IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 2. Cells Acting in the Immune Response

ANTIGEN-PRESENTING CELLS

Antigen-presenting Cells (APCs) constitute a heterogeneous population of leukocytes with pronounced immunostimulatory activity. Certain APCs play a central role in inducing the functional activity of Th cells, while others interact with other cells of The Immune System.

APCs are localized predominantly in the Skin, Lymph Nodes, Spleen, epithelial and subepithelial layers of most mucous membranes, and in the Thymus (Fig. 2.29). Langerhans cells from the skin and other stratified squamous epithelia migrate as veiled cells via afferent Lymphatic vessels into the paracortical areas of regional lymph nodes. There, they interact with numerous T cells and become interdigitating cells (IDCs) (Fig. 2.30). This migration provides an efficient mechanism for delivering Antigens from the skin and mucous membranes to lymph node Th cells. These APCs abundantly express MHC Class II Proteins, which are essential for antigen presentation to helper T cells.

Fig. 2.29. Bone Marrow-derived antigen-presenting cells (APCs) are found primarily in lymphoid tissue, skin, and mucous membranes. In the epidermis, they appear as Langerhans cells with characteristic tennis racket-like Birbeck granules in their Cytoplasm. These cells, rich in MHC class II proteins and loaded with processed antigen, migrate via afferent lymphatic vessels (referred to as veiled cells at this Location) to the paracortical (T-dependent) areas of regional lymph nodes. Here, as interdigitating cells, they contact T cells and present antigen to them. Antigen presentation to B cells occurs on follicular dendritic cells (FDCs) in germinal centers within B-Cell follicles. Certain macrophages of the outer cortical area and subcapsular sinus of lymph nodes also act as APCs. In the thymus, APCs are represented by interdigitating (interlacing process) Cells of the medullary zone.

Fig. 2.30. Ultrastructure of an interdigitating dendritic cell (IDC) in the T-dependent area of a rat lymph node. Characteristic features: tight contact with The Plasma Membrane of surrounding T cells, a well-developed endosomal system in the cytoplasm, and an absence of the Birbeck granules typical of cutaneous Langerhans cells. T - T-Cell Nucleus; I - IDC nucleus; M - IDC membrane, x 2000. (Photomicrograph kindly provided by Dr. W. Balfour.)

Follicular dendritic cells (FDCs), which present antigens to B cells, are found in the Primary and secondary follicles of B-cell areas in lymph nodes, spleen, and mucosa-associated lymphoid tissue (MALT). Firmly connected by process desmosomes to form a stable network, they do not migrate from their sites of residence. FDCs do not express MHC class II proteins, but bind antigens via receptors for Complement components (CD21 and CD35) associated in this case with immune complexes (iccosomes). In addition, FDCs express Fc receptors. Recently, another type of APC has been discovered in germinal centers within secondary B-cell follicles—germinal center dendritic cells, which, unlike FDCs, express MHC class II proteins and are capable of migration. Within the germinal center, they interact with T cells.

APCs are present in the thymus, where they function as interdigitating cells, just as in lymph nodes; their concentration is particularly high in the thymic medulla. In this organ, which plays a primary role in T-cell proliferation and maturation, IDCs appear to be responsible for the elimination of T cells reactive against the body's own antigens. This process is termed negative Selection (see Chapters 12 and 14).

Most APCs originate in the bone marrow, although their hematopoietic precursor remains unknown. For example, 100 days after bone marrow transplantation (see Chapter 27), all Langerhans cells in the recipient's skin are of donor origin. Monocytes activated in vitro by granulocyte-macrophage colony-stimulating factor and interleukin-4 lose their phagocytic capacity and transform into APCs, acquiring dendritic cell Morphology and beginning to express MHC class II proteins. FDCs of primary and secondary lymphoid follicles are thought to be of mesenchymal rather than bone marrow origin.

Classical B cells abundantly express MHC class II proteins (especially after activation) and are therefore capable of Processing and presenting specific antigens to activated T cells (see Chapter 11). Some markers of various APC types are summarized in Fig. 2.31.

Fig. 2.31. Langerhans cells (LCs), interdigitating cells (IDCs), germinal center dendritic cells (GCDCs), and B cells abundantly express MHC class II proteins for interaction with CD4⁺ T cells. Some APCs also express CD4, making them potential targets for HUMAN IMMUNODEFICIENCY VIRUS infection (see Chapter 22). Macrophages synthesize too little MHC class II protein to present antigens and thus function mainly as phagocytic cells. Follicular dendritic cells (FDCs) located in primary and secondary follicles do not express MHC class II proteins, but are rich in FcγR, CR1, and CR2, enabling them to bind immune complexes (iccosomes) and present the antigen contained within these complexes to B cells. (NSE - non-specific esterases.)

Non-immune body cells do not normally express MHC class II proteins, but upon induction by cytokines such as IFNγ and TNFα, certain types of somatic cells, such as keratinocytes, thyrocytes, and endothelial cells, are capable of synthesizing MHC class II products and presenting antigens. The induction of this 'inappropriate' expression is likely a component in the Pathogenesis of autoimmune diseases and chronic inflammatory processes.