{"id":25,"date":"2019-04-12T06:53:01","date_gmt":"2019-04-12T06:53:01","guid":{"rendered":"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/?post_type=chapter&#038;p=25"},"modified":"2022-01-10T06:11:58","modified_gmt":"2022-01-10T06:11:58","slug":"history-of-immunology","status":"publish","type":"chapter","link":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/chapter\/history-of-immunology\/","title":{"rendered":"History of Immunology"},"content":{"raw":"<ol>\r\n \t<li style=\"text-align: justify;\">Objectives<\/li>\r\n<\/ol>\r\n<ul style=\"text-align: justify;\">\r\n \t<li>\u00a0To study the various milestones in the development of immunology<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify;\">\r\n \t<li>\u00a0To understand how the immune distinguishes between self and non-self<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify;\">\u00a0To see the various Nobel Prizes awarded in this area over the years<\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n<strong>2. Concept Map<\/strong>\r\n\r\n<img class=\"aligncenter size-full wp-image-27\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled.png\" alt=\"\" width=\"524\" height=\"136\" \/>\r\n<ol start=\"3\">\r\n \t<li><strong>Description<\/strong><\/li>\r\n<\/ol>\r\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify;\">Immunology is the science aiming to understand how vertebrates (credited with having an \u201cimmune system\u201d) distinguish between \u201eself\u201f and \u201enon-self\u201f!<\/p>\r\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify;\">In chemistry and life sciences, \u201cmolecular recognition\u201d enables interactions between two chemical specie with a broad range of specificity.<\/p>\r\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify;\">How do immune system of the vertebrates fine tune a recognition mechanism which makes it possible for the system to detect that a particular protein is a \u201eself\u201f molecule and another protein is a \u201enon-self\u201f molecule?<\/p>\r\n<strong>\u00a0<\/strong>\r\n<p style=\"text-align: justify;\">Furthermore, the immune system is able to recall that a previous encounter with a particular microbe has taken place.<\/p>\r\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify;\">Without having any clue beforehand about the nature of an infection, the immune system is able to mount a very efficient response to this infection. Part of this response is fairly specific towards the invading pathogen. How does this \u201especific response\u201f arise like a conjurer\u201fs trick?<\/p>\r\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify;\">History of immunology is the story of a scientist\u201fs search for answers to these and associated questions.<\/p>\r\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify;\">Like other traits of living organisms, immune system also has evolutionary history. Cells do recognize each other. Colonies of sponges when placed together either merge to form a larger colony or destroy each other upon contact. The first event happens if these cells are genetically related and the latter phenomenon takes place if these colonies are not genetically related.<\/p>\r\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify;\">We also know that during tissue\/organ grafting, the grafted cells and the cells of the host have to be \u201cmatched\u201d.<\/p>\r\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify;\">So, the capacity to distinguish between \u201cself\u201d and \u201cnon-self\u201d is not limited to vertebrates.<\/p>\r\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\r\n<p style=\"text-align: justify;\">What distinguishes the immune system of the vertebrates is the existence of large number of soluble factors and cells which act in a highly interdependent and synergistic fashion.<\/p>\r\n<p style=\"text-align: justify;\">Immunology in the beginning overlapped with microbiology as it was concerned with understanding and preventing infectious diseases.<\/p>\r\n&nbsp;\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Girolamo Fracastoro, a contemporary of Copernicus at the University of Padua gave the concept of \u201ccontagion\u201d in 1546. Contagion, according to the brilliant conclusion by him, were too small to be visible to the naked eye. It was later that the idea was taken up by others.<\/p>\r\n<img class=\"aligncenter size-full wp-image-29\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-1.png\" alt=\"\" width=\"362\" height=\"323\" \/>\r\n\r\nNotably:\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Chinese were the first ones to adopt the practice of exposing infants to the scabs from the infected individual by rubbing it in (after scratching the skin) or through inhalation.<\/p>\r\n<img class=\"aligncenter size-full wp-image-30\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-2.png\" alt=\"\" width=\"400\" height=\"366\" \/>\r\n<p style=\"text-align: justify;\">In 1718, Lady Mary Wortley Montague, wife of the English ambassador in Constantinople, Turkey, against the advice of the priest, tried this with her children and thereby saved them from small pox.