Worldwide deaths annually from mucosal infections Acute respiratory infections (4 million) Diarrheal diseases (2.2 million) Tuberculosis (1.5 million) HIV/AIDS (2 million) Measles (400,000) Hepatitis B (103,000*) Whooping cough (294,000) Roundworm and hookworm (6000) 0 4 million3 million2 million1 million
Because of their physiological functions in gas exchange (the lungs), food absorption (the gut), sensory activities (eyes, nose, mouth, and throat), and reproduction (uterus and vagina), the mucosal surfaces are thin and permeable barriers to the interior of the body. The importance of these tissues to life means that effective defense mechanisms are essential to protect them from invasion. Equally significant is that their fragility and permeability create obvious vulnerability to infection, and it is not surprising that the vast majority of infectious agents invade the human body by these routes (Fig. 12.3). Diarrheal diseases, acute respiratory infections, pulmonary tuberculosis, measles, whooping cough, and worm infestations continue to be the major causes of death throughout the world, especially in infants in developing countries. To these must be added the human immunodeficiency virus (HIV), a pathogen whose natural route of entry via a mucosal surface is often overlooked, as well as other sexually transmitted infections such as syphilis.
The mucosal surfaces are also portals of entry for a vast array of foreign antigens that are not pathogenic. This is best seen in the gut, which is exposed to enormous quantities of food proteins—an estimated 30–35 kg per year per person. At the same time, the healthy large intestine is colonized by at least a thousand species of bacteria that live in symbiosis with their host and are known as commensal microorganisms, or the microbiota. These bacteria are present at levels of at least 1012 organisms per milliliter in the colon contents, making them the most numerous cells in the body by a factor of 10. Substantial populations of viruses and fungi are also found in the healthy intestine. In normal circumstances these organisms do no harm, and many are beneficial to their hosts, having important metabolic functions, as well as being essential for normal immune function. The other mucosal surfaces are also colonized by substantial populations of resident commensal organisms (Fig. 12.4).
As food proteins and the microbiota contain many foreign antigens, they are capable of being recognized by the adaptive immune system. Generating protective immune responses against these harmless agents would, however, be inappropriate and wasteful. Indeed, aberrant immune responses of this kind are now believed to be the cause of some relatively common diseases, including celiac disease (caused by a response to the wheat protein gluten; discussed in Chapter 14) and inflammatory bowel diseases such as Crohn’s disease (a response to commensal bacteria). As we shall see, the intestinal mucosal immune system has evolved means of distinguishing harmful pathogens from antigens in food and the normal microbiota. Similar issues are faced at other mucosal surfaces, such as the respiratory tract and female genital