The Immune System - W2024 PDF

**The Immune System \-- An Overview  ** The immune system is composed of mechanisms and cell types that collectively protect the body from bacterial, parasitic, fungal, viral infections (pathogens or antigens) and from the growth of tumor cells -- potentially any non-self cell (antigen). It is a bi...

**The Immune System \-- An Overview  ** The immune system is composed of mechanisms and cell types that collectively protect the body from bacterial, parasitic, fungal, viral infections (pathogens or antigens) and from the growth of tumor cells -- potentially any non-self cell (antigen). It is a big, messy and unique "system". It is a multi-layered, interlocking activation of subsystems. Virtually all the other human systems have components of the immune system imbedded within. The immune system can distinguish between normal, healthy cells and unhealthy cells by recognizing a variety of \"danger\" markers on their membranes. Healthy immune cells have a variety of receptors that enable them to recognize non-self cells generally (pattern recognition receptors) and some specifically (T and B lymphocytes). Cells may become non-self because of infection or because of cellular damage caused by non-infectious agents like sunburn or cancer. Infectious microbes such as viruses and bacteria release another set of signals/membrane markers recognized by the immune system. When the immune system first recognizes these signals, it responds. If an immune response cannot be activated when there is sufficient need, problems arise, like infection. The immune system is complex. There are numerous cell types that either circulate throughout the body or reside in a particular tissue. Each cell type plays a unique role, with different ways of recognizing problems, communicating with other cells, and performing their functions. By understanding all the details behind this network, researchers may optimize immune responses to confront specific issues, ranging from infections to cancer. **Location:** Our immune cells come from precursors in the bone marrow and develop into mature cells through a series of changes that can occur in different parts of the body. ***Bone marrow***: The bone marrow contains stems cells that can develop into a variety of cell types. The common myeloid progenitor stem cell in the bone marrow is the precursor to innate immune cells---neutrophils, eosinophils, basophils, mast cells, monocytes, dendritic cells, and macrophages---that are important first-line responders to infection. The common lymphoid progenitor stem cell leads to adaptive immune cells---B cells and T cells---that are responsible for mounting responses to specific microbes based on previous encounters (immunological memory). Natural killer (NK) cells also are derived from the common lymphoid progenitor and share features of both innate and adaptive immune cells, as they provide immediate defenses like innate cells but also may be retained as memory cells like adaptive cells. B, T, and NK cells also are called lymphocytes. ***Bloodstream and lymph*:** Immune cells constantly circulate throughout the bloodstream and lymph, patrolling for problems. When blood tests are used to monitor white blood cells, another term for immune cells, a snapshot of the immune system is taken. If a cell type is either scarce or overabundant in the bloodstream, this may reflect a problem. ***Thymus*:** T cells mature in the thymus, a small organ located in the upper chest. This means they learn self-tolerance -- to leave self-cells alone and activate against non-self cells. B cells learn self-tolerance in the bone marrow. Cell that are unable to learn self-tolerance are destroyed to prevent auto immune pathology. ***Lymphatic system***: The lymphatic system is a network of vessels and tissues composed of lymph, an extracellular fluid, and lymphoid organs, such as lymph nodes. The lymphatic system is a conduit for travel and communication between tissues and the bloodstream. Immune cells are carried through the lymphatic system and converge in lymph nodes, which are found throughout the body. **Lymph nodes** are a collection hub where immune cells sample antigens brought in from the body. For instance, if adaptive immune cells in the lymph node recognize pieces of a microbe brought in from a distant area, they will activate, replicate, and leave the lymph node to circulate and address the pathogen. Thus, swollen lymph nodes may indicate an active immune response. ***Spleen***: The spleen is an organ located behind the stomach. While it is not directly connected to the lymphatic system, it is important for processing information from the bloodstream. Immune cells are enriched in specific areas of the spleen, and upon recognizing blood-borne pathogens, they will activate