learning goals
- explain adaptive immunity
- Describe the cell-mediated immune response and the humoral immune response.
- Describe immune tolerance.
The adaptive or acquired immune response takes days or even weeks to establish itself, much longer than the innate response; However, adaptive immunity is more specific to an invading pathogen.adaptive immunityIt is the immunity that occurs after exposure to an antigen, either from a pathogen or a vaccine. AAntigenIt is a molecule that stimulates a response in the immune system. This part of the immune system is activated when the innate immune response is insufficient to control an infection. Indeed, the adaptive response could not be mobilized without input from the innate immune system. There are two types of adaptive responses:cell-mediated immune response, which is controlled by activatedT cells, it's athumoral immune response, which is controlled by activatedB cellsand antibodies. Activated T and B cells, whose surface binding sites are specific for pathogen molecules, proliferate and attack the invading pathogen. Their attack can kill pathogens directly, or they can secrete antibodies that enhance phagocytosis of pathogens and stop infection. Adaptive immunity also involves memory to provide the host with long-term protection against reinfection with the same type of pathogen; Upon re-exposure, this host memory facilitates a quick and vigorous response.
B and T cells
Lymphocytes, which are white blood cells, form with other blood cells in the red bone marrow, which is found in many flat bones, such as the shoulder or pelvic bones. The two types of lymphocytes in the adaptive immune response are B and T cells.Figure 17.12). Whether an immature lymphocyte becomes a B cell or a T cell depends on where in the body it matures. B cells remain in the bone marrow to mature (hence the name "B" for "bone marrow"), while T cells migrate to the thymus where they mature (hence the name "T" for "thymus").
The maturation of a B or T cell involves making it immunocompetent, meaning that after binding it can recognize a specific molecule or antigen (see below). During the maturation process, B and T cells that attach too tightly to the body's own cells are removed to minimize the immune response against the body's own tissues. What's left are those cells that respond poorly to the body's own cells, but have highly specific receptors on their cell surfaces that allow them to recognize a foreign molecule or antigen. This process occurs during fetal development and continues throughout life. The specificity of this receptor is determined by the individual's genetics and is present before a foreign molecule enters or is found in the body. So it is genetics, not experience, that initially provides a wide range of cells, each capable of binding to a different specific foreign molecule. Once immunocompetent, T and B cells migrate to the spleen and lymph nodes, where they remain until required during an infection. B cells are involved in the humoral immune response that targets pathogens residing in the blood and lymph, and T cells are involved in the cell-mediated immune response that targets infected cells.
Figure17.12 This scanning electron micrograph shows a T lymphocyte. T and B cells are indistinguishable by light microscopy, but can be differentiated experimentally by examining their surface receptors. (Credit: modified NCI work; scale bar data by Matt Russell)
humoral immune response
As mentioned earlier, an antigen is a molecule that stimulates a response in the immune system. Not all molecules are antigenic. B cells participate in a chemical reaction to antigens present in the body, producing specific antibodies that circulate throughout the body and bind to the antigen whenever they are encountered. This is called a humoral immune response. As mentioned earlier, during B cell maturation, a highly specific set of B cells is produced that have many antigen receptor molecules in their membrane.Figure 17.13).
Figure17.13 B cell receptors are embedded in B cell membranes and bind a variety of antigens through their variable regions.
Each B cell has only one type of antigen receptor, making each B cell different. Once B cells mature in the bone marrow, they migrate to lymph nodes or other lymphoid organs. When a B cell encounters an antigen that binds to its receptor, the antigen molecule enters the cell by endocytosis and reappears on the cell surface attached to a B cell.MHC class II molecule. When this process is complete, the B cell becomes sensitized. In most cases, the sensitized B cell must encounter a specific type of T cell called a helper T cell before it can be activated. The helper T cell must already have been activated by an antigen encounter (discussed below).
The helper T cell binds to the MHC class II antigenic complex and is induced to release cytokines that cause the B cell to divide rapidly and produce thousands of identical (clonal) cells. These daughter cells become plasma cells or memory B cells. Memory B cells remain dormant at this point until a subsequent encounter with antigen caused by reinfection by the same bacteria or virus causes them to divide into a new population of plasma cells. Plasma cells, on the other hand, produce and secrete large amounts of antibody molecules, up to 100 million molecules per hour. Aantibody, also known as immunoglobulin (Ig), is a protein produced by plasma cells after stimulation by an antigen. Antibodies are the agents of humoral immunity. Antibodies are found in blood, gastric and mucous secretions, and breast milk. Antibodies in these body fluids can bind to pathogens and mark them for destruction by phagocytes before they can infect cells.
