Historical Perspectives in Immunology PDF

HISTORICAL 1 PERSPECTIVES by: JPSC  Intended learning outcomes: At the end of the unit, the students will be able to: Trace the historical development of immunology from ancient times to the present. Explain the key experiments and discoveries that shaped t...

HISTORICAL 1 PERSPECTIVES by: JPSC  Intended learning outcomes: At the end of the unit, the students will be able to: Trace the historical development of immunology from ancient times to the present. Explain the key experiments and discoveries that shaped the field. Describe the contributions of major figures in immunology. Compare and contrast different theories and concepts in the history of immunology. Analyze the impact of historical developments on current immunological practices. Define accurately the basic terminologies in immunology and serology. by: JPSC  IMMUNOLOGY Defined as resistance to disease, specifically infectious disease. Study of a host's reactions when foreign substances are introduced into the body. by: JPSC  SUBDIVISIONS OF IMMUNOLOGY Immunity encompasses the processes that occur to defend the body against foreign organisms or molecules by: JPSC  SUBDIVISIONS OF IMMUNOLOGY Infectious Disease a pathogenic condition caused by microorganisms that produce injurious effects by: JPSC  SUBDIVISIONS OF IMMUNOLOGY Hypersensitivity an unpleasant or damaging condition of the body tissues caused by antigenic stimulation by: JPSC  SUBDIVISIONS OF IMMUNOLOGY Autoimmunity the body's immune cells are no longer able to recognize self from non-self this result to an immune response against the body's own antigens by: JPSC  SUBDIVISIONS OF IMMUNOLOGY Immunodeficiency There is a disfunction in body defense that causes a failure to detect foreign antigens, and the body is unable to produce antibodies against these foreign substances by: JPSC  immunity Also termed as: RESISTANCE Sum total of the defense mechanisms of the human body to resist infectious disease. by: JPSC  Specific immunity Nonspecific immunity aka acquired immunity; this develops as a result of exposure to a variety inherent or innate immunity of agents capable of inducing an immune composed of external and internal factors. response. by: JPSC  Antigen, Immunogen, and Antibody Antigen a foreign substance that stimulates antibody production Immunogen any substance that is capable of inducing an immune response Antibody a substance produced in response to antigenic stimulation that is capable of specific interaction with a provoking immunogen by: JPSC  SEROLOGY Study of serum (general) Study of invitro antigen-antibody reactions. It deals with the identification of antibodies in serum by: JPSC  Historical PerspectiveS Thucydides (430 BC) Plague of Athens His observation prompted the early people to make deliberate attempts to induce immunity. “Immunites”- Latin the exemption of individual from service or duty to the state. by: JPSC  China (1500) VARIOLATION an obsolete method of immunizing patients against small pox by infecting them with substance from the pustules of patients with a mild form of a disease variolation was named after the virus that causes small pox (Variola virus) by: JPSC  Johan Christian Fabricius (1590) Bursa of Fabricius The Bursa of Fabricius is a primary lymphoid organ in birds that is responsible for the amplification and differentiation of B lymphoid progenitors within its follicular micro environment by: JPSC  Johann Conrad Peyer (1690) identified lymphoid nodules in the small intestine and called them PEYER’S PATCHES Peyer’s patches are found in the ileum, they are aggregated lymphoid nodules, they monitor intestinal bacteria populations and prevents the growth of pathogenic bacteria in the intestines England (1718) Wife of a British Ambassador to Turkey, Lady Mary Wortley Montagu, introduced variolation in England; had her family variolated. by: JPSC  Edward Jenner (1798) - FOUNDER OF IMMUNOLOGY Introduced “vaccination” the basis for vaccination began when an English doctor observed that milk maids who had gotten cow pox did not show any symptoms of small pox after variolation. Sarah Nelmes and James Phipps The first experiment to test this theory involved milk maid Sarah Nelmes and James Phipps the 9-year-old son of Jenner’s Gardener. Dr. Jenner took a cow pox sore on a Nelmes hand and inoculated it in Phipps’ arm. Months later Jenner exposed Phipps a number of times to variola virus but Phipps never developed small pox. Vaccinia virus