and respond accordingly. ***Mucosal tissue***: Mucosal surfaces are prime entry points for pathogens, and specialized immune hubs are strategically located in mucosal tissues like the respiratory tract and gut. For instance, Peyer\'s patches and the tonsils are important areas where immune cells can access samples from the gastrointestinal tract. The immune system can be divided into a specific and non-specific set of mechanisms. Non-specific is also known as innate and this part of the immune system simply blocks, traps or kills anything non-self. It is generally quick but does not adapt. Specific mechanisms are slower to respond initially but memory cells are formed so that subsequent exposures bring a rapid, aggressive response often preventing any symptoms or clinical presentations at all. **NON SPECIFIC MECHANISMS (INNATE):** **First Lines of Defense**: Physical barriers, better known as our skin and the mucous membranes that line our systems' openings. Recall that the outer layers of cells in the epidermis are dead, avascular and shed daily. Hair, cilia and secretions like sweat, tears and saliva contribute to these barriers providing chemical defenses. These secretions can trap pathogens or contain enzymes or acids that help make them ineffective. **Inflammation**: When tissues are injured or damaged, chemicals are released that activate more chemicals and cells in the circulation. This chemical alarm initiates the inflammatory reaction causing pain, vasodilation and leaky blood vessels near the site of the injury. Often the injury results in loss of function (temporarily). These events identify the cardinal signs and symptoms of inflammation: redness, heat, swelling and pain. Inflammation is good because it isolates the injured site, cells arrive to clean up the debris (neutrophils and later, macrophages) and prepare for a complete repair process that involves blood clotting and tissue regeneration or replacement. **Fever:** Pyrogens are produced by activated immune cells or pathogens and released during the injury/infection. In either case pyrogens are chemical signals that are received by the hypothalamus to reset the temperature regulation higher = fever. The increased body temperature often reduces the effectiveness of a pathogen 2 ways: Raising the environmental temperature interferes with the metabolism of the invading organism and our liver will conserve nutrients like zinc, preventing their availability to pathogens for nutrition. **The Cells:** Many of these cell types have specialized functions. The cells of the immune system can engulf bacteria, kill parasites or tumor cells, or kill viral-infected cells. These [cells](http://sciencelearn.org.nz/About-this-site/Glossary/cell) are white blood cells (leukocytes), which seek out and destroy disease-causing organisms or substances. There are different types of [leukocytes](http://sciencelearn.org.nz/About-this-site/Glossary/leukocytes). Each of these cell types has a specific function, but they all work together to protect you. **[Neutrophils](http://sciencelearn.org.nz/About-this-site/Glossary/neutrophils):** These cells primarily attack [bacteria](http://sciencelearn.org.nz/About-this-site/Glossary/bacteria) by endocytosis. They are the "first responders" to the site of incoming bacteria to fight them, but don't live long. Neutrophils are early, aggressive phagocytes and able to produce a neutrophil extracellular net made of strands of DNA with enzymes and other proteins designed to trap and degrade antigens at the site inflammation. Neutrophils only last a few days in the body (before they self-destruct), but our [bone marrow](http://sciencelearn.org.nz/About-this-site/Glossary/bone-marrow) produces more every day. Some bacteria avoid neutrophils by hiding inside cells. **T helper cells**: These cells are like the bosses. They give instructions to other cells by producing signals. Each T helper cell only looks out for one type of [pathogen](http://sciencelearn.org.nz/About-this-site/Glossary/pathogen). Therefore there are many T helper cells needed to watch for many different [diseases](http://sciencelearn.org.nz/About-this-site/Glossary/diseases) or invaders. **Cytotoxic (killer) T cells**: These are natural killer cells (NK-cells). They punch holes in the walls of the pathogen cell so that the contents ooze out. **Macrophages:** [Macrophage](http://sciencelearn.org.nz/About-this-site/Glossary/macrophage-cells) means 'big eater'. These cells 'eat' (ingest) or clean up the mess of dead cells. **Dendritic cells:** These cells are like the spies. They notice if there is an invader and then present [evidence](http://sciencelearn.org.nz/About-this-site/Glossary/evidence) of the invader to Helper T cells in the [lymph nodes](http://sciencelearn.org.nz/About-this-site/Glossary/lymph-nodes). They