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The Immune System 4/7/2015 Immune System Overview | Principles of Biology from Nature Education contents Principles of Biology 165 Immune System Overview The Immune System The animal body is a self­contained, stable environment rich in nutrients that provides ideal habitat for many microorganisms, including bacteria, fungi, and protists. While some of these microorganisms are able to form a neutral or mutually beneficial relationship with their host, others live at the expense of the host. Left unchecked, these organisms, known collectively as pathogens, can destroy cells and damage tissues, resulting in disease that may lead to death. Another threat to the animal body is cancer cells that arise from spontaneous mutations in the DNA. Cancer cells exhibit unregulated cell division and, like a pathogen, can damage or destroy tissues. The immune system provides a collection of defenses against pathogens and cancer cells (Figure 1). All animals have an innate immune system that provides a rapid, general defense against pathogens. Vertebrates additionally have an adaptive immune system that is able to recognize specific molecular determinants, known as antigens, which are present on certain pathogens. The adaptive immune response is slow, and the innate immune system provides the first line of defense against pathogens. Figure 1: The immune system. All animals have an innate immune system that provides general, rapid defense. Additionally, vertebrates have an adaptive immune system that provides a slower specific immunity against certain pathogens. © 2014 Nature Education All rights reserved. The innate immune system. The innate immune system includes barrier, cell­mediated, and humoral http://www.nature.com/principles/ebooks/principles­of­biology­104015/29145887/1 1/4 4/7/2015 Immune System Overview | Principles of Biology from Nature Education defenses. Barrier defenses, which include physical barriers and chemical defenses, are provided by the epithelium. Epithelial tissue, which includes skin and mucus membranes, blocks pathogen entry into the body and produces mucus, saliva, tears, sweat, and digestive fluids, all of which have antibacterial properties. Innate cell­mediated immunity is provided by phagocytes, which are able to engulf and digest pathogens and cancer cells, and by cells that secrete cytotoxins or cytokines. Cytotoxins are chemicals that are able to kill cells. Cytokines are chemicals that bind receptors on target cells and trigger a response. Some cytokines trigger apoptosis in infected or damaged cells, while others modulate the immune response. One immune response, called the inflammatory response, causes vasodilation and increased permeability of blood vessels, resulting in pain, redness, and swelling. Pattern­recognition receptors (PRRs) present in the plasma membrane of many innate immune cells are able to recognize molecular signatures associated with certain pathogens, called pathogen­associated molecular patterns (PAMPs). Molecules that circulate in body fluid provide innate humoral immunity. In vertebrates, these components include the complement system and two circulating proteins: mannose­binding lectin and C­reactive protein. The complement system, which consists of about thirty proteins, is able to kill pathogens and to trigger an immune response. Mannose­binding lectin is a protein that recognizes carbohydrates commonly found on microbes and activates the complement system. C­reactive protein, which binds a chemical present on the surface of damaged cells and some bacteria, also activates the complement system. Test Yourself Describe the components of the innate immune system. Submit The adaptive immune system. Adaptive immunity is mediated by T cells and B cells, which both express an antigen receptor on the cell surface. The gene encoding the antigen receptor undergoes genetic recombination during B cell and T cell development, and, as a result, each B cell and T cell expresses a unique receptor capable of recognizing a different antigen. Binding of antigen to the receptor causes the cell to divide, a process called clonal expansion, and differentiate into effector cells and memory cells. Effector cells carry out the immune response, and memory cells remain in the body and produce a much faster, stronger response if the same pathogen is encountered again. T cells, which are responsible for adaptive cell­mediated immunity, can be divided into three classes: cytotoxic T cells (TC), helper T cells (TH), and regulatory T cells (Treg). Cytotoxic T cells are capable of killing infected or cancerous cells. Helper T cells stimulate the immune response, and regulatory T cells dampen the immune response. T cells are only able to recognize antigens that are displayed