Vacca – Latin for cow The term vaccination came from the word Vacca in relation to Cow pox by: JPSC  Theodore Schwann (1798) First description of the role of microbes in putrefaction and fermentation His sugar fermentation studies led to his discovery that yeast originated the chemical process of fermentation. Friedrich Gustav Jakob Henle (1840) Henle was a German anatomist and pathologist who provided intellectual background on to the rise if the GERM THEORY, his essay on Miasma and Contagia was an early argument for the germ theory of disease He also discovered the Loop of Henle and Henle’s Tubules 2 anatomical structures in the kidney. by: JPSC  Ernst Haeckel (1862) First to observe the process of phagocytosis had observed white blood cells digesting di particles at the university of Jena in Jena, Germany. During that time, they are not aware about the process of phagocytosis Joseph Lister (1867) – FATHER OF ANTISEPTIC SURGERY Aseptic practice in surgery Carbolic acid/ phenol by: JPSC  Robert Koch (1876) First demonstration that microbes can cause disease he identified the specific causative agent of Tuberculosis, Cholera, and Anthrax koch’s postulates 1. The microorganism or other pathogen must be present in all cases of the disease. 2. The pathogen can be isolated from the diseased host and grown in pure culture. 3. The pathogen from the pure culture must cause the disease when inoculated into a healthy, susceptible laboratory animal. 4. The pathogen must be re-isolated from the new host and shown to be the same as the originally inoculated pathogen. by: JPSC by: JPSC  Paul Ehrlich (1877) Mast cells are the most closely associated cell types with allergic reactions. Although the discovery of the tissue mast cell is attributed to Paul Ehrlich, these cells were recognized and carefully described as early as 1863 by Frederick von Recklinghausen They are similar in the basophil in terms of function and appearance, both cells express CD 34 Mast cells are present in most tissues, they are very prevalent near the skin surface and mucosa and conjunctiva. Mast cells are best known for their role in allergy anaphylaxis, they also play a key role in inflammatory processes by: JPSC  Louis Pasteur (1880) – FATHER OF IMMUNOLOGY Confirmed the “Germ Theory of Disease”. He proved that heat could kill bacteria; attenuation Discovered vaccines against chicken cholera, anthrax (18801881), and rabies (1885). The microorganism or other pathogen must be present in all cases of the disease. The pathogen can be isolated from the diseased host and grown in pure culture. The pathogen from the pure culture must cause the disease when inoculated into a healthy, susceptible laboratory animal. The pathogen must be re-isolated from the new host and shown to be the same as the originally inoculated pathogen. by: JPSC  Metchnikoff's theory of phagocytosis conflicted with a theory of immunity at the time called the humoral theory. The adherence of humoral theory claimed that an organism's blood serum or components of the bloodstream defended the organism against for foreign bacteria. Metchnikoff's theory challenged the humoral theory for two reasons Methchinkoff found that the process of inflammation in the tissues of vertebrates was similar to the action of the cells digesting foreign particles in the starfish larvae, an organism lacking a vascular system. He established that there was a similar developmental process of the mesodermal cells in various organisms including vertebrates and invertebrates, a system that generated the process of phagocytosis. by: JPSC  EMILE ROUX AND ALEXANDRE YERSIN (1888) Bacterial toxin identification Toxin of diphtheria bacillus In 1888, Emile Roux joined the newly created Baxter institute where with Alexandre Yersin demonstrated that the symptoms of diphtheria are caused by a toxin secreted by the diphtheria bacillus. That discovery together with subsequent findings of other bacteriologists that infection with diphtheria bacillus elicits the production of an anti-toxin lead to the development of diphtheria immunization and serum therapy. by: JPSC  GEORGE NUTTALL (1888) Bacterial action of blood (defibrinated blood is bactericidal) Immunity associated with blood His studies focused on the bacterial action of blood. According to him, immunity is associated with blood. He proposed that phagocytes in blood are responsible in killing engulfed bacteria. by: JPSC  EMIL VON BEHRING AND SHIBASABURO KITASATO (1890) Antibody activity