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Outlines physiology of Immunity


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CONTENT DEFINITION TYPES OF IMMUNITY innate immunity acquired immunity humoral immunity cell mediated immunity (III) HISTORY OF THEORIES OF IMMUNITY (IV) IMMUNE SYSTEM (V) FLUID SYSTEMS OF BODY blood lymph (VI) INNATE IMMUNITY surface barriers or mucosal immunity normal flora phagocytes natural killer cells polymorph nuclear neutrophil complement systems (VII) ACQUIRED IMMUNITY humoral immunity cell mediated immunity (VIII) HEALTH SUPPLEMENTS AND MULTIVITAMINS PROVIDING IMMUNITY

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Immunity is a medical term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide range of pathogens irrespective of antigenic specificity. (I) IMMUNITY - DEFINITION Naturally acquired artificially acquired Innate immunity Acquired immunity active passive active passive (II) TYPES OF IMMUNITY

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(III) HISTORY OF THEORIES OF IMMUNIY A representation of the cholera epidemic of the nineteenth century. The concept of immunity has intrigued mankind for thousands of years. The prehistoric view of disease was that it was caused by supernatural forces, and that illness was a form of punishment for “bad deeds” or “evil thoughts” visited upon the soul by the gods or by one’s enemies. Between the time of Hippocrates and the 19th century, diseases were attributed to an alteration or imbalance in one of the four humors (blood, phlegm, yellow bile or black bile). Also popular during this time was the miasma theory, which held that diseases such as cholera or the Black Plague were caused by a miasma, a noxious form of "bad air“. If someone were exposed to the miasma, they could get the disease. The modern word “immunity” derives from the Latin immunis, meaning exemption from military service, tax payments or other public services.

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The term “immunes”, is also found in the epic poem “Pharsalia” written around 60 B.C. by the poet Marcus Annaeus to describe a North African tribe’s resistance to snake venom. However, it was with Louis Pasteur’s Germ theory of disease that the fledgling science of immunology began to explain how bacteria caused disease, and how, following infection, the human body gained the ability to resist further insults. Louis Pasteur in his laboratory, 1885. The birth of active immunotherapy may have begun with Mithridates VI of Pontus To induce active immunity for snake venom, he recommended using a method similar to modern toxoid serum therapy. In 1888 Emile Roux and Alexander Yersin isolated diphtheria toxin, following the 1890 discovery by Behring and Kitasato of antitoxin based immunity to diphtheria and tetanus, the antitoxin became the first major success of modern therapeutic Immunology

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(IV) IMMUNE SYSTEMS The human immune system is a truly amazing constellation of responses to attacks from outside the body. The system is remarkably effective, most of the time. An antigen is any substance that elicits an immune response. The immune system has a series of dual natures, the most important of which is self/non-self recognition. The others are: general/specific, natural/adaptive = innate/acquired, cell-mediated/humoral, active/passive, primary/secondary. Parts of the immune system are antigen-specific (they recognize and act against particular antigens), systemic (not confined to the initial infection site, but work throughout the body), and have memory (recognize and mount an even stronger attack to the same antigen the next time). Self/non-self recognition is achieved by having every cell display a marker based on the major histocompatibility complex (MHC). Any cell not displaying this marker is treated as non-self and attacked. The process is so effective that undigested proteins are treated as antigens.

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Sometimes the process breaks down and the immune system attacks self-cells. This is the case of autoimmune diseases like multiple sclerosis, systemic lupus erythematosus, and some forms of arthritis and diabetes. The simple substance that elicits the allergic response is called an allergen. There are two main fluid systems in the body: blood and lymph. The blood and lymph systems are intertwined throughout the body and they are responsible for transporting the agents of the immune system. BLOOD Blood is composed of 52–62% liquid plasma and 38–48% cells. The plasma is mostly water (91.5%) and acts as a solvent for transporting other materials (7% protein [consisting of albumins (54%), globulins (38%), fibrinogen (7%), and other stuff (1%)]. Blood is slightly alkaline (pH = 7.40 ± .05) and heavier than water (density = 1.057 ± .009). (V) FLUID SYSTEMS OF THE BODY

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All blood cells are manufactured by stem cells, which live mainly in the bone marrow, via a process called hematopoiesis. The stem cells produce hemocytoblasts that differentiate into the precursors for all the different types of blood cells. Hemocytoblasts mature into three types of blood cells: erythrocytes (red blood cells or RBCs), leukocytes (white blood cells or WBCs), and thrombocytes (platelets). The leukocytes are further subdivided into granulocytes (containing large granules in the cytoplasm) and agranulocytes (without granules). The granulocytes consist of neutrophils (55–70%), eosinophils (1–3%), and basophils (0.5–1.0%). The agranulocytes are lymphocytes (consisting of B cells and T cells) and monocytes. Lymphocytes circulate in the blood and lymph systems, and make their home in the lymphoid organs.