in association with major histocompatibility complex (MHC) molecules on the surface of cells. The presence of an antigen­MHC complex on antigen­presenting cells (APCs) activates helper T cells. The presence of antigen on infected or damaged cells activates cytotoxic T cells. B cells are responsible for adaptive humoral immunity. When an antigen binds a B cell antigen receptor, the cell undergoes clonal expansion and differentiates into a type of effector cell called plasma cells. These cells are http://www.nature.com/principles/ebooks/principles­of­biology­104015/29145887/1 2/4 4/7/2015 Immune System Overview | Principles of Biology from Nature Education able to secrete soluble antigen receptors, which are called antibodies. Coating of a pathogen by antibody flags it for destruction by phagocytic cells, a process called opsonization, and also activates the complement system. Test Yourself Describe the adaptive immune response. Submit IN THIS MODULE The Immune System Types of Immune Cells Summary Test Your Knowledge WHY DOES THIS TOPIC MATTER? Stem Cells Stem cells are powerful tools in biology and medicine. What can scientists do with these cells and their incredible potential? PRIMARY LITERATURE Synthetic ligand may help treat autoimmune disorders Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. View | Download Biodiversity loss increases infectious diseases among humans Impacts of biodiversity on the emergence and transmission of infectious diseases. View | Download A new technique for detecting autoimmune diseases Autoantigen discovery with a synthetic human peptidome. View | Download Classic paper: T cells mediate immunity through MHC restriction (1974) Restriction of in vitro T cell­mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. View | Download Controlling inflammation to stop sepsis Amelioration of sepsis by inhibiting sialidase­mediated disruption of the CD24­ SiglecG interaction. View | Download Live imaging tracks immune rejection of transplanted tissue Visualizing the innate and adaptive immune responses underlying allograft rejection by two­photon microscopy. View | Download Genetically­matched iPS cells more immunogenic than ES cells Immunogenicity of induced pluripotent stem cells. View | Download SCIENCE ON THE WEB Hunt for the Malaria Vaccine Learn how clinical trials are proceeding for this important disease therapy. http://www.nature.com/principles/ebooks/principles­of­biology­104015/29145887/1 3/4 4/7/2015 Immune System Overview | Principles of Biology from Nature Education page 847 of 989 3 pages left in this module http://www.nature.com/principles/ebooks/principles­of­biology­104015/29145887/1 4/4 4/7/2015 Immune System Overview | Principles of Biology from Nature Education contents Principles of Biology 165 Immune System Overview Types of Immune Cells Invertebrate immune cells are called hemocytes. Vertebrate immune cells are called leukocytes or white blood cells. Leukocytes, which are derived from bone marrow stem cells, may differentiate into one of two progenitor lines: the myeloid line and the lymphoid line (Table 1). Myeloid cells are primarily involved in innate immunity. Four types of myeloid cells are phagocytes: neutrophils, eosinophils, basophils, and monocytes. Neutrophils, which primarily target bacteria and fungi, are the most abundant leukocyte and are often the first to arrive at the site of an injury or infection. Neutrophils secrete cytotoxins, and, upon death, they release a web referred to as a neutrophil extracellular trap that can trap pathogens. Neutrophils are a major component of pus. Eosinophils and basophils primarily target large parasites and are involved in the inflammatory response. Basophils also produce heparin, a molecule with anticoagulant (blood­thinning) properties. Monocytes are able to differentiate into two cell types: macrophages and dendritic cells. Both macrophages and dendritic cells are antigen­presenting cells that stimulate T cells. Macrophages often stay at the site of injury or infection and can engulf dead or dying neutrophils and other injured cells. Dendritic cells travel to the lymph nodes, where they present antigen to T cells. Another type of myeloid cell, called mast cells, releases histamine, a molecule that stimulates the inflammatory response, and heparin. Basophils and mast cells are both involved in allergic reactions, which are a type of inappropriate immune response. There are three different lymphoid cells, or lymphocytes: B cells, T cells, and natural killer cells. B cells and T cells are involved in the adaptive immune response. B cells are also antigen­presenting cells. Natural killer cells, which target infected and cancerous cells, are part of the innate immune system. Immune cells may
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