Immunology study guide for Quiz 1 (Part 1) Introduction: What is immunity?Immunity is the ability of an organism to recognize and neutralize a foreign substanceExamples: Bacteria, Fungi, Viruses, parasites, tumor cells, or biochemicals (toxins)The immune system protects against four classes of pathogen1) Extracellular bacteria, parasites, fungi2) Intracellular bacteria, parasites3) Viruses (intracellular)4) Extracellular Parasites (worms)An antigen is a substance that has the potential to elicit an immune responseAn immunogen is a substance that has already generated an immune response.There are two categories of immunity1) Nonspecific (Innate, Natural, Native) Immunity: is always present, repeated exposure does not increase response. It is a property of all living organisms. Examples: Biochemical in blood, tears, saliva, skin secretions; certain blood and tissue cellsa) Innate immunity generally responds to general pathogens2) Specific (Adaptive, Acquired) Immunity: Found in vertebrates and a few other organismsa) Recognition can be very specificb) Repeated encounters evoke stronger and more efficient responses: Immunological memoryc) Basis of immunizationThere are two arms of Effectors of specific immunity1) Humoral: mediated by antibodies; responsible for detecting and destroying antigens on or outside of cells (humoral effectors float around in body fluids; like lymph ect)2) Cellular: mediated by cells: responsible for detecting and destroying antigens inside of the cell (Example: lymphocytes)Each arm can recognize and discriminate between billions of different antigensImmunoglobulin (Ig) structure and antigen (Ag) terminologyImmunoglobulin is another name for antibodies (These are effector molecules)Antibodies (Abs) are the effectors of humoral immunityThe epitope is the area where the Abs targets the moleculeThe Lymphocyte is the effector of cellular immunityThe History of ImmunologyThe earliest efforts in immunology were based on folk medicine●In the 1500s, Indians (Asian) inhaled smallpox scabs●In 1720, Lady Montague (A member of English royalty) observed the practice in turkey and brought it to England●In 1796, Edward Jenner discovered "vaccination"fi He noticed that milkmaids who had gotten cowpox did not get smallpoxfi This phenomenon is cross-reactivity: Ab against one agent cross-reacts with a related agent, i.e., the two agents are biochemically similar enough that the Ab can see both.fiJenner deliberately exposed patients to cowpox then challenged them with smallpoxfi Predicted that his technique would wipe out smallpoxfi He was right, but it took 182 years●Benjamin Jesty was an English farmer who deliberately exposed his wife and sons to cowpox, both were later exposed to smallpox without effect. He predated Jenner by ~20 years, but he was not widely known●In the 1880's, Louis Pasteur (The father of immunology) worked with chicken cholera, rabbitsfiHe used attenuated cultures (weakened cultures) as vaccinesfiThe first person to be vaccinated was Joseph Meister●Elie Metchnikoff, a Russian zoologist in the 1880's, asked the question: What is the basis of immunity?fiHe observed cells in tissues attacking bacteria and other foreign objectsfiHe termed them macrophages and microphages (Now called neutrophils)fiHe declared that these cells were the basis for immunity●Emile Roux and Alexandre YersinfiIn 1888, they neutralized diphtheria and tetanus toxins with antisera to toxoids (partially denatured toxins)fi They demonstrated in vitro neutralization; therefore, cells could not be the basis of immunityExperiment: In vitro neutralization = Temporary protection 1) They injected an animal with a toxinfiThe animal died2) They injected the animal with a toxoidfi The animal did not die(3) The combined the serum* of the toxoid injected animal with the toxin and injected this cocktail into a new animal and there is no harmful effect**Key here is that the serum does not contain cells*** fiThe animal livedfiThe antibodies in the serum neutralized the toxinThis experiment demonstrated that the cells are not the basis of immunity ●Emil (von) Behring and Shibasaburo KitasatofiIn 1890, described passive immunity.fi Antiserum to diphtheria and tetanus toxin protected animals when injected prior to bacterial or toxin exposure.Experiment: In vivo neutralization: Passive immunity = Temporary Protection1) Injecting the animal resulted in a dead animal, same as in last experiment2) They injected an animal with toxoid, the animal did not die, and then they took serum from that animal3) Instead of mixing the serum with a toxoid, they injected just the serum into a different animal4) After a period of time, they injected the animal with the toxin and the animal survived.The animal does not develop memory because the immunity was acquired from the serum, which has no cells, only molecules, and the molecules have finite half life (in the order of weeks Once the antibodies decay, there is no more immunity.●Paul Ehrlich's side chain theory 1896fiProposed that cells produce side chains (What we now recognize as antibodies) that have varying specificities.fi Antigen binds specific side chain and induces increased production and secretionfi He imagined that there must be cells in the body that had complimentary molecules on their surface to the toxinfiThere must be some interaction between the toxin and the side chain that would stimulate the cell to produce more side chainsCellular immunity rediscovered ●(Sir) Peter Brian Medawar (RAF) in the 1940's (WWII)fi He was a flight surgeon and was faced with the treatment of a lot of burn victimsfi He experimented with tissue grafts and observed the following:If he gave patient a skin graft, and if was not from the patient himself (an allograph), it would eventually be rejected- become necrotic and slough off. This would happen even if the graft was taken from a live donor. If he tried to de a second graft from the same donor, the graft would be rejected much more quickly than the first time. If the second graph was not from the same donor, it would be rejected just as slowly as the first graft. (Due to immunological memory)He determined that this was an immunological issue and he was able to demonstrate that there were no antibodies involved.Experiment: Adoptive transfer of immunity =