WAR AGAINST THE IMMUNE SYSTEM OF THE HUMAN BODY

Between 1348 and 1666, the Black Plague killed over 25 million people and in the eighteenth century, sixty million died from small pox. There were 300,000 victims of cholera in the year 1866 in Eastern Europe. Between 1876 and 1877, as many as 18 million died in India from that same disease. Then in 1889 and 1890, over 40 percent of the world's population died from influenza. Between then and 1917, many more millions died from the plague and cholera and then between the years 1917 and 1919, twenty-five million died from influenza with half a million of the victims dying from that disease in North America alone.

Mankind has been victimized by infectious diseases since the beginning of recorded time but has somehow managed to avoid total extinction by pestilence.

The victims of these diseases couldn't protect themselves from the onslaught of the pestilence because most if not all the diseases were in some way airborne, or the victims were infected by the bite of insects and in millions of cases, the diseases were easily transmittable by mere touch by other human beings alone. However many more millions were attacked by the diseases and yet they survived because their immune systems came to their aid and fought off the pestilent invaders.

 The immune system works in a miraculous way that can only be described as being both incredible and miraculous. A hypothetical scenario of this miracle is as follows;

The year is 1935 and John Davidson works at the docks and stops to light up his cigarette. Unbeknown to him, a rat from Uganda which somehow got off the nearby ship and is now dead and lying nearby, is infected with Bubonic Plague. One of the infected fleas has jumped over to John and lands on his shoe. Its next jump takes it to John's sock and finally the persevering flea jumps to John's bare leg. While John is still standing beside a crate having his cigarette, the flea bites into John's leg in search of blood.

The flea injects into John's leg a chemical that is used by the flea to stimulate local blood flow in John’s leg so that it can draw out the blood from his leg. At the same time, it also injects about fifteen thousand Yersina pestis bacilli (a rod-shaped form of bacteria which causes plague in rats and humans). Some of John's cells are killed outright by the insertion of the fleas' proboscis, (narrow tube) through his skin.

 Chemical messages in John’s body sent from the invasion point alert John's cellular armies and the defensive cells (called histiocytes) that are closest to the tiny wound begin moving toward the minute injury in John’s skin which are guided by the increasing concentration of chemical messengers as they near the beachhead of the invasion.

 As John’s defensive histiocytes move closer to the scene of the invasion, they enlarge two and three times their normal size to become macrophages. These new warriors can engulf as many as one hundred ordinary bacteria and destroy them before they in turn perish in the battle.

Alas, the Yersina. pestis is not an ordinary bacterium. The Yersina pestis owes its fearsome reputation to the fact that it has a secret defense system of its own.  While the thousands of bacilli were growing in the low temperature of the flea, it was unable to make any of three important proteins; the capsular antigen called F-1; and two other virulent antigens, V and W.  However, now that the bacilli are in John’s warm body, they can manufacture all three.

Six hours after the invasion begun, the bacilli have surrounded themselves with capsular antigen and have made the other two antigens. The newly created macrophages rushing into the original fray can engulf some of the invaders but by the time the invasion is six hours old, they cannot for the most part engulf any more of the attackers or destroy them.  For this reason, a large proportion of the plague organisms originally injected by the flea multiply freely in the tissue and some that were engulfed originally by the macrophages, begin to multiply in the dead bodies of the macrophages also.

That evening while John is at home eating his supper, he occasionally and absentmindedly scratches his leg. The tiny invasion point by now is infested with  some twenty-two thousand Yersina pestis. Chemical messages announcing the alarm have been sent to every point in John's body to begin fortifying his body’s defenses.

Like defending armies in a country under attack, defensive cells and proteins are mobilized and head toward the invasion site. Some of the chemicals released from the damaged cells break through the walls of the tiny blood vessels near the injury so that the vessels become more porous. Through these minute holes in the blood vessels, the defensive cells, (which are white blood cells called leucocytes) coming to the rescue, pour out and join in the fight against the invaders.

About two-thirds of the white blood cells are called neutrophils and they number up to a hundred thousand for each drop of blood. They each can gobble up five to twenty plague bacilli before dying in the battle from their wounds.

While John is listening to the radio at ten at night, the neutrophils try to halt the invasion while the forces of the Yersina pestis are still in disarray. If the neutrophils succeed, John will never know that he was the victim of Bubonic Plague, albeit only temporarily,.

Unfortunately in John's case, they fail to annihilate the invaders but they in their heroic fight, do kill off more of the bacilli than originally were injected into John's body by the flea. By the time John is ready to go to bed, the tide of the battle seems to be in his favour.