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">In 1774, an English farmer Benjamin Jesty used cowpox instead of small pox to \u201cvariolate\u201d (\u201cvariola\u201d in Latin means small pox) his children.<\/p>\r\n<img class=\"aligncenter size-full wp-image-31\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-3.png\" alt=\"\" width=\"536\" height=\"329\" \/>\r\n<p style=\"text-align: justify;\">While Jesty did not publish his results formally, he is not generally credited for his discovery. In 1798, Edward Jenner, an English physician confirmed Jesty\u201fs observations, published them and is regarded as the father of vaccination (\u201cvacca\u201d in Latin means cow).<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">While Jenner's interest in the protective effects of cowpox began during his apprenticeship with George Harwicke, it was 1796 before he made the first step in the long process whereby smallpox, the scourge of mankind, would be totally eradicated. For many years, he had heard the tales that dairymaids were protected from smallpox naturally after having suffered from cowpox. Pondering this, Jenner concluded that cowpox not only protected against smallpox but also could be transmitted from one person to another as a deliberate mechanism of protection. In May 1796, Edward Jenner found a young dairymaid, Sarah Nelms, who had fresh cowpox lesions on her hands and arms. On May 14, 1796, using matter from Nelms' lesions, he inoculated an 8-year-old boy, James Phipps. Subsequently, the boy developed mild fever and discomfort in the axillae. Nine days after the procedure he felt cold and had lost his appetite, but on the next day he was much better. In July 1796,\u00a0Jenner inoculated the boy again, this time with matter from a fresh smallpox lesion. No disease developed, and Jenner concluded that protection was complete.<\/p>\r\n<img class=\"aligncenter size-full wp-image-32\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-4.png\" alt=\"\" width=\"446\" height=\"537\" \/>\r\n<p style=\"text-align: justify;\">In 1879, Louise Pasteur in France was investigating the bacteria responsible for fowl cholera. He asked his assistant to infect some fowls with the bacteria. The assistant instead went on vacation but did the experiment upon return after several weeks.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Chickens remained healthy so Pasteur decided to infect them again with fresh culture. The fowls still remained healthy. Pasteur brilliantly deducted that his \u201caged culture\u201d worked just like Jenner\u201fs cowpox. The credit for extending this approach to other diseases like anthrax and rabies belongs to Pasteur. Till today, France honours Pasteur as Pasteur\u201fs Institute at Paris still focuses on developing vaccines.<\/p>\r\n<img class=\"aligncenter size-full wp-image-33\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-5.png\" alt=\"\" width=\"515\" height=\"387\" \/>\r\n<p style=\"text-align: justify;\">We will, in a later module, resume the development of vaccines in later years after learning about some necessary fundamentals.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Part of the history of Immunology is best learnt through recalling some controversies which often continued for a considerable period and often resulted in bitter debates.<\/p>\r\n&nbsp;\r\n<div>\r\n\r\n<strong><em>Humoral vs Cellular Immunity<\/em><\/strong>\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify;\">In 1890, Emil von Behring and Shibasaburo Kitasato in Berlin proposed the idea of \u201cfactors\u201d in the blood called \u201cantibodies\u201d were responsible for the effect of vaccination. In the next few years, three key discoveries were made:<\/p>\r\n\r\n<ul>\r\n \t<li style=\"text-align: justify;\">\u00a0 Paul Ehrlich, a German chemist, showed that antibodies couls protect animals against even non-bacterial \u201ctoxins\u201d<\/li>\r\n \t<li style=\"text-align: justify;\">\u00a0 Richard Pfeiffer, another German showed that antibodies could clump and destroy vibrio cholera which causes cholera in humans<\/li>\r\n \t<li style=\"text-align: justify;\">\u00a0 In 1894, Emile Roux discovered \u201cpassive immunization\u201d by transferring serum from an \u201cimmunized\u201d horse against diphtheria and tetanus to protect respective patients against the two diseases.<\/li>\r\n \t<li style=\"text-align: justify;\">\u00a0 In 1893, a \u201cheat labile component\u201d was thought to be antibodies but (we will learn later about it) was a complement.<\/li>\r\n<\/ul>\r\n<\/div>\r\n<p style=\"text-align: justify;\">Hence the major thinking was that some soluble factors (Humor means were responsible for the defense mechanism.<\/p>\r\n<img class=\"aligncenter size-full wp-image-34\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-6.png\" alt=\"\" width=\"466\" height=\"193\" \/>\r\n<p style=\"text-align: justify;\">In 1893, a Russian Elie Metchnikoff showed that white blood cells of vertebrates could cause phagocytosis of some fungal spores. This debate about humoral vs cellular agents involved in the defense against infections divided scientists into two groups.