Antigen-Presenting Cells

Published on 09/02/2015 by admin

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Last modified 09/02/2015

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Antigen-Presenting Cells

Learning Objectives

• Differentiate between professional and amateur antigen-presenting cells

• Compare and contrast monocytes and macrophages

• Recognize dendritic cell subpopulations

• Compare and contrast the roles of follicular dendritic cells and interdigitating dendritic cells in antigen presentation

• Explain the roles of plasmacytoid dendritic cells in innate immunity and adaptive immunity

• Recognize the differences between a phagosome and an endosome

• Explain the roles of the invariant chain protein in antigen presentation

• Define class II-associated invariant chain peptide (CLIP)

• Recognize the biological roles of HLA-DM and HLA-DO in antigen presentation

• Identify the differences between phagocytosis and receptor-mediated endocytosis

• Discuss the concept of dendritic cell cross-priming and its usefulness in developing cancer vaccines

Key Terms

Class II-associated invariant chain peptide (CLIP)

Cross-priming

Dendritic cell

Endosome

Follicular dendritic cell

Iccosomes

Interstitial dendritic cell

Invariant chain

Langerhans cell

Macrophage

Monocyte

Phagosome

Plasmacytoid dendritic cell

Receptor-mediated endocytosis

Introduction

The previous chapter discussed molecules that present antigens to T cells. Prior to loading class I and II molecules with antigens, large-molecular-weight proteins must be degraded to a length of 8 to 30 amino acids. This chapter discusses the cells involved in antigen recognition and the processing of exogenous antigens. The processing of endogenous antigens is discussed later in Chapter 18.

To generate the small peptides, inhaled, ingested, or injected antigens are internalized by specialized antigen-presenting cells (APCs) and processed in an endocytic pathway.

APCs can be divided into “professional” and “amateur” subsets. Professional APCs such as monocytes, macrophages, dendritic cells, and B cells are fully committed to antigen presentation as an integral part of their function in the generation of the immune response. Other cells such as endothelial cells, fibroblasts, glial cells, pancreatic β- cells, keratinocytes, and thyroid cells present antigens only under select conditions. These cells are considered “amateur” APCs.

Professional Antigen-Presenting Cells

Monocytes and Macrophages

Monocytes and macrophages are responsible for the digestion of foreign material and for the presentation of antigenic epitopes to immunocompetent cells. Monocytes circulate in the blood, whereas macrophages are found in most tissues, for example, the brain (microglia), bone (osteoclasts), and connective tissue (histiocytes). Kupffer cells in the liver are the largest concentration of macrophages in the body.

Macrophages participate in both innate and adaptive immune responses. As part of innate immunity, macrophages are activated by antigens that are bound to PAMP, Toll-like, scavenger, and mannose receptors. In an adaptive response, antigens are recognized using receptors for intermediary molecules, such as antibody and complement fragments.

Dendritic Cells

In 1973, Steinman described a rare peripheral blood cell with membrane dendrites similar to a neuron. Other studies demonstrated that the dendritic cell (DC) is a “professional” antigen-producing cell present in lymphoid and nonlymphoid tissues. Dendritic cell precursors arise in bone marrow from committed CD34+ stem cells; differentiate into immature myeloid, monocytic, and lymphoid DCs; and are seeded into blood. Because of heterogeneity in cell surface markers, populations of DCs are difficult to identify. However, a putative hematopoietic differentiation pathway for DCs is shown in Figure 5-1.

Several DC subsets localize in tissues or circulate in peripheral blood. Two populations of dendritic cells are derived from a myeloid stem cell: (1) One population migrates to the lymph node where it becomes follicular dendritic cells. (2) A second population is found in nonlymphoid tissue and is referred to as interstitial dendritic cells. Lymphoid or plasmacytoid dendritic cells localize in the T cell compartment within the lymph node. Monocyte precursors may remain in peripheral blood as monocytic dendritic cells, although this concept is still being debated.

Dendritic cells are uniquely suited for antigen presentation. High numbers are concentrated at likely sites of microbial entry into the body (e.g., intestine and respiratory tract). Most DCs can efficiently capture and process antigen for presentation to T cells. Moreover, they are mobile and can migrate through tissue or stimulate immune responses in the regional lymph nodes.

Follicular Dendritic Cells

Follicular dendritic cells (FDCs) are found in the lymph node germinal follicles (Figure 5-2) and have several different functions, including activation of B cells and maintenance of immunologic memory.

Unlike other DCs, FDCs do not process antigen for presentation to T cells. Rather, they stimulate a CD4Th2 response and maintain memory by a unique mechanism. Using a repertoire of receptors, FDCs bind processed and unprocessed antigens onto beaded, three-dimensional structures called iccosomes (Figure 5-3).

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Figure 5-3

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