the development of immature B and T cellsfunction in the removal of damaged erythrocytes from the circulationact as the major source of stem cells and thus help maintain hematopoiesisprovide an infrastructure that on antigenic stimulation contains large populations of B lymphocytes and plasma cellsare the sites of NKT cell differentiation4 Which of the following sequences correctly describes lymphocyte migration from lymph nodes to blood?postcapillary venules, efferent lymphatic vessels, thoracic duct, vena cava, heartpostcapillary venules, afferent lymphatic vessels, thoracic duct, vena cava, heartpostcapillary venules, efferent lymphatic vessels, vena cava, thoracic duct, heartpostcapillary venules, afferent lymphatic vessels, vena cava, thoracic duct, heart
ANSWERS TO REVIEW QUESTIONS
1 E. Neutrophils are derived from myeloid progenitor cells in the bone marrow.
2 C. Terminal differentiation of B cells into plasma cells occurs only in secondary lymphoid organs, such as the spleen and lymph nodes. Circulation of lymphocytes and cellular proliferation (but not antigen‐dependent responses of terminal differentiation) also take place in the primary lymphoid organs, such as the bursa of Fabricius, or its equivalent, and the thymus. The bone marrow is the site where pluripotent stem cells differentiate into precursor B and T cells.
3 D. On antigenic stimulation, the germinal centers contain large populations of B lymphocytes undergoing mitosis and plasma cells secreting antibodies. Virgin immunocompetent lymphocytes are developed in the primary lymphoid organs, not in the secondary lymphoid organs, such as the spleen and lymph nodes. Germinal centers do not participate in the removal of damaged erythrocytes, nor are they a source of stem cells; the latter are found in the bone marrow.
4 A. Blood lymphocytes enter the lymph nodes through the afferent lymphatic vessel via postcapillary venules. They leave the lymph nodes through efferent lymphatic vessels, which eventually converge in the thoracic duct. This duct empties into the vena cava, the vessel that returns the blood to the heart, thus providing for the continual recirculation of lymphocytes.
3 CELLS OF THE INNATE IMMUNITY
INTRODUCTION
Innate immunity refers to immune mechanisms that are present from birth and serve as the first line of defense against microbes and other offending pathogens. Responses occur within minutes of exposure to invading pathogens. Every living organism is confronted by continual intrusions from its environment and sometimes, such intrusions involve pathogens which, in the absence of host defense mechanisms, would otherwise take advantage of our bodies for their own survival. Early defense provided by the innate immune system is therefore critical to survival of the host. These defenses range from physical and chemical barriers—elements of innate immunity—to highly sophisticated systems that constitute the adaptive immune system. In this chapter, we describe the principal elements of innate immunity. We will discuss the participating organs, cells, and molecular components of innate immunity and their physiological roles that, in many cases, include dynamic interactions with elements of the adaptive immune system. Thus, innate immune responses are important not only because they are an independent arm of the immune system but also because they profoundly influence the nature of adaptive immune responses.
The innate immune system is a phylogenetically ancient defense system which appeared during evolution of multicellular organisms ~750 million years ago, in contrast with adaptive immune mechanisms which appeared ~350–500 years ago in vertebrates. During its long evolutionary history, the system co‐evolved with microbes to protect multicellular organisms from infection. It is noteworthy that several components of the mammalian innate immune system are remarkably similar to those found in plants and insects, suggesting a common genetic ancestry. Examples include structurally similar peptides called defensins which are toxic to bacteria and fungi. Another example is a family of receptors called Toll‐like receptors (TLRs) that will be discussed in detail later in this chapter. TLRs recognize pathogenic microbes by virtue of their ability to bind to structural shapes or molecular patterns expressed on whole groups of pathogens but not the host. Hence, TLRs are said to provide defense against pathogens through pattern recognition. Interactions between innate immune cells expressing TLRs and pathogens expressing pathogen‐associated molecular patterns triggers a cascade of host cell intracellular events leading to selected gene expression and cell activation that, in many instances, ends with destruction of the invading pathogen. In other instances, innate immune mechanisms, while partially protective, are not fully capable of preventing an ensuing infection. Fortunately, the adaptive immune system is then mobilized over time (days to weeks) to generate a pathogen‐specific response that has the advantage of establishing long‐term memory responses to help prevent future infection caused by invading pathogens.
PHYSICAL AND CHEMICAL BARRIERS OF INNATE IMMUNITY
Most organisms and foreign substances cannot penetrate intact epithelial layers that insulate the body’s interior from pathogens in the environment (Figure 3.1). These epithelial layers include the skin and the tissue surfaces located at body openings: the respiratory, gastrointestinal and urogenital tracts, and the ducts of secretory glands (salivary, lacrimal, and mammary glands). These anatomical barriers also contribute to the physical and mechanical mechanisms of innate defense against pathogens (e.g., eye blinking, coughing, sneezing, directional flow of fluids to the stomach and intestine). In addition, epithelial cells at these and other anatomical sites generate active chemical and biochemical defenses by producing and deploying antimicrobial peptides and proteins.
Figure 3.1. Skin and other epithelial barriers to infection. In addition to serving as physical barriers, the skin and mucosal and glandular epithelial layers are protected from microbial colonization mechanically (cilia, fluid flow, smooth muscle contraction), chemically (pH, antimicrobial peptides, enzymes) and through cellular innate defense mechanisms (dendritic cells, macrophages).
Some microorganisms can enter through sebaceous glands and hair follicles. However, the acid pH of sweat and sebaceous secretions and the presence of various fatty acids and hydrolytic enzymes (e.g., lysozymes) all have some antimicrobial effects, therefore minimizing the importance of this route of infection. In addition, soluble proteins, including the interferons (see Chapter 11) and certain members of the complement system (see Chapter 4) found in the serum, contribute to nonspecific immunity. Interferons are a group of proteins made by cells in response to viral infection, which essentially induces a generalized antiviral state in surrounding cells. Activation of complement components in response to certain microorganisms results in a controlled enzymatic cascade, which targets the membrane of pathogenic organisms and leads to their destruction.
An important innate immune mechanism involved in the protection of many areas of the body, including the respiratory and gastrointestinal tracts, involves the simple fact that surfaces in these areas are covered with mucus. In these areas, the mucous membrane barrier traps microorganisms, which are then swept away by ciliated epithelial cells toward the external openings. The hairs in the nostrils and the cough reflex are also helpful in preventing organisms from infecting the respiratory tract.
The elimination of