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All of the major cells in the blood system are illustrated below. There are 5000–10,000 WBCs per mm3 and they live 5-9 days. About 2,400,000 RBCs are produced each second and each lives for about 120 days. A healthy male has about 5 million RBC per mm3, whereas females have a bit fewer than 5 million.

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2. LYMPH Lymph is an alkaline (pH > 7.0) fluid that is usually clear, transparent, and colorless. It flows in the lymphatic vessels and bathes tissues and organs in its protective covering. There are no RBC in lymph and it has a lower protein content than blood. Like blood, it is slightly heavier than water (density = 1.019 ± .003). The lymph flows from the interstitial fluid through lymphatic vessels up to either the thoracic duct or right lymph duct, which terminate in the subclavian veins, where lymph is mixed into the blood. (The right lymph duct drains the right sides of the thorax, neck, and head, whereas the thoracic duct drains the rest of the body.) Lymph carries lipids lipid-soluble vitamins absorbed from the gastrointestinal (GI) tract. Since there is no active pump in the lymph system, there is no back-pressure produced. The lymphatic vessels, like veins, have one-way valves that prevent backflow. Additionally, along these vessels there are small bean-shaped lymph nodes that serve as filters of the lymphatic fluid. It is in the lymph nodes where antigen is usually presented to the immune system.

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The human lymphoid system has the following: -   primary organs: bone marrow (in the hollow center of bones) thymus gland (located behind the breastbone above the heart) secondary organs at or near possible portals of entry for pathogens: adenoids, tonsils, spleen (located at the upper left of the abdomen), lymph nodes (along the lymphatic vessels with concentrations in the neck, armpits, abdomen, and groin), Peyer's patches (within the intestines), appendix.

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(VI) INNATE IMMUNITY The innate immunity system is what we are born with and it is nonspecific; all antigens are attacked pretty much equally. It is genetically based and we pass it on to our offspring. SURFACE BARRIERS OR MUCOSAL IMMUNITY The first and, arguably, most important barrier is the skin. The skin cannot be penetrated by most organisms unless it already has an opening, such as a nick, scratch, or cut. Mechanically, pathogens are expelled from the lungs by ciliary action as the tiny hairs move in an upward motion; coughing and sneezing abruptly eject both living and nonliving things from the respiratory system; the flushing action of tears, saliva, and urine also force out pathogens, as does the sloughing off of skin. Sticky mucus in respiratory and gastrointestinal tracts traps many microorganisms.

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4. Acid pH (< 7.0) of skin secretions inhibits bacterial growth. Hair follicles secrete sebum that contains lactic acid and fatty acids both of which inhibit the growth of some pathogenic bacteria and fungi. Areas of the skin not covered with hair, such as the palms and soles of the feet, are most susceptible to fungal infections. Think athlete's foot. 5. Saliva, tears, nasal secretions, and perspiration contain lysozyme, an enzyme that destroys Gram positive bacterial cell walls causing cell lysis. Vaginal secretions are also slightly acidic (after the onset of menses). Spermine and zinc in semen destroy some pathogens. Lactoperoxidase is a powerful enzyme found in mother's milk. 6. The stomach is a formidable obstacle insofar as its mucosa secrete hydrochloric acid (0.9 < pH < 3.0, very acidic) and protein-digesting enzymes that kill many pathogens. The stomach can even destroy drugs and other chemicals.

