Specific Defense Mechanisms A.J. Lanigan Ozone has the ability to kill or inactivate quite a number of pathogens (if it can make contact). Ozonides, agents that are formed by ozone in the blood, have a certain degree of ablity to do this same job. Many tout the abilty of ozone to perform in a test tube & assume an identical action occurs inside the body. It is possible to saturate a _test tube_ of material with ozone and measure the effectiveness afterwards. I have never had a person volunteer to be ground up & "tested" after an ozone treatment. So how do you find out if the treatment is doing any good? I have always stressed the need to establish a baseline before you start to compare how effective ozone (or any therapy) will be over time. Not to do this, IMO, leaves one to how one "feels" at the end of each period of work. Since most people who are serious end up investing hundreds if not thousands of dollars over time to pursue such work, hard evidence is very good to have in hand to put the issue to rest. Immune testing is one of the standard methods to determine if a therapy is performing or if changes need to be made. The fact that ozone reacts & is gone in nanoseconds and ozonides not long thereafter, it is the state of the immune system that has to be evaluated to see if it is capable of carrying out the battle to conclusion. Ozone plays a part in the general "non-specific" activation & modulation of the immune system. Immune "fax messages" such as cytokines, lymphokines, tumor necrosis factor(TNF), interferon(INF), interleukins(IL), etc. are known to increase during an ozone regimen. It is these profound increases that have led many researchers to the belief that ozone therapies' main value lies not in its ability to start a kill off of pathogens but to cause the immune system to finish that process and keep the body healthy over the long run. As one learns the importance of the immune system in a total approach to returning/conserving health, one needs to know how it works. Oxytherapy may be a trigger but here is the ultimate weapon. Have a happy day, a.j. SPECIFIC DEFENSE MECHANISMS: THE IMMUNE RESPONSE The immune system is a recognition system that distinguishes self from non-self. Antigen = A foreign substance which elicits a proliferation of cells that either attack specific invaders directly or produce antibodies. The immune response must be primed by the presence of an antigen. Exposure to a particular foreign agent enhances future response by that same invader. Vaccination = The immune response is presented with a nonvirulent or attenuated (weakened) form of a pathogen which initiates a long-term capability to respond quickly to the real infective agent. Active immunity occurs when the body is stimulated to produce antibodies. Passive immunity occurs when the body acquires injected antibodies. When antibodies cross the placenta from mother to fetus; When you get an injection of antibodies; Provides only temporary immunity since the antibodies circulate in the blood stream for only a few weeks or months. A. Duality of the Immune System 1.The immune system has two components mediated by two different kinds of cell. i.Humoral immunity results in production of antibodies which circulate as soluble proteins in blood and lymph. (B cells) a.Defends against free bacteria and viruses in body fluids. ii.Cell-mediated immunity is carried out by specialized cells circulating in blood and lymph. (T cells) a.Protects against bacteria and viruses that have already infected cells. b.Also protects against fungi and protozoa. c.Reacts against foreign tissue transplants and possibly against cancerous cells. B. Cells of the Immune System 1.Lymphocytes = White blood cells responsible for the immune response. i.Originate from common stem cells in red bone marrow. ii.Lymphocytes that continue maturation in bone become B cells which function in humoral immunity. iii.Lymphocytes that migrate to the thymus become T cells which function in cell-mediated immunity. 2.As lymphocytes mature, they develop immunocompetence, a rigid commitment to identify and respond to a specific antigen. i.Involves synthesis of surface receptor proteins (in B cells these are bound copies of the antibody secreted during the immune response). ii.Each lymphocyte becomes programmed to recognize and respond to a specific antigen before it actually encounters that antigen. The immune system is prepared for an almost unlimited variety of potential pathogens that may never invade the body. iii.Immunocompetent cells then migrate to the lymph nodes and spleen, where most first encounters with pathogens occur. 3.Once activated by antigens, lymphocytes multiply and develop into effector cells, derivatives equipped to respond to antigens. i.Effector cells are mobilized through circulatory and lymphatic vessels. C. Antigens 1.In general, antigens are large molecules (MW=10,000 daltons or more). i.Most are proteins or large polysaccharides. ii.Often are outer components of invading microbes (biochemical markers not the whole organism). iii.May be foreign molecules associated with other blood cells or may be transplanted tissues. 2.Antigenic determinants = Localized surface regions of an antigen recognized by antibodies. i.May have many different determinants on one antigen; therefore, one antigen may stimulate synthesis of many different antibodies. D. Clonal Selection 1.The versatility of the immune system depends on the great diversity of lymphocytes with different receptor specificities. 