Lec 5a - Innate Immunity - Nurs1230 PDF

Topic 5a: Immunity (Innate defenses) Objectives for this Section The Innate Immune System, Chapter 21 1. Explain the difference between innate and adaptive defense systems. P 782 2. Describe the surface barriers for the innate. P 782-783 3. In terms of internal defense mechanisms explain the follow...

Topic 5a: Immunity (Innate defenses) Objectives for this Section The Innate Immune System, Chapter 21 1. Explain the difference between innate and adaptive defense systems. P 782 2. Describe the surface barriers for the innate. P 782-783 3. In terms of internal defense mechanisms explain the following: ◦ Phagocytes and phagocytosis P 784-785 ◦ Natural killer (NK) Cells P 785 ◦ Inflammation process P 785-787 Fig 21.4 ◦ Complement proteins P 788-789 ◦ Fever P 789 Immune system Introduction Immune system provides resistance to disease ◦ Considered a “functional system” instead of anatomical Made up of two intrinsic systems 1. Innate (nonspecific) defense system ◦ Constitutes first and second lines of defense ◦ First line of defense: external body membranes ◦ Second line of defense: antimicrobial proteins, phagocytes, and other cells 2. Adaptive (specific) defense system ◦ Third line of defense attacks specific foreign substances, ie) previously seen foreign substances Immune system Introduction The Innate and Adaptive immune systems work together Figure 21.1 Innate Defenses: Surface Barriers “First line of defense” Includes skin and mucous membranes https://fineartamerica.com/featured/medieval-fortress-of-rhodes-fernando-barozza.html Skin (epidermis) is keratinized membrane ◦ Resistant to weak acids/ bases, bacterial enzymes, toxins Surface Barriers: Protective Chemicals Acidity: the acid mantle inhibits growth Enzymes: lysozymes kill microorganisms Mucin: lines digestive, respiratory tract, traps microorganisms Defensins: secreted antimicrobial peptides http://www.wakehealth.edu/Nephrology/Medullary-Kidney-Disease/Genetics- Mucin-1-Kidney-Disease.htm Dermicidin: in sweat, toxic to bacteria Innate Defenses: Surface Barriers Summary Table Table 21.1 Cells and Chemicals: Second Line of Defense If protective surface barriers (first line) are breached, internal defenses are stimulated: Nonspecific cellular and chemical means for protection ◦ Phagocytes ◦ Natural killer (NK) cells ◦ Inflammatory response ◦ Macrophages, mast cells, WBCs, and inflammatory chemicals ◦ Antimicrobial proteins ◦ Interferons and complement proteins ◦ Fever  Phagocytes Phagocytes: white blood cells that ingest and digest (eat) foreign invaders Neutrophils: ◦ Most abundant WBC ◦ Become phagocytic on exposure to infectious material Macrophages: ◦ Develop from monocytes ◦ Free macrophages: wander through tissue spaces; example: alveolar macrophages ◦ Fixed macrophages: permanent residents of Figure 21.1 some organs; examples: stellate macrophages (liver) and microglia (brain) Phagocytes Destruction of pathogens via phagolysosomes ◦ Phagosome (particle within membrane bound vesicle) fuses with lysosome ◦ Acidic conditions destroys pathogen Some pathogens resistant to lysosomal enzymes ◦ Require Helper T cells (part of adaptive immune response) ◦ Respiratory burst (to kill pathogens) ◦ Produces free radicals ◦ Produces oxidizing chemicals Some pathogens destroys by defensins punching holes in pathogen’s membranes Phagocytosis Phagocyte can recognize and adhere to pathogen’s carbohydrate “signature” Some microorganisms have external capsules that hide their surface carbohydrates Opsonization: immune system uses antibodies or complement proteins as opsonins that coat pathogens Opson: ancient Greek for delicious side dish http://www.nature.com/ni/journal/v12/n12/full/ni.2161.html?message-global%3Dremove Phagocytosis Video: https://youtu.be/ohF QEl4z0Yc Figure 21.1  Natural Killer (NK) Cells Nonphagocytic, large granular lymphocytes Function before adaptive immune system is activated Attack cells that lack “self” cell- surface receptors (MHC class 1) Kill by inducing apoptosis in cancer cells and virus-infected cells Secrete potent chemicals that Results in cell destruction enhance inflammatory response https://www.slideshare.net/sanaabdurhim/natural-killer-cells Inflammation: Tissue Response to Injury Inflammation a response when tissue is injured Stages of inflammation 1. Inflammatory chemical release 2. Vasodilation and increased vascular permeability 3. Phagocyte mobilization Four major signs, one additional sign 1. Redness 2. Heat 3. Swelling 4. Pain https://live.staticflickr.com/4357/35692393863_be478e0830_b.jpg 5. (Impaired Function) Figure 21.4 Inflammation Stages: Inflammatory Chemical Release Chemicals are released by injured tissues, immune cells, or blood proteins ◦ Eg. histamine (potent inflammatory chemical) released by mast cells https://bembu.com/histamine-intolerance/ Toll-like receptors (TLRs) on macrophages and some epithelial tissues, bind to pathogens, triggering response ◦ Cytokines released, promoting inflammation https://www.slideshare.net/DrTusharPatil/toll-like-receptors Inflammation Stages: Inflammatory Chemical Release Other chemicals (Kinins, prostaglandins (PGs), and complement) ◦ Cause vasodilation of local arterioles ◦ All make capillaries leaky ◦ Many attract leukocytes to area ◦ Some have other inflammatory roles, such as triggering pain receptors, or prompting release of more inflammatory