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Paul Ehrlich proposed a side chain theory which tried to combine the role of cells and soluble factors. The side chains were supposed to be present on cell surfaces and upon \u201cblocking\u201d of these side chains, the cells responded by secreting these side chains in large numbers.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Paul Ehrlich was a leading immunologist of that early era. He was one of the early people to speculate about the nature of substances in the body which neutralized toxins and was referred to as \u201cantibody\u201d [Ehrlich 1897].<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">In a presentation before The Royal Society of Chemistry in 1900, Erhlich proposed that cells have receptors which combine with the toxin (antigen). This binding released the receptor molecules and neutralization of the toxin continues. In his model, he also tried to explain the action of complement which in those days was called alexin.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">In many ways Ehrlich\u201fs ideas were brilliantly precinct. The triggering of B-lymphocytes does involve \u201cantigen\u201d binding to Ig receptor leading to the release of Ig and making more of Ig receptors. Ehrlich also invoked cellular level picture in explaining immune response.<\/p>\r\n&nbsp;\r\n\r\n<strong><em>Instruction vs. Selection Theories<\/em><\/strong>\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Around the same time, Hans Buchner postulated that combination of \u201cantigens\u201d with serum proteins led to a specific antibody structure. This later on developed into template theory which was part of the \u201cinstruction\u201d school of thought.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Karl Landsteiner, using many haptens, showed that one could produce many antibodies against any given antigen. So how does one explain unlimited number of receptors? This period also coincided (1920s) with the rapid studies in our understanding of protein structure and protein chemistry. No antigens were detected in the blood. People still found merit in the template theory but were divided on whether the amino acid sequence or induced folding was responsible for the specific antibody formation.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">In 1940, Linus Pauling joined the debate. Following up on the earlier ideas of Breinl and Haurowitz, Pauling proposed that terminal ends of \u201cantibody\u201d assumed specific and complementary shape to an antigen.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">All the scientific contribution of Linus Pauling have one merit. A clear pictoral quality was inherent. So was the case in this particular area. Pauling implied that antibody has two combining sites for the antigen. As we will see later, he was right in this prediction but his prediction was based upon the wrong premise!<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Burnet and Fenner (1949), having the emerging information about the protein biosynthesis at that time, enunciated the adaptive enzyme concept according to which an animal synthesized antibody de novo in response to an antigen.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">The well known Monod\u201fs operon theory, however, stated that the organism synthesized a protein at the low level but could raise this level upon the addition of a substrate.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">This led to Burnet (1963) revisiting his ideas and propose clonal selection theory which is a selection theory. According to the selection concept, antibody diversity pre exist, antigen merely selects.<\/p>\r\n<img class=\"aligncenter size-full wp-image-35\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-7.png\" alt=\"\" width=\"393\" height=\"286\" \/><img class=\"aligncenter size-full wp-image-37\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-8.png\" alt=\"\" width=\"319\" height=\"526\" \/>\r\n\r\n<strong>The Contributions of Niels Jerne<\/strong>\r\n\r\n&nbsp;\r\n<ul>\r\n \t<li style=\"text-align: justify;\">\u00a0Niels Jerne was awarded the Nobel prize in 1984 for \u201ctheories concerning the specificity in development (lymphocyte clonality) and control of the immune system\u201d.<\/li>\r\n \t<li style=\"text-align: justify;\">\u00a0It was Jerne\u201fs overview of the understanding of the immune system at that time which sort of crystallized the concept of clonal selection theory.<\/li>\r\n \t<li style=\"text-align: justify;\">\u00a0Jerne also initiated the concept of \u201cepitope\u201d and \u201cidiotopes\u201d.He envisaged a network of epitopes and idiotopes. That is why his theory is called network theory.<\/li>\r\n<\/ul>\r\n<p style=\"text-align: justify;\"><strong><em>Serology<\/em><\/strong><\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">We have referred to Karl Landsteiner. Landsteiner can be called Father of Serology as he also discovered the blood group antigens and corresponding agglutinins. Blood transfusions are possible because of his pioneering work.