principles of innate and adaptive immunity

Transcription

1 Paper No.: 10: Module :01: Development Team Principal Investigator: Co-Principal Investigator: Paper Coordinator: Content Writer: Content Reviewer: Prof. Neeta Sehgal Head, Department of Zoology, University of Delhi Prof. D.K. Singh Department of Zoology, University of Delhi Prof. Anju Srivastava Department of Zoology, University of Delhi Dr Ravi Toteja Acharya Narendra Dev College, University of Delhi Prof. Sukhmahendra Singh Banaras Hindu University 1

2 Description of Module Subject Name Paper Name Module Name/Title Module ID Keywords Zool 010: Overview of Immune system M01 Components of the immune system,principles of innate and adaptive immunity Innate immune response, Adaptive immune response, Active immunity, Passive immunity, Inflammation Why have an immune system in the first place? An organism's integrity is under daily threat from external sources. The integrity of the individual must be protected from challenges which can be grouped into five main categories. Competition for survival. We live on an over populated world. Not just humans but many species within their own spatial niches are competing for limited space and food. To protect against assimilation. The constant battle involves avoiding cell fusion. Single cell organisms can be readily fused together. A more aggressive species or subspecies may attempt to "assimilate" non-aggressive or weaker cells into the more aggressive population. In this way the aggressive cell population reduces the competition for food space and light and may obtain added advantages from receiving some of the weaker population's DNA. At the single cell level, fusion can be accomplished between widely different species and the remnants of this cell fusion acceptance can be observed in humans. Siamese twins are the result of partial fusion of embryos. Frequently, one twin becomes dominant over the other. This twin will try to assimilate the other (unconsciously of course) and will thrive while the other becomes steadily weaker. Extreme examples of this dominance of one Siamese twin over another may be observed in the total assimilation of one twin while still within the womb. The only clue to this assimilation may be the Fossilized remnants of weaker twin revealed during X-ray of the survivor. To protect against organ damage and aid repair. Penetration of the body by a sharp rock. An extremity lost during a fight. A tissue succumbing to attack by bacteria. These, and other destroyers of tissue, can endanger the welfare of an individual. To protect against Parasitism. A parasite is an organism that lives on another organism and depends on it entirely for nourishment and protection. Within this definition we can include macroscopic parasites such as tape worms and microscopic 2

3 parasites" (pathogens). Every species is the potential host for numerous parasites. The parasite may feed on the host to exhaustion and ultimate death, or the parasite may remain almost unnoticed. Regardless, parasites are a threat to the host's integrity and welfare. At the very least they compromise the host by taking nourishment intended for the host's cells. At worst they hijack the host's body functions for the use of the parasite leading ultimately to death of the host. Microorganisms are perhaps the greatest threat to humans. While some are benign others have the ability to cause disease (dis-ease) in other words they have pathogenicity, they are pathogenic organisms. Invasion of the host is an infection and if transfer from host to host is possible, then the pathogen is capable of infectious disease and the initiation of an epidemic within a host population. Regulation of integrity. Multi-celled organisms develop from a highly regulated division of cells. Variants or mutants may occur during duplication of cells in the development and maintenance of the individual. These variant cells may be the result of viral contamination, chemical modification, or even the imperfect cell division mechanisms and duplication of DNA. At best the variant cells are benign, they simply take up space and nutrients. At worst, the cells are a threat to the host integrity, proliferating out of control, threatening to use up all the nutrients and resources available. They are neoplasms or tumors. In this sense, the variant cells are very much parasites except the danger comes from the individual's own cells rather than a different, invading species. Regardless of being benign or cancerous, the variant cells are a drawback compromising the optimum functioning of the individual. THEY MUST BE REMOVED. Source: The Germ Theory of Disease Louis Pasteur's main contributions to microbiology and medicine were instituting changes in hospital/medical practices to minimize the spread of disease by microbes or germs. Discovering that weak forms of disease could be used as an immunization against stronger forms and that rabies was transmitted by viruses too small to be seen under the microscopes of the time introducing the medical world to the concept of viruses. Biography of Louis Pasteur Louis Pasteur was born in Dole France, married to Marie Laurent and had five children. Three of his children died of typhoid fever, maybe leading to Pasteur's drive to save people from disease. He graduated in 1842 from Besancon College Royal de la Franche with honors in physics, mathematics, Latin, and drawing. Louis Pasteur later 3

