Biology

SIGNS AND SYMPTOMS OF INFECTIOUS DISEASE

lose weight and fall ill. The mutual grooming of monkeys is not just a ritual, it is preventive health care.

PAIN AND MALAISEJ ust as an itch can motivate defensive scratching, pain is an adap- tation that can lead to escape and avoidance. The skin, sensibly enough, is highly sensitive to pain. If it is being damaged, some- thing is clearly wrong, and all other activities should be dropped until the damage is stopped and repair can begin. Other kinds of

pain can also be helpful. While an abstract realization that chewing is impaired because of an abscessed tooth might possibly lead to more chewing with other, unimpaired teeth, the tormenting pain of a toothache far more effectively prevents the pressure on the tooth that would delay healing and spread bacteria. Continued pain from infec- tion or injury is adaptive because continued use of damaged tissue may compromise the effectiveness of other adaptations, such as tis- sue reconstruction and antibody attacks on bacteria. Pain motivates us to escape quickly when our bodies are being damaged, and the memory of the pain teaches us to avoid the same situation in the future.

The simplest way to determine the function of an organ like the thyroid gland is to take it out and then see how the organism mal- functions. The capacity for pain cannot be removed, but very occa- sionally someone is born without it. Such a pain-free life might seem fortunate, but it is not. People who cannot feel pain don’t experience discomfort from staying in the same position for long periods, and the resulting lack of fidgeting impairs the blood supply to the joints, which then deteriorate by adolescence. People who cannot feel pain are nearly all dead by age thirty.

Generalized aches and pains, or merely feeling out of sorts (malaise, in medical terminology), are also adaptive. They encourage a general inactivity, not just disuse of damaged parts. That this is adaptive is widely recognized in the belief that it is wise to stay in bed when you are sick. Inactivity also likely favors the effectiveness of immunological defenses, repair of damaged tissues, and other host adaptations. Medication that merely makes a sick person feel less sick will interfere with these benefits. This is fine when patients are

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WHY WE GET SICK

well informed about the risks and realize that they are sicker than they feel and should make a special effort to take it easy. Otherwise, a drug-induced feeling of well-being may lead to activity levels that interfere with defensive adaptations or repairs.

DEFENSES BASED ON EXPULSION

he body must have openings for breathing, for the intakeT of nutrients and expulsion of wastes, and for reproduc- tion. Each of these openings offers pathogens an invasion route, and each is endowed with special defense mecha-

nisms. The constant washing of the mouth with saliva kills some pathogens and dislodges others so they can be destroyed by the acid and enzymes in the stomach. The eyes are washed by tears laden with defensive chemicals and the respiratory system by antibody and enzyme-rich secretions that are steadily propelled up to the throat, where they can be swallowed so the invaders can be killed and the protein in the mucus recycled. The ears secrete an antibacterial wax. Projections inside the nose, called turbinates, provide a large surface that warms, moistens, and filters pathogens from the incoming air. Mouth-breathers don’t get the full benefit of this defense and are more subject to infection. The nose and ears have hairs strategically arrayed to keep out insects.

The defenses at each body opening can be quickly increased if danger threatens. Irritation of the nose by a viral infection provokes the discharge of such copious mucus that one can go through a whole box of tissues in a day. Millions of people use nasal sprays each year to block this useful response, but there are remarkably few studies that have investigated whether the use of such devices delays recov- ery from a cold. If they do not demonstrably delay recovery, as seems to be the case from the limited data, it would be evidence that a runny nose is not a defense but an example of a pathogen manipulating the host’s physiology in order to spread itself. Sneezing is obviously a defensive adaptation, but not every sneeze need be adaptive for the sneezer. Some sneezing may possibly be an adaptation that viruses use to disperse themselves.

Irritation deeper in the respiratory tract induces coughing. Cough- ing is made possible by an elaborate mechanism that involves detect-

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SIGNS AND SYMPTOMS OF INFECTIOUS DISEASE

ing foreign matter, processing this information in the brain, stimulat- ing a cough center at the base of the brain, and then coordinating muscle contractions in the chest, the diaphragm, and the tubes in the respiratory tract. All along the lining of these tubes tiny hairs called cilia beat in a steady rhythm, sweeping pathogen-trapping mucus upward. In the urinary tract, periodic flushing washes pathogens away along with the cells on the surface of the urethral lining, which are systematically shed like those on the skin. When the bladder or urethra becomes infected, urination understandably becomes more frequent.

The digestive system has its own special defenses. Bacterial decomposition and fungal growths produce repulsive odors, the repulsiveness being our adaptation to be disinclined to put bad- smelling things into our mouths. If something already in the mouth tastes bad, we spit it out. Taste receptors detect bitter substances that are likely to be poisonous. After we swallow something, there are receptors in the stomach to detect poisons, especially those made by bacteria that multiply in the gastrointestinal tract. When absorbed toxins enter the circulation, they pass by a special group of cells in the brain, the only brain cells directly exposed to the blood. When these cells detect toxins, they stimulate the brain’s chemoreceptor trigger zone to respond first with nausea and then with vomiting. This is why so many drugs are so nauseating, especially the toxic ones used for cancer chemotherapy.

