Smallpox: The End of the Eternal War

　　Scientific knowledge
　　variola virus belongs to the pox family of viruses, double-stranded DNA virus, its genome is all the people infected with the virus in the body’s largest, viruses or oval-shaped brick structure, a diameter of about 200nm. Unlike most other DNA viruses, VARV does not replicate in the nucleus of susceptible cells, but in the cytoplasm.

Smallpox virus structure diagram
(1) Frontline

　　Here is the front line.
　　For any immune cell assigned to this zone, the mucosal tissue of the respiratory tract is by no means a place for them to do nothing. Here, every second, there will be a large number of enemies trying to destroy it. Although there are a large number of immune cells, especially lymphocytes, they can only continue to work hard to lock, intercept, and block the unscrupulous people who have crossed the defense line one by one. kill. And then new enemies will appear, endless and endless.
　　① aerobic respiration
　　is movable higher, mainly in the form of respiration of plants, it refers to a cell or microorganism the participation of oxygen by the catalytic action of the various enzymes, the complete oxidative decomposition of organic matter (usually decomposed mainly glucose), to produce carbon dioxide and water, the process of releasing energy and synthesizing large amounts of ATP (exception: nitrifying bacteria produce nitric acid and water by aerobic respiration).
　　The mode of transmission of variola virus
　　smallpox virus is mainly spread through the air in aerosol form, the virus is typically present in the nasopharyngeal secretions of smallpox infection. When an infected person talks, coughs, or sneezes, the virus is excreted in the form of fine aerosol particles, and the susceptible person inhales and becomes infected. Some studies have shown that a few smallpox virus particles may be transmitted through aerosols, causing people to be infected.
　　In addition to aerosol transmission, the virus also exists in the scabs that fall off the skin lesions of convalescent patients, but this is not the main form of transmission. Subcutaneous inoculation of human pox can also cause infection, but the infection caused by these methods does not spread by droplets symptoms are severe.
　　② phagocytic cells in
　　the body have the function of phagocytic cells referred to as macrophages, phagocytic cells and foreign bodies phagocytic and digestive functions of the body aging and death, it is one of the important mechanisms of the body’s natural defenses. Macrophages are a type of phagocytic cells.
　　Since the advent of aerobic respiration, the vast majority of terrestrial organisms must continuously exchange gases and inhale oxygen from the outside to maintain a series of biochemical reactions necessary for survival. But every breath is also dangerous, and in its natural state, the air is full of dangerous molecules: tiny, allergy-causing pollen and biological debris, wind-drifting fungal spores, thriving bacteria and other single cells Organisms, harmful inhalable particulate matter, and the most intractable class of pathogens—viruses. These guys would swarm with every breath, trying to find a breakthrough on the surface of the sizable airway, get into the body, and gain a foothold in this paradise.
　　But the vast majority of them were unsuccessful.
　　”Point 15! Peripheral defenses breached!”
　　”Point 21! Unknown cells touch the lymphatic network!”
　　”Point 40! Specific antigens identified! Confirmed known danger exists! Attack! Attack! Attack!”
　　” Watch out for increased patrols around point 55, which has just suffered an unusually high temperature! A large number of epithelial cells and goblet cells are necrotic, and defenses have been severely weakened, and watch out for possible cancerous insurgents!”
　　”Point 70, the rhinovirus swarm has been captured. A batch of cells! Where’s the devourer support team? Can’t let them get a foothold!”
　　For this batch of immune cells, today is naturally an ordinary, but also extremely busy day. Massive amounts of pathogens and potentially suspicious molecules of all kinds mingled in the contamination frenzy have attacked the area with greater ferocity than ever before. Over the past few days, there have been numerous false alarms all over the mucous membranes of the respiratory tract, as the amount of mixed grass pollen, shrub pollen and dust in the air has surged. Small-scale allergic reactions caused by disordered immune response mechanisms are like wildfires in the wasteland, constantly being ignited by a large amount of dust accumulated on the surface of the respiratory mucosal wall. Ironically, despite the immune system’s best efforts to “fight the fire”, many pathogens managed to get past the initial defense, and were then intercepted, trapped, and eliminated one by one in the second line of defense beneath the mucosal wall, the lymphatic system. . Numerous phagocytes ② commandos continue to attack, wiping out bacteria and other single-celled organisms that have successfully invaded by “hitchhiking” with dust. Interferon and properdin were continually dropped by defenders, sweeping away smaller, more dangerous attackers—viruses.
　　While busy identifying and intercepting a handful of rhinoviruses and human coronaviruses—those that produce only cold symptoms, not dangerous, but troublesome—the immune molecular guards missed a raider. Although this guy is a big guy by virus standards, when more guys with a size in the micrometer flock here, his size of about 300nm is still very inconspicuous, and he is very low-key mixed with a large number of Between invading microbes, the use of a small area of ​​damage caused by a minor burn avoids being dragged by mucus secreted by epithelial cells. At the same time, it did not arouse the alertness of other defenders – they are now rushing to deal with the enemies who directly attack the airway cells, surround and destroy the enemy, or simply destroy the cells that have been hijacked and occupied, and have no time to pay attention. this infiltrator.
　　This is a huge and dangerous misstep.
(2) Veterans

