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IMM250 - TEST NOTES Lecture 1.docx

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University of Toronto St. George

“The Immune System - A Historical Perspective” The History of Immunology The Black Death, one of the deadliest pandemics in human history  Black Death/Bubonic Plague  Responsible for killing 30-60% of all Europeans from 1350-1400  Europe‟s population did not recover until 1550. Plagues / Pandemics change the shape of history…..  Plague was thought to be spread through the trade routes. Migrations to cities resulted in further disease propagation.  Rats carried the fleas which harboured Yersinia pestis,a bacteria that is the causal agent. Unfortunately cats were deemed “evil” during this period, not helping matters.  Farmers were affected by disease and food supplies are cut off causing starvation  Mongol Empire collapsed in Central Asia as a result of the black death  In the absence of a mechanism of disease, superstitious views dominated and persecutions of Jewish groups occurred as others suspected them of poisoning wells.  Civic services were shut down and to keep up, peasants were further taxed. A peasant revolt occurred in 1371. Education and Architecture were put on hold.  Survivors of the Black Death may have had an Immunological advantage and retrospective studies have identified some genes that differ between survivors and those who perished.  Survivors may have benefited from greater resources due to the mass deaths. Some speculate this led to the Renaissance period. Or perhaps it was the disillusionment with the church or the collapse of feudalism, systems that did not protect people from Black Death that brought on the subsequent Renaissance. What is immunity?  the quality or state of being immune ; especially : a condition of being able to resist a particular disease 2000 BC: The Babylonian Epic of Gilgamesh Accounts of disease and pestilence Thucydides  Thucydides reported the concept of immunity after exposure to disease during a plague outbreak in 430 B.C. which caused greater loss of human life than the rest of the Archidamian War. (A mass grave discovered in 1994 illustrates the terrible death rate.) Thucydides' elder colleague Herodotus of Halicarnassus would have said that "the gods wanted it" or something like it, but Thucydides refuses to do so. Abū Bakr Muhammad ibn Zakariyā Rāzī (Ar-Razi)  was a persian physician and alchemist  He died in 930 A.D.  First to diagnose smallpox versus measles and recognized the epidemic force of smallpox  First to describe allergic asthma (he wrote a paper on it)  First to understand that fever is a mechanism for fighting infection How to treat disease… Depends on the imbalance of “humours” Avicenna  Persian philosopher/physician  Died in 1037 A.D.  “Father of modern medicine” The Canon of Medicine (Avicenna)  How to run a clinical trial  Experimental medicine  Evidence-based medicine  Contagious nature of infectious disease  Acquired Immunity Girolamo Fracastoro (1478-1553)  Proposed a model to explain contagion  Suggested that contagious particles transmitted disease even over long distances  Wrongly though that immunity to measles conferred immunity to smallpox The advent of variolation  Variolation: The old practice (as early as 1000 A.D. in China) of inoculating someone with the virus of smallpox to produce immunity to the disease. Unfortunately, the identification of a suitable strain of the virus was not an exact science and grievous disease and death from variolation were not uncommon. From variola, a synonym for smallpox.  In 1717, Lady Mary Wortley Montagu, the wife of the British ambassador, learned about variolation in Constantinople. In 1721, at the urging of Montagu and the Princess of Wales, several prisoners and abandoned children were inoculated by having smallpox inserted under the skin. Several months later, the children and prisoners were deliberately exposed to smallpox. When none contracted the disease, the procedure was deemed safe and members of the royal family were inoculated. The procedure then became fashionable in Europe Sarah Nelmes meet Edward Jenner…(1796) From Variolation to Vaccination  Smallpox was greatly feared in Europe. 1 in 3 infected persons died from it. Voltaire estimated that 60% of Europe had it.  Noting the common observation that milkmaids did not generally get smallpox, Jenner theorized that the pus in the blisters which milkmaids received from cowpox (a disease similar to smallpox, but much less virulent) protected the milkmaids from smallpox.  On 14 May 1796, Jenner tested his theory by inoculating James Phipps, a young boy of 8 years old, with material from the cowpox blisters of the hand of Sarah Nelmes, a milkmaid who had caught cowpox from a cow called Blossom. James developed a slight fever but nothing more.  Subsequently Jenner exposed James to varriolation. No symptoms were observed suggesting he had acquired immunity via cowpox innoculation.  After significant deliberation, the Royal Society eventually published Jenner‟s work (after several more test cases) and vaccinations were then provided to the public. Louis Pasteur (1880s): Attenuated “germ” cultures…Vaccines are born  Along with Ferdinand Cohn and Robert Koch, he is one of thefounders of modern microbiology  He is buried beneath the Institut Pasteur, a rare honor in France, where being buried in a cemetery is mandatory save for the fewer than 300 "Great Men" who are entombed in the Panthéon.  Using attenuated “spoiled” cholera cultures, it was determined that he could induce acquired immunity in chickens to virulant cholera (due to a serendipitous vacation taken by his assistant).  The same held true for cattle anthrax, and rabies (with Emile Roux). Pasteur gave the name vaccine to this process to honour Jenner‟s discovery with 9-year old Joseph Meister cow(vacca)pox. Importance of vaccination  Small pox vaccination started in 1796.  In 1979 WHO declared virus had been eradicated. Vaccinations: Risk benefit analysis  Vaccinations have nearly eliminated diseases that were once common among children (measles, mumps, diptheria etc). The rate of brain damage from measles is 1/1000, the death rate 1/3000.  Approximately 5 in 400,000 children born in Canada each year will experience a severe reaction to a vaccine.  MMR (Measles Mumps Rubella) vaccine is the most controversial. A small study of less than 20 children examined a link with autism. This study has been since thoroughly debunked and many authors on this publication have retracted their findings. Some are being investigated for scientific misconduct. And Yet… A persistent perception that vaccines are deleterious… Koch's postulates are: 1. The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy animals. 2. The microorganism must be isolated from a diseased organism and grown in pure culture. 3. The cultured microorganism should cause disease when introduced into a healthy organism. 4. The microorganism must be re-isolated f
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