Figure 11.4.1: Pathogen-Associated Molecular Patterns Binding to Pattern-Recognition Receptors on Defense Cells. Glycoprotein molecules known as pattern-recognition receptors are found on the surface of a variety of body defense cells. They are so named because they recognize and bind to pathogen-associated molecular patterns - molecular components associated with microorganisms but not found as a part of eukaryotic cells. These include bacterial molecules such as peptidoglycan, teichoic acids, lipopolysaccharide, mannans, flagellin, pilin, and bacterial DNA. There are also pattern-recognition molecules for viral double-stranded RNA (dsRNA) and fungal cell walls components such as lipoteichoic acids, glycolipids, mannans, and zymosan. Many of these pattern recognition receptors are known as toll-like receptors.
Most body defense cells have pattern-recognition receptors or PRRs for these common PAMPs enabling an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 103 of these microbial molecular patterns.
Early induced innate immunity begins 4 - 96 hours after exposure to an infectious agent and involves the recruitment of defense cells as a result of pathogen-associated molecular patterns or PAMPS binding to pattern-recognition receptors or PRRs. Pathogen-associated molecular patterns or PAMPs are molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells.
Early induced innate immunity begins 4 - 96 hours after exposure to an infectious agent and involves the recruitment of defense cells as a result of pathogen-associated molecular patterns or PAMPS binding to pattern-recognition receptors or PRRs and danger-associated molecular patterns or DAMPs binding to danger-recognition receptors or DRRs. Endocytic pattern-recognition receptors are found on the surface of phagocytes and promote the attachment of microorganisms to phagocytes.
Cytokines are low molecular weight, soluble proteins that are produced in response to an antigen and function as chemical messengers for regulating the innate and adaptive immune systems. Cytokines are pleiotropic, meaning meaning that a particular cytokine can act on a number of different types of cells rather than a single cell type. Cytokines are redundant, meaning that a number of different cytokines are able to carry out the same function.
In severe bacterial infections, pathogen-associated molecular patterns or PAMPs can trigger the synthesis and secretion of excessive levels of inflammatory cytokines and chemokines leading to systemic inflammatory response syndrome or SIRS. People born with underactive PRRs or deficient PRR immune signaling pathways are at increased risk of infection by specific pathogens due to a decrease innate immune response.
Resting phagocytes are activated by inflammatory mediators and produce surface receptors that increase their ability to adhere to the inner surface of capillary walls enabling them to squeeze out of the capillary and enter the tissue, a process called diapedesis. Activation also enables phagocytes to produce endocytic pattern-recognition receptors that recognize and bind to microbial PAMPs in order to attach the microbe to the phagocyte, as well as to exhibit increased metabolic and microbicidal
Natural Killer (NK) cells are able to recognize infected cells, cancer cells, and stressed cells and kill them. In addition, they produce a variety of cytokines, including proinflammatory cytokines, chemokines, colony-stimulating factors, and other cytokines that function as regulators of body defenses. When body cells are either under stress, are turning into tumors, or are infected, various stress-induced molecules are produced and are put on the surface of that cell.
The inflammatory response is an attempt by the body to restore and maintain homeostasis after injury and is an integral part of body defense. Most of the body defense elements are located in the blood and inflammation is the means by which body defense cells and defense chemicals leave the blood and enter the tissue around the injured or infected site. Inflammation is essentially beneficial, however, excess or prolonged inflammation can cause harm.
Iron is needed as a cofactor for certain enzymes in both bacteria and humans. Both bacteria and human cells produce iron chelators that trap free iron from their environment and transport it into the cell. During infection, the body makes considerable metabolic adjustment in order to make iron unavailable to microorganisms. The lack of iron can inhibit the growth of many bacteria.
Activated macrophages and other leukocytes release inflammatory cytokines such as TNF-alpha, IL-1, and IL-6 when their pattern-recognition receptors (PRRs) bind pathogen associated molecular patterns or PAMPs. These cytokines stimulate the anterior hypothalamus of the brain, the part of the brain that regulates body temperature, to produce prostaglandin E2, which leads to an increase bodily heat production and increased vasoconstriction.
The acute phase response is an innate body defense seen during acute illnesses and involves the increased production of certain blood proteins termed acute phase proteins. Inflammatory cytokines produced during innate immunity travel through the blood and stimulate hepatocytes in the liver to synthesize and secrete acute phase proteins. Two important acute phase proteins are C-reactive protein and mannose-binding protein, both functioning as soluble pattern-recognition receptors.
Most of the T-lymphocytes and B-lymphocytes in the body are involved in the adaptive immune responses wherein specific receptors on T-lymphocytes (T-cell receptors or TCRs) and B-lymphocytes (B-cell receptors or BCRs) recognize specific antigens of specific microbes. Intraepithelial T-lymphocytes and B-1 cells, however, are subpopulations of T-lymphocytes and B-lymphocytes that possess a more limited diversity of receptors and are designed to directly recognize the more common microbes.
