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    cells that constitute part of your nonspecific internal defenses. their function is to kill infected body cells by inducing apoptosis.

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    Immune System

    Associate Degree Nursing Physiology Review

    Immune System Content

    Immune System Functions

    Physical and Chemical Barriers (Innate Immunity)

    Nonspecific Resistance (Innate Immunity)

    Specific Resistance (Acquired Immunity)

    Antibodies Types of T cells

    Immune System Functions

    Scavenge dead, dying body cells

    Destroy abnormal (cancerous)

    Protect from pathogens & foreign molecules: parasites, bacteria, viruses

    The Immune System has 3 Lines of Defense Against Foreign Pathogens:

    1. Physical and Chemical Barriers (Innate Immunity)

    2. Nonspecific Resistance (Innate Immunity)

    3. Specific Resistance (Acquired Immunity)

    Physical and Chemical Barriers (Innate Immunity)

    Physical and chemical barriers form the first line of defense when the body is invaded.

    Physical Barriers

    The skin has thick layer of dead cells in the epidermis which provides a physical barrier. Periodic shedding of the epidermis removes microbes.

    The mucous membranes produce mucus that trap microbes.

    Hair within the nose filters air containing microbes, dust, pollutantsCilia lines the upper respiratory tract traps and propels inhaled debris to throatUrine flushes microbes out of the urethraDefecation and vomiting -expel microorganisms.Chemical BarriersLysozyme, an enzyme produced in tears, perspiration, and saliva can break down cell walls and thus acts as an antibiotic (kills bacteria)Gastric juice in the stomach destroys bacteria and most toxins because the gastric juice is highly acidic (pH 2-3)Saliva dilutes the number of microorganisms and washes the teeth and mouthAcidity on skin inhibit bacterial growthSebum (unsaturated fatty acids) provides a protective film on the skin and inhibits growthHyaluronic acid is a gelatinous substance that slows the spread of noxious agents

    Nonspecific Resistance (Innate Immunity)

    The second line of defense is nonspecific resistance that destroys invaders in a generalized way without targeting specific individuals:

    Phagocytic cells ingest and destroy all microbes that pass into body tissues. For example macrophages are cells derived from monocytes (a type of white blood cell). Macrophages leave the bloodstream and enter body tissues to patrol for pathogens. When the macrophage encounters a microbe, this is what happens:

    The microbe attaches to the phagocyte.

    The phagocyte's plasma membrane extends and surrounds the microbe and takes the microbe into the cell in a vesicle.

    The vesicle merges with a lysosome, which contains digestive enzymes.

    The digestive enzymes begin to break down the microbe. The phagocyte uses any nutrients it can and leaves the rest as indigestible material and antigenic fragments within the vesicle.

    The phagocyte makes protein markers, and they enter the vesicle.

    The indigestible material is removed by exocytosis.

    The antigenic fragments bind to the protein marker and are displayed on the plasma membrane surface. The macrophage then secretes interleukin-1 which activates the T cells to secrete interleukin 2, as described below under specific resistance .

    Inflammation is a localized tissue response that occurs when your tissues are damaged and in response to other stimuli. Inflammation brings more white blood cells to the site where the microbes have invaded. The inflammatory response produces swelling, redness, heat, painFever inhibits bacterial growth and increases the rate of tissue repair during an infection.

    Specific Resistance (Acquired Immunity)

    The third line of defense is specific resistance. This system relies on antigens, which are specific substances found in foreign microbes.

    Most antigens are proteins that serve as the stimulus to produce an immune response. The term "antigen" comes from ANTI-body GENerating substances.

    Here are the steps in an immune response:

    When an antigen is detected by a macrophage (as describe above under phagocytosis), this causes the T-cells to become activated.

    The activation of T-cells by a specific antigen is called cell-mediated immunity. The body contains millions of different T-cells, each able to respond to one specific antigen.

    The T-cells secrete interleukin 2. Interleukin 2 causes the proliferation of certain cytotoxic T cells and B cells.

    From here, the immune response follows 2 paths: one path uses cytotoxic T cells and the other uses B cells.

    Cytotoxic T Cell Pathway

    The cytotoxic T cells are capable of recognizing antigens on the surface of infected body cells.

    The cytotoxic T cells bind to the infected cells and secrete cytotoxins that induce apoptosis (cell suicide) in the infected cell and perforins that cause perforations in the infected cells.

    Both of these mechanisms destroys the pathogen in the infected body cell.

