Antigen-Presenting Cells

Dendritic Cells

Dendritic cells are immune cells that function to process antigens and present them to T cells.

Learning Objectives

Discuss the mechanism of action for dendritic cells

Key Takeaways

Key Points

  • Dendritic cells function as antigen presenting cells.
  • Dendritic cells are present in small quantities in tissues that are in contact with the external environment, mainly the skin (where there is a specialized dendritic cell type called Langerhans cells) and the inner lining of the nose, lungs, stomach and intestines.
  • Once activated, dendritic cells migrate to the lymphoid tissues where they interact with T cells and B cells to initiate and shape the adaptive immune response.

Key Terms

  • lymphoid organs: lymph nodes, spleen, and gut-associated lymphoid tissue where lymphocytes reside.

Dendritic cells are present in lymphoid organs, the epithelia of the skin, the gastrointestinal and respiratory tracts, and in most parenchymal organs. These cells are identified morphologically by their membranous projections that resemble spines. All dendritic cells are thought to arise from bone marrow precursors. Most, called myeloid dendritic cells, are related in lineage to mononuclear phagocytes. Immature dendritic cells (e.g. Langerhans cells of the epidermis) are located in main portals of entry of microbes (skin and gut epithelia). The function of epithelial dendritic cells is to capture microbial protein antigens and to transport the antigens to draining lymph nodes. During their migration to the lymph nodes, the dendritic cells mature to become extremely efficient at presenting antigens and stimulating naive T cells, hence their classification as antigen presenting cells. Mature dendritic cells reside in the T cell zones of the lymph nodes, and in this location they display antigens to T cells. Subsets of dendritic cells can be distinguished by the expression of cell surface markers. Different subpopulations of dendritic cells may stimulate distinct types of T cell effector responses. Some may even inhibit T cell activation.

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Dendritic cell: Dendritic cell characterized by membranous projections that resemble spines.

Dendritic cells are constantly in communication with other cells in the body. This communication can take the form of direct cell-to-cell contact based on the interaction of cell-surface proteins. An example of this includes the interaction of the membrane proteins of the B7 family of the dendritic cell with a CD28 cell surface molecule present on the lymphocyte. However, the cell-cell interaction can also take place at a distance via soluble factors such as cytokines. For example, stimulating dendritic cells in vivo with microbial extracts causes the dendritic cells to rapidly begin producing interleukin 12 (IL-12). IL-12 is a signal that helps differentiate naive CD4 T cells into a helper T cell phenotype. The ultimate consequence is priming and activation of the immune system for attack against the antigens which the dendritic cell presents on its surface.

Macrophages

Phagocytosis is a front-line defense against pathogen attack requiring the concerted action of macrophages.

Learning Objectives

Describe the role of macrophages in the immune system

Key Takeaways

Key Points

  • Macrophages are cells produced by the differentiation of monocytes in tissues.
  • They are specialized phagocytic cells that attack foreign substances and infectious microbes through destruction and ingestion.
  • Macrophages can be identified by specific expression of a number of proteins measured by flow cytometry or immunohistochemistry.

Key Terms

  • phagocyte: A cell of the immune system, such as a neutrophil, macrophage or dendritic cell, that engulfs and destroys viruses, bacteria and waste materials, or in the case of mature dendritic cells; displays antigens from invading pathogens to cells of the lymphoid lineage.
  • interferon-gamma: a cytokine that is critical for innate and adaptive immunity against viral and intracellular bacterial infections.

Macrophages are antigen presenting cells that actively phagocytose large particles. Therefore, they play an important role in presenting antigens derived from phagocytosed infectious organisms such as bacteria and parasites. In the effector phase of cell-mediated immunity, differentiated effector T cells recognize microbial antigens on phagocytes and activate the macrophages to destroy these engulfed microbes. Most macrophages express high levels of interferon-gamma, a mechanism through which antigen presentation and T cell activation is enhanced. Macrophages can be identified by specific expression of a number of proteins including CD14, CD40, CD11b, F4/80(mice)/EMR1(human), lysozyme M, MAC-1/MAC-3 and CD68. They move by the action of amoeboid movement.

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Macrophage: Macrophages are antigen presenting cells that engulf microbes.

Macrophages are not cells exclusive to the immune system; they also play a central function in many other aspects of embryonic development, homeostasis and wound repair. Resident macrophages become adapted to perform particular functions in different organs; so that brain macrophages (microglia) are very different from alveolar macrophages of the lung, Kupffer cells of the liver, or the largest tissue macrophage population, those lining the wall of the gut.

Monocytes are recruited into tissues in response to a very wide range of different stimuli. Where a pathogen is involved, they are commonly preceded by neutrophils, which release a range of toxic agents designed to kill extracellular pathogens. The macrophage then has the task of clearing both the dead pathogens and the dead neutrophils. To enter a tissue, the monocyte in peripheral blood must adhere to the vessel wall, cross the endothelial cell barrier, and then migrate towards the stimulus; a process known as chemotaxis.

The process of recruitment of neutrophils and macrophages involves the resident macrophages which act as sentinels. They respond to local stimuli by producing cytokines that make the endothelial cells more sticky (through the increased expression of cell adhesion molecules such as P-selectin) and so-called chemokines, that promote the directed migration of inflammatory cells. Monocytes may also migrate towards increasing concentrations of molecules produced by microorganisms themselves, by damaged tissues, or by the activation of the complement or clotting cascades which release bioactive peptides such as C5a.