Introduction (Page 1 of 18) COMMON CHARACTERISTICS OF B AND T LYMPHOCYTES Sate UCM Mia e ice com encecan adaptive immunity, the body’s third line of defense. These lymphocytes. are like soldiers defending a medieval castle. Like archers, ieee eu at ee MmR Ch ccautantomere antibodies, not arrows. Some T cells are like Pacer erect ten tam nn eat ere ht Creme mee LCT meet elena T cells act like officers and help direct the battle. B and T lymphocytes have different ereane atta cma ter ESTE CeO MUON eLU See Wc ODED features are the focus of this topic.Introduction (Page 1 of 25) hee Host DEFENSES » In this topic we will learn about the innate host defen The first line of defense consists of surface barriers: skin, mucous membranes, and secretions keep invaders out (like castle moats and walls). The Perera Dae Da eRe SMe (es Coane SMe LCom NTC ue TOs Colo cells and extracellular fluid chemicals respond to EUs eRe EM oa Mee rCeMe OL Corte} COT cemetery When infection does occur, innate and adaptive defense mechanisms cooperate to clear pathogens from the body.Goals (Page 2 of 25) GOALS * Describe the physical and chemical surface barriers to infection. + Describe the cells, antimicrobial proteins, and processes that form the innate internal defenses. Understand the purpose, sequence of events, and cardinal signs of inflammation, + Recognize that innate defense mechanisms may be insufficient to prevent or clear infections. Learn that innate and adaptive defenses interact in many ways and that innate defenses often trigger and define the nature of adaptive defense responses. WHAT YOU NEED TO KNOW © What enzymes are and how they work, » Lysosomes contain hydrolytic enzymes. * The nature of proteins, nucleic acids, and polysaccharides. © What endothelial cells are, and that capillary walls consist only of endothelial cells and a basement merobrane. To see definitions of terms, click the bold red words Click Next to go to the next page.Surface Barriers: Introduction (Page 3 of 25) The first line of defense prevents pathogens from entering the body and includes physical barriers such as = Intact skin = Mucous membranes of the Respiratory tract = Gastrointestinal tract » Genitourinary tract Click Next ta go to the next pageSurface Barriers: Skin (Page 4 of 25) Skin acts as a physical barrier to infection. Properties of the skin that help it resist invasion: © Keratin, a tough protein in skin cells, forms an abrasion- and water-resistant outermost lager © Intercellular junctions hold skin cells tightly together. \ © Skin secretions are acidic and contain chemicals that make the skin inhospitable for pathogens One secretion is the enzyme lysozyme, which can digest cell walls of certain bacteria Click the skin to see it resist pathogens. |Surface Barriers: Mucous Membranes (Page 5 of 25) Mucous membranes line the digestive, respiratory, urinary, and reproductive tracts Click the mucous membranesSurface Barriers: Mucous Membranes (Page 5 of 25) Mucous membranes line the digestive, respiratory, urinary, and reproductive tracts Mucous membrane secretions are acidic and contain lysozyme. Some surface membranes have special properties In the stomach, pathogens encounter both digestive eazymes and a very low pH. @ The digestive and respitatory passageways are fined with sticky mucus that traps pathogens. Click the trachea to see mucus trap pathogensSurface Barriers: Mucous Membranes (Page 5 of 25) Pathogens and other particles in the air enter through the nasal cavity. Most are trapped in the thick mucous layer covering the epithelium of the nasal cavity, pharynx, trachea, and bronchi Cilia move the mucus up toward the back of the throat where the mucus is swallowed, Stomach acid and enzymes kill most of the trapped pathogens. Click the cilia to see thern in action.Five Lines of Innate Internal Defense (Page 6 of 25)Five Lines of Innate Internal Defense (Page 6 of 25) The five lines of internal defense: Phagocytic cells—neutrophils and macrophages B Natural killer (NK) cells—kill body cells that have become virus-infected of anicerous, we Antimicrobial proteins—complement and interferons & Inflammation ww Fever Click the phagocyte to continueFive Lines of Innate Internal Defense (Page 6 of 25) —— Sometimes the innate defenses are no match for invading pathogens, just.as a massive invasion can overwhelm the guards on a casile wall. In this ease, the armies of the adaptive defenses must be called out Having already tet the enemy, the