In vertebrates, the first encounters with infectious organisms are typically at the epithelial surfaces that form the skin and line the respiratory, digestive, urinary, and reproductive tracts. These epithelia provide both physical and chemical barriers to invasion by pathogens: tight junctions between epithelial cells bar entry between the cells, and a variety of substances secreted by the cells discourage the attachment and entry of pathogens. The keratinized epithelial cells of the skin, for example, form a thick physical barrier, and the sebaceous glands in the skin secrete fatty acids and lactic acid, which inhibit bacterial growth. In addition, epithelial cells in all tissues, including those in plants and invertebrates, secrete antimicrobial molecules called defensins. Defensins are positively charged, amphipathic peptides that bind to and disrupt the membranes of many pathogens, including enveloped viruses, bacteria, fungi, and parasites.
The epithelial cells that line internal organs such as the respiratory and digestive tracts also secrete slimy mucus, which sticks to the epithelial surface and makes it difficult for pathogens to adhere. The beating of cilia on the surface of the epithelial cells lining the respiratory tract and the peristaltic action of the intestine also discourage the adherence of pathogens. Moreover, as we discuss in Chapter 23, healthy skin and gut are populated by enormous numbers of harmless (and often helpful) commensal microbes, collectively called the normal flora, which compete for nutrients with pathogens; some also produce antimicrobial peptides that actively inhibit pathogen proliferation.
pattern recognition receptors (prrs) recognize conserved Features of pathogens
Pathogens do occasionally breach the epithelial barricades, in which case underlying, nonepithelial cells of the innate immune system provide the next line of defense. These cells sense the presence of pathogens largely through the use of receptor proteins that recognize microbe-associated molecules that either are not present or are sequestered in the host organism. Because these microbial molecules often occur in repeating patterns, they are called pathogen-associated molecular patterns (PAMPs), even though they are not unique to microbes that can cause disease. PAMPs are present in various microbial molecules, including nucleic acids, lipids, polysaccharides, and proteins.
The special receptor proteins that recognize PAMPs are called pattern recognition receptors (PRRs). Some PRRs are transmembrane proteins on the surface of many types of host cells, where they recognize extracellular pathogens; on professional phagocytic cells (phagocytes) such as macrophages and neutrophils (discussed in Chapter 22), they can mediate the uptake of the pathogens into phagosomes, which then fuse with lysosomes, where the pathogens are destroyed. Other PRRs are located intracellularly, where they can detect intracellular pathogens such as viruses; these PRRs are either free in the cytosol or associated with
Figure 24–2 The two main classes of adaptive immune responses.
Lymphocytes carry out both classes of adaptive responses—shown here as responses to a viral infection. In one class, B cells secrete antibodies that specifically bind to and neutralize extracellular viruses, by preventing the viruses from infecting host cells. In the other, T cells mediate the response; in this example, they kill the virus-infected host cells. In both cases, innate immune responses help activate the adaptive immune responses through pathways that are not shown.