Immunology. Richard Coico

Immunology - Richard Coico


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cascade. These will be discussed further in Chapter 4.

      Intracellular and Extracellular Killing of Microorganisms

       Phagocytosis.

      Phagocytosis is the ingestion by individual cells of invading foreign particles, such as bacteria. It is a critical protective mechanism of the immune system. Many microorganisms release substances that attract phagocytic cells. Phagocytosis may be enhanced by a variety of factors that make the foreign particle an easier target. These factors, collectively referred to as opsonins (the Greek word meaning “prepare food for”), consist of antibodies and various serum components of complement (see Chapter 4). After ingestion, the foreign particle is entrapped in a phagocytic vacuole (phagosome), which fuses with lysosomes, forming the phagolysosome. The latter releases its powerful enzymes, which digest the particle.

      Phagocytes can also damage invading pathogens through the generation of toxic products in a process known as the respiratory burst. Production of these toxic metabolites is induced during phagocytosis of pathogens such as bacteria and catalyzed by a set of interrelated enzyme pathways. The most important of these are nitric oxide (inducible nitric oxidase synthase), hydrogen peroxide and superoxide anion (phagocyte NADPH oxidase), and hypochlorous acid (myeloperoxidase), each of which is toxic to bacteria. These microbicidal products can also damage host cells. Fortunately, a series of protective enzymes produced by phagocytes controls the action of these products so that their microbicidal activity is primarily limited to the phagolysosome (i.e., fused phagosomes and lysosomes; see Figure 3.8), thereby focusing their toxicity on ingested pathogens. These protective enzymes include catalase, which degrades hydrogen peroxide, and superoxide dismutase, which converts the superoxide anion into hydrogen peroxide and oxygen. The absence of, or an abnormality in, any one of the respiratory burst components from phagocytic cells results in a form of immunodeficiency that predisposes individuals to repeated infections (see Chapter 16).

Schematic illustration of endocytosis and phagocytosis by phagocytes.

      As a physiological process, inflammation is typically initiated by tissue damage caused by endogenous factors (such as tissue necrosis or bone fracture) and by exogenous factors. The latter includes various types of damage, such as mechanical injury (e.g., cuts), physical injury (e.g., burns), chemical injury (e.g., exposure to corrosive chemicals), immunological injury (e.g., hypersensitivity reactions; see Chapters 1315) and biological injury (e.g., infections caused by pathogenic microorganisms; see Chapter 19). Indeed, infection can be thought of as pathogen‐induced injury when considering inflammatory responses, since the innate immune cells called into play and the inflammatory responses that manifest are essentially identical, regardless of the cause of injury. While perhaps paradoxical in light of the discomfort associated with certain types of inflammatory responses (e.g., hypersensitivity to poison ivy), inflammation is a normal immunological process designed to restore immune homeostasis by bringing the injured tissue back to its normal state.

      As noted above, inflammation does not have to be initiated by pathogens that cause infection, but can also be caused by tissue injuries. Such injuries cause release of damaged cellular contents at local sites even in the absence of breaks in physical barriers that would allow pathogens to enter. The inflammatory reaction triggers mobilization of phagocytic cells and other innate immune cells to the damaged area to clear cellular debris and to set the stage for wound repair, as discussed in later in this chapter Such mobilization is, in part, the result of transendothelial migration of leukocytes, as discussed below. This happens when damaged cells release their contents into the local environment which initiates release of potent inflammatory mediators from mast cells in and around the area. Inflammatory mediators include histamine, leukotrienes, and prostaglandins. Histamine increases the diameter of local blood vessels (vasodilation), causing an increase in blood flow. Histamine also increases the permeability of local capillaries, causing plasma to leak out and form interstitial fluid causing the swelling associated with inflammation.

      Transendothelial Migration of Leukocytes


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