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BIOC 401 Immunochemistry By Yasmene F. Alanazi  INNATE AND ADAPTIVE IMMUNITY Immunity is defined as resistance to disease, specifically infectious disease. The collection of cells, tissues, and molecules that mediate resistance to infections is called the immune system, and t...

BIOC 401 Immunochemistry By Yasmene F. Alanazi  INNATE AND ADAPTIVE IMMUNITY Immunity is defined as resistance to disease, specifically infectious disease. The collection of cells, tissues, and molecules that mediate resistance to infections is called the immune system, and the coordinated reaction of these cells and molecules to infectious microbes comprises an immune response. Immunology is the study of the immune system, including its responses to microbial pathogens and damaged tissues and its role in disease. The most important physiologic function of the immune system is to prevent or eradicate infections  INNATE AND ADAPTIVE IMMUNITY Host defenses are grouped under innate immunity, which provides immediate protection against microbial invasion, and adaptive immunity, which develops more slowly and provides more specialized defense against infections. Innate immunity, also called natural immunity or native immunity, is always present in healthy individuals (hence the term innate), prepared to block the entry of microbes and to rapidly eliminate microbes that do succeed in entering host tissues. Adaptive immunity, also called specific immunity or acquired immunity, requires expansion and differentiation of lymphocytes in response to microbes before it can provide effective defense; that is, it adapts to the presence of microbial invaders. Innate immunity is phylogenetically older, and the more specialized and powerful adaptive immune response evolved later. Principal mechanisms of innate and adaptive immunity. The mechanisms of innate immunity provide the initial defense against infections. Some mechanisms (e.g., epithelial barriers) prevent infections, and other mechanisms (e.g., phagocytes, natural killer [NK] cells and other innate lymphoid cells [ILCs], the complement system) eliminate microbes. Adaptive immune responses develop later and are mediated by lymphocytes and their products. Antibodies block infections and eliminate microbes, and T lymphocytes eradicate intracellular microbes. The kinetics of the innate and adaptive immune responses are approximations and may vary in different infections.  Cont. In innate immunity, the first line of defense is provided by epithelial barriers of the skin and mucosal tissues and by cells and natural antibiotics present in epithelia, all of which function to block the entry of microbes. If microbes do breach epithelia and enter the tissues or circulation, they are attacked by phagocytes, specialized lymphocytes called innate lymphoid cells, which include natural killer cells, and several plasma proteins, including the proteins of the complement system. All these mechanisms of innate immunity specifically recognize and react against microbes. In addition to providing early defense against infections, innate immune responses enhance adaptive immune responses against the infectious agents  Cont. The adaptive immune system consists of lymphocytes and their products, such as antibodies. Adaptive immune responses are especially important for defense against infectious microbes that are pathogenic for humans (i.e., capable of causing disease) and may have evolved to resist innate immunity. Whereas the mechanisms of innate immunity recognize structures shared by classes of microbes, the cells of adaptive immunity (lymphocytes) express receptors that specifically recognize a much wider variety of molecules produced by microbes as well as non infectious substances. Any substance that is specifically recognized by lymphocytes or antibodies is called an antigen.  Cont. Adaptive immune responses often use the cells and molecules of the innate immune system to eliminate microbes, and adaptive immunity functions to greatly enhance these antimicrobial mechanisms of innate immunity. For example, antibodies (a component of adaptive immunity) bind to microbes, and these coated microbes avidly bind to and activate phagocytes (a component of innate immunity), which ingest and destroy the microbes.  TYPES OF ADAPTIVE IMMUNITY The two types of adaptive immunity, called humoral immunity and cell- mediated immunity, are mediated by different cells and molecules and provide defense against extracellular microbes and intracellular microbes, respectively. Types of adaptive immunity. In humoral immunity, B lymphocytes secrete antibodies that eliminate extracellular microbes. In cell-mediated immunity, different types of T lymphocytes recruit and activate phagocytes to destroy ingested microbes and kill infected cells  Humoral immunity Humoral immunity is mediated by proteins called antibodies, which are produced by cells called B lymphocytes. Secreted antibodies enter the circulation and mucosal fluids, and they neutralize and eliminate microbes and microbial toxins that are present outside host cells, in the blood, extracellular fluid derived from plasma, and in the lumens of mucosal organs such as the gastrointestinal and respiratory tracts. One of the most important functions of antibodies is to stop microbes that are present at mucosal surfaces and in the blood from gaining access to and colonizing host cells and connective tissues. In this way, antibodies prevent infections from ever being established. Antibodies cannot gain access to microbes that live and divide inside infected cells.  