenting Cells (APCs)?

• Professional APCs

• Non-professional APCs

• Induced APCs

What is the primary role of professional APCs, and which three cell types belong to this group?

Their main role is antigen presentation. They include dendritic cells, macrophages, and B lymphocytes.

What defines non-professional APCs, which cells do they encompass, and can they activate naive T cells?

They are cells that express MHC-1 but not MHC-2, which encompasses most nucleated cells. While they expose infections to the immune system, they cannot normally activate naive T cells or start adaptive immunity on their own.

What are induced APCs, what determines their activation, and where does their antigen presentation take place?

They are phagocytic polymorphonuclear cells that have a limited, cytokine-dependent ability to upregulate MHC-2 and co-stimulatory receptors under specific situations. This is a secondary function that takes place at peripheral sites rather than in secondary lymphoid organs.

What are the most important "professional" APCs that activate a primary adaptive immune response in a naive host?

Dendritic cells and macrophage-derived dendritic cells (DCs).

What defines the "naive host" in which dendritic cells and macrophage-derived DCs trigger a primary adaptive response?

A host who has not previously been exposed to the triggering antigen.

What physical features characterize dendritic cells, and what functional advantage do they provide?

They have multiple elongate cytoplasmic processes called dendrites that extend into the surrounding matrix, providing a large surface area for contact with potential antigens.

How are dendritic cells broadly divided, and from which bone marrow precursors do conventional DCs develop?

They are divided into conventional and non-conventional groups. They arise from macrophage and DC precursors (MDPs) in the bone marrow, which differentiate into common DC precursors before exiting the bone marrow as pre-DCs to mature in tissues.

What are two other names for conventional DCs (cDCs), and what is their primary physical and functional specialty?

Also called classical DCs or myeloid DCs. They are irregularly shaped cells with many cell membrane processes specialized for absorbing antigens for presentation to naive T cells to initiate adaptive immunity.

Where are DCs distributed in the body, what do they do, and what is an example of a specialized DC located at a physical barrier?

They are widely distributed in tissues (such as the intestine, liver, lung, kidney, and dermis) where they capture antigen and migrate to regional lymphoid tissue in order to induce adaptive immune responses, and are prominent at body surfaces. The epidermal Langerhans cell (of macrophage lineage) is a prime example, perfectly located to interact with antigens penetrating the skin barrier.

What is the primary role of immature DCs, and what two processes do they use to sample their environment?

Constant sampling of extracellular fluid and cell debris. They use micropinocytosis (for fluid) and phagocytosis (for particulate material), though they have limited killing potential in the absence of inflammation.

True or False: Immature dendritic cells express only a select few Pattern Recognition Receptors (PRRs).

Dendritic cells express the full repertoire of PRRs to constantly scan for the presence of pathogens and their products.

What triggers dendritic cells (DCs) to undergo maturation and migrate to lymphoid tissues, and what pathway do they use?

Maturation is triggered when they capture a foreign antigen (recognized by PRRs) in the presence of a pro-inflammatory environment. They migrate to lymphoid tissues via the afferent lymphatics.

In preparation for presenting antigens and activating T cells, what do mature dendritic cells downregulate vs. upregulate?

• Downregulate: PRR expression and phagocytic activity.

• Upregulate: MHC-II and co-stimulatory molecules.

What is a "veiled dendritic cell", and where does this morphological transformation occur?

It is a dendritic cell in transit through the lymphatics whose long, cytoplasmic dendrites have been temporarily replaced by broader and shorter cytoplasmic projections known as "veils."

Once a migrating DC reaches a draining lymph node, where does it go, and how does it optimize and initiate interaction with T cells?

It concentrates in the paracortex region, reverts to its dendritic morphology to optimize the contact area, and secretes chemokines to actively attract T cells to the region.

What is an Interdigitating DC (IDC)?

It is the typical mature dendritic cell specialized in presenting antigens to CD4 T cells.

What are plasmacytoid DCs, when are they active, and what is their function?

They are specialized dendritic cells activated in the presence of virally infected cells. They specialize in antigen presentation and activation of CD8 T cells and secrete IFN-alpha and IFN-beta.

are macrophages good antigen presenters?

no. they clean up cell debris mainly

compare the activated and resting states of macrophages

resting: low levels of MHC II and/or co-stimulatory molecules

activated: MHC II and co-stimulatory molecules are up-regulated

can be efficient APCs in the tissues

What is the lineage and origin of Follicular Dendritic Cells (FDCs), and where do they reside?

They are stromal cells (not bone-marrow derived, not myeloid lineage) and are non-migratory, residing in the primary follicles and germinal centers (B-cell areas) of secondary lymphoid organs (e.g., lymph nodes).

What unique capacity do FDCs have in secondary lymphoid organs, and what do they shape as a result?

They can bind and retain native antigens in B-cell follicles for long periods, which crucializes their role in B-cell activation and shapes the B-cell antigenome (the sum of all B-cell antigens).

Unlike conventional dendritic cells, do FDCs perform phagocytosis or express MHC-II?

No. FDCs are non-phagocytic and do not express MHC-II.

What surface receptors do FDCs use to capture immune complexes and foreign material drained from tissues?

They express complement and Fc receptors to bind complexes already coated with complement and/or antibodies.

What are iccosomes, and how are they used by B cells?

They are bead-like structures shed from the surface of FDCs that display captured antigens, which are then taken up by B cells.

How long can antigens persist on the surface of FDCs?

FDCs act as a reservoir where antigens can persist for many months.

How do FDCs work?

these cells express complement and Fc receptors to capture immune complexes and foreign material that have been bound to complement and/or antibodies and were drained from peripheral tissues via the lymphatics.