UPDATED: 12/22/99 UPDATED: 12/22/99 
MICROBIOLOGY | GENETICS | MEDICAL
Gene Therapy To Activate Entire Human Immune System Against Cancer
Possibility of flu epidemic; Nasal spray vaccine against flu.
Detecting Nosocomial Legionnaires' Disease For the Nurses and Civil Engineers (Why the latter?)
The universal principle of molecular recognition. Biological molecules interact by recognizing and binding with one another in a highly specific manner. Pairs of molecules that interact in this way are called RECEPTORS or BINDING SITES and LIGANDS respectively. Specific regions of atoms (molecular domains) on a receptor molecule have the characteristic of binding or attaching (docking) specifically to unique molecular domains on specific ligands. Following this binding something happens depending on the system involved. In this chapter we will see how the defense system of our bodies recognizes certain molecules of pathogens which in turn triggers a specific series of defensive reactions that defend us from many pathogens. Permission to use this cartoon was granted by Sigma Chemical Co.
Time once again for some rote memory stuff to provide a BASE for advancing to true understanding. Many of these terms are familiar to you as they have been used previously.
DISEASE = Any change from a state of good health. Classes of diseases include:
- Hereditary diseases: Cystic fibrosis; many genetic mutations in a certain gene cause this.
- Dietary diseases: Vitamin, mineral, protein deficiencies; mental/physical problems
- Environmental diseases: Smog/air pollution; lung diseases. Also includes poverty & host (child) abuse leading to mental illness.
- Microbial Induced Diseases
- INFECTIOUS DISEASES: Diseases caused by the growth of a microbe in a host. In this section we will be concerned only with this type.
- TOXIN INDUCED DISEASES: Disease caused by toxins produced by microbes, in which case the living microbe does not have to be present in the affected host.
FAQ: "What do you mean exactly by GOOD HEALTH?"
ANSWER: This is a statistical definition based on appearance and knowledge of a person's physical condition. That is, one looks at the general population and defines people as being healthy or ill at the moment of viewing them. For example, a person may have a headache or a mild cold one day & thus is said to be ill, but 2 days later this same person would be defined as healthy. However, if that same person is then diagnosed with an HIV infection they would immediately be switched to the ill category regardless of how they appeared or felt.
ETIOLOGICAL AGENT = This
is the organism (species or strain) responsible for producing a disease.
SYMBIOSIS = An association between two or more different organisms that has evolved to a
state where they are generally found in association with each other under natural
conditions and where one or both members of the association benefits from the
relationship; e.g. E. coli and humans.
NORMAL FLORA = The organisms normally found on or in a healthy
host MOST OF THE TIME.
For example, if we were to culture organisms in the mouths of every healthy person in this
audience, we would probably find that all of them had a large percentage of the same
microbes inhabiting their mouths.
PARASITE = A type of symbiosis where an organism lives on or in a host & OBTAINS NUTRIENTS from that host.
Note that a parasite DOES NOT NECESSARILY harm the host and in some cases their presence is even beneficial to the host.
However, in most of these cases ONLY ONE of the associates TRULY BENEFITS from the association.
- Head lice
- Fleas on your pets
- Pin Worms
For example, older people, like yours truly, often have tiny mites that live in our ever-expanding eyebrows. These insects apparently live off the dead skin cells, oil and excretions from our sweat glands and they do us no apparent harm or good. They are just one more inhabitant of the planet HURLBERT.
PATHOGEN = A parasite that causes a
disease in its host.
INFECTION = Growth on or in a host. Again this growth may or may not harm the host.
INFESTATION = An infection with a larger (than single cell) organism. Click here for a
really gross example of an infestation (I dare you!). Click here for a
picture of the pubic louse; if this doesn't make you want to practice SAFE SEX I don't
know what will.
MUTUALISTIC SYMBIOSIS = A
situation where two or more species live together in a situation where BOTH BENEFIT from the association.
