A pathogen that breaches the host’s anatomic and chemical barriers will encounter the cellular defenses of innate immunity. Cellular immune responses are initiated when sensor cells detect inflammatory inducers (Fig. 1.6). Sensor cells include many cell types that detect inflammatory mediators through expression of many innate recognition receptors, which are encoded by a relatively small number of genes that remain constant over an individual’s lifetime. Inflammatory inducers that trigger these receptors include molecular components unique to bacteria or viruses, such as bacterial lipopolysaccharides, or molecules such as ATP, which is not normally found in the extracellular space. Triggering these receptors can activate innate immune cells to produce various mediators that either act directly to destroy invading microbes, or act on other cells to propagate the immune response. For example, macrophages can ingest microbes and produce toxic chemical mediators, such as degradative enzymes or reactive oxygen intermediates, to kill them. Dendritic cells may produce cytokine mediators, including many cytokines that activate target tissues, such as epithelial or other immune cells, to resist or kill invading microbes more efficiently. We will discuss these receptors and mediators briefly below and in much greater detail in Chapter 3.
Innate immune responses occur rapidly on exposure to an infectious organism (Fig. 1.7). In contrast, responses by the adaptive immune system take days rather than hours to develop. However, the adaptive immune system is capable of eliminating infections more efficiently because of exquisite specificity
Fig. 1.7 Phases of the immune response.
Innate immune response Phases of the immune response Response Duration of response Typical time after infection to start of response Infammation, complement activation, phagocytosis, and destruction of pathogen Emigration of effector lymphocytes from peripheral lymphoid organs Interaction of T cells with B cells, formation of germinal centers. Formation of effector B cells (plasma cells) and memory B cells. Production of antibody Interaction between antigen-presenting dendritic cells and antigen-specifc T cells: recognition of antigen, adhesion, co-stimulation, T-cell proliferation and differentiation Adaptive immune response Activation of antigen-specifc B cells Formation of effector and memory T cells Immunological memory Elimination of pathogen by effector cells and antibody Maintenance of memory B cells and T cells and high serum or mucosal antibody levels. Protection against reinfection Minutes Days Hours Days Hours Days Weeks Days Weeks Days A few days Weeks A few days Weeks Days to weeks Can be lifelong
Principles of innate immunity.
of antigen recognition by its lymphocytes. In contrast to a limited repertoire of receptors expressed by innate immune cells, lymphocytes express highly specialized antigen receptors that collectively possess a vast repertoire of specificity. This enables the adaptive immune system to respond to virtually any pathogen and effectively focus resources to eliminate pathogens that have evaded or overwhelmed innate immunity. But the adaptive immune system interacts with, and relies on, cells of the innate immune system for many of its functions. The next several sections will introduce the major components of the innate immune system and prepare us to consider adaptive immunity later in the chapter.
1-4 The myeloid lineage comprises most of the cells of the innate immune system.
The common myeloid progenitor (CMP) is the precursor of the macrophages, granulocytes (the collective term for the white blood cells called neutrophils, eosinophils, and basophils), mast cells, and dendritic cells of the innate immune system. Macrophages, granulocytes, and dendritic cells make up the three types of phagocytes in the immune system. The CMP also generates megakaryocytes and red blood cells, which we will not be concerned with here. The cells of the myeloid lineage are shown in Fig. 1.8.