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Chapter 51

Biology 1202B Chapter 51: Defences Against Disease

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Biology 1202B
Patrick Mc Donald

Chapter 51: Defences against Disease Chapter Introduction Bacteria, viruses, and parasites can all cause disease in their hosts • • Immune systems are able to regulate or eliminate the majority of pathogens that cause disease • Combat other pathogens by developing effective drug treatments that eliminate the disease- causing organism or by vaccines that provide protection from infection • Immune system: The combined defences, innate and acquired, a body uses to eliminate infections • Vaccination takes advantage of the immune system • Disease and parasites are not the same thing - Parasite (pathogen) is an organism that may infect us whereas a disease is a manifestation of symptoms we show (sneezing, diarrhea, swollen liver, fever) 51.1 Three Lines of Defence against Invasion • Humans and other animals have 3 lines of defence against threats • 1st line: Involves physical barriers that prevent entry of pathogens • 2nd line: Innate immune system - Inherited mechanisms that protect the body from pathogens in a nonspecific way • 3rd line: Adaptive immune system - Found only in vertebrates - Involves inherited mechanisms that lead to the synthesis of molecules such as antibodies that target pathogens in a specific way • Reaction to infection takes minutes with the innate immune system • The adaptive immune system takes several days to respond • Adaptive responses include a memory of previous infections and a much more rapid response to the same pathogen in subsequent infections 51.1a The Epithelium is a Barrier to Infection • First line of defence is the body surface • Forms a barrier of tight junctions between epithelial cells that keeps most parasites and pathogens from entering • Respiratory tract - Ciliated cells constantly sweet the mucus with its trapped bacteria ad other foreign matter into the throat - Where it is coughed out or swallowed o Cystic fibrosis patients - Mucus is too thick to cough up - Leads to bacterial infections in the lungs 51.1b Immune Systems Protect the Body • Second line of defence is a series of generalized internal chemical, physical, and cellular reactions that attack pathogens that have surpassed the first line • Defenses such as inflammation - Creates internal conditions that inhibit or kill many pathogens - Specialized cells engulf or kill pathogens or infected body cells • Initial nonspecific (Are specific in the sense that it can recognize "self" from non-self" molecules) responses are components of the innate immune system • Recognition of parasite/pathogen as non-self is the first essential step in initiating any immune response • Innate Immunity: Nonspecific line of defence against pathogens that includes inflammation, which creates internal conditions that inhibit or kill many pathogens, and specialized cells that engulf or kill pathogens or infected body cells - Provides immediate, nonspecific response - Targets any invading pathogen and has no memory of prior exposure to that specific pathogen • Invertebrates, fungi, and plants rely solely on innate immune responses • Vertebrates use innate immune system in conjunction with the adaptive response for a more powerful overall response Adaptive (or acquired) immunity: Specific line of defence against invasion of the body in which • individual pathogens are recognized and attacked to neutralize and eliminate them - Triggered by specific molecules on pathogens that are recognized as being foreign to the body • Body retains memory of the first exposure to the foreign molecule - Enables it to respond more quickly if the same pathogen is encountered again in the future - Basis of vaccination technologies • Innate immunity and adaptive immunity together constitute the immune system • The defensive reactions of the system are termed the immune response 51.1c Organisms Can Recognize Pathogens • Immunity - Organisms can recognize a pathogen as being different from the host • Termed - recognition of non-self and is the essential first step before any immune response can be initiated • Recognition of non-self: o Unique pathogen-associated molecular patterns (PAMPs) recognized by host molecule called pattern recognition receptors (PRRs) o Major invertebrate PRRs - Gram-negative bacteria binding protein and beta 1,3-glucan recognition proteins that recognize and bind to common molecules found on many groups of pathogenic organisms rather than recognizing each pathogen species individually o Once PRRs are activated by presence of PAMP - Signalling cascades are initiated that activate various components of the innate or acquired immune responses • Plants have 2 branches of immune responses: o System that uses transmembrane PRRs that respond to the PAMPs o Intracellular response that uses protein products encoded by R genes - Respond to infection and systemic signals from nearby infected cells o Signalled by damage to the plant cells by pathogens - Activates expression of plant R proteins o Different PAMPs may activate the same or different signalling pathways and cause different responses o Recognizing the parasite/pathogen activates a complex chain of events that ultimately produces an effective immune response and often a complete elimination of the microorganism 51.2 Nonspecific Defences: Innate Immunity • Invertebrates only have an innate response (present at birth) - Activated by the PAMP-PRR interactions • Active processes such as phagocytosis: Cells engulf bacteria or other cellular debris • Melanotic encapsulation: Hemocytes (blood cells) move toward and form a capsule around pathogens that are too big to phagocytose - Capsule may be melanized by the deposition of phenolic compounds that further isolate the pathogen • Antimicrobial peptides: Small antibiotic peptides that are used by hosts collectively to eliminate bacterial and fungal pathogens • Vertebrates use similar types of specific host cell surface receptors that recognize the various PAMPs found on microbial pathogens • The innate responses that recognize and initiate immune pathways I plants, invertebrates, and vertebrates are similar Antimicrobial Peptides • Epithelial surfaces: Skin, lining of gastrointestinal tract, lining of nasal passages, gills, lungs, lining of genitourinary tracts - Protected by antimicrobial peptides - Ex. The defensins - Attack plasma membranes of the pathogens - Disrupting them and thereby killing the cells • Defensins are ubiquitous cationic molecules used in the defences of essentially all organisms • Defensins are of ancient origin and have been maintained throughout evolution due to its importance in limiting the growth of microbial pathogens Diagram: Model of a defensin molecule showing the arrangement of the coined alpha-helix (red) and beta-sheets (blue) that are held together by disulfide bridges (yellow) Inflammation • Tissue's rapid response to injury • Inflammation: The heat, pain, redness, and swelling that occur at the site of an infection • Interconnecting mechanisms initiate inflammation • Monocytes (white blood cell) - Enter the damaged tissue from the bloodstream through the endothelial wall of the capillary • Inside damaged tissue - Monocytes go into macrophages - First to recognize pathogens at the cellular level • Cell surface receptors of the macrophages recognize and bind to surface molecules on the pathogen - Activate macrophage to engulf (phagocytize) the pathogen • Activated macrophages secrete cytokines - Small proteins released by cells that affect the behaviour of other cells and may signal, activate, and recruit more immune cells Diagram: Steps producing inflammation The Complement System • Complement system: Nonspecific defence mechanism activated by invading pathogens - Group of more than 30 interacting soluble plasma proteins that circulate in the blood and interstitial fluid (surrounds tissue cells) o Normally inactive - Activated when they recognize molecules on the surface of pathogens o Activated complement proteins - Cascade of reactions o Membrane attack complexes: Cascade reaction that brings blood proteins together, binds them to the cell wall, and then inserts them through the cell membrane 51.2a Three Main Strategies are Used to Combat Pathogenic Viruses • Specific molecules on pathogens such as bacteria are key to initiating innate immune responses • Innate immune system cannot distinguish between surface molecules of viral pathogens and host cells, or cannot enter host cells • Host must use other strategies to provide immediate protection against infections until the adaptive immune system (can discriminate between pathogen and host proteins) is effective Three main strategies: RNA interference, interferon, and natural killer (NK) cells • • Natural killer (NK) cells: A type of lymphocyte that destroys pathogen-infected cells • These strategies involve targeting the infected cell as well as the virus - It is difficult for the immune system to target the virus specifically RNA Interference • RNA interference (RNAi) is a cellular mechanism that is triggered by double-stranded (ds) RNA molecules - Same mechanism that miRNA uses to regulate gene expression • dsRNA interferes with ability of cell to transcribe specific genes • Use of RNAi can inhibit the dsRNA found in many viruses and eliminate the infection Interferon • Viral double-stranded RNA may also cause the infected host cell to produce two cytokines: Interferon-alpha and interferon - Cell signalling molecules • Interferons: A cytokine produced by infected host cells affected by viral dsRNA, which acts on both the infected cell that produces it, an autocrine effect, and neighbouring uninfected cells, a paracrine effect • Produced by most cells of the body • Bind to cell surface receptors - Triggering a signal transduction pathway that changes the gene expression pattern of the cells - Ex. Activation of a ribonuclease enzyme that degrades most cellular RNA/Inactivation of a key protein required for protein synthesis - Inhibiting most protein synthesis in the cell • Effects on RNA and protein synthesis inhibit pathogen replication - Putting cell in a weakened state from which it can often recover Apoptosis • Programmed cell death - Process inherent to all eukaryotic cells • Highly conserved through evolution • Tightly regulated by internal and external cellular signals to avoid killing healthy, productive cells • Used to sculpt tissues, remove old and dying cells, and eliminate embryonic cells with damaged DNA • Used as an immune response against pathogens and parasites - triggers abnormal cellular activity - indices apoptotic pathways that dismantle the cell's structure - Actives the effector caspases - cell is destined to die • Some pathogens have developed mechanisms to inactivate this response Natural Killer Cells • Cells that have been infected with a virus must be destroyed • NK cells - Type of lymphocyte (white blood cell) • Circulate in the blood and kill target host cells - Cells infected with virus and cells that have become cancerous • Activated by cell surface receptors or by interferons secreted by virus-infected cells • Not phagocytes - Secrete granules (small particles) containing perforin - Protein that creates pores in the target cell's membrane • Diffusion of ions and molecules through the pores causes osmotic imbalance, swelling, and rupture of the infected cell • Also target cells indirectly through the secretion of proteases (protein-degrading enzymes) that pass through the pores • Proteases trigger apoptosis - Activate other enzymes that cause the degradation of DNA - Induces pathways leading to cell's death • NK cell distinguishing a target cell from a normal cell - Surfaces of vertebrate cells contain particular major histocompatibility complex (MHC) proteins NK cells monitor level of MHC proteins and respond differently depending on their level • 51.3 Specific Defences: Adaptive Immunity • Adaptive immunity - Defence mechanism that recognizes specific molecules as being foreign and clears these molecules from the body • Free abnormal molecules - toxins • Found on surface of a virus or cell - Pathogenic bacteria, cancer cells, virus, pathogen infected cells, pollen, cells of transplanted organs • Adaptive immunity develops in response to the presence of foreign molecules and therefore takes several days to become effective - Time delay - Why innate i
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