In some cases one or more of the symbiotic species are totally dependent on the other.
Consider the following when you are FRENCH KISSING your "significant other";
many microbial species inhabit our mouths. Some of these species do us harm by
contributing to the production of cavities in our teeth, but many of them are thought to
be beneficial because they OUT-COMPETE harmful microbes that otherwise would live in our
oral cavity and do us harm in the process; they act as guards protecting our teeth from
the bad guys all for a little food we toss them three times/day.
PATHOGENICITY = The ability to CAUSE A DISEASE. Many organisms are
pathogenic under certain conditions, but some are almost always pathogenic.
For example, chicken pox and the flu are almost always pathogenic. However, photosynthetic
and nitrogen-fixing bacteria are never pathogenic, while the normal bacteria in our gut,
which usually doing us no harm, can become highly pathogenic under specific circumstances
(e.g. getting shot or stabbed in the gut).
VIRULENCE = The DEGREE of pathogenicity. A virulent
organism is one that usually produces a violent and severe disease, often leading to
death. For example, chickenpox and the common cold viruses, while clearly pathogens, are
not considered to be virulent. Whereas Yersinia pestis, the etiological
agent of bubonic plague, and the Ebola virus are both considered virulent.
- These two terms are sometimes used almost interchangeably which can lead to confusion. A practical way of differentiating them is to consider how worried you would be if you were a non-immune person exposed to a potential pathogen. If you find upon having been exposed to organism "X", you yawn, and think "I'll keep my eye on what happens, it is a pathogen, but one unlikely to do me serious harm". Whereas if you get so scared you are unable to poop (or the opposite), it is probably a VIRULENT PATHOGEN.
- The PUCKER FACTOR is another way of expressing the difference. If your exposure to an organism causes you to lose control over certain sphincter muscles in your body you are dealing with a seriously virulent organism.
AVIRULENT
ORGANISM = An avirulent organism is the term used to describe a
mutant of a virulent pathogen that has LOST its ability to produce a disease.
OPPORTUNISTIC PATHOGEN = A normal
flora organism that NORMALLY is not a pathogen, but that becomes pathogenic when inoculated into the WRONG PLACE or when the host becomes
WEAKENED and IMMUNOLOGICALLY COMPROMISED. An
immunologically compromised host is one whose immune system is NOT WORKING to its full capacity and
thus the host's defenses are weak. Generally people who are undergoing chemotherapy for
cancer treatment are immunologically compromised because the drugs harm the immune system.
However, people under stress, such as STUDENTS AT EXAM TIME, often have a lowered immunity
and are more susceptible to catching infections. Do you tend to gets COLDS around exam
time?
Can you identify someone who is seriously immunocompromised (not a stressed out student)?
Symbioses are EXTREMELY COMMON and are probably the norm among life on earth. Further, the majority of the symbioses are probably mutualistic and most of the remainder are likely to be neutral, at least most of the time. That is, the pathogenic symbioses are RARE EXCEPTIONS. I realize that this is of little comfort when you are suffering from the pain and misery of the symbiosis known as the flu, but it is never-the-less true.
I would enjoy taking you through some of the intricate and extraordinary symbioses that have been discovered, but you will have to wait until you get to Chapter 21 for this story. However, the next time you look at a cow munching grass in a field producing your milk or next hamburger, consider that it is a prime example of a mutualistic symbiosis between a mammal and microbes, neither of which could exist on earth without the other. So ponder this question; "Is the cow here to preserve the many microbial species that require it as a host or are the microbes here to maintain the cow?"
We are in the era of defining the MOLECULAR EVENTS that allow a pathogen to do its thing by defeating the rather impressive defense systems that hosts throw up against them. By the end of most of your lifetimes we will understand the pathogenicity of most disease organisms. This section will begin by describing the various levels of DEFENSE AGAINST PATHOGENS that humans are born with; you might say they are the "standard equipment" we all come with. Following that will be a description of the ways various pathogens use to defeat, subvert or avoid these defense systems. The Nonspecific defense systems (NDS) refer to those defenses that come standard; that is they are the ones everyone ("normal") is born with and they work against a whole range of potential pathogens. The NDSs are considered our FIRST LINE of defense against pathogens. What follows is a list of the NDSs and a brief description of how they work. This knowledge will help you remain healthy by giving you information that will help you prevent infection by pathogens.