While he is sleeping, the proteins in his body which have been arriving steadily at the invasion site pour out of the holes in the blood vessels. They assist in the mopping up operation. They build a wall around the site in the form of blood clots to prevent the invading bacilli from going beyond the immediate area of the beachhead.

The plague bacilli however secrete enzymes, much like explosives placed against a stone wall by sappers, and the blood-clotted wall is dissolved here and there, making it possible for the remaining surviving invaders to slip through the holes in the wall. After escaping the trap, they fan out and attack the surrounding tissue.

John's body knows that the invading bacilli will live off the land and thrive on iron in John’s body (there are many chemical elements in the human body such as iron) so a signal is sent throughout his body that the stores of iron are to be removed from the blood stream, that network of highways that provides food to all the cells in the body.

Like an embattled city, the fight is fast and furious and the site of the invasion is soon a mass of ruins. Healthy tissue is destroyed and turned into a viscid soup called pus which comprises of tissue debris and dead cells that are both human and bacterial.

The dead defenders have turned into a form of acid and consequently the entire area of the invasion turns more acidic as the battle rages. Like all dead bodies from which poisons and gases escape, substances escaping from the dead defending neutrophil cells causes John's temperature to rise.

Unbeknown to the surviving invaders, when the neutrophil cells originally left the blood vessels to attack the bacilli, they were accompanied by a much smaller number of white cells called monocytes. In the early stages of the invasion after their entry into the tissues, they slowly transformed into the voracious macrophages who could survive the acid conditions. Like soldiers who are recipients of the Congressional Medal of Honor, they charge headlong into the battle ignoring what their possible fate might be.

While John is still sleeping, his body is recognizing the situation it is in and that many of its defenders are being killed off so a signal is sent to John's bone marrow for mobilization of its reserves. The bone marrow contains thirty to a hundred times the number of white blood cells circulating John's body through his blood stream at any one time.  The reserves which are always on duty, comprise of some thirty billion reservists so as an army of home guard, their numbers are immense.

Like armament factories suddenly called into play when in time of war, the bone marrow manufactures more white cells as the defenders at the invasion site are killed off.

The next morning, John goes to work and feels fine except for  the  persistent  itch  and  he is  completely  unaware  of  the immense battle which is taking place in the area of his lower leg.

Many of the plague organisms swallowed by the defenders are not killed and to make matters worse, they are multiplying at an enormous rate. Macrophages are bursting with Yersina pestis and chain-like columns of plague bacilli unharmed by the weapons of the defenders, are breaking out the bodies of the defensive cells.

A general paralysis of the cellular defenses is now taking place. The endotoxin in the bacillis is stopping the entry of the defending white cells from going into the battle zone. The invaders have gained a firm foothold in John's lower leg.  But the bacilli don't intend to encamp there. They intend to conquer John's entire body.

To do so, they must break free from the ruins of the battle zone and reach the bloodstream either directly to the arteries, those super highways in the body, or to the slower but more extensive secondary roads--the lymphatic system. They choose the latter because with the exception of the intestine, the walls of blood vessels are impermeable to bacteria, even Yersina pestis.

The lymphatics are scavengers and are receptive to visitors from the outside and inside the human body, such as bacteria and cell debris entering its system. This scavenging ability of the lymphatics is essential to the human body because without it we would die within twenty-four hours. Unfortunately the receptiveness of accepting bacteria makes the lymphatic vessels a perfect entry point for the Yersina pestis.  The lymphatics can't distinguish between harmless bacteria and the deadly plague bacterium and for this reason, they wave the invaders on through.  Having entered the hinterland of John's body through the entry points of his lymphatic system, the real invasion of John's body has begun.

A week has now passed since John Davidson was bitten by a flea carrying the Bubonic Plague and the deadly bacilli that survived the defenses of John's body at the site of the initial invasion; has by now entered John’s lymph vessels without any response from the defensive forces in his body. .

When the bacilli entered the lymphatic vessels near the point where the plague carrying flea had made its injection, they couldn't return to the beachhead and the ruins of the immediate surrounding areas from whence they had come. John’s lymphatic vessels have built walls that are constructed of overlapping cells laid side by side like shingles on a roof. The invading bacterium are now borne on a minuscule current in the extracellular fluid, which causes each shingle-like cell of the vessels to bend inwards permitting each and every plague bacilli to enter the vessels. Once inside, the bacilli are unable to return from whence they came by returning through the temporary opening created for them by their infinitesimal weight because the pressures inside the vessels only permitted the cells to open inward and not outward.