4 attended Ecole Normaleto study physics and chemistry, specializing in crystals. In his early research Pasteur worked with the wine growers of France, helping with the fermentation process to develop a way to pasteurize and kill germs. He was granted U.S. patent 135,245 for "Improvement in Brewing Beer and Ale Pasteurization." Pasteur then worked within the textile industry finding a cure for a disease affecting silk worms. He also found cures for chicken cholera, anthrax and rabies. The Pasteur Institute: The Pasteur Institute was opened in During Louis Pasteur's lifetime it was not easy for him to convince others of his ideas, controversial in their time but considered absolutely correct today. Pasteur fought to convince surgeons that germs existed and carried diseases, and dirty instruments and hands spread germs and therefore disease. Pasteur's pasteurization process killed germs and prevented the spread of disease. Source: History of Time Line 1718 Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople, observed the positive effects of variolation on the native population and had the technique performed on her own children Edward Jenner, Smallpox vaccination 1862 Ernst Haeckel, Recognition of phagocytosis 1877 Paul Erlich, recognition of mast cells 1879 Louis Pasteur, Attenuated chicken cholera vaccine development 1883 Elie Metchnikoff Cellular theory of vaccination 1885 Louis Pasteur, Rabies vaccination development 1888 Pierre Roux & Alexandre Yersin, Bacterial toxins 1888 George Nuttall, Bactericidal action of blood 1891 Robert Koch, Delayed type hypersensitivity 1894 Richard Pfeiffer, Bacteriolysis 1895 Jules Bordet, Complement and antibody activity in bacteriolysis 1900 Paul Erlich, Antibody formation theory 1901 Karl Landsteiner, A, B and O blood groupings Carl Jensen & Leo Loeb, Transplantable tumors 1902 Paul Portier & Charles Richet, Anaphylaxis 1903 Almroth Wright & Stewart Douglas, Opsonization reactions 1906 Clemens von Pirquet, coined the word allergy 1907 Svante Arrhenius, coined the term immunochemistry 1910 Emil von Dungern, & Ludwik Hirszfeld, Inheritance of ABO blood groups 1910 Peyton Rous, Viral immunology theory 4

5 1914 Clarence Little, Genetics theory of tumor transplantation Leonell Strong & Clarence Little, Inbred mouse strains 1917 Karl Landsteiner, Haptens 1921 Carl Prausnitz & Heinz Kustner, Cutaneous reactions 1924 L Aschoff, Reticuloendothelial system 1926 Lloyd Felton & GH Bailey, Isolation of pure antibody preparation John Marrack, Antigen-antibody binding hypothesis 1936 Peter Gorer, Identification of the H-2 antigen in mice 1940 Karl Lansteiner & Alexander Weiner, Identification of the Rh antigens 1941 Albert Coons, Immunofluorescence technique 1942 Jules Freund & Katherine McDermott, Adjuvants 1942 Karl Landsteiner & Merill Chase, Cellular transfer of sensitivity in guinea pigs (anaphylaxis) 1944 Peter Medwar, Immunological hypothesis of allograft rejection 1948 Astrid Fagraeus, Demonstration of antibody production in plasma B cells 1948 George Snell, Congenic mouse lines 1949 Macfarlane Burnet & Frank Fenner, Immunological tolerance hypothesis 1950 Richard Gershon and K Kondo, Discovery of suppressor T cells 1952 Ogden and Bruton, discovery of agammagobulinemia antibody immunodeficiency 1953 Morton Simonsen and WJ Dempster, Graft-versus-host reaction 1953 James Riley & Geoffrey West, Discovery of histamine in mast cells 1953 Rupert Billingham, Leslie Brent, Peter Medwar, & Milan Hasek, Immunological tolerance hypothesis Niels Jerne, David Talmage, Macfarlane Burnet, Clonal selection theory 1957 Ernest Witebsky et al., Induction of autoimmunity in animals 1957 Alick Isaacs & Jean Lindemann, Discovery of interferon (cytokine) Jean Dausset et al., Human leukocyte antigens Rodney Porter et al., Discovery of antibody structure 1959 James Gowans, Lymphocyte circulation Jaques Miller et al., Discovery of thymus involvement in cellular immunity Noel Warner et al., Distinction of cellular and humoral immune responses 1963 JaquesOudin et al., antibody idiotypes Anthony Davis et al., T and B cell cooperation in immune response 1965 Thomas Tomasi et al., Secretory immunoglobulin antibodies 1967 Kimishige Ishizaka et al., Identification of IgE as the reaginic antibody 1971 Donald Bailey, Recombinent inbred mouse strains 1974 Rolf Zinkernagel& Peter Doherty, MHC restriction 1975 Kohler and Milstein, Monoclonal antibodies used in genetic analysis 1984 Robert Good, Failed treatment of severe combined immunodeficiency (SCID, David 5