Figure 1. Location of major non-specific defense mechanisms.
SKIN: The skin is tough, dry, salty, oily, rich in fatty acids and urea, low in nutrients (lots of dead, empty cells) & thick. The sweat glands secrete a mixture of salt, & fatty acids that inhibit many microbes. It also is home for a host of #NORMAL FLORA organisms that are ANTAGONISTIC to potential pathogens. Also, the normal flora scarf up potential nutrients on the skin surface. We are taught by our mothers from an early age to keep our skin clean, usually to forestall a serious antisocial ODOR PROBLEM. However, the real benefit of this training is that it serves to PROTECT US from potential pathogens. This was amply illustrated during the 1960s when some "HIPPIES" decided to forgo cleanliness as a protest against the establishment (talk about shooting yourself-in-the-foot). The only problem was that they were not very MICROBIOLOGICALLY SMART (in contrast to you), since the only thing this protestation helped was the education of the physicians that saw some skin diseases that hadn't been seen in the western world since the MIDDLE AGES when people were seriously filthy. It seems that by not washing, the balance on the skin was disturbed and pathogens flourished in the rich nutrient provided by a protester's smelly, dirty bodies (kind of takes the bloom off the hippie idea of "free love", doesn't it?). Remember, MOTHER IS USUALLY RIGHT, even for the wrong reasons.
In the early submarines there were no washing amenities, so crews wore the same clothes and did not bath throughout the entire time at sea. It is reported, that on returning to base, sailors standing by the hatches when they were opened sometimes fainted from the fumes. |
FAQ is "Can I wash too much?" ANSWER: Of course you can--one can do anything too much (and many of us do). However, outside of taking 20 showers per day and using sandpaper or a scouring pad to clean with, it is unlikely that any of us are going to overdo cleanliness. My 66 years of observations indicate that the trend is clearly in the opposite direction.
MOUTH AND GASTROINTESTINAL TRACT: Basically we are designed as an inverted tube. The skin on the outside forms a long tube which makes up our DIGESTIVE SYSTEM (Fig. 1). This means that the cells lining this tube are a form of skin cells. As discussed above, the mouth harbors a host of microbes that live more or less permanently, on the inside surface and in the nooks and crannies of the mouth tissues. These microbes are mostly symbiotic and usually do us little harm as long as we remain healthy. Regardless of how thoroughly we brush our teeth this NATURAL FLORA remains literally attached to us. As you might guess from this description, mouth microbes have evolved elaborate systems for "sticking" to things: remember #pili? By preventing other, potential pathogens from establishing themselves, they protect us. In addition, there is a continuous flow of fluid (saliva) through the mouth which FLUSHES loose microbes into the stomach.
The stomach (Fig. 1), as anyone who has barfed, or belched strongly, knows, contains a strong (hydrochloric) acid. Many microbes are killed by this acidic environment and digested by the proteolytic enzymes in the digestive system. Until fairly recently it was even suggested that the stomach was essentially sterile due to the low pH. However, with the discovery of the bacterium #Helicobacter pylori that lives happily in the stomach and causes dreadful things like ulcers and stomach cancer, we know this is not the case. This knowledge is not being applied as rapidly as necessary to the #treatment of ulcers.
The small intestine (Fig. 1) is full of DIGESTIVE ENZYMES and DETERGENTS (bile) that agreeably digests microbes as well as hamburger & pizza. Further, even though the small intestine may be full of nutrients, the adsorption system of the healthy body is so efficient that these nutrients are ABSORBED from the intestine so rapidly that residential microbes have little to live on. Further, the intestines are anaerobic, so obligate aerobes are unable to grow there even if they should survive the trip through the stomach.