Although the walls of the lymphatic vessels generally engulf and dissolve invading bacterium, which then releases substances from the dying defending cells which in turn causes bright red streaks marking the lymph vessels; nothing like that actually occurs when the plague bacilli enter the vessels. Instead, the deadly plague bacilli are borne undetected and uneventfully they flow along the lymphatic vessels through the pressure of the muscles of the body in motion, towards the body's next line of defense, that bristling fortification known as the lymph nodes.

The beanlike lymph nodes into which lymph vessels enter and from which larger ones exit; are located at various places throughout the body but especially at the elbows, knees, armpits and the groin. It is at the lymph nodes that the granular leukocytes are manufactured and are crammed with these cellular defenders. The nodes thus form a secondary line of defense. Since John was bitten by the infected flea in his lower leg, the attacking plague bacilli headed directly towards the deep lymphatic nodes in his thigh. If they are to conquer John's entire body, they have to first annihilate this fortress.

Over a period of a week, little groups of plague bacilli have been formed here and there along the lymph vessel only to die by the thousands as their food supply is exhausted or by the never-ending suicidal onslaught of the unforgiving defensive cells sent down the lymphatic vessel from the fortress in his thigh. Despite these skirmishes, the attacking bacilli have multiplied and what was an initial invading force of 15,000 plague bacilli, is now an enormous army of three million invaders.

Deep within the area of John's thigh rages a struggle between the millions of invaders and the equally large number of defenders. Millions on both sides die in the struggle but the invaders are multiplying faster than the defenders can kill them. When  the  invaders  die,  toxins  are  released,  and  with  the substances released from his own dead defensive cells, John's sense of well being is effected. The battle is so fierce and the death of so many defenders and attackers alike so great that it eventually demands his conscious attention. The temperature of his body has risen to 100º F (38.6º C.) and his skin is hot to the touch.

The next day, several million plague bacilli have arrived at the lymph nodes in his thigh. Here they encounter a vast labyrinthine sponge consisting of defensive cells. It is the role of these desperate defenders to fight off the attackers because if they fail, there will be nothing to stop the invading army from spreading outwards towards John's vital organs and when that happens, there is nothing that can save John's life.

The battle is furious as the attacking bacilli enter the convoluted maze of lymph nodes in John's thigh. The Yersina pestis attempt to paralyze the macropages with their toxin, antigen and enzyme.  If they succeed, they will render the macrophages  harmless and therefore prevent them from engulfing and destroying the invading bacilli. 

Alas, the invaders do succeed because the attacking bacilli have coagulated John's blood in the area of the battle and unfortunately sealed off the battle zone so that John’s white blood cells rushing into to help the macrophages cannot reach them in time to stop the invasion force from proceeding further.

Millions more of the entrapped defenders inside the battle zone die and the lymph nodes swell with the bloated bodies of the macrophages. As the swelling increases, the nodes merge into a formless lump, which at first is quite small, but eventually grows in size until it becomes quite noticeable and very painful. The pain is usually caused by the decay or decomposure of the skin while the person is still alive.  (Mumps causes the same kind of swelling in the lymphatic nodes of the neck)

John now stays home and as the day wears on; he develops an agonizing headache and walks pathetically around the house. He loses his balance, the room reeling as if he had just stepped off of a spinning ride at an amusement park.  His back and legs ache and what little he eats, he promptly vomits. He gets under the covers of his bed and shivers with cold. Then his temperature rises to 103º F. (39.5º C.)

By the next morning, many thousands of the invaders have reached John's bloodstream. The blood-cleansing organs—liver, spleen and bone marrow quickly trap and destroy most of the invaders that entered the bloodstream for the invader's numbers are small and can't fight off the larger masses of defenders sent by these organs. But others escape the fury of the defenders and proceed through the bloodstream for the most  part, unmolested.  John can take no more of the pain so he calls his doctor who then rushes him to the hospital.

By now his temperature is 104 º F. (40 º C.) and he staggers about, his co-ordination poor and he slurs his words as if he is a drunk. The doctors notice a small sore area high on his leg between his thigh and his scrotum. His tongue is coated with a creamy-like fur substance.

The battle in the femoral lymph nodes is only beginning. The macrophages still alive in the nodes join the neutrophils and blood proteins from the surrounding blood vessels in their desperate attempt to kill of the marauding plague bacilli. For the defenders, there can be no strategic withdrawal. What was an invasion and later a skirmish and later on a battle, is now an outright war in which no quarter can be given.

As the war rages in the area of the femoral lymph nodes, thousands of bacilli that had survived the skirmishes in the bloodstream have reached John's lungs. There they briefly position themselves, then multiply, only to be overcome by the defending macrophages in the lungs.

