EFE Veterinary Science The Immune System Intro Antigen (Ag): Any foreign molecule capable of stimulating an immune response Typically large, complex molecules, foreign to the body (organ donors) Lymphatics Lymph Node (home of the lymphocyte), lymphatic vessels, lymph Passive movement of lymph, not pumped by the heart (“stocking up”) Lymph nodes filter out antigens Each lymphocyte is programmed to respond to one specific antigen. Increased exposure to this antigen leads to clonal expansion, reproduction of the lymphocytes that respond to that antigen. Spleen Filters blood, contains immune cells and cells that produce antibodies Can live without spleen: tumors, trauma -> splenectomy Bone Marrow produces WBCs (white blood cells), the functional immune cells Phagocytosis mainly by neutrophils and macrophages Inside a WBC: phagocytosis, AG “presented” on cell surface->macrophages release stimulating factors->more immune response. WBC function: virucidal, decrease replication of foreign organisms, attract more immune cells, promote phagocytosis, kill damaged cells, influence the hypothalamus to initiate a fever Fever can destroy virally infected cells, and stimulates activity of lymphocytes, phagocytes and antibodies Inflammation can result from physical injury or invasion of a pathogen. It consists of local blood vessel dilation-> local increase in RBC and WBC. 4 hallmarks of inflammation: warm, red, swollen, edematous. Inflammation increases number of WBC, increases contact between lymphocytes and antigen presenting cells. B lymphocytes (B cells) are lymphocytes that mature in the Bone marrow Each B cell responds to 1 antigen; they become plasma cells and secrete antibodies (Abs). Abs then bind to a part of the antigen and form and Ab:Ag complex, which either: Prevents attachment of antigen to cells Destroys the antigen Promotes phagocytosis Antibodies are produced in the lymph nodes, spleen, and bone marrow. Humoral immunity is the name for the above process: In the Primary response 3-14 days after the first exposure to an antigen, the antigen is recognized as foreign by the lymphocytes, clonal expansion takes place, and Abs are produced by plasma cells Some of the clonal cells become memory cells. They have long survival, allowing for a faster response and higher antibody production if the animal is exposed to the antigen again. In the Secondary response, the faster response and increased Ab level are why vaccines work. Cell Mediated Immunity (CMI) T lymphocytes (T cells) mature in the Thymus Each T cell is antigen specific: bone marrow releases the T cell; it migrates to the thymus and matures, then is released into circulation. The thymus is very active in young animals; it loses lymphoid tissue as an organism ages. CMI works with humoral immunity: increased Abs->increased T cells, macrophages This is the mechanism of transplanted tissue/organ rejection T cell exposure to Ags-> clonal expansion-> lasting immunity CMI is hard to measure Cells migrate to the site of infection: neutrophils, lymphocytes, macrophages These cells, plus debris = pus (adj. purulent) Edward Jenner and the Smallpox vaccination Immunity Natural exposure Vaccination-> memory cells Modified Live : Sometimes single dose effective Killed: First dose stimulates a primary immune response; in 2-4 weeks, a second dose is used to increase Ab production and produce memory cells Toxoid: Similar to Killed vaccine, example, tetanus toxoid Subsequent exposure stimulates a memory response, resulting in milder or no illness. Active Immunity >6 months old; annual booster vaccination activates immune system Passive Immunity Maternal Abs via colostrum: Only produced and absorbed during the first few days after birth. Failure of Passive Transfer may result from orphan status, poor colostral quality, decreased quantity available, or decreased consumption If no colostral immunity, can use commercial products with high level of antibodies Passive immunity is temporary; it lasts weeks to months. If passive immunity is present (maternal antibodies), vaccines are inactivated. We repeat vaccines in young animals to try to “close the window” between when the maternal antibodies fade and the antigen can stimulate immunity in the animal. Newborns have a competent immune system but no previous exposure to antigens, so no existing immunity. Passive transfer via colostrum, followed by vaccination, is the solution. Inappropriate Immune Responses Allergies: Normal environmental molecules stimulate an immune response: IgE antibodies are produced; histamine and serotonin are released, causing inflammation and pruritus Atopy: allergy to environmental molecules (dust, pollen, mold, mites) Atopic dogs and cats itch; atopic humans sniffle and sneeze. Antihistamines prevent symptoms, but cannot alleviate them once present Anaphylaxis: generalized, life-threatening allergic response. Treated with epinephrine Autoimmune disease: lupus, AIHA, AITP Titer: measures the antibody level in the blood to a specific antigen Seroconversion: >4x increase in titer between acute and convalescent sample ELISA tests: Used in-clinic to quickly diagnose some diseases (heartworm Ag, FeLV Ag, FIV Ab) Activity #2, bottom of page 170