innate defenses can influence the kind of response the adaptive immune system makes by passing chemical messages to the adaptive immune system. This process is one of the many ways in which the innate and adaptive defenses work together Click Next to go to the next page.Phagocytes: Neutrophils vs. Macrophages (Page 7 of 25) Recall from the Anatomy Review topic that neutrophils and macrophages are the twa main types of phagocytes These phagocytes perform essential functions for both innate and adaptive itnmunity. Neutrophils are © The most abundant of the leukocytes " Antimicrobial (50-70% af white blood cells), Ne proteins Normally not found in healthy tissues. ‘oaiie « The first cells to leave the blood and enter tissue at sites of infection or trauma, Click the neutrophilPhagocytes: Recognizing the Enemy (Page 8 of 25) Pathogens that enter the body are often rapidly ingested by phagocytes. This process begins when a phagocyte recognizes and binds a pathogen Mannose receptor Phagocytes use special cell membrane receptors, such as the mannose receptor and the Toll-like receptors (TLRs), to recognize and bind T 1 molecules that are found on pathogens and not on normal body cells aS i Click a TLR to learn more about them. Toll-ike receptor (TLR) MacrophagePhagocytes: Recognizing the Enemy (Page 8 of 25) Atleast 10 different TLRs have been identified on human phagocytes, cach binding to a different type of pathogen molecule. When a phagocyte recognizes a pathogen it triggers 1. Ingestion of the pathogen. y y 2, Release of chemical alarm signals that mobilize other cells T of innate and adaptive immnunity. aS i Click the phagocyte to see it bind pathogens MacrophagePhagocytes: Recognizing the Enemy (Page 8 of 25) Click Next ta go to the next pagePhagocytes: Killing Mechanisms (Page 9 of 25) ‘Once the phagocyte detects a pathogen, it engulfs the pathogen by extending its cell menabrane and cytoplasm around it, bringing the pathogen inside its cell body wrapped within a vesicle. This vesicle is called a phagosome. Click the phagocyte to engulf the bacteria —Phagocytes: Killing Mechanisms (Page 9 of 25) The phagosome contains the pathogen and begins the killing process. Because there is such a wide variety of pathogens, phagocytes require a correspondingly wide range of techniques for killing |, His pumped into the phagosome, making it acidic Phagosome Click the phagosome to acidliffy itPhagocytes: Killing Mechanisms (Page 9 of 25) The phagosome contains the pathogen and begins the killing process. Because there is such a wide variety of pathogens, phagocytes require a correspondingly wide range of techniques for killing |, His pumped into the phagosome, making it acidic 2. Enzymes convert 03 into toxic reactive oxygen intermediates, a process called the respiratory burst, while other enzymes produce tose nitric oxide Click a bacterium to induce a respiratory burst. ¥Phagocytes: Killing Mechanisms (Page 9 of 25) The phagosome contains the pathogen and begins the killing process. Because there is such a wide variety of pathogens, phagocytes require a correspondingly wide range of techniques for killing |, His pumped into the phagosome, making it acidic 2. Enzymes convert 03 into toxic reactive oxygen intermediates, a process called the respiratory burst, while other enzymes produce tose nitric oxide 3. Phagosome fuses with a lysosome to form a phagolysosome where © Hydrolytic enzymes digest the pathogen. * Defensins poke holes in bacterial membranes * Enzymes convert reactive oxygen intermediates ta chemicals similar ta household bleach. Drag the lysosome to the phagosome to form a phagolysosomePhagocytes: Evasion Tactics of Pathogens (Page 10 of 25) Many pathogens have evolved strategies to avoid being killed by phagocytes Unencapsulated —x Try dragging the macrophage to one of — bacterium. the two kinds of bacteria—encapsulated or unencapsulated. Capsule Encapsulated — = bacterium of ~ Macrophage ——Phagocytes: Evasion Tactics of Pathogens (Page 10 of 25) Many pathogens have evolved strategies to avoid being killed by phagocytes Some bacteria have evolved cansules, making it difficult for phagocytes to grab them, Molecules produced by the immune system can coat these bacteria and etihance phagocytosis by providing “hand-holds.” This process of coating bacteria to enhance phagocytosis is called opsonization. Two factors that can act as opsonins are: x * Antibodies * Complement . Here we will focus on antibodies Click a bacterium