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NORMAL FLORA are the microbes, mostly bacteria, that live in and on the body with, usually, no harmful effects to us. We have about 1013 cells in our bodies and 1014 bacteria, most of which live in the large intestine. There are 103–104 microbes per cm2 on the skin (Staphylococcus aureus, Staph. epidermidis, diphtheroids, streptococci, Candida, etc.). Various bacteria live in the nose and mouth. Lactobacilli live in the stomach and small intestine. The upper intestine has about 104 bacteria per gram; the large bowel has 1011 per gram, of which 95–99% are anaerobes or bacteroides. The urogenitary tract is lightly colonized by various bacteria and diphtheroids. After puberty, the vagina is colonized by Lactobacillus aerophilus that ferment glycogen to maintain an acid pH. A PHAGOCYTE is a cell that attracts (by chemotaxis), adheres to, engulfs, and ingests foreign bodies. Promonocytes are made in the bone marrow, after which they are released into the blood and called circulating monocytes, which eventually mature into macrophages (meaning "big eaters").

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Some macrophages are concentrated in the lungs, liver Kupffer cells, lining of the lymph nodes and spleen, brain microglia, kidney mesoangial cells, synovial A cells, and osteoclasts. They are long-lived, depend on mitochondria for energy, and are best at attacking dead cells and pathogens capable of living within cells. Once a macrophage phagocytizes a cell, it places some of its proteins, called epitopes, on its surface. These surface markers serve as an alarm to other immune cells. All cells that do this are called antigen presenting cells (APCs). Emigration of macrophages by squeezing through the capillary walls to the tissue is called diapedesis or extravasation. The presence of histamines at the infection site attract the cells to their source.

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NATURAL KILLER CELLS move in the blood and lymph to lyse infected body cells. They are large granular lymphocytes that attach to the glycoproteins on the surfaces of infected cells and kill them. POLYMORPHONUCLEAR NEUTROPHILS, are phagocytes that have no mitochondria and get their energy from stored glycogen. They are non dividing, short-lived (half-life of 6–8 hours, 1–4 day lifespan), and have a segmented nucleus. They constitute 50–75% of all leukocytes. The neutrophils provide the major defense against pyogenic (pus-forming) bacteria and are the first on the scene to fight infection. They are followed by the wandering macrophages about three to four hours later. The COMPLEMENT SYSTEM is a major triggered enzyme plasma system. It coats microbes with molecules that make them more susceptible to engulfment by phagocytes. Vascular permeability mediators increase the permeability of the capillaries to allow more plasma and complement fluid to flow to the site of infection. They also encourage polymorpho nuclear lymphocytes to adhere to the walls of capillaries (margination) from which they can squeeze through to arrive at a damaged area. Once phagocytes do their job, they die and their "corpses," pockets of damaged tissue, and fluid form pus.

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Eosinophils are attracted to cells coated with complement C3B, where they release major basic protein (MBP), cationic protein, perforins, and oxygen metabolites, all of which work together to burn holes in cells and helminths (worms). About 13% of the WBC are eosinophils. Dendritic cells are covered with a maze of membranous processes that look like nerve cell dendrites. Most of them are highly efficient antigen presenting cells. There are four basic types: Langerhans cells, interstitial dendritic cells, interdigitating dendritic cells, and circulating dendritic cells. Our major concern will be Langerhans cells, which are found in the epidermis and mucous membranes, especially in the anal, vaginal, and oral cavities. These cells make a point of attracting antigen and efficiently presenting it to T helper cells for their activation.

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Each of the cells in the innate immune system bind to antigen using pattern-recognition receptors. These receptors are encoded in the germ line of each person. This immunity is passed from generation to generation. Over the course of human development these receptors for pathogen-associated molecular patterns have evolved via natural selection. There are several hundred of these receptors and they recognize patterns of bacterial lipopolysaccharide, peptidoglycan, bacterial DNA, dsRNA, and other substances. Clearly, they are set to target both Gram-negative and Gram-positive bacteria. (VII) ADAPTIVE OR ACQUIRED IMMUNITY Lymphocytes come in two major types: B cells and T cells. The peripheral blood contains 20–50% of circulating lymphocytes; the rest move in the lymph system. Roughly 80% of them are T cells, 15% B cells and remainder are null or undifferentiated cells. Lymphocytes constitute 20–40% of the body's WBCs. Their total mass is about the same as that of the brain or liver.