The large intestine (Fig. 1) is a different story as it collects and processes undigested material that passes through the small intestine. Bacteria, including some very nasty potential pathogens, grow robustly on this debris and yet they rarely manage to invade the body. The wall of the large intestine is coated with a PROTECTIVE MUCOUS LAYER that separates the contents from direct contact with the cells lining the large intestine. The normal flora of the large intestine evolved to live on the available food supply in the anaerobic conditions found there. Feces are approximately 40% bacteria by weight.
Epithelial cells of the mucosal epithelium lining bodily channels that communicate with the air (e.g. the gut, lungs etc.) secrete antibiotic peptides (DEFENSINS) that kill bacteria by membrane disruption.
FAQ: "Are the intestinal gases inflammable?"
ANSWER: Yes, the anal-gases we vent are indeed highly flammable, so I wouldn't recommend demonstrating it to your friends unless you have a fire extinguisher available; Does "TOAST" mean anything to you?
One problem with antibiotics taken by mouth is that they may upset the natural microbial balance and allow unusual microbes to establish themselves in our mouth, intestinal tract or bowel. This often results in intestinal problems (e.g. excess gas and diarrhea) until the original mix of microbes is again established.
GENITOURINARY TRACT: This region of the body is a rich source of infection for obvious reasons. The urine is a good nutrient for many microbes (Fig. 1). In addition the kidneys provide numerous nooks and crannies where microbes can hide from the body's defense systems. Sexual activity SIGNIFICANTLY INCREASES the exposure to potential pathogens. The efficiency of our NDS is shown by the fact that we don't suffer more urogenital infections than we do. Microbes are prevented from reaching the bladder and kidneys mainly due to the vigorous flushing of urine out of the body through the urethra. However, because the urethra is shorter in women than men, bladder infections are more common in women. If you are subject to frequent bladder infections, you should drink lots of water and you should urinate soon after sex to wash out potential pathogens that may have entered the urethra during intercourse. Microbial pathogens that infect this region have #adhesive pili that attach them to the cells lining the urethra and bladder. Cranberry juice has long been reported to help resist urinary track infections and may, in some cases, assist the body in curing such an infection. Recently it has been reported that an antimicrobial substance in cranberry juice has been identified.
The vaginal area (Fig. 1) is another region where infections are easily established. However, the vagina is normally acidic due to the growth of #lactobacilli that produce lactic and acetic acid. Further, there is a continuous outward flow of mucus that expels microbes from the vagina. Finally the entry to the reproductive organs is blocked by a mucous plug much of the time. However, the vaginal lining is THIN AND EASILY DAMAGED by unsuitable physical activity, including the improper use of sanitary napkins, and its rich blood supply makes it an easy entry point for pathogens. The ease of damage to the vaginal lining is a major reason why women are more likely to become infected with the HIV from fewer exposures.
The anal area is another potential source of infection if the natural defenses are not sustained. The anal region is continually exposed to fecal microbes, some like Clostridium perfringens can produce serious or even fatal diseases if they are introduced into the blood or tissue. The mucous covering, while protective as long as it is maintained, is easily breached as is the delicate anal membrane lining itself. Thus anal penetration by foreign objects is very dangerous and explains why STDs are so readily contracted through anal intercourse; i.e., because of the rupture of the membranes blood is released and infectious agents like HIV can more easily enter the blood stream. Regardless of any moral perspective, anal intercourse is not biologically safe as evolution simply did not design it for that purpose (one should listen to Mother Nature!).