<\/p>\r\n<img class=\"aligncenter size-full wp-image-38\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-9.png\" alt=\"\" width=\"579\" height=\"309\" \/>\r\n<p style=\"text-align: justify;\">In 1901, Bordat and Gengou developed complement fixation test.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\"><strong><em>Cellular Immunology<\/em><\/strong><\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Coons (1941-42) used immunofluorescence to show that both antigens and antibodies are present inside cells. Around the same time, Chase and Landsteiner showed that \u201cdelayed higher sensitivity\u201d (a phenomenon which is a part of the immune response in some situations) was transferable via cells and not via serum.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Medawar\u201fs group in 1953 demonstrated acquired immunological tolerance. In the subsequent years, identification and characterization of many cells and proteins associated with the immune systems took place. In 1982-83, T-cell receptor isolation was reported and by then cell mediated immunity was firmly accepted as one arm of the immune response.<\/p>\r\n&nbsp;\r\n<p style=\"text-align: justify;\">Perhaps no other area in biology has fetched so many nobel prizes. Below is the list of some names associated with the important developments of immunology in early years. The names with \u201c*\u201d were awarded Nobel Prize for their work in immunology.<\/p>\r\n&nbsp;\r\n\r\n<strong><em>Table 1:<\/em><\/strong>\r\n\r\n<img class=\"aligncenter size-full wp-image-39\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-10.png\" alt=\"\" width=\"562\" height=\"312\" \/><img class=\"aligncenter size-full wp-image-40\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-11.png\" alt=\"\" width=\"558\" height=\"180\" \/>\r\n\r\nSummary\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify;\"><strong><em>We have looked at the several milestones in the development of immunology which help in understanding how the immune system<\/em><\/strong><\/p>\r\n\r\n<ul style=\"text-align: justify;\">\r\n \t<li><strong><em>Distinguishes between self and non-self<\/em><\/strong><\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify;\">\r\n \t<li><strong><em>Have Memory<\/em><\/strong><\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify;\"><strong><em>Can react against unforeseen infectious agents!<\/em><\/strong><\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n&nbsp;","rendered":"<ol>\n<li style=\"text-align: justify;\">Objectives<\/li>\n<\/ol>\n<ul style=\"text-align: justify;\">\n<li>\u00a0To study the various milestones in the development of immunology<\/li>\n<\/ul>\n<ul style=\"text-align: justify;\">\n<li>\u00a0To understand how the immune distinguishes between self and non-self<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify;\">\u00a0To see the various Nobel Prizes awarded in this area over the years<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong>2. Concept Map<\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-27\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled.png\" alt=\"\" width=\"524\" height=\"136\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled.png 524w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-300x78.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-65x17.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-225x58.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-350x91.png 350w\" sizes=\"auto, (max-width: 524px) 100vw, 524px\" \/><\/p>\n<ol start=\"3\">\n<li><strong>Description<\/strong><\/li>\n<\/ol>\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">Immunology is the science aiming to understand how vertebrates (credited with having an \u201cimmune system\u201d) distinguish between \u201eself\u201f and \u201enon-self\u201f!<\/p>\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">In chemistry and life sciences, \u201cmolecular recognition\u201d enables interactions between two chemical specie with a broad range of specificity.<\/p>\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">How do immune system of the vertebrates fine tune a recognition mechanism which makes it possible for the system to detect that a particular protein is a \u201eself\u201f molecule and another protein is a \u201enon-self\u201f molecule?<\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">Furthermore, the immune system is able to recall that a previous encounter with a particular microbe has taken place.<\/p>\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">Without having any clue beforehand about the nature of an infection, the immune system is able to mount a very efficient response to this infection. Part of this response is fairly specific towards the invading pathogen. How does this \u201especific response\u201f arise like a conjurer\u201fs trick?<\/p>\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">History of immunology is the story of a scientist\u201fs search for answers to these and associated questions.