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Lecture notes

continuation of bacteriology

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bacterial diseases & immunology

INTRODUCTION:

 

In spite of our considerable knowledge about diseases most people in undeveloped countries still die of the same infectious diseases that killed their ancestors 10,000 years ago and that are mostly PREVENTABLE. The WHO estimates that approximately 15 million CHILDREN die each year of preventable infectious disease.

 

An infectious disease agent must be able to grow on or in a host and it must do harm to that host. Every infectious disease is characterized by the SYMPTOMS produced in the average victim of that infectious disease. These symptoms, referred to as CLINICAL SYMPTOMS, are used by physicians and health care personnel to identify a particular infectious disease or group of infectious diseases. For example, one set of symptoms identify common upper respiratory diseases (colds). However, the mumps virus has a UNIQUE set of symptoms that are used in diagnosing this particular infectious agent. That is, a single pathogen may produce a clear set of symptoms that allows its easy recognition, whereas a set of identical symptoms (e.g. the ‘runs’, colds, pneumonia) may be produced by a number of different infectious disease agents. Finally, some infectious disease agents cause a variety of different symptoms in different hosts of the same species; AIDS & tuberculosis are two such examples.

 

In describing an infectious disease the agent is identified, if known, the symptoms are described, along with the prognosis & the manner in which the infectious disease is contracted. Molecular biology has given us tools to rapidly identify the probable etiological agent of many common diseases. The combination of DNA fingerprinting and #PCR make it possible to obtain an accurate diagnosis from as little as 10 microliters of a patient’s body fluid (blood, urine, spit, etc) within a few hours rather than the days it has taken in the recent past. The use of fluorescent-labeled antibodies allows organisms in body fluids and tissues to be detected (identified) in a few minutes or less. New techniques (biochips) are in the pipeline that will cut diagnosis time down to a FEW SECONDS in many cases. While it is crucial, diagnosis only IDENTIFIES the etiological agent, but it does not explain how the disease process works or how the patient contacted the infectious disease agent in the first place.

 

HOW MICROBES CAUSE DISEASE

 

Once introduced into a suitable environment, infectious agents begin to grow. At this point the non-specific defense systems of the body often eliminates the intruders without harm, but if the pathogen has the proper weapons it may establish itself and render serious harm on the host. In order to establish itself and produce the subsequent disease a pathogen employs, disease-inducing factors called VIRULENCE FACTORS or VIRULENCE DETERMINANTS. Identification of a pathogen’s virulence determinants and an understanding of their molecular mechanisms of action, allows us to design ways to neutralize or destroy the virulence determinants, thus rendering the pathogen harmless, i.e. we can ‘pull its teeth’ or otherwise ‘neutralize’ it.

 

SEPTICEMIA: This describes the case where the pathogen grows massively within the host. In effect the host becomes a virtual ‘culture tube’ for the pathogen. Bacteria and viruses can be found in the blood and all the organs. Death often ensues when this happens.

 

TOXINS: Toxins are products of a pathogen that destroy/damage/inactivate one or more vital component of the host thus allowing the pathogen to survive and flourish.

EXOTOXINS are toxins that are SECRETED from the cell or leak out of the cell after it dies. Generally they are soluble proteins and thus are carried throughout the body in the blood or lymph, doing damage at a distance from the infection site. Toxins tend to target specific cells in the body. Some are enzymes and others are proteins that bind to and inhibit crucial cellular activities which eventually lead to the death of cells. A special group of toxins, produced only by G-bacteria are called ENDOTOXINS or #LPS.

Examples of toxic virulence determinants include:

  • Diphtheria toxin: an enzyme that blocks protein synthesis in many cells. The bacterium producing this potent toxin grows mainly in the throat, Toxin production only occurs if the bacterium is infected with a certain bacteriophage.
  • Botulism toxin: Inhibits acetylcholine release from motor nerve endings and kills the nerve cells. As will be discussed in the section on “#Food Borne Diseases”, this is the most deadly toxin known. This is an exception to the “infection rule”, since C. botulinum does not have to infect fro the toxin to kill (however, it can infect grow and produce lethal toxin doses in babies). Toxin production only occurs if the bacterium is infected with a certain bacteriophage (different from the diphtheria toxin)
  • Tetanus toxins: Blocks the function certain nerve cells which leads to spastic paralysis of host. The bacterium that produces this toxin is anaerobic and usually grows locally in a puncture wound, such as that from a nail or rose thorn, yet it readily kills grown horses and humans.
  • Endotoxins are composed of #LPS which is only produced by G-bacteria. Endotoxins have a general basic structure, but differ significantly in composition between species. Endotoxins are released in relatively small amounts as the cells grow, but in copious amounts when the cells die. Different endotoxins differ in their degree of toxicity, but all are heat stable and can tolerate autoclaving. Endotoxins harm many systems in the body and hence are very dangerous./ They are often responsible fro the cause of death by G-cells.
  • Endotoxins B: This is a cysteine protease produced by FLESH EATING STREPS that dissolves the material between cells. These streps can move through the tissue at the rate of an inch per hour and antibiotics do not reach them efficiently. Other toxins are released and the tissues dies, sloughs off, tissue fluid and blood leaks out, spreading the infection and the combination of toxins and trauma leads to death. In an attempt to save patients doctor cut off limbs and large areas of flesh in an effort to remove microbes. 