against toxins (antitoxins) Clostridium diphtheriae Humoral theory of immunity by: JPSC  ROBERT KOCH (1891) Delayed (cutaneous) hypersensitivity He introduced the concept of delayed hypersensitivity. by: JPSC  WILLIAM COLEY (1893) Father of immunotherapy Coley's toxins he injected streptococcal organisms into a patient with inoperable cancer. He thought that the infection he produced would have a side effect of shrinking the malignant tumor. These products became known as Coley’s toxins. These criticisms along with the development of radiation therapy and chemotherapy caused Coley’s toxins to gradually disappear from use. by: JPSC  EMIL ROUX (1894) Passive immunization Emile Roux together with Alexandre Yersin characterized diphtheria toxin in 1888. Roux was the first to use horses for immunization and reported a reduction from 50.7% fatal outcome of diphtheria without treatment to 24.5% with horse serum therapy. He immunized horses against diphtheria; the serum of the horses were then injected to humans. He was the one who introduced the concept of passive immunization. This is the temporary immune protection resulting from transfer of antibodies from another individual who has actively formed the antibodies. by: JPSC  RICHARD PFEIFFER (1894) Bacteriolysis Pfeiffer’s phenomenon He was the first to study the process of bacteriolysis and he called it the Pfeiffer’s phenomenon. Bacteriolysis is the destruction or dissolution of bacteria. In his studies, he made use of the cholera bacterium. JULES BORDET (1896) Complement 1919 Nobel Prize Antibody Heat-sensitive substance-complement by: JPSC  PAUL EHRLICH (1900) Side chain theory: This theory explained the immune responses to living cells, the theory discussed the interaction of antibodies and antigens in the blood and how antibodies are produced. Horror autotoxicus literally the horror of self-toxicity. This is a coin termed by Ehrlich to describe the body’s innate aversion to immunological self-destruction. by: JPSC  KARL LANDSTEINER Discovered ABO blood group system (1901) Hapten (1917) comes from the Latin word meaning “to fasten” because when this small molecules bind to larger proteins, they elicit an immune response. In other words, they stimulate the production of antibodies. Haptens on their own do not stimulate an immune reaction which means that they are not immunogenic. Yet, when they are fastened to a protein, the entire complex becomes highly immunogenic. -- Haptens stimulate the production of antibodies. by: JPSC  PAUL PORTER AND CHARLES RITCHET (1902) Anaphylaxis this is a life threatening response to an antigen characterized by systemic release of histamine the term anaphylaxis was coined by Charles Ritchet and Paul Portier when they tried to immunize dogs with actinia extracts or sea anemone venom. After a repeated injection of a small amount of the toxin, the dog died within 25 minutes. The discovery of the phenomenon of anaphylaxis showed that by immunization, not only protection, but also harmful events could be induced. by: JPSC  ALMROTH WRIGHT (1903) He resolved the conflict of Metchnikoff, the champion of cellularism, and Erlique, the leading exponent of humoralist doctrine. He showed that acquired immunity resulted from both humoral and cellular elements and they are equally important and interdependent. NICOLAS MAURICE ARTHUS (1903) Discovered Arthus Reaction localized inflammatory response belonging to a typical, local, sub-acute type III hypersensitivity reaction. characterized by pain, swelling, induration, and edema even accompanied by severe necrosis or ulceration at the injection sites. by: JPSC  CLEMENS VON PIQUET AND BELA SCHICK Serum sickness (1905) a type III hypersensitivity reaction that results from the injection of heterologous or foreign protein or serum caused by the deposition of immune complexes resulting from exposure to foreign proteins or haptens. Coined the word “allergy” (1906) Von Pirquet proposed the term allergy for the altered reactivity induced by what he termed an allergen which is a foreign substance. He recognized that sensitization to an allergen leads to accelerated responses on subsequent allergen administration analogous to differences between primary and subsequent small pox vaccine responses. by: JPSC  CARL PRAUSNITZ AND HEINZ KUSTNER (1921) Cutaneous Allergic Reaction reaction based on passive transfer of allergic sensitivity in which serum from an allergic individual is injected into cutaneous sites on a normal individual and the injected sites are then exposed to antigens to which the donor is allergic.. Reagin antibodies shown that it was possible to transfer one person’s allergy to another person via what they called reagin antibodies. by: JPSC  ALEXANDER FLEMING 2 Discoveries: 1. The enzyme lysozyme Discovered by Flemming in 1921 when he demonstrated that his own nasal mucus had the ability to inhibit the growth of a certain strain of bacteria. He realized that this was largely due to the action of a protein within the mucus that caused the bacterial cells to lyse or break apart. 