Many pathogens have evolved to resist innate immunity, and protection against these infections requires the more specialized and powerful mechanisms of adaptive immunity (also called acquired, or specific, immunity). Adaptive immunity is normally silent and responds (or adapts) http://ebooksmedicine.net
Fig. 5.1 The principal components and kinetics of response of the innate and adaptive immune systems. NK cells, Natural killer cells.
to the presence of infectious agents by generating potent mechanisms for neutralizing and eliminating the pathogens. By convention, the terms immune system and immune response generally refer to adaptive immunity.
The major components of innate immunity are epithelial barriers that block the entry of microbes, phagocytic cells (mainly neutrophils and macrophages), dendritic cells (DCs), natural killer (NK) cells and other innate lymphoid cells, and several plasma proteins, including the proteins of the complement system. The various cells are discussed later in this chapter; the complement system was discussed in Chapter 3.
Phagocytes, dendritic cells and many other cells, such as epithelial cells, express receptors that sense the presence of infectious agents and substances released from dead cells. The microbial structures recognized by these receptors are called pathogen-associated molecular patterns; they are shared among microbes of the same type, and they are essential for the survival and infectivity of the microbes (so the microbes cannot evade innate immune recognition by mutating these molecules). The substances released from injured and necrotic cells are called damage-associated molecular patterns. The cellular receptors that recognize these molecules are often called pattern recognition receptors. It is estimated that innate immunity uses about 100 different receptors to recognize 1000 molecular patterns.
Receptors of Innate Immunity
Pattern recognition receptors are located in all the cellular compartments where pathogens may be present: plasma membrane receptors detect extracellular pathogens, endosomal receptors detect ingested microbes, and cytosolic receptors detect microbes in the cytoplasm (
Fig. 5.2 ). Several classes of these receptors have been identified.
NOD-like receptor Nucleic acids of ingested Bacterial microbes peptidoglycan; products of TLR damaged cells
Fig. 5.2 Cellular receptors for microbes and products of cell injury. Phagocytes, dendritic cells, and many types of epithelial cells express different classes of receptors that sense the presence of microbes and dead cells. Toll-like receptors (TLRs) located in different cellular compartments, as well as other cytoplasmic and plasma membrane receptors, recognize products of different classes of microbes. The major classes of innate immune receptors are TLRs, NOD-like receptors in the cytosol (NLRs), C-type lectin receptors, RIG-like receptors for viral RNA, named after the founding member RIG-I, and cytosolic DNA sensors.
The best known of the pattern recognition receptors are the Toll-like receptors (TLRs). There are 10 TLRs in mammals that recognize a wide range of microbial molecules. The plasma membrane TLRs recognize bacterial products such as lipopolysaccharide (LPS), and endosomal TLRs recognize viral and bacterial RNA and DNA (see