<\/p>\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">Like other traits of living organisms, immune system also has evolutionary history. Cells do recognize each other. Colonies of sponges when placed together either merge to form a larger colony or destroy each other upon contact. The first event happens if these cells are genetically related and the latter phenomenon takes place if these colonies are not genetically related.<\/p>\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">We also know that during tissue\/organ grafting, the grafted cells and the cells of the host have to be \u201cmatched\u201d.<\/p>\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">So, the capacity to distinguish between \u201cself\u201d and \u201cnon-self\u201d is not limited to vertebrates.<\/p>\n<p style=\"text-align: justify;\"><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: justify;\">What distinguishes the immune system of the vertebrates is the existence of large number of soluble factors and cells which act in a highly interdependent and synergistic fashion.<\/p>\n<p style=\"text-align: justify;\">Immunology in the beginning overlapped with microbiology as it was concerned with understanding and preventing infectious diseases.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Girolamo Fracastoro, a contemporary of Copernicus at the University of Padua gave the concept of \u201ccontagion\u201d in 1546. Contagion, according to the brilliant conclusion by him, were too small to be visible to the naked eye. It was later that the idea was taken up by others.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-29\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-1.png\" alt=\"\" width=\"362\" height=\"323\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-1.png 362w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-1-300x268.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-1-65x58.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-1-225x201.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-1-350x312.png 350w\" sizes=\"auto, (max-width: 362px) 100vw, 362px\" \/><\/p>\n<p>Notably:<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Chinese were the first ones to adopt the practice of exposing infants to the scabs from the infected individual by rubbing it in (after scratching the skin) or through inhalation.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-30\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-2.png\" alt=\"\" width=\"400\" height=\"366\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-2.png 400w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-2-300x275.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-2-65x59.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-2-225x206.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-2-350x320.png 350w\" sizes=\"auto, (max-width: 400px) 100vw, 400px\" \/><\/p>\n<p style=\"text-align: justify;\">In 1718, Lady Mary Wortley Montague, wife of the English ambassador in Constantinople, Turkey, against the advice of the priest, tried this with her children and thereby saved them from small pox.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">In 1774, an English farmer Benjamin Jesty used cowpox instead of small pox to \u201cvariolate\u201d (\u201cvariola\u201d in Latin means small pox) his children.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-31\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-3.png\" alt=\"\" width=\"536\" height=\"329\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-3.png 536w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-3-300x184.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-3-65x40.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-3-225x138.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-3-350x215.png 350w\" sizes=\"auto, (max-width: 536px) 100vw, 536px\" \/><\/p>\n<p style=\"text-align: justify;\">While Jesty did not publish his results formally, he is not generally credited for his discovery. In 1798, Edward Jenner, an English physician confirmed Jesty\u201fs observations, published them and is regarded as the father of vaccination (\u201cvacca\u201d in Latin means cow).<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">While Jenner&#8217;s interest in the protective effects of cowpox began during his apprenticeship with George Harwicke, it was 1796 before he made the first step in the long process whereby smallpox, the scourge of mankind, would be totally eradicated. For many years, he had heard the tales that dairymaids were protected from smallpox naturally after having suffered from cowpox. Pondering this, Jenner concluded that cowpox not only protected against smallpox but also could be transmitted from one person to another as a deliberate mechanism of protection. In May 1796, Edward Jenner found a young dairymaid, Sarah Nelms, who had fresh cowpox lesions on her hands and arms. On May 14, 1796, using matter from Nelms&#8217; lesions, he inoculated an 8-year-old boy, James Phipps. Subsequently, the boy developed mild fever and discomfort in the axillae. Nine days after the procedure he felt cold and had lost his appetite, but on the next day he was much better. In July 1796,\u00a0Jenner inoculated the boy again, this time with matter from a fresh smallpox lesion. No disease developed, and Jenner concluded that protection was complete.