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A Summary of the Immune System Every day your body is exposed to various foreign substances that could harm your body. Most of them are repelled by your outer defenses. These non-specific barriers include such things as the skin, tears, and acid pH. But your body’s outer defenses also have two main areas of weakness, the openings to your nose and mouth. To bolster your defenses in these areas your body uses nasal hairs, mucus membranes, and lysozymes in saliva. If anything should get past these barriers, several masses of lymphatic tissue, the tonsils, are stationed at the opening to the throat. These tonsils are packed with lymphocytes, important cells in the fight against disease. However, disease causing agents can sometimes get past these defenses. Imagine that you have cut your finger on a sharp, rusty, dirty object. Bacteria have been allowed to by-pass your first line of defense, a mechanical barrier called the skin. Immediately blood flows from the wound. Flowing out through the wound are all kinds of blood cells, red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). As the platelets flow over the jagged edges of the cut vessels they break apart and release platelet factor which begins the clotting process and stops the flow of blood. However, the deadly tetanus bacterium, Clostridium tetani has already entered the wound and has imbedded in the tissues and blood. The immune system can recognize the bacterium as an invader (non-self) because it displays different surface antigens from your own cells. The bacterium may encounter and be eaten by any of several different types of phagocytic leukocytes that are non-specific, Neutrophils, Monocytes and Macrophages (enlarged monocytes). The engulfing of a bacterium by a phagocyte is made easier when the bacterium has already been attacked by complement proteins or by antibodies, a process called opsonization. Eventually, an accumulation of dead phagocytic cells, damaged tissue, and fluid forms. This is called pus. After engulfing the pathogen (a disease causing agent), the phagocyte will bind portions of the pathogen's antigens to the phagocyte's cell membrane. At this point we may refer to the phagocyte as an APC, an antigen presenting cell. Then, it migrates through the body, eventually reaching the lymph nodes or spleen to present the antigen to a type of lymphocyte called a T-cell. Phagocytes and the injured tissues may also produce a number of inflammatory chemicals and cytokines (chemicals that stimulate or inhibit normal cell functions), including such things as interleukins, chemotactic factor (attracts macrophages to the area), macrophage activating factor or interferon (stimulates macrophages to eat), and lymphotoxins (cell poisons that kill cells). Other inflammatory chemicals such as prostaglandins and histamine may induce dilation of the blood vessels which produces redness, swelling, heat, and pain to the area. This also speeds up the movement of phagocytes out of the bloodstream and into the tissues (diapedesis). Pyrogens may turn up the thermostat to produce a fever which slows or inhibits the growth of bacteria. One other type of non-specific cell that should be mentioned is the NK or Natural Killer cell. These cells patrol the body looking for cells that are cancerous or virus infected. They attack the cell membranes of infected cells, releasing chemicals called perforins that “punch” holes in the infected cells membrane and destroy it. Also within the body are millions of different lymphocytes, each carrying a different surface protein that may act as an antigen receptor. If it comes in contact with the matching antigen (a substance that provokes an immune response) the lymphocyte begins a complex immune reaction. This contact may come about directly or through an antigen presenting cell. T-cells are special lymphocytes that migrate from the bone marrow to the thymus gland to mature. There are millions of different kinds of T-cells residing in the lymphatic tissue, each with the ability to recognize and bind to a specific foreign antigen. How do all these different kinds of T-cells develop? It's coded into your genes. You are born with T-cells that will recognize diseases that you may not ever be exposed to! The T-cell must be stimulated in two ways: antigen recognition and costimulation. Antigen recognition is taken care of by coming in contact with the matching antigen (either directly, or by contact with a macrophage displaying the antigens). Costimulation is brought about by chemicals (cytokines) such as interleuken-1 and interleuken-2. When a T-cell has received two signals, both recognition and costimulation, it is said to be activated. It then begins to reproduce forming thousands of clones (identical cells) that can recognize the foreign antigen. There are several different types of T-cells. The main two are helper T cells (TH) and cytoxic killer T cells (TC). Activated helper T-cells produce a number of cytokines, including interleuken-2, which enhances activation and proliferation (reproduction) of T-cells and B-cells by serving as a costimulator to cells that have already come in contact with their matching antigen (antigen recognition). Cytotoxic (killer) T-cells (TC) are the only T-cells that can attack other cells. They attach to infected cells and release chemicals such as perforins, lymphotoxins, or tumor necrosis factor. Thousands of memory T-cells are stored to prevent a later infection with the same pathogen. Due to their large numbers, memory cells can react faster than the first infection and often destroy the pathogens before any sign or symptoms of disease occur. The first reaction to infection is called a primary response. A second response by memory cells is called a secondary response. Since T-cells do battle directly, cell to cell, the immunity they produce is called cell-mediated immunity. B-cells are lymphocytes that remain in the bone marrow to mature. There are also millions of different types of B-cells each capable of recognizing a specific antigen. While T-cells can leave lymphatic tissue and the blood, and migrate into the tissues, B-cells remain in the blood. Upon activation they differentiate into plasma cells that produce specific antibodies that circulate in the lymph and blood and memory cells for storage. Since antibodies are non-cellular structures that circulate in the body fluids (humor), the B-cell lymphocytes are said to produce humoral immunity. Activated plasma cells produce approximately 2000 antibodies per second for several days. Antibodies (also known as immunoglobulins) are made of amino acid chains that contain an antigen combining site that matches the epitope (unique combining site found on each specific antigen). This combining site is responsible for recognizing and attaching to a specific antigen. Each antibody has two combining sites, which allows them to attach to several pathogens, clumping the pathogens together. There are several main categories of antibodies (immunoglobulins): IgG - Most abundant, found in blood, lymph, intestines, protect against bacteria & viruses IgA - Found mainly in sweat, tears, saliva, mucus, milk, and GI secretions IgM - 5-10% of antibodies in blood, first to be secreted by plasma cells IgD - Less than 1% of all antibodies, involved in activation of B-cells IgE - Located on basophils, involved in allergic hypersensitivity reactions Antibodies attack antigens in several ways. They may neutralize antigens, immobilize bacteria, agglutinate antigens, enhance phagocytosis through agglutination and opsonization (the covering of antigens with antibodies helps phagocytes attach and eat), and activate complements. Complement consist of inactive proteins (about 20) that "complement" or enhance the immune reactions. They may assist in opsonization, cause cytolysis (they form a ring and punch a hole in the microbe's membrane), or activate inflammation. Inflammation dilates blood vessels, increasing blood flow to the area, increasing the permeability of the blood capillaries, enabling the white blood cells to more easily penetrate the tissues. Types of Immunity: Active natural Active artificial Passive natural Passive artificial