to coat it with antibody.Phagocytes: Evasion Tactics of Pathogens (Page 10 of 25) Phagocytes hawe receptors that attach to the opsonins. The opsonins form a link binding together the pathogen and the phagocyte, triggering phagocytosis Drag the opsonized vacterium to the macrophage so that both its receptors attach to the antibody stems.Phagocytes: Evasion Tactics of Pathogens (Page 10 of 25) There are several other strategies that pathogens have evolwed to escape destruction by phagocytes. Strategies include: * Secreting molecules that block the fusion of lysosomes with the phagosome Lysosome Macrophage = Developing resistance to the effects of - lysosomal enzymes and reactive oxygen - intermediates, » © Finding ways to escape the phagosome, take up residence, and replicate within the cytoplasm of the phagocyte. fPhagocytes: Evasion Tactics of Pathogens (Page 10 of 25) The bacterium that causes tuberculosis is known for its ability to replicate inside macrophages. In response te bacterial strategies such as those listed, the immune system has evolved a counter-stratezy. Certain T cells of the adaptive defense mechanisins can enhance the entire killing process within the macrophage. This enhancement only happens when the macrophage presents antigen from such bacteria to the T cel. The interaction between T cells and phagocytes is another example of the interaction between innate and adaptive defense systems a - Lysosome Macrophage = Tuberculosis — bacteriumPhagocytes: Evasion Tactics of Pathogens (Page 10 of 25) The bacterium that causes tuberculosis is known for its ability 1a replicate inside macrophages. In response ta bacterial slrategies such as those listed, the - immune system has evolved a counter-strategy. Certain T cells of the adaptive defense mechanisms can enhance the entire billing process within the macrophage. This enhancement only z happens when the macrophage presents antigen from such bacteria to the T cel 3 The interaction between T cells and _- phagocytes is another example of the interaction between innate and adaptive defense systems = Enhance the macrophage’ killing ~— J ability by dragging the T cell to it 4 —NK Cells: Characteristics (Page 11 of 25) Natural Killer (NE) cells are a type of up 10-15% of blood lymphocytes. Let's compare these unusual lymphocytes to B and T cells Click the NK cell. ‘Antimicrobial proteins Natural killer cell apNK Cells: Characteristics (Page 11 of 25) Like T cells, NK cells kill the body's own. cells under two circumstances Ifa body cell has been invaded by intracellular pathogens «Ifa body cell has become cancerous. NK cells also attack transplanted tissues, playing a role in the rejection of transplanted organs Click the T cell Target Size Antigen receptor ae NK cell Beell Teel Infected or | Extracelular | Infected or cancerous cells | pathogens | cancerous cellsNK Cells: Characteristics (Page 11 of 25) Like T cells, NK cells kill the body's own. cells under two circumstances Ifa body cell has been invaded by intracellular pathogens «Ifa body cell has become cancerous. NK cells also attack transplanted tissues, playing NK cell EB cell Teell a role in the rejection of transplanted organs NK cells are larger than B and T cell, Infected or | Extracelular | Infected or and contain granules in their cytoplastn. Target) cancerous cells pathogens | cancerous cells Thus, NK cells are sometimes called “large granular lymphocytes.” Sie| Larger Smaller Smaller Click the B cell Antigen receptorNK Cells: Characteristics (Page 11 Like T cells, NK cells kill the body's own. cells under two circumstances Ifa body cell has been invaded by intracellular pathogens «Ifa body cell has become cancerous. NK cells also attack transplanted tissues, playing a role in the rejection of transplanted organs NK cells are larger than B and T cells, and contain granules in their cytoplasm, Target Thus, NK cells are sometimes called “large granular lymphocytes.” While B and T cells express specific Sie receptors for antigen, no such receptors are found on NK cells, ‘Yet, NK cells can recognize a variety of Antigen cells as abnormal, bind to them and kill receptor them. On the next page, we'll see how the NK cells recognize abnormal cells v, NK cell Beell Teel Infected or | Extracelular | Infected or cancerous cells | pathogens | cancerous cells Larger Smaller Smaller No Yes YesNK Cells: Identification of Target Cells (Page 12 of 25)NK Cells: Identification of Target Cells (Page 12 of 