2. The antibiotic penicillin In 1928, Flemming noted that mold belonging to the genus Penicillium inhibited the growth of bacteria. He called this unknown antibacterial substance as Penicillin. It was hailed as a “miracle drug” and it saved countless lives in World War II. by: JPSC  JOHN MARRACK (1938) Antigen-antibody (ag-ab) binding interactions Lattice formation KARL LANDSTEINER AND ALEXANDER WIENER (1940) Discovery of Rh factor a type of protein found on the outside of red blood cells. from the rhesus monkey JULES FREUND (1942) He introduced the use of adjuvants which are substances that enhances the immune systems response to the presence of an antigen. commonly used to improve the effectiveness of a vaccine. by: JPSC by: JPSC  Peter Medawar (1944) Allograft rejection: transplant of an organ or tissue from one individual to another of the same species with a different genotype George Snell (1946) Discovered the first components of the major histocompatibility complex in the 1940s through their role in rejecting transplants in mice. Astrid Fagraeus (1948) Ab production by plasma cells Plasma cells: immune cells that make large amounts of specific antibodies. develop from B-cells that have been activated. by: JPSC  James Riley and Geoffrey West (1953) Histamine is present in mast cells key participant in allergic, and anaphylactic reactions. Frank MacFarlane Burnet (1957) widely regarded as the greatest scientist Australia has ever produced. Clonal Selection Theory Scientific theory that explains the functions of cells of the immune system, in response to specific antigens invading the body. Frank MacFarlane Burnet (1957) widely regarded as the greatest scientist Australia has ever produced. Clonal Selection Theory Scientific theory that explains the functions of cells of the immune system, in response to specific antigens invading the body. Immunological tolerance Failure to mount an immune response to an antigen by: JPSC  Alick Isaacs and Jean Lindenmann (1957) Interferon: first cytokine interferes with viral proliferation; it is a defense against viruses. It was the first described member of the class of protein molecules (now known as cytokines). Nowadays, interferons are well-known to participate in the innate immune system mediating responses against viral infections. Cytokines: cell signaling group of a low molecular weight extracellular polypeptides or glycoproteins synthesized by different immune cells responsible to promote and regulate immune responses. by: JPSC  Jean Dausset (1958) He looked for and found the major histocompatibility complex in humans, in relation to the discovery of Snell. Human Leukocyte Antigen system an important part of the immune system and is controlled by genes located on chromosome number 6. Georges Kohler and Cesar Milstein (1975) Monoclonal Antibody Production It is an antibody produced by a single clone of cells (single pure type of antibody) laboratory produced molecules that served as substitute antibodies and they can restore, enhance, or mimic the immune system’s attack on cancer cells. susumu Tonegawa (1978) He was recognized for his discovery of the genetic principle for the generation of antibody diversity. According to this, genetic material rearranges itself to form millions of antibodies. by: JPSC  Elvin Abraham Kabat (1980) regarded as the Father of Modern Immunology He was a founder of immunochemistry the study of the chemical reactions and phenomena of immunity. Dr. Kabat set the course for mapping their molecular structures. He studies shed light on the basic mechanisms of immunohematology. He also developed a laboratory technique used in the study of multiple sclerosis and other human by: JPSC  year vaccine 1949 Polio vaccine (Salk and Sabin) 1951 Vaccine against yellow fever (Reed) 1986 Hepatitis B vaccine by genetic engineering 1996-1998 Toll-like receptors 2005 Human papillomavirus vaccine (Frazer) by: JPSC