Inflammation is described clinically by the Latin words calor, dolor, rubor, and tumor, meaning heat, pain, redness, and swelling. Each of these features reflects an effect of cytokines or other inflammatory mediators on the local blood vessels. Heat, redness, and swelling result from the dilation and increased permeability of blood vessels during inflammation, leading to increased local blood flow and leakage of fluid and blood proteins into the tissues. Cytokines and complement fragments have important effects on the endothelium that lines blood vessels; the endothelial cells themselves also produce cytokines in response to infection. These alter the adhesive properties of the endothelial cells and cause circulating leukocytes to stick to the endothelial cells and migrate between them into the site of infection, to which they are attracted by chemokines. The migration of cells into the tissue and their local actions account for the pain.
The main cell types seen in the initial phase of an inflammatory response are macrophages and neutrophils, the latter being recruited into the inflamed, infected tissue in large numbers. Macrophages and neutrophils are thus also known as inflammatory cells. The influx of neutrophils is followed a short time later by the increased entry of monocytes, which rapidly differentiate into macrophages, thus reinforcing and sustaining the innate immune response. Later, if the inflammation continues, eosinophils also migrate into inflamed tissues and contribute to the destruction of the invading microorganisms.
Principles of adaptive immunity.
1-7 Innate lymphocytes and natural killer cells are effector cells that share similarities with lymphoid lineages of the adaptive immune system.
The common lymphoid progenitor (CLP) in the bone marrow gives rise both to antigen-specific lymphocytes of the adaptive immune system and to several innate lineages that lack antigen-specific receptors. Although the B and T lymphocytes of the adaptive immune system were recognized in the 1960s, the natural killer (NK) cells (Fig. 1.11) of the innate immune system were not discovered until the 1970s. NK cells are large lymphocyte-like cells with a distinctive granular cytoplasm that were identified because of their ability to recognize and kill certain tumor cells and cells infected with herpesviruses. Initially, the distinction between these cells and T lymphocytes was unclear, but we now recognize that NK cells are a distinct lineage of cells that arise from the CLP in the bone marrow. They lack the antigen-specific receptors of the adaptive immune system cells, but express members of various families of innate receptors that can respond to cellular stress and to infections by very specific viruses. NK cells play an important role in the early innate response to viral infections, before the adaptive immune response has developed.
More recently, additional lineages of cells related to NK cells have been identified. Collectively, these cells are called innate lymphoid cells (ILCs). Arising from the CLP, ILCs reside in peripheral tissues, such as the intestine, where they function as the sources of mediators of inflammatory responses. The functions of NK cells and ILC cells are discussed in Chapter 3.
Summary.