25)NK Cells: Identification of Target Cells (Page 12 of 25)Page 13 of 25) ( = o 3 <¢ pe ism oO NK Cells: Mechan ‘ytotoxic T cellsNK Cells: Mechanism of Action (Page 13 of 25) NK cells use the same killing mechanistns as cells called cytotoxic T cells (Topic 4). This kaling inwolves direct contact and induces the target cell to undergo apoptosis NK cells are important in the early response to pathogens. They continue to play a role after B and T cells are activated, Like macrophages, NK cells become more effective lallers following * Activation by cytokines from cerlain T cells. © Coating of cells with antibody. These are two examples of interaction between innate and adaptive defenses Click Next to go to the next page.Interferons (Page 14 of 25) The first set of antimicrobial proteins we wil consider are the interferons Interferons are cytokines that: © Interfere with vital replication © Modulate inflammation. © Activate immune cells The three types of interferon are: © Alpha interferon Beta interferon © Gamma interferon Gamma interferons act ina variety of ways (0 signal other immune and non-immune cells. We will look at the anti-viral properties of alpha and beta interferons Phagocytes Inflatnmation.Interferons (Page 14 of 25) The first set of antimicrobial proteins we will consider are the interferons, Interferons are cytokines that: © Interfere with vital replication © Modulate inflammation. © Activate immune cells The three types of interferon are: © Alpha interferon Beta interferon © Gamma interferon Gamma interferons act ina variety of ‘ways to signal other immune and non-immune cells. We will look at the anti-viral properties of alpha and beta interferons, Let’s examine how viruses replicate within cells Click the virus to beginInterferons (Page 14 of 25) Recall that viruses must enter cells to replicate. This is becanse a virus is little Virus —zh more than a protein-covered packet of nucleie acids—the genetic instructions for how to createa new winas. When a virus penetrates the target cell's membrane, the virus releases its nucleic acid and takes over the host cell's machinery to make more copies of that virus DNA (in nucleus) Interferon. receptorsInterferons (Page 14 of 25) Recall that viruses must enter cells to replicate. This is because a virus is little more than 4 protein-cowered packet of nucleic acids —the genetic instructions for how to create a new virus. When a virus penetrates the target cell's membrane, the virus releases its nucleic acid and takes over the host cell's machinery to make more copies of that virus Viral infection causes the cell to produce and secrete interferons, Click the nucleus of the infected cell to see it produce and secrete interferonsInterferons (Page 14 of 25) Recall that viruses must enter cells to replicate. This is because a virus is little more than 4 protein-cowered packet of nucleic acids —the genetic instructions for how to create a new virus. When a virus penetrates the target cell's membrane, the virus releases its nucleic acid and takes over the host cell's machinery to make more copies of that virus Viral infection causes the cell to produce and secrete interferons,Interferons (Page 14 of 25) Interferons bind to receptors on nearby cells. They act as a warning signal for as-yet-uninfected cells. In response, the uninfected cells produce proteins that inhibit viral replication by: * Degrading viral RNA. © Preventing the synthesis of viral proteins Drag the interferon to its receptor to see how it actsInterferons (Page 14 of 25) Interferons bind to receptors on nearby cells. They act as a warning signal for as-yet-uninfected cells. In response, the uninfected cells produce proteins that inhibit viral replication by: © Degrading viral RNA, * Preventing the synthesis of viral proteins Drag the virus into the cell alerted by interferon to see if the virus can still make copies of itselfInterferons (Page 14 of 25) Chewing up viral RNA and blocking protein synthesis are not specific; they work against any virus. In the short term, these mechanisms protect uninfected cells not only against the virus that invaded its neighbor, but also against any other viruses in the area Viral RNA fragments Click Next to go to the next page‘Complement: Introduction (Page 15 of 25) The next set of antimicrobial proteins we will consider is the complement system. Complement gets its name from the fact that it complements or enhances other components of both innate and adaptive