Circulating toxins almost always originate in the stomach, so it is easy to see how vomiting is useful: it ejects the toxin before more is absorbed. What about nausea? The distress of nausea discourages us from eating more of the noxious substance, and its memory discour- ages future sampling of whatever food seemed to cause it. Just a single experience of nausea and vomiting after eating a novel food will cause rats to avoid it for months; people may avoid it for years. This remarkably strong onetime learning was named the “sauce bearnaise syndrome” by Martin Seligman, a psychologist who recognized its sig- nificance after contemplating the untimely loss of his gourmet dinner. Why is the body capable of such a strong association after a single exposure to a food that produces illness? Imagine, for a moment, what would happen to the person who ate poisonous foods repeatedly.

The other end of the intestinal tract has its own defense, diar- rhea. People understandably want to stop diarrhea, but if relief comes from merely blocking the defense, there is likely to be some

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WHY WE GET SICK

penalty. Indeed, H. L. DuPont and Richard Hornick, infectious dis- ease experts at the University of Texas, found just this. They infected twenty-five volunteers with Shigella, a bacterium that induces severe diarrhea. Those who were treated with drugs to stop the diarrhea stayed feverish and toxic twice as long as those who did not. Five out of six who received the antidiarrheal drug Lomotil continued to have Shigella in their stools, compared to two out of six who did not receive the drug. The researchers concluded, “Lomotil may be contraindicated in shigellosis. Diarrhea may rep- resent a defense mechanism.” Consumers will no doubt want to know when they should and should not take such medications for more commonplace diarrhea, but the needed research has not been done. There are dozens of studies of side effects, of safety, and of the effectiveness of medications that block diarrhea, but few con- sider the consequences of the main effect of blocking a normal defense.

Our reproductive machinery requires yet another opening, which in males is the same as that of the urinary tract, whose defenses thereby do double duty. Women have a separate opening that poses a special problem for defense against infection. While the female reproductive tract uses many defenses, such as cervical mucus and its antibacterial properties, one largely unappreciated defense is the normal outward movement of secretions that makes it difficult for bacteria and viruses to gain access. These secretions move steadily from the abdominal cav- ity through the fallopian tubes, uterus, cervix, and vagina to the out- side. There is one noteworthy exception to this constant downstream movement. Sperm cells swim upstream, from the vagina through the uterus into the fallopian tubes and the pelvic cavity. Unusually small for human cells, sperm are still large compared to bacteria. Potential pathogens can stick to sperm cells and be transported from the outside to deep within a woman’s reproductive system.

Only recently has the threat of sperm-borne pathogens been rec- ognized. Biologist Margie Profet notes that menstruation has sub- stantial costs and argues that it must therefore give some compensating benefit. After a consideration of the evidence, she con- cluded that many aspects of menstruation seem designed as an effec- tive defense against uterine infection. The same anti-infection benefits that come from sloughing off skin cells are achieved by the periodic extrusion of the lining of the uterus. This is supported by evidence that menstrual blood differs from circulating blood in ways

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SIGNS AND SYMPTOMS OF INFECTIOUS DISEASE

that make it more effective in destroying pathogens while minimizing losses of nutrients. Studies of menstruation in other mammals sug- gest that each species menstruates to just the extent appropriate for its vulnerability to sperm-borne pathogens. The threat is small for species that restrict their sexual behavior to widely separated fertile periods, but women’s continuous sexual attractiveness and receptiv- ity are largely unrelated to the ovulatory cycle. This extraordinary amount of human sexual activity may have its benefits, as we will dis- cuss in Chapter 13, but it substantially increases the risk of infection. This risk may be responsible for the unusually profuse human men- strual discharge, as compared to other mammals’.

We have mentioned several times that evolutionary hypotheses need to be and can be tested. Beverly Strassmann has mounted a chal- lenge to the hypothesis that menstruation protects against infection. She maintains that the pathogen load in the reproductive tract is the same before and after menstruation, that menstruation does not increase when there is infection, and that there is no consistent rela- tionship between the amount of sperm females in a particular species are exposed to and the amount of menstrual flow. As an alternative explanation, Strassmann proposes that the degree of shedding or reabsorption of the uterine lining depends on the metabolic costs of maintaining it or shedding it, a hypothesis that she supports with comparisons between species and the relationship between menstru- ation and the body weight of the female and her neonate. Obviously, we have not heard the last word on this issue.

MECHANISMS TO ATTACK INVADERSV vertebrates in general, and mammals in particular, have amazingly effective immunological defenses that are in essence a system of carefully targeted chemical warfare. Cells called macrophages constantly wander the body

searching for any foreign protein, whether from a bacterium, a bit of dirt in the skin, or a cancer cell. When they find such an intruder, the macrophages transfer it to a helper T cell, which then finds and stim- ulates whichever white blood cells can make a protein (called an anti- body) that binds specifically to that particular foreign protein (an antigen). Antibodies bind to antigens on the surfaces of bacteria,

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