2.Clonal selection = The selective activation (by an antigen) of a tiny fraction of quiescent lymphocytes, which grow and divide to form a clone of effector cells. E. Immunological Memory 1.Primary immune response occurs when a first exposure to antigen stimulates production of memory cells and effector cells. i.Characterized by a lag period of several days (necessary time to produce effector cells). 2.A secondary immune response occurs when another exposure to the same antigen reactivates memory cells which, already sensitized by the first exposure, rapidly produce more memory cells and a large number of effector cells. i.Faster, more effective and more prolonged than the primary immune response. ii.Memory cells may live for decades: effector cells live only a few days. iii.May confer lifetime immunity (e.g. mumps, chicken pox). F. The Humoral Immune Response 1.The humoral response is provoked by binding of antigens to antibodies producing form B cell plasma membranes. 2.B cells are activated by: i.Capping, when a polyvalent (having multiple copies of antigenic determinants) antigen binds to several receptors on an immunocompetent B cell surface, pulling receptors together to form a cap which is taken into the cell by endocytosis. ii.A more common mechanism involving B cell interaction with T cells, discussed later. 3.Plasma cells = Effector cells that develop from B cells and secrete as many as 2,000 antibody molecules per second during their 4 to 5 day lifetime. These free, discharged antibodies circulate in blood and lymph, binding and destroying antigens. 4.Antibodies constitute a class of immunoglobins (Ig), able to recognize an antigen and assist in elimination. 5.The antigen-variable region interaction involves several weak bonds which form between contiguous chemical groups on the respective molecules. 6.There are 5 types of constant regions, hence 5 classes of antibodies - IgM, IgG, IgA, IgD, and IgE. 7.In humoral effector mechanisms, soluble antibodies "tag" molecules for destruction by a variety of effector mechanisms. 8.Antibodies are used widely in research and clinical testing since they specifically recognize molecules. 9.Antibodies for vaccination or research used to be produced by injection of an antigen into an animal. i.A problem with this method was than animals make more than one antibody since each antigen has many antigenic determinants. ii.The solution was monoclonal antibodies. 10.With monoclonal antibodies, all cells producing antibodies are descendants of a single cell, thus, all produce identical antibody molecules. i.Made by hybridomas [fusion of a myeloma (tumor) cell to a normal antibody] producing lymphocytes. 11.The hybridoma is grown in an artificial medium. (Normal cells do not grow indefinitely in culture, thus, the g=function to a myeloma cell.) i.Used in clinical assays such as pregnancy testing. ii.Used in bone marrow transplants. iii.May be coupled to a toxin, and then use the antibody's specificity to target the toxin for a particular cell type (potential use in chemotherapy). G. Cell-Mediated Immunity 1.T cells are the main agents of cell-mediated immunity. i.Cannot be activated by free antigens. ii.Respond only to antigenic determinants displayed on surfaces of the body's own cells. 2.T cell receptors = Specific proteins embedded in T cell plasma membranes which allow recognition of bound antigens. i.Recognizes only a self-nonself complex formed by an antigen displayed on the cell surface by antigen presenting cells (APCs) such as macrophages along with an MHC protein. 3.MHC (major histocompatibility complex) = A group of glycoproteins unique to each individual that are present on cell surfaces. i.MHC I markers are present on all nucleated cells. ii.MHC II markers are found only on macrophages, B cells and some T cells. 4.Histocompatibility restriction = The constraint on a T cell's responsiveness. Although an MHC molecule can associate with many different antigens, the T cell receptor is specific to one antigen. 5.Activated T cells proliferate and form memory cells and cytotoxic T cells that actually attack infected cells. 6.There are three main types of effector cells derived from T cells: i.Helper T cells mobilize humoral and cell-mediated immune responses. a.Helper T cells activated by binding to APC. b.Binding stimulates macrophages to release interleukin I, a cytokine (chemical secreted by one cell as a regulator of neighboring cells). c.IL I stimulates T cells to grow, divide and produce more helper T cells specific to the antigen-MHC complex. d.These produce interleukin II, which stimulates further helper T cell growth and division and amplifies proliferation of cytotoxic T cells. e.IL II also stimulate B cells to become activated (T dependent antigens can activate only B cells stimulated by interleukin II). ii.Cytotoxic T cells are the only T cells that actually kill other cells. a.Identify targets by the fit of their receptor to an MHC- antigen complex. b.Kills cells by attaching to the cell surface and releasing perforin, a protein that inserts into the plasma membrane forming a lesion that causes the cell to lyse. c.Probably attack cancer cells and foreign tissue grafts and organ transplants. iii.Suppressor T cells release cytokines that inhibit other T cell and B cell activity. a.Occurs late in the immune response to terminate immune activities no longer required.