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-32\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-4.png\" alt=\"\" width=\"446\" height=\"537\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-4.png 446w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-4-249x300.png 249w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-4-65x78.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-4-225x271.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-4-350x421.png 350w\" sizes=\"auto, (max-width: 446px) 100vw, 446px\" \/><\/p>\n<p style=\"text-align: justify;\">In 1879, Louise Pasteur in France was investigating the bacteria responsible for fowl cholera. He asked his assistant to infect some fowls with the bacteria. The assistant instead went on vacation but did the experiment upon return after several weeks.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Chickens remained healthy so Pasteur decided to infect them again with fresh culture. The fowls still remained healthy. Pasteur brilliantly deducted that his \u201caged culture\u201d worked just like Jenner\u201fs cowpox. The credit for extending this approach to other diseases like anthrax and rabies belongs to Pasteur. Till today, France honours Pasteur as Pasteur\u201fs Institute at Paris still focuses on developing vaccines.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-33\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-5.png\" alt=\"\" width=\"515\" height=\"387\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-5.png 515w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-5-300x225.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-5-65x49.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-5-225x169.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-5-350x263.png 350w\" sizes=\"auto, (max-width: 515px) 100vw, 515px\" \/><\/p>\n<p style=\"text-align: justify;\">We will, in a later module, resume the development of vaccines in later years after learning about some necessary fundamentals.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Part of the history of Immunology is best learnt through recalling some controversies which often continued for a considerable period and often resulted in bitter debates.<\/p>\n<p>&nbsp;<\/p>\n<div>\n<p><strong><em>Humoral vs Cellular Immunity<\/em><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">In 1890, Emil von Behring and Shibasaburo Kitasato in Berlin proposed the idea of \u201cfactors\u201d in the blood called \u201cantibodies\u201d were responsible for the effect of vaccination. In the next few years, three key discoveries were made:<\/p>\n<ul>\n<li style=\"text-align: justify;\">\u00a0 Paul Ehrlich, a German chemist, showed that antibodies couls protect animals against even non-bacterial \u201ctoxins\u201d<\/li>\n<li style=\"text-align: justify;\">\u00a0 Richard Pfeiffer, another German showed that antibodies could clump and destroy vibrio cholera which causes cholera in humans<\/li>\n<li style=\"text-align: justify;\">\u00a0 In 1894, Emile Roux discovered \u201cpassive immunization\u201d by transferring serum from an \u201cimmunized\u201d horse against diphtheria and tetanus to protect respective patients against the two diseases.<\/li>\n<li style=\"text-align: justify;\">\u00a0 In 1893, a \u201cheat labile component\u201d was thought to be antibodies but (we will learn later about it) was a complement.<\/li>\n<\/ul>\n<\/div>\n<p style=\"text-align: justify;\">Hence the major thinking was that some soluble factors (Humor means were responsible for the defense mechanism.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-34\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-6.png\" alt=\"\" width=\"466\" height=\"193\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-6.png 466w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-6-300x124.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-6-65x27.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-6-225x93.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-6-350x145.png 350w\" sizes=\"auto, (max-width: 466px) 100vw, 466px\" \/><\/p>\n<p style=\"text-align: justify;\">In 1893, a Russian Elie Metchnikoff showed that white blood cells of vertebrates could cause phagocytosis of some fungal spores. This debate about humoral vs cellular agents involved in the defense against infections divided scientists into two groups.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Paul Ehrlich proposed a side chain theory which tried to combine the role of cells and soluble factors. The side chains were supposed to be present on cell surfaces and upon \u201cblocking\u201d of these side chains, the cells responded by secreting these side chains in large numbers.