are phagocytes found all over the body but especially in the skin and mucous membranes. They "recognize" non-self cells with their pattern recognition receptors (PRRs) and become antigen-presenting cells (APCs) when they display new markers on their cell membranes for presentation to Helper T cells in lymph nodes to link the innate immune system with the adaptive one **SPECIFIC (ADAPTIVE) IMMUNE MECHANISMS:** **T-Cells** \-- T lymphocytes are usually divided into two major subsets. The T helper subset is the coordinator of immune regulation. The main function of the T helper cell is to augment or potentiate immune responses by the secretion of specialized factors (chemicals known generally as cytokines) that activate other white blood cells to fight off infection. Another important type of T cell is called the T killer cell (cytotoxic). These cells are able to directly killing certain tumor cells, viral-infected cells and sometimes parasites. Both types of T cells can be found throughout the body. They often depend on the secondary lymphoid organs (the lymph nodes and spleen) as sites where activation occurs, but they are also found in other tissues of the body, most conspicuously the liver, lung, blood, and intestinal and reproductive tracts. **B Cells** \-- The major function of B lymphocytes is the production of antibodies in response to foreign proteins of bacteria, viruses, and tumor cells. Antibodies are specialized proteins that specifically recognize and bind to one particular protein that specifically recognize and bind to one particular protein. Antibody production and binding to a foreign substance or antigen, often is critical as a means of signaling other cells to engulf, kill or remove that substance from the body. **The Immune Response** An immune response to foreign antigen requires the presence of an antigen-presenting cell (APC), (usually either a macrophage or dendritic cell) in combination with a B cell or T cell for **RECOGNITION**. The B cell is then **ACTIVATED** to **PROLIFERATE** and produce antibodies that specifically bind to that antigen. When the antibodies bind to antigens on bacteria or parasites it signals macrophages to engulf (phagocytose) and kill them. Another important function of antibodies is to initiate the \"complement destruction cascade.\" When antibodies bind to cells or bacteria, serum proteins called complement bind to the immobilized antibodies and destroy the bacteria by creating holes in them. Antibodies can also signal natural killer cells and macrophages to kill viral or bacterial-infected cells. If the APC presents the antigen to T cells, RECOGNITION occurs and the T cells become ACTIVATED. Activated T cells PROLIFERATE to kill target cells. The production of antibodies and the activity of killer T cells are highly regulated by the helper T cell subset. Helper T cells provide growth factors or signals to these cells that signal them to proliferate and function more efficiently. The multitude of cytokines that are produced and secreted by helper T cells are often crucial to ensure the activation of natural killer cells. The key feature of the adaptive immune system is the development of **memory cells** specific to each encounter with a pathogen. This give specificity and almost life long immunity to subsequent exposures to the same pathogen. **IMMUNITY:** **Naturally acquired passive immunity**: Occurs when there is no exposure to an antigen but immunity is conferred. This occurs when some types of antibodies cross the placenta. A mom confers some immunity to her newborn -- it is temporary **Naturally acquired active immunity**: Each exposure to an antigen that elicits an immune response will confer almost life long immunity from subsequent exposures. EXAMPLE: If you are exposed to mumps as a child and generate a specific immune response, antibodies and memory cells will be made to prevent further infections from mumps. This is the most effective way to gain and maintain immunity **Artificially acquired passive immunity**: No previous exposure to a toxin or poison has allowed for immunity but the toxin may life threatening so a serum is required. The serum is essentially a ready made solution of antibodies for that particular toxin as in rabies or snake bites --it is temporary as there is no RECOGNITION, ACTIVATION or PROLIFERATION and therefore no memory cells. **Artificially acquired active immunity**: Antigens are injected into a host as a vaccine strong enough to initiate RECOGNITION, ACTIVATION and PROLIFERATION and then memory cells but bot so strong as to cause the signs and symptoms of disease. Typically to create this balance the virus or pathogen is attenuated (weakened) but this also means a full immune response is less likely therefore boosters are required.