Basic Concepts in Immunity 2023 PDF

Basic Concepts in Immunity Dr Allison Imrie Immunity Immunology is the study of immune responses - of the cellular and molecular events that occur aEer an organism encounters microbes and other foreign macromolecules Immunity is derived from the La4n word immunitas - the protec4on from legal prosecu...

Basic Concepts in Immunity Dr Allison Imrie Immunity Immunology is the study of immune responses - of the cellular and molecular events that occur aEer an organism encounters microbes and other foreign macromolecules Immunity is derived from the La4n word immunitas - the protec4on from legal prosecu4on offered to Roman senators during their tenures in office Historically, immunity meant protec4on from disease and, more specifically, infec4ous disease The cells and molecules responsible for immunity cons4tute the immune system , and their collec4ve and coordinated response to the introduc4on of foreign substances is called the immune response The physiologic func4on of the immune system is defense against infec4ous microbes; however, even noninfec4ous foreign substances and products of damaged cells can elicit immune responses Importance of the Immune System in Health and Disease This table summarizes some of the physiologic func4ons of the immune system and its role in disease. AIDS, Acquired immunodeficiency Protection against pathogens relies on several levels of defense The first defence is the anatomic barrier provided by the body’s epithelial surfaces Second,various chemical and enzymatic systems, including complement, act as an immediate antimicrobial barrier near these epithelia If epithelia are breached, nearby various innate lymphoid cells can coordinate a rapid cell-mediated defense If the pathogen overcomes these barriers, the slower-acting defenses of the adaptive immune system are brought to bear The immune system consists of immune cells and the lympha;c system Defense against microbes is mediated by sequen;al and coordinated responses that are called innate and adap;ve immunity Innate immunity is mediated by mechanisms that are in place even before an infec4on occurs (hence innate ) and that facilitate rapid responses to invading microbes Adap.ve immunity (also called specific immunity or acquired immunity ) develops as a response to infec4on and adapts to the infec4on The mechanisms of innate immunity provide the ini4al defense against infec4ons. Adap4ve immune responses develop later and require the ac4va4on of lymphocytes. The kine4cs of the innate and adap4ve immune responses are approxima4ons and may vary in different infec4ons. Only selected cell types are shown. ILC, Innate lymphoid cell; NK, natural killer. Most infectious agents activate the innate immune system and induce an inflammatory response Pattern recognition receptors of the innate immune system provide an initial discrimination between self and non-self Cardinal Features of Adap;ve Immune Responses: Specificity and diversity Adap4ve immune responses are specific for dis4nct an4gens and oEen for different por4ons of a single complex protein, polysaccharide, or other macromolecule The parts of complex an4gens that are specifically recognized by lymphocytes are called determinants or epitopes This fine specificity exists because individual lymphocytes express membrane receptors that can dis4nguish subtle differences in structure between dis4nct epitopes. Clones of lymphocytes with different specifici4es are present in unimmunized individuals and are able to recognize and respond to foreign (non-self) an4gens - this is called clonal selec.on B and T cell receptors The total number of an4genic specifici4es of the lymphocytes in an individual, called the lymphocyte repertoire, is extremely large. Immune system of an individual can discriminate 10 7 to 10 9 dis4nct an4genic determinants. This ability of the lymphocyte repertoire to recognize a very large number of an4gens, called diversity , is the result of variability in the structures of the an4gen-binding sites of lymphocyte receptors for an4gens. In other words, there are many different clones of lymphocytes and each clone has a unique an4gen receptor and therefore a singular an4gen specificity, contribu4ng to a total repertoire that is extremely diverse. The expression of different an4gen receptors in different clones of T and B cells is the reason why these receptors are said to be clonally distributed. Cardinal Features of Adap;ve Immune Responses: Memory Exposure of the immune system to a foreign an4gen enhances its ability to respond again to that an4gen Responses to second and subsequent exposures to the same an4gen, called secondary immune responses, are usually more rapid, greater in magnitude, and oEen qualita4vely different from the first, or primary, immune response to that an4gen Immunologic memory occurs because each exposure to an an4gen generates long-lived memory cells specific for the an4gen The secondary response is typically stronger than the primary immune response because: B cell memory cells accumulate and become more numerous than the naive lymphocytes specific for the an4gen that exist at the 4me of ini4al an4gen exposure memory cells react more rapidly and vigorously to an4gen challenge than do naive lymphocytes Memory enables the immune system to mount heightened responses to persistent or recurring exposure to the same an4gen and thus to combat infec4ons by microbes that are prevalent in the environment and are encountered repeatedly Specificity, memory, and contrac;on of adap;ve immune responses An4gens X and Y induce the produc4on of different an4bodies (specificity). The secondary response to an4gen X is more rapid and larger than the primary response (memory) An4body levels decline with 4me aEer each immuniza4on (contrac4on, the process that maintains homeostasis). The same features are seen in T cell–mediated immune responses Cardinal Features of Adap;ve Immune Responses: Nonreac5vity to self (tolerance) A normal individual's immune system can recognize, respond to, and eliminate many foreign (nonself) an4gens while not reac4ng harmfully to that individual's own (self) an4gens Immunologic unresponsiveness is also called tolerance. Tolerance to self an4gens, or self-tolerance, is maintained by several mechanisms – elimina4ng lymphocytes that express receptors specific for some self an4gens inac4va4ng self-reac4ve lymphocytes suppressing these cells by the ac4ons of other (regulatory) cells Abnormali4es in the induc4on or maintenance of self-tolerance lead to immune responses against self (autologous) an4gens, which may result in autoimmune diseases Ini;a;on and Development of Adap;ve Immune Responses Adap4ve immune responses consist of dis4nct steps, the first three being the recogni4on of an4gen, the ac4va4on of lymphocytes, and the elimina4on of an4gen (the effector phase). The response contracts (declines) as an4gen-s4mulated lymphocytes die by apoptosis, restoring homeostasis, and the an4genspecific cells that survive are responsible for memory The dura4on of each phase may vary in different immune responses Types of adap;ve immunity Humoral immunity and cell-mediated immunity are induced by different types of lymphocytes and func4on to eliminate different types of microbes In humoral immunity, B lymphocytes secrete an4bodies that prevent infec4ons and eliminate extracellular microbes In cell-mediated immunity, helper T lymphocytes ac4vate macrophages and neutrophils to kill phagocytosed microbes, or cytotoxic T lymphocytes directly destroy infected cells Matura;on and ;ssue distribu;on of lymphocytes Lymphocytes develop from precursors in the genera4ve lymphoid organs (bone marrow and thymus). Mature lymphocytes enter the peripheral lymphoid organs, where they respond to foreign an4gens and recirculate in the blood and lymph. Some immature B cells leave the bone marrow and complete their matura4on in the spleen (not shown). B and T lymphocytes originate in bone marrow, and mature in different organs All lymphocytes arise from common lymphoid precursor cells in the bone marrow. B lymphocytes mature in the bone marrow, and T lymphocytes mature in an organ called the thymus. These sites in which mature lymphocytes are produced (generated) are called the genera4ve (or central ) lymphoid organs. Mature lymphocytes leave the genera4ve lymphoid organs and enter the circula4on and peripheral (secondary) lymphoid organs , which are the major site of immune responses where lymphocytes encounter an4gens and are ac4vated. Ac;ve and Passive Immunity Ac4ve immunity is conferred by a host response to a microbe or microbial an4gen, whereas passive immunity is conferred by adop4ve transfer of an4bodies or T lymphocytes specific for the microbe. Both forms of immunity provide resistance to infec4on and are specific for microbial an4gens, but only ac4ve immune responses generate immunologic memory. Therapeu4c passive transfer of an4bodies, but not lymphocytes, is done rou4nely and also occurs during pregnancy (from mother to fetus). Change in propor;ons of naive and memory T cells with age The propor4ons of naive and memory T cells are based on data from mul4ple healthy individuals. The es4mate of thymic output is an approxima4on Herd Immunity Herd immunity occurs when a large por4on of a community (the herd) becomes immune to a disease, making the spread of disease from person to person unlikely. As a result, the whole community becomes protected — not just those who are immune Run the SIMVID-19 sim: h^ps://www.npr.org/sec4ons/health-shots/2021/02/18/967462483/how-herd-immunity-works-and-what-stands-in-its-way Understanding adaptive immune responses is important for the control of allergies, autoimmune disease, and the rejection of transplanted organs Immunopathology: Immune systems may become dysregulated and induce disease – examples of such autoimmune diseases are rheumatoid arthri4s; allergy; systemic lupus erythematosis; hypothyroidism; coeliac disease Vaccination is the most effective means of controlling infectious diseases Summary Protec4ve immunity against microbes is mediated by the early reac4ons of innate immunity and the later responses of adap4ve immunity. Innate immune responses are s4mulated by molecular structures shared by groups of microbes and by molecules expressed by damaged host cells. Adap4ve immunity is specific for different microbial and nonmicrobial an4gens and is increased by repeated exposures to an4gen (immunologic memory) Many features of adap4ve immunity are of fundamental importance for its normal func4ons. These include specificity for different an4gens, a diverse repertoire capable of recognizing a wide variety of an4gens, memory of an4gen exposure, and the ability to discriminate between foreign an4gens and self an4gens Immunity may be acquired by a response to an4gen (ac4ve immunity) or conferred by transfer of an4bodies or effector cells (passive immunity) Lymphocytes are the only cells capable of specifically recognizing an4gens and are thus the principal cells of adap4ve immunity. The total popula4on of lymphocytes consists of many clones, each with a unique an4gen receptor and specificity. The two major subsets of lymphocytes are B cells and T cells, and they differ in their an4gen receptors and func4ons Summary The adap4ve immune response is ini4ated by the recogni4on of foreign an4gens by specific lymphocytes. Specialized APCs capture microbial an4gens and display these an4gens for recogni4on by lymphocytes. Lymphocytes respond by prolifera4ng and by differen4a4ng into effector cells, whose func4on is to eliminate the an4gen, and into memory cells, which show enhanced responses on subsequent encounters with the an4gen. The elimina4on of an4gens oEen requires the par4cipa4on of various effector cells. Humoral immunity is mediated by an4bodies secreted by B lymphocytes and is the mechanism of defense against extracellular microbes. An4bodies neutralize the infec4vity of microbes and promote the elimina4on of microbes by phagocytes and by ac4va4on of the complement system. Cell-mediated immunity is mediated by T lymphocytes and their products, such as cytokines, and is important for defense against intracellular microbes. CD4 + helper T lymphocytes help macrophages to eliminate ingested microbes and help B cells to produce an4bodies. CD8 + CTLs kill cells harboring intracellular pathogens, thus elimina4ng reservoirs of infec4on. Herd immunity occurs when a large por4on of a community (the herd) becomes immune to a disease, making the spread of disease from person to person unlikely