defenses. Complement is actually a complex cascade of interdependent plasma proteins, each activating the other in turn until the final product is formed. ‘When activated, these proteins can ‘Mark cells for phagocytosis © Promote inflammation, © Kill some bacteria all by themselves Drag the complement proteins to this bacterium to see it being lysed by the end-products of the complement cascade‘Complement: Introduction (Page 15 of 25) The next set of antimicrobial proteins we will consider is the complement system. Complement gets its name from the fact that it complements or enhances other components of both innate and adaptive defenses. Phagocyies / wash Inflatamation Complement is actually a complex cascade of interdependent plasma proteins, each activating the other in turn until the final product is formed. ‘When activated, these proteins can © Mark cells for phagocytosis. © Promote inflammation, © Kill some bacteria all by themselves Click Next to go to the next page.Complement: Activation (Page 16 of 25) Because of its potentially lethal effects to the body’s own cells, the activation of complement is tightly regulated. Each step of the sequence provides a point of regulation that keeps the process from engaging until it is needed, Both the adaptive and innate defense systems can activate this cascade. As is often the case in the immune system, the enemy can be identified by either: © Finding chemical markers that should not normally be present on cells * Not finding chemicals that should be present, Click the bacterium to continue,Complement: Activation (Page 16 of 25) Antibodies are chemical markers of the adaptive immune system that should not normally be found on cells. These activate complement via the classical pathway. Click the antibody to continue. AntibodyComplement: Activation (Page 16 of 25) Antibodies are chemical markers of the adaptive immune system that should not normally be found on cells. These activate complement via the classical pathway. Certain polysaccharides, or sugars, are found only on the surface of bacteria and not on normal bedy cells Lectin ‘When special sugar-binding proteing in the extrac eliular fluid called lectins bind these sugars, they trigger the lectin pathway of complement activation.Complement: Activation (Page 16 of 25) The absence of inhibitory proteins normally found on the body's cells can also result in spontaneous complement activation. This spontaneous activation is the beginning of the alternative pathway. Click the two boxes that represent activation pathways due to the prosence of chemical markers not normally found on our own cellsComplement: Activation (Page 16 of 25) The absence of inhibitory Dies aie BP UNUSUAL CReinaT Wares Absence of normal proteins normally found on chemical markers the body's cells can also result in spontaneous complement activation. This spontaneous activation is the beginning of the alternative pathway, Click Next to go to the next page.Complement: Pathways (Page 17 of 25) Each of these three pathways requires other complement proteins (for example, C2, C4, factor B, and factor D), but they all eventually cause activation of a protein called C3 Click the C3 to activate it di!Complement: Pathways (Page 17 of 25) ‘When C3 is activated, it splits into two fragments, now called C3a and C3h 3a causes inflammation, a process that we will study in detail later. C3b acts as an opsonin. Many individual Cis are split by the enzymatic cascade into many copies of C3aand C3b. Click the C3 to split another copyComplement: Pathways (Page 17 of 25) C3b participates in. cleaving C5 into two parts: C5a and C5b. Click the C5 to cleave and activate it ©. [Seman] @ (Sees) oie‘Complement: Pathways (Page 17 of 25) Ca, like C3a, promotes inflammation. However, CSb combines with several other complement proteins on the surface of a bacterial cell to form a large pore called the membrane attack complex (MAC). Click the CSb to see formation of a MAC. ©. teComplement: Pathways (Page 17 of 25) The tnembrane attack complex punctures the menibrane, which allows water to flow in and solutes to flow out. Asa result, the targeted cell Iyses, Complement’s ability to lyse some bacteria directly makes it a powerful defense mechanism. Even more powerful, however, ae are its other two roles © The ability to opsonize a wide variety of pathogens # The ability 10 enhance A inflammation, which aleris and attracts elements of both the innate and adaptive immune systems ‘We will