　　The guy who infiltrated the chaos was a dangerous foe, a veteran of a long war. In this long battle, he has evaded countless sieges and interceptions, and time and time again he has passed the defenses of the human immune system, which are regarded by other pathogens as a formidable path. By replicating himself millions of times, ancient war experiences were inscribed in his genetic information, along with the veteran’s memory.
　　The genetic information of the veterans records the glorious era of the smallpox family. Before tens of thousands of winters and summers, they first discovered this host organism called “human” that could be infected by them, and tried to live here. transmission between species of host organisms. New mutations are constantly being made, most of which are failures, and a few successful experiences are written into genetic information and accumulated. Slowly, as they became specialized and highly adapted to humans, the latter also became the sole host for smallpox. In one tough battle after another, the veterans have already figured out the routines of the human immune system. Although the defense of the immune system may seem like a cobweb, there are no gaps, but for veterans, it is useless. Later, the old soldier and his comrades even gradually learned to “eat the enemy because of food”

　　Scientific knowledge
　　of smallpox symptoms of
　　smallpox virus susceptible after being inhaled, respiratory mucosa will implant, causing infection. The virus then metastasizes to the regional lymph nodes, where it replicates and multiplies. In the next three or four days, the virus enters the bloodstream and viremia occurs, but at this time the infected person is asymptomatic. After that, the virus can invade the organs of the whole body through the blood circulation, and continue to replicate and multiply in the spleen, bone marrow and lymph nodes. As the virus continues to replicate and proliferate, after 8 to 10 days, the infected person will develop high fever and toxemia, and the virus in the human leukocytes will also circulate with the blood to the small blood vessels under the dermis and oropharyngeal mucosa, and infect adjacent cells. . At this point, rash lesions develop on the skin, which then develop into blisters and pustules. Because the virus replicates faster at temperatures slightly below 37°C, the rash lesions are more pronounced on the face, hands and legs. Because there is no cuticle in the oropharynx, the injury will soon form an ulcer and release a large amount of smallpox virus into the saliva. The virus titer in the saliva is the highest during this period. Therefore, the patient is also the most infectious.