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    Barrier Defenses and the Innate Immune Response

    Barrier Defenses and the Innate Immune Response

    LEARNING OBJECTIVES

    By the end of this section, you will be able to:

    Describe the barrier defenses of the body

    Show how the innate immune response is important and how it helps guide and prepare the body for adaptive immune responses

    Describe various soluble factors that are part of the innate immune response

    Explain the steps of inflammation and how they lead to destruction of a pathogen

    Discuss early induced immune responses and their level of effectiveness

    The immune system can be divided into two overlapping mechanisms to destroy pathogens: the innate immune response, which is relatively rapid but nonspecific and thus not always effective, and the adaptive immune response, which is slower in its development during an initial infection with a pathogen, but is highly specific and effective at attacking a wide variety of pathogens (see Figure 1).

    Figure 1. The innate immune system enhances adaptive immune responses so they can be more effective.

    Any discussion of the innate immune response usually begins with the physical barriers that prevent pathogens from entering the body, destroy them after they enter, or flush them out before they can establish themselves in the hospitable environment of the body’s soft tissues. Barrier defenses are part of the body’s most basic defense mechanisms. The barrier defenses are not a response to infections, but they are continuously working to protect against a broad range of pathogens.

    The different modes of barrier defenses are associated with the external surfaces of the body, where pathogens may try to enter (see Table 1). The primary barrier to the entrance of microorganisms into the body is the skin. Not only is the skin covered with a layer of dead, keratinized epithelium that is too dry for bacteria in which to grow, but as these cells are continuously sloughed off from the skin, they carry bacteria and other pathogens with them. Additionally, sweat and other skin secretions may lower pH, contain toxic lipids, and physically wash microbes away.

    Table 1. Barrier Defenses

    Site Specific defense Protective aspect

    Skin Epidermal surface Keratinized cells of surface, Langerhans cells

    Skin (sweat/secretions) Sweat glands, sebaceous glands Low pH, washing action

    Oral cavity Salivary glands Lysozyme

    Stomach Gastrointestinal tract Low pH

    Mucosal surfaces Mucosal epithelium Nonkeratinized epithelial cells

    Normal flora (nonpathogenic bacteria) Mucosal tissues Prevent pathogens from growing on mucosal surfaces

    Another barrier is the saliva in the mouth, which is rich in lysozyme—an enzyme that destroys bacteria by digesting their cell walls. The acidic environment of the stomach, which is fatal to many pathogens, is also a barrier. Additionally, the mucus layer of the gastrointestinal tract, respiratory tract, reproductive tract, eyes, ears, and nose traps both microbes and debris, and facilitates their removal. In the case of the upper respiratory tract, ciliated epithelial cells move potentially contaminated mucus upwards to the mouth, where it is then swallowed into the digestive tract, ending up in the harsh acidic environment of the stomach. Considering how often you breathe compared to how often you eat or perform other activities that expose you to pathogens, it is not surprising that multiple barrier mechanisms have evolved to work in concert to protect this vital area.

    Cells of the Innate Immune Response

    A phagocyte is a cell that is able to surround and engulf a particle or cell, a process called phagocytosis. The phagocytes of the immune system engulf other particles or cells, either to clean an area of debris, old cells, or to kill pathogenic organisms such as bacteria. The phagocytes are the body’s fast acting, first line of immunological defense against organisms that have breached barrier defenses and have entered the vulnerable tissues of the body.

    Phagocytes: Macrophages and Neutrophils

    Many of the cells of the immune system have a phagocytic ability, at least at some point during their life cycles. Phagocytosis is an important and effective mechanism of destroying pathogens during innate immune responses. The phagocyte takes the organism inside itself as a phagosome, which subsequently fuses with a lysosome and its digestive enzymes, effectively killing many pathogens. On the other hand, some bacteria including Mycobacteria tuberculosis, the cause of tuberculosis, may be resistant to these enzymes and are therefore much more difficult to clear from the body. Macrophages, neutrophils, and dendritic cells are the major phagocytes of the immune system.

    A macrophage is an irregularly shaped phagocyte that is amoeboid in nature and is the most versatile of the phagocytes in the body. Macrophages move through tissues and squeeze through capillary walls using pseudopodia. They not only participate in innate immune responses but have also evolved to cooperate with lymphocytes as part of the adaptive immune response. Macrophages exist in many tissues of the body, either freely roaming through connective tissues or fixed to reticular fibers within specific tissues such as lymph nodes. When pathogens breach the body’s barrier defenses, macrophages are the first line of defense. They are called different names, depending on the tissue: Kupffer cells in the liver, histiocytes in connective tissue, and alveolar macrophages in the lungs.

    fuente : courses.lumenlearning.com

    Innate Immunity

    Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends in part on the adaptive immune system (discussed in Chapter 24), which remembers previous encounters with specific pathogens and destroys them when they attack again. Adaptive immune responses, however, are slow to develop on first exposure to a new pathogen, as specific clones of B and T cells have to become activated and expand; it can therefore take a week or so before the responses are effective. By contrast, a single bacterium with a doubling time of one hour can produce almost 20 million progeny, a full-blown infection, in a single day. Therefore, during the first critical hours and days of exposure to a new pathogen, we rely on our innate immune system to protect us from infection.