explore inflammation newt. Click Next ta go to the next pageInflammation: Cardinal Signs (Page 18 of 25) ‘When the body is injured—such as with a cut, abrasion, or bruise—a sequence of events called inflammation is initiated. -— ‘When the walls of the castle are breached, defenders and j construction crews are called into the area, In our bodies, cells and proteins are recruited to the area of injury so that defenses are ready and repairs can begin, Inflammation occurs many tires throughout our lives. All of the “ities” you've ever had are inflammations. Usually these are short-lived problems, called acute inflammations such as © Tonsillitis * Tendonitis © Laryngitis But sometimes inflammation becomes a long-term, or chronic, problem such as: © Arthritis Inflammation is one of the most common problems that health care professionals face Click the castle to continue.Inflammation: Cardinal Signs (Page 18 of 25) Thee are four cardinal signs that health care professionals use to identify inflammation. See if you can pick them out from this lst. Drag your choices to the box. Fewer Colh Pain Numbness Plallor Stelling Ren ebness Cingling HeatInflammation: Cardinal Signs (Page 18 of 25) Thee are four cardinal signs that health care professionals use to identify inflammation. See if you can pick them out from this lst. Sour Cardinal Signs 1. Swelling Drag your choices to the box. Well done! Chick Next to go to the next page. 2 Rebness Fewer Plallor Colh Numbness CinglingInflammation: Vasodilation and Permeab ity (Page 19 of 25) The purpose of inflammation is to bring white blood cells and plasma proteins into an injured area This action accomplishes three things Prevents the spread of injurious agents # Disposes of pathogens and dead cells © Sets the stage for repair Click the injured fingerInflammation: Vasodilation and Permeability (Page 19 of 25) Chemical messengers called ] inflammatory me are centralto this process. Virtually all inflammatory 4 Seinen mediators cause two key effects: © Vasodilation | # An increase in vascular permeability Click the splinter to release 1 inflammatory mediatorsInflammation: Vasodilation and Permeability (Page 19 of 25) Chemical messengers called ] inflammatory mediators are central to | this process. Virtually all inflammatory mediators cause two key effects: ] © Vasodilation | An increase in vascular permeability ] ‘Vasodilation (increased arteriolar diameter) leads to increased localized blood flow ta the injured area, This increase causes bothl the redness and heat that are cardinal | signs of inflammation f Increased vascular permeability occurs as the gaps between adjacent endothelial ces] enlarge. This increased permeability occure in capillaries and posteapillary { venules, allowing plasma proteins and phagocytes to enter the tissues. I | Click Next to go to the next page 1Inflammation: Phagocytes (Page 20 of 25) ‘White blood calls normally pass ] through capillaries and postcapillary venules without stepping. However, inflammation requires that white blood J cells exit the blood and enter the injured area ‘When tissues are injured, macrophages and other tissue cells release inflammatory mediators. In response to these messages, endothelial cells are activated, sprouting special surface { markers called cell cules. | Neutrophils and monocytes bind to these molecules and stick to the blood vessel wall, a process called margination, Click the endothelial cell to see ( margination.‘Inflammation: Phagocytes (Page 20 of 25) Asa result of binding to cell adhesion — molecules in the presence of | inflammatory mediators, neutrophils are activated and begin to make their way out of the bload vessel. The process of leaving the capillary is called iapedesis, | Click the neutr:Inflammation: Phagocytes (Page 20 of 25) Asa result of binding to cell adhesion — molecules in the presence of | inflammatory mediators, neutrophils are activated and begin to make their way out of the bload vessel. The process of leaving the capillary is called diapedesis. | Once in the tissue, neutrophils follow the J trail of inflammatory mediators up their concentration gradient like a dog sniffing atrail,a process called chemotaxis. This process is how they find their way to the site of injury. Click the neutrophil to see chemotaxis.Inflammation: Plasma Proteins (Page 21 of 25) As part of endothelial cell activation, the clefts between endothelial cells become larger and leaker. This increased Ieakiness allows