 

Most axotoxins are destroyed by heating to 100oC but some like those of S. aureus food poisoning are resistant to boiling. Some toxins can be converted to TOXOIDS which are no longer, but can stimulate #ANTIBODY PRODUCTION against the toxin. In general the toxins are so powerful that only minimal growth of the producing bacterium is required to effect the disease and the toxin can exert its effects in the absence of the bacterium that produced it.

 

ENZYMES: Pathogens use a variety of enzymes to assist them in establishing infection and producing a disease. There are virulence determinant enzymes that dissolve the glue between cells, thus allowing the bacteria to spread rapidly through the tissue. There are enzymes (hemolysins) that lyse red blood cells and others that lyse white blood cells. There are enzymes that degrade DNA, lipids and proteins.

 

ATTACHMENT SYSTEMS: Since many of the non-specific defenses involve mechanically flushing away pathogens, a common virulence determinant of pathogens are cell components that stuck the bacteria to the target cells. Like the attachment or docking proteins of viruses, these systems stick things to one another. Two general attachment systems have been found. The pili are short protein rods or curled protein strands that have binding proteins on the ends that attach firmly to receptor molecules on the surface of other (host) cells. The other system is that of the capsule. Capsules, as you recall, are composed of sugar polymers (occasionally of protein polymers) that tend to be sticky. These capsules are often produced in large quantities which entrap microbes in sticky masses. For example, the plaque on out teeth is generally composed of a group of microbes acting symbiotically together, through the production of pili and capsules, to stick (like super-glue) to our teeth, gums and tongue. Figure 2 illustrates the action of attachment systems which include pili, capsules and cell wall proteins.

 

SELF DESTRUCTION: Pathogens frequently cause disease by tricking the host cells into doing something they normally wouldn’t  do. One trick is to induce the host system to produce self-destructive chemicals that kill or inhibit its own cells. In doing this the body’s own defense system is redirected towards its own destruction, leaving the invading pathogen to enjoy the delicious and nutritious remains. In fact many of “diseases” caused by both viruses and bacteria are the result of the pathogen “throwing a chemical monkey wrench” into the finely turned and balanced machinery of the host’s body. Pathogens do this by producing chemicals that mimic host’s regulatory chemicals. These “FAKE” substances bind to the host’s cell receptors, or regulatory sites, causing them to turn on or off at in appropriate times. By disrupting the normal   processes of the host, the pathogen may escape destruction or detection; like a crook trying to escape the police who are advancing on him by yelling “fire” in a crowd.

 

CAMOUFLAGE: In this case the pathogen camouflages itself so the host doesn’t recognize the invader as being “non-self” and thus dangerous. One trick is to coat itself with a capsule which the white blood cells either doesn’t recognize or for some other reason avoids ingesting (a YUCK capsule), thus allowing the capsule-covered pathogen to remain free and unhindered. In other cases the pathogen may enter and hide within host cells, thus escaping the patrolling white blood cell guards and their antibody guard dogs. Some pathogens have even developed ways of moving or tunneling from one host cell to another without of the cell so they avoid detection by the defending immune system.

 

STEPS IN THE DISEASE PROCESS

 

For convenience, the disease process is discussed in a series of sequential stages.

 

INFECTION = The pathogen establishes itself in or on the host. It overcomes or avoids the nonspecific defenses and gains a “foothold” which allows it to grow and reproduce. No symptoms are yet present and the host is unaware of then infection. However, with newer molecular biology methods (PCR), we may soon be able to detect the presence of pathogen at this early stage when it is more vulnerable. In many cases the host mounts a successful counter attack once the infection gets large enough for the host to detect it. For example, this is the case with ZITS.

 

INCUBATION PERIOD = This is the period of time it takes for the pathogen to establish itself to the point where the first disease symptoms appear. This varies widely, for most bacteria it takes 2 -5 days, nut for some like T.B. or leprosy it may be 20-30 years. For many viruses it is 3 days to 2 weeks, but for rabies it may take several weeks or even months, whereas AIDS may take up to 10 years to clinically develop if left untreated and with treatment it may take much longer.

 

INITIAL SYMPTONS = These refer to the first symptoms that clearly demonstrate an illness. Since symptoms vary widely between hosts this is statistical matter. One person may have a subclinical case, where they feel mildly ill, but with no clear symptoms, to others that show unusual symptoms that can be mistaken for other diseases. Subclinical cases (asymptomatic cases) are very common as indicated by the large number of people who have antibodies against various diseases, but who have never been clinically diagnosed as having had a given disease.

