Immune response to chapter 17 Infectious diseases F A PATHOGEN IS TO ESTABLISH AN INFECTION IN A susceptible host, a series of coordinated events must rcumvent both innate and adaptive immunity. One of the first and most important features of host innate immunity is the barrier provided by the epithelial surfaces of the skin and the lining of the gut. The difficulty of penetrat- ing these epithelial barriers ensures that most pathogens never gain productive entry into the host. In addition to pro viding a physical barrier to infection, the epithelia also pro duce chemicals that are useful in preventing infection. The Neisseria gonorrheae Attaching to Urethral Epithelial Cells secretion of gastric enzymes by specialized epithelial cells lowers the pH of the stomach and upper gastrointestinal Viral Infections tract, and other specialized cells in the gut produce antibac terial peptides. a Bacterial Infections a major feature of innate immunity is the presence of the a Protozoan Diseases ormal gut flora, which can competitively inhibit the bind- ing of pathogens to gut epithelial cells. Innate responses can Diseases Caused by Parasitic Worms(Helminths) also block the establishment of infection. For example, the m Emerging Infectious Diseases cell walls of some gram-positive bacteria contain a peptido- glycan that activates the alternative complement pathway resulting in the generation of C3b, which opsonizes bacteria and enhances phagocytosis(see Chapter 13). Some bacteria produce endotoxins such as LPS, which stimulate the pro luction of cytokines such as TNF-ac, IL-1, and IL-6 by nacrophages or endothelial cells. These cytokines can acti- tively or to regulate it so that a branch of the immune system vate macrophages Phagocytosis of bacteria by macrophages is activated that is ineffective against the pathogen Contin and other phagocytic cells is another highly effective line of ual variation in surface antigens is another strategy that nnate defense. However, some types of bacteria that com- enables a pathogen to elude the immune system. This anti- monly grow intracellularly have developed mechanisms that genic variation may be due to the gradual accumulation of allow them to resist degradation within the phagocyte mutations, or it may involve an abrupt change in surface Viruses are well known for the stimulation of innate antigens responses. In particular, many viruses induce the production oth innate and adaptive immune responses to patho of interferons, which can inhibit viral replication by induc- gens provide critical defense, but infectious diseases, which ing an antiviral response. viruses are also controlled by nK have plagued human populations throughout history, still cells As described in Chapter 14, NK cells frequently form cause the death of millions each year. Although widespread he first line of defense against viral infections use of vaccines and drug therapy has drastically reduced enerally, pathogens use a variety of strategies to escape mortality from infectious diseases in developed countries, destruction by the adaptive immune system. Many patho- such diseases continue to be the leading cause of death in the gens reduce their own antigenicity either by growing within Third World. It is estimated that over 1 billion people are host cells, where they are sequestered from immune attack, infected worldwide, resulting in more than 11 million deaths or by shedding their membrane antigens. Other pathogens every year (Figure 17-1). Despite these alarming numbers camouflage themselves by mimicking the surfaces of host estimated expenditures for research on infectious diseases cells, either by expressing molecules with amino acid se- prevalent in the Third World are less than 5%of total health- quences similar to those of host cell-membrane molecules or research expenditures worldwide. Not only is this a tragedy by acquiring a covering of host membrane molecules. Some for these countries, but some of these diseases are begin pathogens are able to suppress the immune response selec- ning to emerge or re-emerge in developed countries. Fc■ Viral Infections ■ Bacterial Infections ■ Protozoan Diseases ■ Diseases Caused by Parasitic Worms (Helminths) ■ Emerging Infectious Diseases Neisseria gonorrheae Attaching to Urethral Epithelial Cells Immune Response to Infectious Diseases I           susceptible host, a series of coordinated events must circumvent both innate and adaptive immunity. One of the first and most important features of host innate immunity is the barrier provided by the epithelial surfaces of the skin and the lining of the gut. The difficulty of penetrat￾ing these epithelial barriers ensures that most pathogens never gain productive entry into the host. In addition to pro￾viding a physical barrier to infection, the epithelia also pro￾duce chemicals that are useful in preventing infection. The secretion of gastric enzymes by specialized epithelial cells lowers the pH of the stomach and upper gastrointestinal tract, and other specialized cells in the gut produce antibac￾terial peptides. A major feature of innate immunity is the presence of the normal gut flora, which can competitively inhibit the bind￾ing of pathogens to gut epithelial cells. Innate responses can also block the establishment of infection. For example, the cell walls of some gram-positive bacteria contain a peptido￾glycan that activates the alternative complement pathway, resulting in the generation of C3b, which opsonizes bacteria and enhances phagocytosis (see Chapter 13). Some bacteria produce endotoxins such as LPS, which stimulate the pro￾duction of cytokines such as TNF-, IL-1, and IL-6 by macrophages or endothelial cells. These cytokines can acti￾vate macrophages. Phagocytosis of bacteria by macrophages and other phagocytic cells is another highly effective line of innate defense. However, some types of bacteria that com￾monly grow intracellularly have developed mechanisms that allow them to resist degradation within the phagocyte. Viruses are well known for the stimulation of innate responses. In particular, many viruses induce the production of interferons, which can inhibit viral replication by induc￾ing an antiviral response. Viruses are also controlled by NK cells. As described in Chapter 14, NK cells frequently form the first line of defense against viral infections. Generally, pathogens use a variety of strategies to escape destruction by the adaptive immune system. Many patho￾gens reduce their own antigenicity either by growing within host cells, where they are sequestered from immune attack, or by shedding their membrane antigens. Other pathogens camouflage themselves by mimicking the surfaces of host cells, either by expressing molecules with amino acid se￾quences similar to those of host cell-membrane molecules or by acquiring a covering of host membrane molecules. Some pathogens are able to suppress the immune response selec￾tively or to regulate it so that a branch of the immune system is activated that is ineffective against the pathogen. Contin￾ual variation in surface antigens is another strategy that enables a pathogen to elude the immune system. This anti￾genic variation may be due to the gradual accumulation of mutations, or it may involve an abrupt change in surface antigens. Both innate and adaptive immune responses to patho￾gens provide critical defense, but infectious diseases, which have plagued human populations throughout history, still cause the death of millions each year. Although widespread use of vaccines and drug therapy has drastically reduced mortality from infectious diseases in developed countries, such diseases continue to be the leading cause of death in the Third World. It is estimated that over 1 billion people are infected worldwide, resulting in more than 11 million deaths every year (Figure 17-1). Despite these alarming numbers, estimated expenditures for research on infectious diseases prevalent in the Third World are less than 5% of total health￾research expenditures worldwide. Not only is this a tragedy for these countries, but some of these diseases are begin￾ning to emerge or re-emerge in developed countries. For chapter 17