face rash caused by smallpox virus

　　Scientific knowledge
　　appears smallpox virus
　　, according to historians and virologists speculate that smallpox in humans the beginning of agriculture 10,000 BC settlers appeared. Skin pustules are evident on mummified remains of the 18th Dynasty of Egypt (1580-1350 BC).
　　Scientific knowledge
　　of history of smallpox vaccine
　　history and humanity against smallpox is very long, a thousand years ago, China and India by crusted lesions or pustules liquid human tissues in patients with smallpox vaccination into the skin or by Nasal inhalation for human pox vaccination. This kind of vaccination will cause the vaccinated person to get sick, but its morbidity is not as serious as that of natural infection caused by droplet transmission, and the fatality rate is far lower than that of natural infection. The risk of this vaccination method is not low, and an infected person may transmit smallpox to others.
　　By the late eighteenth century, the dairy regions of Germany and Great Britain knew that people who had vaccinia could no longer get smallpox. In 1796, Edward Jenner scientifically demonstrated experimentally that pustular extracts from people infected with vaccinia could be inoculated into the skin of others, allowing the recipient to develop a localized and limited infection and later to protect the recipient from smallpox. Infect. He called these extracts, which protected the vaccinated from smallpox, “Vaccine,” a word from the Latin “Vacca” for cattle. Later, in memory of Edward Jenner, Pasteur used “Vaccine” to refer to all preventive vaccination substances, which is the term “vaccine” as we know it now. After Edward Jenner demonstrated the effectiveness of the vaccinia vaccine, humans continued to advance the use of vaccinia vaccination to prevent smallpox virus infection.

Edward Jenner vaccinates babies

　　⑧ effector T cell
　　effector T cells are T cells stimulated by antigen, after proliferation, differentiation,
　　cell formation. It is specific and recognizes host cells invaded by antigens. tactics, began to use the defender’s resources to dismantle its own lines of defense. In the past battles, the smallpox virus once achieved countless brilliant and splendid victories, captured one target after another with abundant biomass, and reproduced trillions of compatriots. During that wonderful time, the veterans once thought that the smallpox family would prosper forever and ever…
　　but that was not the case.
　　Not long ago, the veteran had just completed the last replication in a conquered cytoplasm, and fled the previous battlefield with a group of surviving companions, and went their separate ways in the droplets. Unbeknownst to him, most of the Companions either failed to find a new host, or fell to pieces at the start of the invasion. At the end of this long battle, their enemies have firmly gained the upper hand through a technology called “vaccine”.
　　But the veterans attacked nonetheless.
　　After mixing into the mucosal tissue of the respiratory tract, the veteran noticed that the immune cells that were scurrying around did not notice him. Although the surrounding body fluids were full of various antibodies, none of them were directed against him—this was a pleasant surprise. Unlike those compatriots who once ravaged Eurasia and were the first to be wiped out, the veterans are now in the far-flung Horn of Africa, one of the most backward and remote areas on earth for medical technology. Here, the terrible weapon called “vaccine” has not yet spread to every corner.
　　After dodging the ranks of immune cells busy besieging other invaders, the veteran locked down his first target: a lone effector T-cell ③ guard who had been running around the lymphatic vessels on defensive combat missions. The veteran knows well that guys like him are all highly specialized combatants with an impeccable level of performance in their area of ​​expertise. But extreme specialization is a double sword: this guy doesn’t recognize veterans, much less how to fight them. He was overwhelmed when he found out that the veteran had appeared, and this was the opportunity.
　　”You are the one!”
　　As had been done countless times in the long war, the veterans charged at the guard, holding the other down. By binding the protein membrane to the target’s cell membrane, his genetic material quickly entered the cell, began to disassemble the cell’s constituents from the inside, and replicated massively in the cytoplasm, reconfiguring the target into its own components. Soon, the guard was disintegrated into an empty shell full of holes, and the replicas of a large number of veterans quickly took shape in this empty shell.
　　Everything is done neatly, as has been done in the tens of billions of battles that have happened in the past.
　　Although the fact that the companion was raided was discovered, the antigen-specific immune cells in the lymphatic vessels were helpless – they were too specialized in fighting a specific enemy, and there was no way to deal with an opponent like a veteran who had never met. The veteran was relieved by the reaction of these guys: In the distant past, before the odious opponent known as the “vaccine” appeared, there was a high probability that he would encounter this kind of bewildered and inexperienced pitiful Target. But now, there are very few prey that can be easily obtained. This may be his last luck.
　　Veterans will never let go of such luck.
(3) Raid

　　Of course, even if nothing is known about the true identities of the veterans, the enemy is not inactive—they have their own set of rules for engaging unidentified invaders. Soon, a group of huge and ferocious devourers rushed over and locked the immune cells that had become veterans to breed the same raw materials. Then, they opened their bloody mouths and swallowed the apparently abnormal former companion directly.