Consider the value of sneezing and coughing to the spreading of AIRBORNE RESPIRATORY #VIRUSES to new hosts; a nice evolutionary touch don't you think? Alternatively, it may be a way the host rids itself of the pathogen. |
MISCELLANEOUS NDSs: A variety of other nonspecific defense systems exist. These are summarized in the table below.These include the enzyme LYSOZYME in tears and other body secretions. Lysozyme is an enzyme that LYSES many prokaryotic cells by digesting the #peptidoglycan in their cell walls. Most pathogens require IRON in order to survive, but the blood contains a substance, TRANSFERRIN, that binds free iron so TIGHTLY that many microbes can not obtain enough. The blood also contains various WHITE BLOOD CELLS (WBC-about which we will learn more #shortly) that are programmed to attack anything they don't immediately recognize as being "SELF"; in a nasty world "NONSELF" is likely to be bad, so they "SHOOT FIRST AND ASK QUESTIONS LATER". FEVER seems to inhibit the growth of many pathogens and perhaps speeds up the activities of other defense systems. Finally, there is the series of reactions that contribute to inflammation; including the DILATION (expanding) of blood vessels, and the FORMATION OF CLOTS, which result in localized pain, heat and swelling. These reactions attract WBC & antibodies to any sites of damage and the clots tend to LOCALIZE INFECTIONS so they can be cleaned up by the body's defenses before they spread.
In summary, the combination of mechanical barriers, chemical inhibitors, enzymes and flushing actions all serve to keep us healthy most of the time. Evolution has superbly selected us for survival; we are a very tough species, but our defenses are all too easily breached if we choose (our life-styles) poorly (such as the villain in "Indiana Jones and the Last Crusade" did at the end of the movie).
When viewed from an evolutionary standpoint, the NDS systems are awesome, taking into account the fact that for over 5 million years we humans lived in and survived filth and squalor that would gag a maggot, only being washed when we accidentally got caught in a rain storm or fell into water. Remember, that, not all that long ago, ladies strolled the streets of London holding umbrellas over their heads, not to keep the rain off, but to protect them from the contents of the chamber pots (honey pots) routinely emptied from the upper stories into the streets below. Also perfume was invented to cover up the fact that most humans stank-to-high-heaven for lack of bathing and changing their undies more than monthly (if then). Even in these "enlightened" times well over half of the world's 6 billion peoples live in unsanitary conditions where they are exposed daily to serious pathogens. Yet a significant portion of these people live reasonably long, if odoriferous, lives.
EXAMPLES OF EVOLVED FACTORS AFFECTING HEALTH |
|
| EVOLVED CHARACTERISTIC | EFFECT ON HEALTH AND SURVIVAL |
| COUGHING | CLEAR PATHOGENS; PREVENT PNEUMONIA |
| PAIN | REACTS TO DANGER; AVOIDANCE |
| FEVER | INHIBITS GROWTH OF MANY PATHOGENS |
| IRON SEQUESTERING | STARVES PATHOGENS FOR REQUIRED IRON |
| MORNING SICKNESS | PREVENTS MOTHER FROM EATING FOOD HARMFUL TO FETUS |
| ANXIETY | KNOWING "WHEN TO FOLD" |
| DIARRHEA | EXPELS PATHOGENS |
| RUNNY NOSE | EXPELS PATHOGENS |
| FAT STORAGE | SURVIVE LEAN TIMES |
| NICOTINE, COCAINE, OPIUM ADDICTION | PROTECTS PLANTS FROM INSECTS; HUMANS SHARE COMMON HEREDITY SO THEY BIND TO OUR NERVOUS SYSTEM |
| NAUSEA; VOMITING | EXPEL POSSIBLE TOXINS (BETTER TO PUKE OFTEN THAN DIE ONCE) |
http://129.109.136.65/microbook/ch006.htm; Excellent discussion of the NORMAL FLORA of the body.
Copyright © Dr. R. E. Hurlbert, 1999.
This material may be used for educational purposes only and may not be duplicated for
commercial purposes.
SCIENCE HALL, ROOM 440CA
PHONE: 509-335-5108
FAX: 509-335-1907
E-MAIL: hurlbert@wsu.edu or hurlbert@pullman.com
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