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Paul Ehrlich was a leading immunologist of that early era. He was one of the early people to speculate about the nature of substances in the body which neutralized toxins and was referred to as \u201cantibody\u201d [Ehrlich 1897].<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">In a presentation before The Royal Society of Chemistry in 1900, Erhlich proposed that cells have receptors which combine with the toxin (antigen). This binding released the receptor molecules and neutralization of the toxin continues. In his model, he also tried to explain the action of complement which in those days was called alexin.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">In many ways Ehrlich\u201fs ideas were brilliantly precinct. The triggering of B-lymphocytes does involve \u201cantigen\u201d binding to Ig receptor leading to the release of Ig and making more of Ig receptors. Ehrlich also invoked cellular level picture in explaining immune response.<\/p>\n<p>&nbsp;<\/p>\n<p><strong><em>Instruction vs. Selection Theories<\/em><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Around the same time, Hans Buchner postulated that combination of \u201cantigens\u201d with serum proteins led to a specific antibody structure. This later on developed into template theory which was part of the \u201cinstruction\u201d school of thought.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Karl Landsteiner, using many haptens, showed that one could produce many antibodies against any given antigen. So how does one explain unlimited number of receptors? This period also coincided (1920s) with the rapid studies in our understanding of protein structure and protein chemistry. No antigens were detected in the blood. People still found merit in the template theory but were divided on whether the amino acid sequence or induced folding was responsible for the specific antibody formation.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">In 1940, Linus Pauling joined the debate. Following up on the earlier ideas of Breinl and Haurowitz, Pauling proposed that terminal ends of \u201cantibody\u201d assumed specific and complementary shape to an antigen.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">All the scientific contribution of Linus Pauling have one merit. A clear pictoral quality was inherent. So was the case in this particular area. Pauling implied that antibody has two combining sites for the antigen. As we will see later, he was right in this prediction but his prediction was based upon the wrong premise!<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Burnet and Fenner (1949), having the emerging information about the protein biosynthesis at that time, enunciated the adaptive enzyme concept according to which an animal synthesized antibody de novo in response to an antigen.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">The well known Monod\u201fs operon theory, however, stated that the organism synthesized a protein at the low level but could raise this level upon the addition of a substrate.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">This led to Burnet (1963) revisiting his ideas and propose clonal selection theory which is a selection theory. According to the selection concept, antibody diversity pre exist, antigen merely selects.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-35\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-7.png\" alt=\"\" width=\"393\" height=\"286\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-7.png 393w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-7-300x218.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-7-65x47.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-7-225x164.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-7-350x255.png 350w\" sizes=\"auto, (max-width: 393px) 100vw, 393px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-37\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-8.png\" alt=\"\" width=\"319\" height=\"526\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-8.png 319w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-8-182x300.png 182w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-8-65x107.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-8-225x371.png 225w\" sizes=\"auto, (max-width: 319px) 100vw, 319px\" \/><\/p>\n<p><strong>The Contributions of Niels Jerne<\/strong><\/p>\n<p>&nbsp;<\/p>\n<ul>\n<li style=\"text-align: justify;\">\u00a0Niels Jerne was awarded the Nobel prize in 1984 for \u201ctheories concerning the specificity in development (lymphocyte clonality) and control of the immune system\u201d.<\/li>\n<li style=\"text-align: justify;\">\u00a0It was Jerne\u201fs overview of the understanding of the immune system at that time which sort of crystallized the concept of clonal selection theory.<\/li>\n<li style=\"text-align: justify;\">\u00a0Jerne also initiated the concept of \u201cepitope\u201d and \u201cidiotopes\u201d.He envisaged a network of epitopes and idiotopes. That is why his theory is called network theory.