　　But the veterans are not afraid.
　　These non-specific immune cells are indeed terrifying ultimate predators of all kinds of big fish, especially the mess of cocci, streptococci and bacilli. Once captured and swallowed, there is no reason to escape. But for the veteran, the clumsy Devourers make for a very suitable target, especially now that he has managed to take his first target and create many of his kind. Following the old soldier’s order, his new born kind soon swarmed up and began to attack the Devourers.

　　④ viremia
　　medical terminology, refers to the case of the virus into the bloodstream. The virus first replicates and proliferates in the local mucosa or subcutaneous tissue that invades the body, then spreads to the regional lymph nodes, and then enters the blood circulatory system through the distal lymphatic vessels and thoracic duct to form viremia.
　　The gigantic Devourers were bewildered—their way of fighting was always to attack foes of similar size, rather than face these tiny but aggressive “wolves.” In the blink of an eye, the swarms of tiny enemies invaded the bodies of the Devourers one after another, dismantling these huge opponents from the inside like David knocking down Goliath. One by one, the Devourers eventually became full of enemies. , and fell apart one after another.
　　A sweeping battle begins immediately.
　　As entire teams of overwhelmed defenders were captured and destroyed, the defenses of the mucous membranes of the respiratory tract began to crumble. The intruders, who found that the guards were severely undernumbered, realized that a godsend had appeared before their eyes. In the cheers, these invaders quickly overwhelmed the severely insufficient defenders and rushed towards the gluttonous feast in front of them. Infection and inflammation broke out one after another, bringing the chaotic storm to every corner, and a large number of immune cells also moved. to stop these intruders.
　　But the veteran is no longer here.
　　Unlike fish-like invaders whose immune systems are terrified, veterans have learned at the dawn of this long war that the most dangerous places can often be the safest places. He commanded his companions to move quickly along the lymphatic system used by the enemy to dispatch troops, constantly attacking the immune cell reinforcements that were ordered to rush to the front but did not know who the real enemy was, and continued to grow himself. The lymphoid tissue near the initial invasion point was first hit hard, and then various cells along the way were also attacked separately, a large number of leukocyte phagocytosis were destroyed in large numbers, and a viremia broke out immediately. At the same time, the veteran took a group of companions to the tonsils, an important stronghold of the Immune System Corps, and his next main base of operations.
　　In the vast majority of cases, an intruder who is lucky enough to break through the epidermal and mucosal defenses will stay away from the tonsils, or only when it occasionally malfunctions, will it take advantage of the emptiness of defenses to launch an attack here. But the veterans didn’t care whether the defenses there were empty or not. For him, a crowd of inexperienced defenders was the best prey in itself.
　　The raid unfolded swiftly, and was a quick success—fast enough to catch the defenders, who had been hastily assembled to fight the burgeoning infection, caught off guard. Soon, the stronghold of this immune cell army became a hunting ground, and a large number of immune cells that were ready to hunt the enemy suddenly found that they had become prey instead. In a very short period of time, veterans and their likes began to spread, replicate in large numbers in the tonsils, and transfer to new battlefields through the extended lymphatic system.
　　Now, timing is everything.
　　Although so far, the group of invaders has not encountered effective resistance, but the experience of the veteran tells him that the other side is not powerless to fight back. As a large number of immune cells in the lymphatic and blood systems are violently attacked, a large number of intracellular substances are released into the blood, which in turn triggers a series of complex immune responses. Sentinel cells such as macrophages recognize cellular damage and immediately produce inflammatory mediators. Inflammatory mediators activate the vascular response and the leukocyte response, causing a large number of leukocytes and plasma proteins to gather and kill foreign enemies. Veterans know that this is an inflammatory response, an important defense response in the body that prevents pathogens from spreading throughout the body and clears overrun cells. As the captured cells are cleaned up by inflammatory weapons one by one, and the virus particles that have not yet matured in them are also annihilated, and the dream of mass replication here is gradually shattered.
　　But veterans don’t see it that way.
(4) Final game

