The spread of a pathogen is often initially countered by an inflammatory response that recruits more effector cells and molecules of the innate immune system out of the blood and into the tissues, while inducing clotting in small blood vessels further downstream so that the microbe cannot spread through the circulation (see Fig. 2.8). The cellular responses of innate immunity act over several days. During this time, the adaptive immune response may also begin if antigens derived from the pathogen are delivered to local lymphoid tissues
Anatomic barriers and initial chemical defenses.
Fig. 2.8 An infection and the response to it can be divided from becoming established. If not, it helps to contain the infection into a series of stages. These are illustrated here for an infectious and also delivers the infectious agent, carried in lymph and inside microorganism entering through a wound in the skin. The infectious dendritic cells, to local lymph nodes. This initiates the adaptive agent must first adhere to the epithelial cells and then cross the immune response and eventual clearance of the infection. epithelium. A local immune response may prevent the infection by dendritic cells (see Section 1-15). While an innate immune response may eliminate some infections, an adaptive immune response can target particular strains and variants of pathogens and protect the host against reinfection by using either effector T cells or antibodies to generate immunological memory.
2-4 Epithelial cells and phagocytes produce several kinds of antimicrobial proteins.
Our surface epithelia are more than mere physical barriers to infection; they also produce a wide variety of chemical substances that are microbicidal or that inhibit microbial growth. For example, the acid pH of the stomach and the digestive enzymes, bile salts, fatty acids, and lysolipids present in the upper gastrointestinal tract create a substantial chemical barrier to infection (see Fig. 2.5). One important group of antimicrobial proteins comprises enzymes that attack chemical features specific to bacterial cell walls. Such antibacterial enzymes include lysozyme and secretory phospholipase A2, which are secreted in tears and saliva and by phagocytes. Lysozyme is a glycosidase that breaks a specific chemical bond in the peptidoglycan component of the bacterial cell wall. Peptidoglycan is an alternating polymer of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), strengthened by cross-linking peptide bridges (Fig. 2.9). Lysozyme selectively cleaves the β-(1,4) linkage between these two sugars and is more effective in acting against Gram-positive bacteria, in which the peptidoglycan cell wall is exposed, than against Gram-negative bacteria, which have an outer layer of LPS covering the peptidoglycan layer. Lysozyme is also produced by Paneth cells, specialized epithelial cells in the base of the crypts in the small intestine that secrete many antimicrobial proteins into the gut (see Fig. 2.6). Paneth cells also produce secretory phospholipase A2, a highly basic enzyme that can enter the bacterial cell wall to access and hydrolyze phospholipids in the cell membrane, killing the bacteria.
The second group of antimicrobial agents secreted by epithelial cells and phagocytes is the antimicrobial peptides. These represent one of the most ancient forms of defense against infection. Epithelial cells secrete these peptides into the fluids bathing the mucosal surface, whereas phagocytes secrete them in tissues. Three important classes of antimicrobial peptides in mammals are defensins, cathelicidins, and histatins.