<\/li>\n<\/ul>\n<p style=\"text-align: justify;\"><strong><em>Serology<\/em><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">We have referred to Karl Landsteiner. Landsteiner can be called Father of Serology as he also discovered the blood group antigens and corresponding agglutinins. Blood transfusions are possible because of his pioneering work.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-38\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-9.png\" alt=\"\" width=\"579\" height=\"309\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-9.png 579w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-9-300x160.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-9-65x35.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-9-225x120.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-9-350x187.png 350w\" sizes=\"auto, (max-width: 579px) 100vw, 579px\" \/><\/p>\n<p style=\"text-align: justify;\">In 1901, Bordat and Gengou developed complement fixation test.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\"><strong><em>Cellular Immunology<\/em><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Coons (1941-42) used immunofluorescence to show that both antigens and antibodies are present inside cells. Around the same time, Chase and Landsteiner showed that \u201cdelayed higher sensitivity\u201d (a phenomenon which is a part of the immune response in some situations) was transferable via cells and not via serum.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Medawar\u201fs group in 1953 demonstrated acquired immunological tolerance. In the subsequent years, identification and characterization of many cells and proteins associated with the immune systems took place. In 1982-83, T-cell receptor isolation was reported and by then cell mediated immunity was firmly accepted as one arm of the immune response.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\">Perhaps no other area in biology has fetched so many nobel prizes. Below is the list of some names associated with the important developments of immunology in early years. The names with \u201c*\u201d were awarded Nobel Prize for their work in immunology.<\/p>\n<p>&nbsp;<\/p>\n<p><strong><em>Table 1:<\/em><\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-39\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-10.png\" alt=\"\" width=\"562\" height=\"312\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-10.png 562w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-10-300x167.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-10-65x36.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-10-225x125.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-10-350x194.png 350w\" sizes=\"auto, (max-width: 562px) 100vw, 562px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-40\" src=\"http:\/\/biocp16.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-11.png\" alt=\"\" width=\"558\" height=\"180\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-11.png 558w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-11-300x97.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-11-65x21.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-11-225x73.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-content\/uploads\/sites\/219\/2019\/04\/Untitled-11-350x113.png 350w\" sizes=\"auto, (max-width: 558px) 100vw, 558px\" \/><\/p>\n<p>Summary<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify;\"><strong><em>We have looked at the several milestones in the development of immunology which help in understanding how the immune system<\/em><\/strong><\/p>\n<ul style=\"text-align: justify;\">\n<li><strong><em>Distinguishes between self and non-self<\/em><\/strong><\/li>\n<\/ul>\n<ul style=\"text-align: justify;\">\n<li><strong><em>Have Memory<\/em><\/strong><\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify;\"><strong><em>Can react against unforeseen infectious agents!<\/em><\/strong><\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"author":3,"menu_order":3,"template":"","meta":{"pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":["dr-m-n-gupta"],"pb_section_license":""},"chapter-type":[],"contributor":[58],"license":[],"class_list":["post-25","chapter","type-chapter","status-publish","hentry","contributor-dr-m-n-gupta"],"part":3,"_links":{"self":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters\/25","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/users\/3"}],"version-history":[{"count":6,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters\/25\/revisions"}],"predecessor-version":[{"id":803,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters\/25\/revisions\/803"}],"part":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/parts\/3"}],"metadata":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapters\/25\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/media?parent=25"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/pressbooks\/v2\/chapter-type?post=25"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/contributor?post=25"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp16\/wp-json\/wp\/v2\/license?post=25"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}