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B cells are produced in the stem cells of the bone marrow; they produce antibody and oversee humoral immunity. T cells are nonantibody-producing lymphocytes which are also produced in the bone marrow but sensitized in the thymus and constitute the basis of cell-mediated immunity. Macrophages engulf antigens, process them internally, then display parts of them on their surface together with some of their own proteins. This sensitizes the T cells to recognize these antigens. All cells are coated with various substances. CD stands for cluster of differentiation and there are more than one hundred and sixty clusters, each of which is a different chemical molecule that coats the surface. Every T and B cell has about 105 = 100,000 molecules on its surface. B cells are coated with CD21, CD35, CD40, and CD45. T cells have CD2, CD3, CD4, CD28, CD45R, and other non-CD molecules on their surfaces. CELL-MEDIATED IMMUNITY

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Cytotoxic or killer T cells (CD8+) do their work by releasing lymphotoxins, which cause cell lysis. Helper T cells (CD4+) serve as managers, directing the immune response. They secrete chemicals called lymphokines that stimulate cytotoxic T cells and B cells and enhance the ability of macrophages to engulf and destroy microbes. Suppressor T cells inhibit the production of cytotoxic T cells once they are unneeded. Memory T cells are programmed to recognize and respond to a pathogen once it has invaded. An immunocompetent B-lymphocyte is stimulated to maturity when an antigen binds to its surface receptors and there is a T helper cell nearby (to release a cytokine). This sensitizes the B cell and it undergoes clonal selection, which means it reproduces asexually by mitosis. Most of the family of clones become plasma cells. These cells, produce highly specific antibodies at a rate of as many as 2000 molecules per second for four to five days. The other B cells become long-lived memory cells. HUMORAL IMMUNITY

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Antibodies, also called immunoglobulins or Igs, constitute the gamma globulin part of the blood proteins. They are soluble proteins secreted by the plasma offspring of B cells. The antibodies inactivate antigens by, complement fixation (proteins attach to antigen surface and cause holes to form, i.e., cell lysis), neutralization (binding to specific sites to prevent attachment—this is the same as taking their parking space), agglutination (clumping), precipitation (forcing insolubility and settling out of solution), and other more arcane methods. Constituents of gamma globulin are: IgG-76%, IgA-15%, IgM-8%, IgD-1%, and IgE-0.002%. IgG is the only antibody that can cross the placental barrier to the fetus and it is responsible for the 3 to 6 month immune protection of newborns that is conferred by the mother.

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IgM is the dominant antibody produced in primary immune responses, while IgG dominates in secondary immune responses. IgM is physically much larger than the other immunoglobulins.

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Notice the many degrees of flexibility of the antibody molecule. This freedom of movement allows it to more easily conform to the nooks on an antigen. The upper part or Fab (antigen binding) portion of the antibody molecule attaches to specific proteins [called epitopes] on the antigen. Thus antibody recognizes the epitope and not the entire antigen. The Fc region is crystallizable and is responsible for effector functions.

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The process by which T cells and B cells interact with antigens is summarized in the diagram below.

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(VIII) HEALTH SUPPLEMENTS AND MULTI – VITAMINS PROVIDING IMMUNITY ONDROXTM is the only specially-formulated antioxidant supplement vitamin that gives body the proper dosage of life-giving, immunity building antioxidants. OndroxTM is a scientifically developed dietary supplement made with vitamins and minerals associated with antioxidants like enzymes, and amino acids focused on building immunity, health maintenance and protection against disease. OndroxTM has low dosages of key multi-vitamins and antioxidants engineered and combined into a single health supplement focused on protection against diseases, and anti-aging and immunity enhancement. Extreme Immunity is the pure IMMUNOLIN natural dietary supplement that boosts the immune system. Taken as a daily supplement to your diet, it will help in boosting immune system, reducing inflammation, preventing the Flu, reducing or eliminating allergies and Irritable Bowel Syndrome. Immunolin is used in Sports Nutrition as a supplement to build immunity that can often become suppressed during intensive training.

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The all natural and lactose free concentrated dose of Immunolin will help to build immunity against bacteria and viruses and can be used by all ages from infants to the elderly. There are no known side effects. Immunolin is a purified immunoglobulin protein isolate that is manufactured in the US and contains a minimum of 45% IgG. Immunolin is a patented protein isolate. ImmunoLin is a rich source of IgG, IgA, and IgM containing IGF-1, TGFb, transferrin, endotoxin binding proteins, and other protein forms that support the immune system.

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