These antibodies circulate in the bloodstream and lymphatic system and bind to the antigen whenever it is encountered. The union can fight the infection in several ways. Antibodies can attach to viruses or bacteria and disrupt the chemical interactions necessary for them to infect or attach to other cells. Antibodies can form bridges between different particles that contain antigenic sites, aggregating them and preventing them from functioning properly. The antigen-antibody complex stimulates the complement system described above and destroys the antigen-bearing cell. Phagocytic cells, such as those described above, are attracted to antigen-antibody complexes, and phagocytosis is enhanced when complexes are present. Finally, antibodies stimulate inflammation and their presence in mucus and skin prevents attack by pathogens.
Antibodies coat and neutralize extracellular pathogens by blocking key sites on the pathogen that increase its infectivity (eg, the receptors that "bind" pathogens to host cells).Figure 17.14). Neutralizing antibodies can prevent pathogens from entering and infecting host cells. Antibody-coated neutralized pathogens can then be filtered through the spleen and excreted in the urine or feces.
Antibodies also mark pathogens for destruction by phagocytes, such as macrophages or neutrophils, in a process called opsonization. In a process called complement fixation, some antibodies provide a place for complement proteins to attach. The combination of antibodies and complement promotes the rapid elimination of pathogens.
The reaction to an antigen is the production of antibodies by plasma cellsactive immunityand describes the active response of the host's immune system to infection or vaccination. there is one toopassive immuneA reaction in which antibodies are derived from an external source, rather than the individual's own plasma cells, and are introduced into the host. For example, antibodies circulating in a pregnant woman's body travel through the placenta to the developing fetus. The child will benefit from the presence of these antibodies for several months after birth. Additionally, a passive immune response is possible by injecting an individual with antibodies in the form of antivenom to a snakebite toxin or antibodies in blood serum to help fight the hepatitis infection. This provides immediate protection as the body does not need time to create its own response.
Figure17.14 Antibodies can inhibit infection by (a) preventing an antigen from binding to its target, (b) marking a pathogen for destruction by macrophages or neutrophils, or (c) activating the complement cascade.
The availability and reliability of antibodies makes them ideal for use in research and medical testing. For example, radioimmunoassays are based on antigen-antibody interaction. Typically, a specific antigen is made radioactive, allowed to bind to its antibody, and then introduced into a sample of substance, such as a patient's blood. By measuring any changes in the amount of bound and unbound antigen, analysts can demonstrate the presence and/or concentration of certain substances. Developed by Rosalyn Sussman Yalow and Solomon Berson in the 1950s, the technique is known for its extreme sensitivity, meaning it can detect and measure very small amounts of a substance. It is used in narcotics screening, blood bank screening, cancer screening, hormone measurement and allergy diagnosis. Because of her significant contribution to the field, Yalow was awarded the Nobel Prize, becoming the second woman to receive the Prize in Medicine.
cell-mediated immunity
Unlike B cells, T lymphocytes cannot recognize pathogens on their own. Instead, dendritic cells and macrophages first engulf and digest pathogens into hundreds or thousands of antigens. then aantigen presenting cell (APC)recognizes, encompasses, and informs the adaptive immune response of infection. When a pathogen is discovered, these APCs engulf and degrade it through phagocytosis. Antigen fragments are then transported to the surface of the APC, where they serve as markers for other immune cells. FORdendritic cellsIt is an immune cell that absorbs antigenic substances from its environment and presents them on its surface. Dendritic cells are found in the skin, lining of the nose, lungs, stomach and intestines. These positions are ideal places to find invading pathogens. Once they are activated by pathogens and mature into APCs, they migrate to the spleen or a lymph node. Macrophages also function as APCs. After phagocytosis by a macrophage, the phagocytic vesicle fuses with an intracellular lysosome. Within the resulting phagolysosome, the components are broken into fragments; The fragments are then loaded into MHC class II molecules and transported to the cell surface for antigen presentation.Figure 17.15). Helper T cells cannot respond adequately to an antigen unless they are processed and incorporated into an MHC class II molecule. APCs express MHC class II on their surfaces, and when combined with a foreign antigen, these complexes signal an invader.
Figure17.15 An antigen-presenting cell (APC), such as a macrophage, engulfs a foreign antigen, partially digests it in a lysosome, and then incorporates it into an MHC class II molecule for presentation on the cell surface. Adaptive immune response lymphocytes must interact with MHC class II molecules incorporated into the antigen to mature into functional immune cells.
connection to learning
concept in action
Look thisRockefeller University Animationto see how dendritic cells act as sentinels in the body's immune system.
T cells have many functions. Some respond to APCs of the innate immune system and indirectly induce immune responses through the release of cytokines. Others stimulate B cells to elicit the humoral response described above. Another type of T cell recognizes APC signals and kills infected cells directly, while some are involved in suppressing inappropriate immune responses to harmless or "self" antigens.