plasma proteins and more fluid than usual to ieak into the injured area, causing edema (increased inlerstitial fluid). Edema causes swelling, which can contribute to the sensation of pain Click the capillary,Inflammation: Plasma Proteins (Page 21 of 25) Three important classes of proteins that enter injured tissue are * Anthodies * Complement © Clotting factors Tissue injury that triggers inflammation often introduces (or may be caused by) the invasion of pathogens. If your body has already been exposed to these pathogens, then you usually have antibodies against them. In that case, ‘your antibodies will bind to the pathogens andl act as opsonins Click an antibody to opsonize a bacterium,Inflammation: Plasma Proteins (Page 21 of 25) Three important classes of proteins that enter injured tissue are * Anthodies * Complement © Clotting factors Tissue injury that triggers inflammation often introduces (or may be caused by) the invasion of pathogens. If your body has already been exposed to these pathogens, then you usually have antibodies against them. In that case, ‘your antibodies will bind to the pathogens andl act as opsonins Click the capillary to leak complement into the interstitial fuid.Inflammation: Plasma Proteins (Page 21 of 25) Three important classes of proteins that enter injured tissue are * Anthodies * Complement © Clotting factors ‘When we discussed complement earlier, we focused on its actions as an opsonin and its ability to form MACs, Two other products of the complement cascade, CSa and C3a, are alsa important. inflammatory mediators. In addition to other actions, they increase vascular permeability and act as chemotaxins. Click a complement molecule to see complement act as opsonins and chemotaxinsInflammation: Plasma Proteins (Page 21 of 25) Three important classes of proteins that enter injured tissue are * Anthodies * Complement © Clotting factors Clotting factors also enter the interstitial fluid from the plasma and are activated in the tissues forming a meshi-like networls of fibrin protein that acts as a temporary scaffold for repair. It also helps keep pathogens from escaping from the injured area Click the capillary to form a clotInflammatory mediators come from many sources, They promote vasodilation, increase vascular permeability, and act as chemotaxins. Components of the complement system are inflammatory mediators, but other chemicals are inflammatory mediators as well One of the most. powerful is histamine, which is released by basophils and mast cells. While basophils are found in the blood, mast cells are found in connective tissue ‘where they can react immediately to injury, Click the mast cell to release histamine. Inflammation: Inflammatory Mediators (Page 22 of 25)Inflammation: Inflammatory Me i Prostaglandins and kinins are inflammatory mediators that are formed when cells are injured. In addition to enhancing vasodilation and vascular permeability, they activate pain receptors. Cytokines are principally involved in regulating leukocyte behavior and function, but they can also act as inflammatory mediators Click Next ta go to the next pageFever (Page 23 of 25) Unlike the localized warrnth of inflammation, fever is a generalized increase in body temperature Bacterial components and cytokines act as pyrogens. They cause the body's thermostat, located in the hypothalamus, to set its temperature higher Click the thermometer.Fever (Page 23 of 25) Fever is a useful part of our defense system. © Most pathogens do not grow as well at higher temperatures © During a fever the liver and spleen sequester iron and zinc, making these essential elements less available to bacteria © Higher temperatures enhance phagocytosis and a variety of enzymatic processes used by the immune system, Click Next ta go to the next pageSummary (Page 24 of 25) ; SUMMARY * The first line of defense consists of the skin and mucous membranes and their secretions © The second line of defense, the innate internal defenses, consists of phagocytes, antimicrobial proteins (complement and interferons), natural killer cells, inflammation, and fever. # Inflammation is a nonspecific local response ta injury that borings leukocytes and plasma proteins ta the injured area Innate defense mechanisms may be insufficient to prevent or clear infections © Innate and adaptive defenses interact in many ways, Innate defenses often trigger and define the nature of adaptive defense responses Click the quiz button to go to the self quiz.