chemicals (Review table 21.2 for more information) Inflammation Stages: Vasodilation and increased vascular permeability Vasodilation causes hyperemia (increased blood flow) ◦ Leads to redness and heat ◦ Bring more immune cells and chemicals to injury area Immune chemicals increase capillary permeability Causes fluid containing clotting factors and antibodies to leak into tissue (exudate) ◦ Results in edema (fluid in tissue space) ◦ Pushes on nerve endings, resulting in pain ◦ Pain also from release of toxins from bacteria or released prostaglandins and kinins Figure 21.4 Inflammation Stages: Vasodilation and increased vascular permeability Benefits of edema: ◦ Surge of fluid in tissue sweeps foreign material into lymphatic vessels for processing in lymph nodes (adaptive immune response) ◦ Delivers clotting proteins and complement to tissue ◦ Clotting factors form fibrin mesh that acts as scaffold for repair ◦ Mesh also isolates injured area so invaders cannot spread http://www.medicinehack.com/2012/10/edema-definition-pathophysiology-causes.html Inflammation Stages: Phagocyte Mobilization Neutrophils flood area first; macrophages follow If inflammation is due to pathogens, complement is activated; adaptive immunity elements arrive 4 Steps: 1. Leukocytosis: ◦ Increase in number of WBCs ◦ Response to leukocytosis- inducing factors from injured cells Figure 21.3 Inflammation Stages: Phagocyte Mobilization 2. Margination: ◦ Endothelial cells of capillaries project cell adhesion molecules (CAMs) into vessel lumen ◦ Grab onto circulating neutrophils, identifies location of inflammation Figure 21.3  Inflammation Stages: Phagocyte Mobilization 3. Diapedesis: ◦ White blood cells move into interstitial spaces, through vessel wall Figure 21.3 Inflammation Stages: Phagocyte Mobilization 4. Chemotaxis: ◦ Chemotactic agents attract neutrophils to injured area ◦ Migrate up gradient of chemotactic agents Neutrophils arrive within an hour, begin attacking foreign material Monocytes arrive later ◦ Transformed to macrophages in 12 hours ◦ Replace dying neutrophils, cleanup prior to repair Figure 21.3 Antimicrobial Proteins Most important antimicrobial proteins ◦ Interferons ◦ Infected cells secrete proteins (interferons) that can protect uninfected cells ◦ ‘interfere’ with viral replication ◦ Complement proteins Functions: ◦ Attacking microorganisms directly, or ◦ Hindering microorganisms’ ability to reproduce Complement System ~20 proteins that circulate in blood in inactive form *do not need to remember specific names* Provides major mechanism for destroying foreign substances ◦ Activation enhances inflammation and also directly destroys bacteria ◦ “Complements / Enhances” both innate and adaptive defenses Activated by 3 pathways http://www.harunyahya.com/image/cell_40/hucre_2_en.jpg Complement System Antibodies 1. Classical pathway ◦ Antibodies first bind to invading organisms ◦ Antibodies then bind to complement components, activating them (double binding) ◦ Once initial complement proteins are activated, an activation cascade https://www.researchgate.net/figure/274781619_fig1_Fig-1-The-classical-lectin-and-alternative-pathways-of-complement-activation-The is triggered Complement System 2. Lectin pathway ◦ Lectins are proteins produced by innate system to recognize foreign invaders ◦ When lectin is bound to specific sugars on foreign invaders, it can also bind and activate complement https://www.researchgate.net/figure/274781619_fig1_Fig-1-The-classical-lectin-and-alternative-pathways-of-complement-activation-The Complement System 3. Alternative pathway ◦ Complement cascade is activated spontaneously when certain complement factors bind directly to foreign invader ◦ Lack of inhibitors on microorganism’s surface allows https://www.researchgate.net/figure/274781619_fig1_Fig-1-The-classical-lectin-and-alternative-pathways-of-complement-activation-The process to proceed  Complement System Each pathway involves activation of proteins in an orderly sequence Each pathway can trigger complement cascade Cell lysis begins when: ◦ Insertion of complement proteins called membrane attack complex (MAC) into membrane ◦ Massive influx of water and lysis of microbial cell Figure 21.6 Complement System Complement system also causes opsonization of pathogen (enhance phagocytosis) Complement protein cleavage products also amplify inflammation by stimulating release of histamine and attracting neutrophils Summary Figure 21.6 Fever Leukocytes and macrophages exposed to foreign substances secrete pyrogens ◦ Body’s thermostat in hypothalamus, raising body temperature ◦ Vasoconstriction, thermogenesis, shivering Benefits of moderate fever ◦ Causes liver and spleen to sequester iron and zinc (needed by microorganisms) ◦ Increases metabolic rate, which increases rate of repair http://www.express.co.uk/life-style/health/708672/feeding-fever-cold-anorexia-professor-Ruslan- Medzhitov-yale-bacteria-virus-myths Why may a very high, prolonged fever be of concern? Second Line Defenses Summary Table Review Questions Explain the 3 different ways complement can help fight pathogens Explain why the symptoms of swelling and redness are common (and important) in the inflammation pathway for fighting pathogens. What are some of the surface chemicals and their roles in innate immunity? How does a macrophage recognize its targets and how does it eliminate these targets?