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    Innate Immunity

    Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends in part on the adaptive immune system (discussed in Chapter 24), which remembers previous encounters with specific pathogens and destroys them when they attack again. Adaptive immune responses, however, are slow to develop on first exposure to a new pathogen, as specific clones of B and T cells have to become activated and expand; it can therefore take a week or so before the responses are effective. By contrast, a single bacterium with a doubling time of one hour can produce almost 20 million progeny, a full-blown infection, in a single day. Therefore, during the first critical hours and days of exposure to a new pathogen, we rely on our innate immune system to protect us from infection.

    Innate immune responses are not specific to a particular pathogen in the way that the adaptive immune responses are. They depend on a group of proteins and phagocytic cells that recognize conserved features of pathogens and become quickly activated to help destroy invaders. Whereas the adaptive immune system arose in evolution less than 500 million years ago and is confined to vertebrates, innate immune responses have been found among both vertebrates and invertebrates, as well as in plants, and the basic mechanisms that regulate them are conserved. As discussed in Chapter 24, the innate immune responses in vertebrates are also required to activate adaptive immune responses.

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    Epithelial Surfaces Help Prevent Infection

    In vertebrates, the skin and other epithelial surfaces, including those lining the lung and gut Figure 25-39), provide a physical barrier between the inside of the body and the outside world. Tight junctions (discussed in Chapter 19) between neighboring cells prevent easy entry by potential pathogens. The interior epithelial surfaces are also covered with a mucus layer that protects these surfaces against microbial, mechanical, and chemical insults; many amphibians and fish also have a mucus layer covering their skin. The slimy mucus coating is made primarily of secreted mucin and other glycoproteins, and it physically helps prevent pathogens from adhering to the epithelium. It also facilitates their clearance by beating cilia on the epithelial cells (discussed in Chapter 22).

    Figure 25-39

    Epithelial defenses against microbial invasion. (A) Cross section through the wall of the human small intestine, showing three villi. Goblet cells secreting mucus are stained The protective mucus layer covers the exposed surfaces of the villi. (more...)

    The mucus layer also contains substances that kill pathogens or inhibit their growth. Among the most abundant of these are antimicrobial peptides, called defensins, which are found in all animals and plants. They are generally short (12–50 amino acids), positively charged, and have hydrophobic or amphipathic domains in their folded structure. They constitute a diverse family with a broad spectrum of antimicrobial activity, including the ability to kill or inactivate Gram-negative and Gram-positive bacteria, fungi (including yeasts), parasites (including protozoa and nematodes), and even enveloped viruses like HIV. Defensins are also the most abundant protein type in neutrophils (see below), which use them to kill phagocytosed pathogens.

    It is still uncertain how defensins kill pathogens. One possibility is that they use their hydrophobic or amphipathic domains to insert into the membrane of their victims, thereby disrupting membrane integrity. Some of their selectivity for pathogens over host cells may come from their preference for membranes that do not contain cholesterol. After disrupting the membrane of the pathogen, the positively-charged peptides may also interact with various negatively-charged targets within the microbe, including DNA. Because of the relatively nonspecific nature of the interaction between defensins and the microbes they kill, it is difficult for the microbes to acquire resistance to the defensins. Thus, in principle, defensins might be useful therapeutic agents to combat infection, either alone or in combination with more traditional drugs.

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    Human Cells Recognize Conserved Features of Pathogens

    Microorganisms do occasionally breach the epithelial barricades. It is then up to the innate and adaptive immune systems to recognize and destroy them, without harming the host. Consequently, the immune systems must be able to distinguish self from nonself. We discuss in Chapter 24 how the adaptive immune system does this. The innate immune system relies on the recognition of particular types of molecules that are common to many pathogens but are absent in the host. These pathogen-associated molecules (called ) stimulate two types of innate immune responses— (discussed below) and phagocytosis by cells such as neutrophils and macrophages. Both of these responses can occur quickly, even if the host has never been previously exposed to a particular pathogen.

    fuente : www.ncbi.nlm.nih.gov

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