For a few hours, John's sputum contains many of the attacking Yersina pestis but they soon disappear. His heartbeat is irregular and much faster, up more than 110 from its usual 72. His eyes are becoming noticeably bloodshot and a foul-smelling coating is forming on his lips, teeth and tongue.  Even when he is near the state of unconsciousness, he screams in agony when an orderly washing him gently presses down on the pea-sized sore spots on his thigh.

By the third day in the hospital, the treatment and medicine he receives brings him little relief. He is getting penicillin but his temperature continues to remain high.  The doctors still don't know what it is that he has because the samples of the plague bacilli taken from his fluids have not yet been cultured enough for further tests.

His speech is no better and much of the time he doesn't know where he is. The pea-sized inflammation on his thigh has now grown to the size of a golf ball and has  become excruciatingly painful to the slightest touch. It has become hard in the centre as the dead defenders and attackers alike are compressed together and the remainder of the growth is surrounded by gelatinous, swollen and inflamed tissue.

The next morning his temperature drops a few degrees but by evening its soars to new heights. The mass on his thigh has now grown to the size of an orange. He cannot speak coherently, and is in immense pain most of his waking hours.

By the time the doctors realize that John has Bubonic Plague, he is already dying from the disease. It is not known at this time if John's defenses can successfully overcome the millions of deadly plague bacilli heading towards his vital organs in the final battle for his life.    

As John Davidson lays dying in the hospital from the effects of the bite from the Bubonic Plague infested flea 11 days earlier, neither he nor his doctors really know just how or if his immune system can pull him through. It is the year 1935 and doctors aren't as informed in the science of immunology as they will be half a century later.

He has been in the hospital for four days and his bone marrow which can produce up to 100 billion defensive white blood cells (neutrophils) a day is working around the clock to replace the millions of foot soldiers that are sent into John's blood stream and dying at every battle.  If while clinging to the blood vessels, they don't find any of the invading bacilli passing by  on  their  way  to  his  vital  organs,  they  will  die  of old age in only six hours.

Most neutrophils in the blood vessels don't actually circulate but instead cling to the inner surfaces of the blood vessels. At any time, at least two-thirds of these foot soldiers crawl along the surface of the vessels like amoebas. They crawl through the tissues with the same speed as when crawling along the blood vessels—approximately three times their own length in any given minute.

The dying invading bacilli, and the immunological defenders, tissues, and clotting blood exuded chemicals that inexorably draw the newly created white blood cells towards unharmed by the weapons of the defenders site of the nearest battle in much the same way a shark is drawn to blood miles away.

From inside the capillary walls, neutrophils and monocytes squeeze through blood vessels and into the tissues by motion alone. Through the pores between the cells of capillary walls, the white blood cells extend fingerlike projections from their soft bodies. With part of their cell membranes on both sides of the capillaries, the neutrophils (defending cells) and monocytes (invading cells) slowly ooze out into the tissues.

The invaders have entered the tissues in John's body and when they come face to face with the neutrophils, the individual struggles begin in earnest. The long thin fingerlike projections of each neutrophil reaches around an invader until the plague bacilli is completely enclosed by the projections. The neutrophil surrounds itself and its enemy in a capsule called phagosome. Then the phagosome breaks free of the neutrophil's outer membrane and the invader and the two fighting entities float in the bubble-like substance. The  neutrophil  releases  a  granule  filled  with powerful  enzymes  which  then  comes  in  contact  with the phagosome. The two chambers fuse and the granule spews its contents into the phagosome, and after the neutrophil discharges a synthetic hydrogen peroxide which is used to burn through the tough bacterial membrane of the bacterium, the latter is disintegrated.

The battle rages on for many hours until the defensive cells have overwhelmed the invaders and killed them off. Millions on both sides were killed in the war but John’s bone marrow is still intact and can manufacture millions of more defensive cells that will fight future invaders and yes, there will be future invaders and John‘s body will be primed and ready for them.                           

Several classes of antibiotics are effective in treating bubonic plague. These include aminoglycosides such as streptomycin and gentamicin, tetracyclines (especially doxycycline), and the fluoroquinolone ciprofloxacin. Mortality associated with treated cases of bubonic plague is about 1-15%, compared to a mortality rate of 50-90% in untreated cases.

John was smart enough to suspect that something was definitely wrong with him and for this reason he went to his doctor and survived the war that was going on inside of him. Now his body has the task of rebuilding the damaged areas in his body where the invaders had entered and to remove the bodies of the deceased invaders and his deceased defenders at the same time.