Sensor Systems

Sensor systems within the blood and tissues lie ready to detect signs of either tissue damage or microbial invasion. They respond to patterns associated with danger, such as bacterial cell wall components, by directly destroying the invading microbe or by recruiting other components of the host defenses.

Toll-Like Receptors

Toll-like receptors (TLRs) are surface receptors that enable certain cells to "see'' molecules that signify the presence of microorganisms or viruses (figure 15.6). The name indicates they are part of a family of receptors called Toll receptors, first identified in Drosophila species (fruit flies). They have only recently been discovered and much is still being learned about them, but already they have caused a tremendous resurgence of interest in innate immunity, which many scientists had thought was well understood. At least 10 TLRs have been described so far, and each recognizes a distinct compound or group of compounds associated with "danger." For example, TLR-2 recognizes peptidoglycan and TLR-4 is triggered by lipopolysaccharide. Other bacterial compounds that activate the receptors include flagellin and specific nucleotide sequences that typify bacterial DNA. When a compound activates a toll-like receptor, which appears to occur by either direct or indirect binding, a signal is transmitted to the nucleus of the host cell, inducing that cell to alter the expression of certain genes. For example, lipopolysaccharide triggers a tolllike receptor of monocytes and macrophages, causing the cells to begin producing chemokines that attract additional phagocytes to the area. Engagement of toll-like receptors on

Production of specific proteins that alert other components of host defenses

Detects flagellin

Detects flagellin

Toll-like receptors

Detects bacterial nucleotide sequences

Detects peptidoglycan

Figure 15.6 Toll-Like Receptors These surface receptors are used by host cells to detect the presence of pathogen-associated molecular patterns. Engagement of a tolllike receptor transmits a signal to the cell's nucleus, inducing the cell to begin producing certain proteins such as cytokines, alerting other components of host defenses.

Toll-like receptors

Detects bacterial nucleotide sequences

Detects peptidoglycan

Figure 15.6 Toll-Like Receptors These surface receptors are used by host cells to detect the presence of pathogen-associated molecular patterns. Engagement of a tolllike receptor transmits a signal to the cell's nucleus, inducing the cell to begin producing certain proteins such as cytokines, alerting other components of host defenses.

endothelial cells, which line blood vessels, causes those cells to produce pro-inflammatory cytokines.

The discovery of toll-like receptors has led to some intriguing ideas about how they function. Perhaps the specific combination of toll-like receptors that have been triggered helps the cell identify the invader. If this is true, cells of the innate defenses might be tailoring their responses to fit specific groups of disease-causing microbes, such as Gram-positive bacteria.

The Complement System

The complement system is a series of proteins that constantly circulate in the blood and the fluid that bathes the tissues. Early studies showed that these proteins augment the activities of the adaptive immune response; in fact, their name is derived from observations that they "complement" the activities of antibodies. They routinely circulate in an inactive form, but in response to certain stimuli indicating the presence of foreign material, a cascade of reactions occurs. This results in the rapid activation of critical complement components. These activated forms have specialized functions that cooperate with other aspects of the host defenses to quickly remove and destroy the offending material.

Three pathways lead to the activation of the complement system (figure 15.7):

■ Classical pathway. Activation by the classical pathway requires antibodies, a component of adaptive immunity. When antibodies bind to antigen, forming antigen-antibody complexes, the "red flag" portion of the antibody can then interact with a complement component, activating it. This, in turn, leads to the activation of other complement proteins.

■ Lectin pathway. Activation by the lectin pathway requires mannan-binding lectins (MBLs); these are pattern-recognition molecules the body uses to detect

Chapter 15 The Innate Immune Response

Chapter 15 The Innate Immune Response

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