There are two main types of T cells: helper T cells (TH) and cytotoxic T lymphocytes (TC). LatHLymphocytes work indirectly to inform other immune cells about possible pathogens. YouHLymphocytes recognize specific antigens presented by APC-MHC class II complexes. There are two populations of T.Hcells: TH1 ano tH2. TH1 secrete cytokines to enhance the activities of macrophages and other T cellsH2 stimulate naive B cells to secrete antibodies. or a tH1 or a THThe immune response that develops depends on the specific types of cytokines secreted by cells of the innate immune system, which in turn depends on the type of invading pathogen.
Cytotoxic T cells (TC) are the key component of the cell-mediated part of the adaptive immune system and attack and destroy infected cells. YouCCells are particularly important in protecting against viral infections; because viruses multiply in cells where they are protected from extracellular contact with circulating antibodies. Once activated, the TCcreates a large clone of cells with a specific set of cell surface receptors, as in the case of proliferating activated B cells. As with B cells, the clone contains active T cells.CT cells and inactive memoryCcells. The resulting active TCThe cells then identify the infected host cells. Due to the time it takes to generate a population of clonal T and B cells, there is a delay in the adaptive immune response compared to the innate immune response.
TCCells try to identify and destroy infected cells before the pathogen can replicate and escape, stopping the progression of intracellular infections. YouCThe cells also help NK cells kill early-stage cancer. Cytokines produced by TH1 response that stimulates macrophages also stimulates TCand improve its ability to identify and destroy infected cells and tumors. A summary of how humoral and cellular immune responses are activated appears inFigure 17.16.
B and T plasma cellsCThe cells are collectively calledeffector cellsbecause they are involved in “triggering” (triggering) the immune response to kill pathogens and infected host cells.
Figure17.16 A helper T cell is activated by binding to an antigen presented by an APC through the MHCII receptor, thereby releasing cytokines. Depending on the cytokines released, this activates either the humoral or cell-mediated immune response.
immunological memory
The adaptive immune system has a memory component that allows a rapid and comprehensive response to re-invasion by the same pathogen. During the adaptive immune response to a previously unknown pathogen known asprimary immune response, antibody-secreting plasma cells and differentiated T cells increase and then plateau with time. As B and T cells mature into effector cells, a subset of the naive populations differentiate into memory B and T cells with the same antigenic specificities.Figure 17.17). Astorage cellit is an antigen-specific B or T lymphocyte that does not differentiate into an effector cell during the primary immune response, but can immediately become an effector cell upon further exposure to the same pathogen. When the infection is cleared and the pathogenic stimuli disappear, the effectors are no longer needed and they undergo apoptosis. In contrast, memory cells persist in circulation.
visual connection
visual connection
Figure17.17 After initially binding an antigen to the B cell receptor, a B cell internalizes the antigen and presents it to MHC class II. A helper T cell recognizes the MHC class II-antigen complex and activates the B cell, whereby memory B cells and plasma cells are produced.
The Rh antigen is found on Rh positive red blood cells. An Rh-negative person can usually carry an Rh-positive fetus to term without any problems. However, a second Rh positive fetus can trigger an immune attack that causes hemolytic disease in the newborn. Why do you think hemolytic disease is only a problem during the second or subsequent pregnancies?
If the pathogen is never encountered again during the individual's lifetime, the memory B and T cells circulate for a few years or even several decades and gradually die without ever having functioned as effector cells. However, when the host is again exposed to the same type of pathogen, the circulating memory cells immediately differentiate into plasma cells and T cells.CCells without APC or T inputHcells. This is known as thesecondary immune response. One of the reasons why the adaptive immune response is delayed is that it takes time to identify, activate, and proliferate naive B and T cells with the correct antigenic specificities. In the case of reinfection, this step is skipped and the result is a faster production of the immune system. Memory B cells that differentiate into plasma cells produce amounts of antibodies tens to hundreds of times greater than those secreted during the primary response.Figure 17.18). This rapid and dramatic antibody response can stop the infection before it takes hold, and the person may not even realize they've been exposed to the infection.
Figure17.18 In the primary response to infection, antibodies are first secreted by plasma cells. When exposed to the same pathogen again, the memory cells differentiate into antibody-secreting plasma cells, which produce increased amounts of antibodies for a longer period of time.
Vaccination is based on the knowledge that exposure to non-infectious antigens derived from known pathogens elicits a mild primary immune response. The immune response to vaccination may not be perceived by the host as a disease, but it still confers immunological memory. When exposed to the corresponding pathogen against which a person was vaccinated, the response is similar to secondary exposure. As each reinfection generates more memory cells and greater resistance to the pathogen, some vaccination cycles include one or more booster doses to simulate repeated exposures.
the lymphatic system
safeIt is the watery fluid that bathes tissues and organs and contains protective white blood cells, but not red blood cells. Lymph moves throughout the body through the lymphatic system, which consists of vessels, lymph ducts, lymph nodes and organs such as the tonsils, adenoids, thymus and spleen.