　　With the main blood circulation and lymphatic system gradually reduced to a messy battlefield, the veterans issued orders to transfer positions. The surviving compatriots gave up and stopped pursuing the defenders who had been beaten to pieces. They withdraw from the main arteries and veins and retreat into the capillaries, the ends of the circulatory system. Through these inconspicuous trails, they were able to get closer to the surface of the human body.
　　What makes the veterans happy is that under the inflammation, the already broken and chaotic immune system legion has not pursued it. Just busy and taking advantage of the various germs and parasites to kill, has already greatly damaged the strength. They are overwhelmed. Because of this, although the newly born lymphocytes have begun to have the ability to recognize and fight against these new enemies, the strategic transfer of the veterans has not been hindered too violently.
　　In the capillaries near the epidermis, the veterans gathered their companions who had escaped the blow of the inflammatory weapon, and began the final action: they began to team up to attack the skin cells that lacked the ability to resist, disintegrate their internal structure, and release the water and nutrients in the cytoplasm. Substances disintegrate, mix, and become the nectar that nourishes the next generation. In one conquered area after another, these short-lived Gardens of Eden are rising one after another, and the final series of replication and reproduction swiftly unfolds. Of course, there is also a battle between more and more immune cells, and as in the past, the opponents of the veterans are by no means incompetent. After the initial catastrophic raid, the immune cells knew exactly what the new enemy was doing and produced targeted antibodies. The reconstituted army of immune cells has become hunters again, and vows to wipe out these daring men in one fell swoop.
　　Scientific knowledge
　　eradication of smallpox virus
　　smallpox virus no animal host, who does not carry a long-term, in order to survive it must continuously spread from person to person, so after the vaccine appeared, there was the possibility of eradication of smallpox. The eradication of smallpox is the result of the concerted efforts of many people, including the large-scale commercial production, preservation, transportation and organization of large-scale, correct and effective vaccination of smallpox vaccine. By October 26, 1979, the United Nations World Health Organization announced in Nairobi, the capital of Kenya, that the world had eradicated smallpox.
　　So far, only the Atlanta Center for Disease Control and Prevention and the Russian National Research Center for Viruses and Biotechnology have preserved smallpox virus. But now, the world’s population has weakened or no immunity to smallpox, so the possibility of smallpox virus as a biological weapon is still a concern of various countries. Therefore, measures to prevent and control smallpox should still be taken into consideration.

WHO declares smallpox eradication

　　When he found a large number of opponents, the veteran knew that his comrades who failed to move in time were mostly dead, and the battle ended in their defeats—but it didn’t matter. The smallpox family has never cared whether the host can survive or not. As long as enough offspring can be reproduced like now, the combat mission itself has been achieved. Soon, as the pustules bulging on the surface of the skin burst one after another, the veteran and his thousands of copies escaped from this already extremely dangerous battlefield–he was confident that these companions would preserve the hope of survival. Down, forever…
　　but this time, he was wrong.
　　This is the last victory for the veteran and the veteran family. In East Africa in 1977, the veteran who completed the last raid finally had nowhere to go. All the infected objects that he and his companions could come into contact with had already been baptized with weapons called “vaccine”. Next time, veterans trying to open up new battlefields will be identified at the beginning of the invasion and annihilated on the spot. And this is also the end of his long journey. Unlike those smart relatives who have already reduced the harm, and even directly inserted their genomes into human genes to “hitchhike”, veteran soldiers who are good at fighting, the ending was doomed as early as the beginning…