Cell mediated immunity Defense against such intracellular microbes is called cell-mediated immunity because it is mediated by cells, which are called T lymphocytes. Some T lymphocytes activate phagocytes to destroy microbes that have been ingested by the phagocytes into intracellular vesicles. Other T lymphocytes kill any type of host cells that are harboring infectious microbes in the cytoplasm. In both cases, the T cells recognize microbial antigens that are displayed on host cell surfaces, which indicates there is a microbe inside the cell. The specificities of B and T lymphocytes differ in important respects. Most T cells recognize only protein antigens, whereas B cells and antibodies are able to recognize many different types of molecules, including proteins, carbohydrates, nucleic acids, and lipids.  Active and passive immunity Immunity may be induced in an individual by infection or vaccination (active immunity) or conferred on an individual by transfer of antibodies or lymphocytes from an actively immunized individual (passive immunity). In active immunity, an individual exposed to the antigens of a microbe mounts an active response to eradicate the infection and develops resistance to later infection by that microbe. In passive immunity, a naive individual receives antibodies or cells (e.g., lymphocytes, feasible only in animal experiments) from another individual already immune to an infection. The only physiologic example of passive immunity is seen in newborns, whose immune systems are not mature enough to respond to many pathogens but who are protected against infections by acquiring antibodies from their mothers through the placenta and breast milk.  PROPERTIES OF ADAPTIVE IMMUNE RESPONSES Specificity and Diversity The adaptive immune system is capable of distinguishing among millions of different antigens or portions of antigens. Specificity is the ability to distinguish between many different antigens. The diversity of the lymphocyte repertoire, which enables the immune system to respond to a vast number and variety of antigens. Clonal selection. Mature lymphocytes with receptors for many antigens develop before encountering these antigens. A clone refers to a population of lymphocytes with identical antigen receptors and therefore specificities; all of these cells are presumably derived from one precursor cell. Each antigen (e.g., X and Y) selects a preexisting clone of specific lymphocytes and stimulates the proliferation and differentiation of that clone..  Cont. Memory The adaptive immune system mounts larger and more effective responses to repeated exposures to the same antigen. This feature of adaptive immune responses implies that the immune system remembers exposure to antigen, and this property of adaptive immunity is therefore called immunologic memory. The response to the first exposure to antigen, called the primary immune response, is initiated by lymphocytes called naive lymphocytes that are seeing antigen for the first time. The term naive refers to these cells being immunologically inexperienced, not having previously responded to antigens  Cont. Subsequent encounters with the same antigen lead to responses called secondary immune responses that usually are more rapid, larger, and better able to eliminate the antigen than primary responses. Secondary responses are the result of the activation of memory lymphocytes, which are long-lived cells that were induced during the primary immune response. Immunologic memory optimizes the ability of the immune system to combat persistent and recurrent infections, because each exposure to a microbe generates more memory cells and activates previously generated memory cells. Memory also is one of the reasons why vaccines confer long-lasting protection against infections. Primary and secondary immune responses. Antigens X and Y induce the production of different antibodies (a reflection of specificity). The secondary response to antigen X is more rapid and larger than the primary response (illustrating memory) and is different from the primary response to antigen Y (again reflecting specificity). Antibody levels decline with time after each immunization. The level of antibody produced is shown as arbitrary values and varies with the type of antigen exposure. Only B cells are shown, but the same features are seen with T cell responses to antigens. The time after immunization may be 1 to 3 weeks for a primary response and 2 to 7 days for a secondary response, but the kinetics vary, depending on the antigen and the nature of immunization.  Other Features of Adaptive Immunity When lymphocytes are activated by antigens, they undergo proliferation, generating many thousands of clonal progeny cells, all with the same antigen specificity. This process, called clonal expansion, rapidly increases the number of cells specific for the antigen encountered and ensures that adaptive immunity keeps pace with rapidly proliferating microbes. Immune responses are specialized, and different responses are designed to defend best against different classes of microbes. All immune responses are self-limited and decline as the infection is eliminated, allowing the system to return to a resting state, prepared to respond to another infection. The immune system is able to react against an enormous number and variety of microbes and other foreign antigens, but it normally does not react against the host’s own potentially antigenic substances—so-called self antigens. This unresponsiveness to self is called immunological tolerance, referring to the ability of the immune system to coexist with (tolerate) potentially antigenic self molecules, cells, and tissues.