6 the bubble boy) by bone marrow grafting Tonegawa, Hood et al., Identification of immunoglobulin genes Leroy Hood et al., Identification of genes for the T cell receptor 1990 Yamamoto et al., Molecular differences between the genes for blood groups O and A and between those for A and B 1990 NIH team, Gene therapy for SCID using cultured T cells NIH team, Treatment of SCID using genetically altered umbilical cord cells onwards Rapid identification of genes for immune cells, antibodies, cytokines and other immunological structures Identification of genes for the T cell receptor 1986 Hepatitis B vaccine produced by genetic engineering 1986 Th1 vs Th2 model of T helper cell function (Timothy Mosmann) 1988 Discovery of biochemical initiators of T-cell activation: CD4- and CD8- p56lck complexes (Christopher E. Rudd) 1990 Gene therapy for SCID 1994 'Danger' model of immunological tolerance (Polly Matzinger) 1995 Regulatory T cells (Shimon Sakaguchi) Identification of Toll-like receptors 2001 Discovery of FOXP3 - the gene directing regulatory T cell development 2005 Development of human papillomavirus vaccine (Ian Frazer) Source: Information provided by: Theories of Paul Ehrlich According to Ehrlich s Side Chain Theory, an antigen binds to a side chain receptor (Nutrient R, ingested via eating) and results in release of the side chain. This induces the cell to produce and release more side chains of the same specificity. This is a selective theory because the side-chain (antibody) repertoire exists independently of exposure to antigen the antigen simply binds to particular side chains and stimulates their production. Karl Landsteiner Landsteiner modified antigens into structures that had never existed before, and found they all induced antibody production. Researchers wondered why people would have antibodies for non-existent antigens, and how this specificity could occur with a limited number of genes. Thus, selective theories lost favor. Linus Pauling

7 Linus Pauling spearheaded instructional theories, which proposed that antigens encountered antibody templates. These antibody templates would wrap around the antigen, forming a complementary molecular which would neutralize similar antigen molecules in the future. While these theories explained specificity and diversity, they did not explain: how the body recognized self from non-self, as a blank template would be blind; memory, since subsequent responses to a particular antigen are exponentially higher and faster than in the initial encounter. Burnett Burnett s Clonal Selection Theory assumes that there are certain cells dedicated to making antibody, and that this is where antibody diversity is generated, stored and expressed. In simple terms: Every cell in this population makes a single kind of antibody with its own unique antigen specificity. The antibody the cell makes is determined randomly, completely independent of the antigenic universe. The cell displays a copy of the antibody it makes on its cell surface.any cell making antibody reactive with self is eliminated or silenced. Source: Interesting Immune system Facts The first layer of our body is the skin and the mucus membrane acts as the physical barrier to the harmful organisms and substances. The second protective layer is the 'innate immune system'. It acts as a short-term non- specific immune response. If this first and second protective barrier is crossed by the microbes, they encounter the third and more active immune response. When the immune system attacks a harmless substance or chemical in the body, it leads to an allergic reaction. There are four phases of an immune response: recognition, amplification of defense, attack and suppression. The environment plays an important role in affecting our immune response. Toxic substances, air pollution, pesticides and second hand cigarette smoke affects the defense system of our body. It is very important to get your beauty sleep for at least 8 hours as under 5 hours of sleep can significantly depress the immune functions. The body has over 50 million white blood cells that work to protect the body's defense system. One may lose five billion WBC's when donating blood and still be left with enough to fight a full fledged immune response. CD8 and catecholamine cells are severely affected by psychological stress. If their normal levels are altered, it may suppress the immune system making the body prone to infections. 7

8 Dieting reduces the number of killer cells, which leads to a weaker immune system. Pumping excessive iron in the gym makes the body produce more cortisol and adrenaline. These hormones temporarily impair the immune function. It is great way to overcome stress and fatigue by regular massages. But these beauty massages also help increase the number and aggressiveness of the natural killer cells and protective antibodies. This boosts the immune system to fight the invading bodies more efficiently. Too much of anything is always harmful. Similarly, some sunlight helps the body produce vitamin D and too much sunlight suppresses the immune system. Quit smoking! You can build your weak immune system within a month of quitting. There is increase in immune cell activity and cortisol, that is a stress hormone. Lymph nodes, the most important defense mechanisms of the body are not found in the feet! Laughter is the best medicine. This is not just an old saying but laughter induces a proactive immune response that leads to a healthy body. Well, these are a few interesting immune system facts. Our body has a defense mechanism that is stronger, more organized and more efficient than the strongest armies in the world. In order to keep your body's defense system impregnable, pump your body with vitamins and minerals following a healthy diet. Exercise regularly and keep away from tobacco, alcohol and narcotics. Stay stress-free and keep laughing for a stronger immune system. Source: Evolution of Immune Response The development of immunity in major animal groups Because the immune system is composed of cells and tissues that do not lend themselves to fossilization, it is impossible to trace the evolution of immunity from the paleontological record. But, because all animals exhibit some general ability to recognize self and to repel foreign substances, it is possible to study the immune capacity of living animals and, based on the relative positions of these animals in the evolutionary tree, to extrapolate a reasonable evolutionary history of the immune system. Immune capacity among invertebrates From the lowliest protozoans to the higher marine tunicates, invertebrates have means of distinguishing self components from nonself components. Sponges from one colony will reject tissue grafts from a different colony but will accept grafts from their own. When tissue grafts are made in animals higher up the evolutionary tree between individual annelid worms or starfish, for example the foreign tissue is commonly invaded by phagocytic cells (cells that engulf and destroy foreign material) and cells resembling 8