Although the immune system is characterized by the circulation of cells throughout the body, the regulation, maturation, and communication of immune factors takes place at specific sites. Blood circulates immune cells, proteins, and other factors throughout the body. About 0.1% of all blood cells are leukocytes, which include monocytes (the precursors of macrophages) and lymphocytes. Most blood cells are red blood cells. Immune system cells can migrate between the various blood and lymphatic circulatory systems separated by an interstitial space by a process called extravasation (passing into the surrounding tissue).
Remember that immune system cells come from bone marrow stem cells. Maturation of B cells occurs in the bone marrow, while progenitor cells migrate from the bone marrow and develop and mature into naive T cells in the organ known as the thymus.
After maturity, T and B lymphocytes circulate to different destinations. Lymph nodes scattered throughout the body harbor large populations of T and B cells, dendritic cells, and macrophages.Figure 17.19). Lymph accumulates antigens as it drains from tissues. These antigens are then filtered by the lymph nodes before the lymph returns to the circulation. APCs in lymph nodes capture and process antigens and inform neighboring lymphocytes about possible pathogens.
Figure17.19 (a) Lymphatic vessels carry a clear fluid called lymph throughout the body. Fluid flows through (b) lymph nodes, which filter lymph that enters the lymph node via afferent vessels and leaves via efferent vessels; The lymph nodes fill with lymphocytes, which eliminate the infecting cells. (Credit a: work modification by NIH; Credit b: work modification by NCI, NIH)
The spleen harbors B and T cells, macrophages, dendritic cells and NK cells.Figure 17.20). The spleen is where APCs that trapped foreign particles in the blood can communicate with lymphocytes. Antibodies are synthesized and secreted by activated plasma cells in the spleen, and the spleen filters foreign substances and pathogens from antibody complexes from the blood. Functionally, the spleen is related to blood, just as the lymph nodes are related to lymph.
Figure17h20 The spleen has the function of immunologically filtering the blood and enabling communication between cells that corresponds to the innate and adaptive immune responses. (Image credit: NCI Working Mod, NIH)
mucosal immune system
Innate and adaptive immune responses make up the systemic (body-wide) immune system, which is distinct from the mucosal immune system. Mucosal-associated lymphoid tissue (MALT) is a critical component of a functioning immune system because mucosal surfaces, such as the nasal passages, are the first tissues where inhaled or ingested pathogens are deposited. Mucosal tissue includes the mouth, pharynx, and esophagus, as well as the gastrointestinal, respiratory, and genitourinary tracts.
Mucosal immunity consists of MALT, which functions independently of the systemic immune system and has its own innate and adaptive components. MALT is a collection of lymphoid tissue combined with the epithelial tissue that lines mucous membranes throughout the body. This tissue acts as an immunological and reactive barrier in areas of the body that are in direct contact with the external environment. The systemic and mucosal immune systems use many of the same cell types. Foreign particles that reach the MALT are picked up by absorptive epithelial cells and delivered to APCs located just below the mucosal tissue. The APCs of the mucosal immune system are primarily dendritic cells, with B cells and macrophages playing minor roles. Processed antigens presented on APCs are detected by T cells on MALT and in the tonsils, adenoids, cecum, or mesenteric lymph nodes of the intestine. Activated T cells then migrate through the lymphatic system and into the circulatory system to sites of mucosal infection.
immune tolerance
The immune system must be regulated in such a way as to avoid unnecessary and useless reactions to harmless substances and, above all, not to attack itself. The acquired ability to prevent an unnecessary or harmful immune response to a recognized foreign substance, known not to cause disease, or self-antigens is described asimmune tolerance. The primary mechanism for the development of immune tolerance to self-antigens occurs during the selection of weakly self-bound cells during T and B lymphocyte maturation. There are T cell populations that suppress the immune response to self antigens and that suppress the immune response after the infection has passed. been removed from damage to minimize host cell damage caused by inflammation and cell lysis. Immune tolerance is particularly well developed in the mucosa of the upper digestive system due to the enormous amount of foreign substances (eg dietary proteins) encountered by APCs in the oral cavity, pharynx and gastrointestinal mucosa. Immune tolerance is mediated by specialized APCs in the liver, lymph nodes, small intestine, and lungs that express harmless antigens to a diverse population of T-regulators (Trecord), specialized lymphocytes that suppress local inflammation and inhibit the secretion of immunostimulatory factors. The combined result of TrecordCells is to prevent immune activation and inflammation in unwanted tissue compartments and allow the immune system to focus on pathogens.