If a pathogen is to establish an infection in a 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 penetrating these epithelial barriers ensures that most pathogens never gain productive entry into the host. In addition to providing a physical barrier to infection, the epithelia also produce 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 antibacterial peptides.
A major feature of innate immunity is the presence of the normal gut flora, which can competitively inhibit the binding 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 production of cytokines such as TNF-a, IL-1, and IL-6 by macrophages or endothelial cells. These cytokines can activate macrophages. Phagocytosis of bacteria by macrophages and other phagocytic cells is another highly effective line of innate defense. However, some types of bacteria that commonly 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 inducing 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 pathogens 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 sequences 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-
■ Viral Infections
■ Bacterial Infections
■ Protozoan Diseases
Diseases Caused by Parasitic Worms (Helminths) ■ Emerging Infectious Diseases tively or to regulate it so that a branch of the immune system is activated that is ineffective against the pathogen. Continual 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 pathogens 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 beginning to emerge or re-emerge in developed countries. For
I I Over age five I I Under age five
Acute AIDS Diarrheal TB respiratory diseases infections (including pneumonia and influenza)
Leading infectious disease killers. Data collected and compiled by the World Health Organization in 2000 for deaths in 1998. HIV-infected individuals who died of TB are included among AIDS deaths.
example, some United States troops returned from the Persian Gulf with leishmaniasis; cholera cases have recently increased worldwide, with more than 100,000 cases reported in KwaZulu-Natal, South Africa, during the summer of 2001;
and a new drug-resistant strain of Mycobacterium tuberculosis is spreading at an alarming rate in the United States.
In this chapter, the concepts described in earlier chapters, antigenicity (Chapter 3) and immune effector mechanisms (Chapters 12-16), as well as vaccine development (which will be considered in Chapter 18) are applied to selected infectious diseases caused by viruses, bacteria, protozoa, and helminths—the four main types of pathogens.
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