9 lymphocytes (white blood cells of the immune system), and it is destroyed. Yet tissues grafted from one part of the body to another on the same individual adhere and heal readily and remain healthy. So it seems that something akin to cellular immunity is present at this level of evolution. Insects engulf and eliminate foreign invaders through the process of phagocytosis ( cellular eating ). They have factors present in their circulatory fluids that can bind to foreign cells and cause clumping, or agglutination, of a number of these cells, an event that facilitates phagocytosis. Insects also seem to acquire immunity to infectious agents. Immune capacity among vertebrates The most sophisticated immune systems are those of the vertebrates. Recognizable lymphocytes and immunoglobulins (Ig; also called antibodies) appear only in these organisms. The most primitive living vertebrates the jawless fishes (hagfish and lampreys) do not have lymphoid tissues corresponding to a spleen or a thymus, and their immune responses, although demonstrable, are very weak and sluggish. Farther up the evolutionary tree, at the level of the cartilaginous fishes (sharks and rays) and the bony fishes, a thymus and a spleen are present, as are immunoglobulins, although only those immunoglobulins of the IgM class are detectable. Fish lack specialized lymph nodes, but they do have clusters of lymphocytes in the gut that may serve an analogous purpose. It is not until the level of the terrestrial vertebrates amphibians, reptiles, birds, and mammals that a complete immune system with thymus, spleen, bone marrow, and lymph nodes is present and IgM and IgG antibodies are made. Antibodies of the IgA class are found only in birds and mammals, and IgE antibodies are confined to mammals. So it appears that the most primitive devices for producing specific, acquired immunity gradually diversified to meet the new environmental hazards as animals moved out of the sea onto the land. The evolution of the complement system (a group of proteins involved in immune responses) may have occurred faster than that of the immunoglobulin system. The jawless fishes have complement components corresponding only to the later-acting (i.e., cytolytic, or cell-killing) aspects of complement function, but all higher vertebrates have components similar to the complete complement system of mammals. The fact that the complement system has been so well conserved during evolution implies not only that it has been of great biological value but also that complement and immunoglobulins have interacted throughout the evolution of the immune system in higher vertebrates. (For more information on the complement system, see Antibody-mediated immune mechanisms.) Source: Evolution-of-the-immune-system 9

10 Glossary Active Immune Response: usually long-lasting immunity that is acquired through the production of antibodies and memory T cells within the organism in response to the presence of antigens. Adaptive Immunity: also called the acquired immune system, this component of the immune system comprises white blood cells, particularly lymphocytes. When it is presented with a new microbe or vaccine, it may take days or weeks to respond or adapt, but the resultant improved immune readiness, or memory, is sustained for long periods (years). Antigen: a substance which reacts with antibody. Immunogen: an agent which evokes an immune response. Inflammation:A buildup of fluid and cells that occurs as the immune system fights a hostile invader. Innate Immunity: component of the immune system that consists of a set of genetically encoded responses to pathogens and does not change or adapt during the lifetime of the organism. Innate immunity involves quickly mobilized defenses triggered by receptors that recognize a broad spectrum of microbes; in contrast to adaptive immunity, it does not acquire memory for an improved response during a second exposure to infection. Passive Immune Response: immunity acquired by the transfer of antibodies (as by injection of serum from an individual with active immunity). Pasteurization: a process by which harmful microbes inperishable food products are destroyed by heat, without destroying the food. Phagocytosis: the process of engulfing and consuming foreign material, such as microorganisms. Variolation: a practice of applying powdered smallpox "crusts" and inserting them with a pin or poking device into the skin. Suggested Readings Richards A. Goldsby, Thomas J. Kindt and Barbara A. Osborne (2009), 10

11 Kuby 6 th Edition. W.H. Freeman and Company. Fahim Khan (2009) The Elements of, Pearson Education. WebLinks