 

ACUTE = This refers to the classical clinical or textbook symptoms, where the disease is in full flower and the patient is usually seriously or clearly ill.

 

 

The intensity of the illness varies with the disease, the strain of the etiological agent and the condition of the patient. Some disease like chickenpox and the “common cold” are almost always relatively mild and without complications. Others, like bubonic plague or measles are usually severe and life-threatening. Some, like rabies, Ebola and AIDS are close to being 100% fatal. In general, every infectious disease is survivable and every infectious disease can prove fatal to some people.

 

The symptoms and outcome of every disease is dependent on a mixture of many factors. Some of the more obvious include:

 

  • The GENETICS of the host
  • The GENETICS infectious agent; virulent determinants, virulence plasmids etc.
  • The PHYSICAL CONDITION of the host
  • The STRESS encountered by the host during the disease.
  • The AGE & SEX of the host.
  • The TREATMENT of the victim.

 

The complex interplay of these factors makes it difficult to predict the outcome of a disease of any given individual. Disease data is ENIRELY STATISTICAL, like a horse race or the lottery.

 

It is very common for people to have a disease and not to show any identifiable symptoms and yet to become as immune as another person who almost dies from the same disease. In the former case, the individual is said to have had a SUBCLINICAL or asymptomatic case.

 

RECOVERY= Period during which the symptoms decline and the patient recovers. Recovery may take many paths. Six major ones are listed below.

 

            In many cases the etiological agent is totally eliminated and the patient returns to full health.

 

            In other cases, the patient shows a full recovery but the infectious agent is still present. Under these conditions the patient becomes a carrier and remains capable of shedding (spreading) the virulent form of the infectious agent for some period, perhaps for the remainder of their lives. This is the case for disease like Typhoid, Herpes and HPV (Human Papilloma Virus)

 

            Some carriers appear to be fully recovered, but the disease may be progressing slowly towards a fatal outcome, such as may occur with syphilis, #HIV and tuberculosis. Magic Johnson is probably such a case.

 

            Some carriers, like those with Herpes (shingles) and hepatitis have occasional outbreaks of the disease throughout their lives, but they are rarely fatal.

 

            In many cases a disease becomes chronic. The victim makes a partial recovery, but they are still less well than normal and continuously demonstrate symptoms of ill health or have frequent relapses. Many infestations (worms and other large parasites) take this path. Lyme disease can become chronic.

 

            In other cases, the patient recovers and eliminates the infectious agent, but their immune system has been damaged and they subsequently fall victim to autoimmune disease like rheumatoid arthritis.

 

SUMMARY

 

Most of us are born with an efficient defense system, designed over millions of years by evolution to protect us from infectious disease. We cannot change our heredity, but we can learn how to work with it to protect ourselves from disease. We are like a finely tuned racing car which will go the distance if run correctly. However, if we make choices that damage the mechanics of our bodies, or of the car, we can significantly shorten the lives of both and harm the efficiency of their running. Wise choices, based on a knowledge oh how things work will not guarantee that harm will not come to you or the car, for the car may be destroyed in a random collision or you may contract a fatal disease through a paper cut or a stray cosmic ray, but it will increase the favorable odds. No degree of understanding about the mechanism of disease or immunity is capable of overcoming poor decisions regarding health habits and lifestyle.

 

HOW Bordetella pertussis CAUSES WHOOPING COUGH?

 

Recently it has been shown that B. pertussis binds to the ciliated cells of the respiratory system that normally sweep away the mucus. They then produce two substances, tracheal cytotoxin and LPS (endotoxin) which, acting together, induces neighboring cells to produce the gas NO (nitric oxide) which kills the ciliated cell. With the ciliated cells gone the only way to clear the airways of mucus is by violent coughing which serves to expel, not only mucus, but the pathogen thus spreading it in the airborne droplets. Sci. 285:811 (1999)

 

Before a pathogen can cause a disease its host must be exposed or come into physical contact with a pathogen or its toxic products. The transmission of disease producing agents within populations is a PUBLIC HEALTH CONCERN. An infectious pathogen must be presented to its host in a way that will allow it to grow in/on the host in an environment where it can cause a disease. The bacterium staphylococcus aureus frequently lives harmlessly in the nose and on the skin. However, if there is a break in the skin, or if it gets into the proper food, S. aureus can cause serious disease. Similarly, a break in the vaginal or anal mucus membranes allows the entry of a STD infectious agent that might otherwise not gain a foothold. The pathogenic E. coli strain #O157:H7 is harmless if it is rubbed on your skin, but if ingested in an undercooked hamburger or other food it can reach your intestine where it can grow, causing its host to die, or survive with seriously damaged kidneys and a few feet less of your intestine. Similarly, the toxin of the food-borne pathogen Clostridium botulinum must be delivered in a way that will allow it to be absorbed into the blood of the victim.

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