memory T cells
Innate Lymphoid Cells
Innate lymphoid cells (ILCs) constitute a heterogeneous family of innate immune cells also derived from common lymphoid progenitors. Currently, ILCs are divided into three functionally distinct groups (ILC1, ILC2, and ILC3) based upon the cytokines they produce (Table 2.3). The first ILCs to be characterized were those defined as NK cells which are now defined as members of the ILC1 group. Not to be confused with the small population of CD4+ NKT cells that express CD4 as described above. NK cells are large granular lymphocytes. They contain intracellular granules with preformed biologically potent molecules that are released when NK cells make contact with target cells. Some of these molecules cause the formation of pores in the membrane of the target cell, leading to its lysis (see Chapter 3). Other molecules enter the target cell and cause apoptosis (programmed cell death) of the target cell by enhanced fragmentation of its nuclear DNA. Hence, they are able to lyse certain virus‐infected cells and tumor cells without prior stimulation. A more detailed discussion regarding the role of ILCs in innate immune responses is given in Chapter 3 but it is noteworthy that our understanding of this population of immune cells is still in its infancy.
Myeloid Lineage Immune Cell Populations
Polymorphonuclear Leukocytes
Polymorphonuclear (PMN) leukocytes are a population of cells also referred to as granulocytes. These include the basophils, eosinophils, and neutrophils. Granulocytes are short‐lived phagocytic cells that contain the enzyme‐rich lysosomes, which can facilitate destruction of infectious microorganisms. They also produce peroxide, superoxide radicals, and nitric oxide, which are toxic to many microorganisms. Some lysosomes also contain bactericidal proteins, such as lactoferrin. PMN leukocytes play a major role in protection against infection. Defects in PMN cell function are accompanied by chronic or recurrent infection.
Figure 2.11. CTL killing of target cells. CTLs interact in a cognate fashion via antigen‐specific TCRs in conjunction with CD8. Antigenic peptides expressed by class I MHC molecules on target cells bind to antigen‐specific TCRs in a process called antigen presentation (see Chapter 8). Following direct cell contact, pore‐forming perforin and granzymes are released by the CTL to promote destruction of the target cell.
Macrophages.
Macrophages are phagocytes derived from blood monocytes (Figure 2.13). The monocyte itself is a small, spherical cell with few projections, abundant cytoplasm, little endoplasmic reticulum, and many granules. Following migration of monocytes from the blood to various tissues, they undergo further differentiation into a variety of histological forms which, historically, have been classified in accordance with their anatomical location as follows.
Kupffer cells, in the liver; large cells with many cytoplasmic projections.
Alveolar macrophages, in the lung.
Splenic macrophages, in the red pulp.
Peritoneal macrophages, free‐floating in peritoneal fluid.
Microglial cells, in the brain and spinal cord.
Osteoclasts, in the bone.
More recently, recognition of the functional heterogeneity of macrophage subsets has given rise to a new paradigm for classification of these innate immune cells. Macrophages are functionally polarized into M1 or M2 macrophages. Such polarization is regulated by the cytokines and other molecules and conditions present in the local environment. M1 macrophages are typically activated by IFN‐γ or lipopolysaccharide, and produce proinflammatory cytokines. M1 cells phagocytize microbes and initiate an immune response. They produce nitric oxide (NO) or reactive oxygen intermediates to protect against bacteria and viruses (discussed further in Chapter 3).
M2 macrophages are alternatively activated by exposure to cytokines such as IL‐4, IL‐10, or IL‐13. M2 macrophages produce either polyamines to induce proliferation or proline to induce collagen production. These macrophages are associated with wound healing and tissue repair.
Although associated with diverse names and locations, many of these cells share common features, such as the ability to bind and engulf particulate materials and antigens. Because of their location along capillaries, these cells are most likely to make first contact with invading pathogens and antigens and, as we shall see later, play a large part in the success of innate as well as adaptive immunity (also called acquired immunity). As noted above and discussed in detail in later chapters, another major function of the macrophages is to take up antigens, process them by denaturation or partial digestion, and present them, on their surfaces, to antigen‐specific T cells (i.e., the process of antigen presentation).
Figure 2.12. Cytokine‐promoted differentiation of naïve CD4+ T cells into TH subsets showing some of their characteristic transcription factors.
Dendritic Cells.
Dendritic cells (DCs) are critically important members of the innate immune system due to their highly efficient antigen‐presenting cells (APCs) (see Chapter 3). Like other innate immune cells, they recognize and phagocytize pathogens and other antigens but their ability to present antigens to T cells far exceeds that of other APCs. They are found as migrating DCs in the blood, nonmigratory follicular dendritic cells (fDCs) in primary and secondary follicles of the B cell areas of lymph nodes and spleen, interdigitating cells of the thymus, and Langerhans cells in the skin. Another type of dendritic cell is the plasmacystoid DC (pDC). Unlike other DC subpopulations that are derived from myeloid precursor cells, pDCs are derived from lymphoid precursors.
