Innate Immunity:Nonspecific Defenses of the Host(Chapter 16)Lecture MaterialsforAmy Warenda Czura, Ph.D.Suffolk County Community CollegeEastern CampusPrimary Source for figures and content:Tortora, G.J. Microbiology An Introduction 8th, 9th, 10th ed. San Francisco: PearsonBenjamin Cummings, 2004, 2007, 2010.Amy Warenda Czura, Ph.D.1SCCC BIO244 Chapter 16 Lecture SlidesSusceptibility = lack of resistanceResistance = ability of host to ward offdisease1. Nonspecific resistance / Innate Immunity-defenses that protect against any pathogen, immediate, no memory2. Specific resistance / Adaptive Immunity-defense against a particular pathogen,requires time to develop, involves specialized cells, has memoryBody defense(on handout)Amy Warenda Czura, Ph.D.2SCCC BIO244 Chapter 16 Lecture SlidesNonspecific Defenses / Innate ImmunityFirst line of defense: keep microbes out1). Skin & Mucous MembranesA. Physical factors: barriers or removal1. Skin(cutaneous membrane = dermis+epidermis)epidermis:-top layer = dead cells,keratin filled, cells tightly linked-dry, unfavorable, constantly shed-impermeable unlessdamaged or moistGoblet cellAmy Warenda Czura, Ph.D.3SCCC BIO244 Chapter 16 Lecture Slides2. Mucous membranes-thick, moist epithelium-less protective than keratinized-has goblet cells for mucus production3. Ciliary escalator-ciliated epithelium of respiratory tract-cilia beat in wave motion: clear microbes in mucus out of respiratory tract4. Lacrimal apparatus(lacrimal gland &lacrimal canals)-constant tears over eye-washes microbes offAmy Warenda Czura, Ph.D.4SCCC BIO244 Chapter 16 Lecture Slides5. Salivary glands-washing of teeth and mouth to reduce colonization6. Vomiting & diarrhea-rapid contractions of gastrointestinal tractto rapidly flush out microbes and toxinsB. Chemical factors1. mucus-glycoproteins + water-thick, inhibits colonization2. sebum-oily, from sebaceous glands-fatty acids & lactic acidsmake skin pH 3-5-acid pH inhibits microbe growth3. perspiration-water + salts-water flushes microbes off skin-salt accumulates inhibiting microbegrowthAmy Warenda Czura, Ph.D.5SCCC BIO244 Chapter 16 Lecture Slides4. lysozyme-enzyme in most body secretions-breaks down peptidoglycan cell walls5. gastric juice-HCl + enzymes + mucus-pH 1-3 destroys most bacteria andtoxins2). Normal Microbiota-microbial antagonism:-compete for nutrients or space-alter environment (pH, oxygen)-produce toxins (e.g. bacteriocins)Second line of defense: if microbes enter,attack and defend3). Leukocytes = White Blood Cells -usually low #s in blood, ↑ during infectionleukocytosis = increase in WBC % in blood(leukopenia = ↓in WBCs due to damage by some pathogens)Amy Warenda Czura, Ph.D.6SCCC BIO244 Chapter 16 Lecture SlidesWhen activated, most leukocytes will producecytokines: intercellular signaling molecules/hormones that will function to trigger, enhance, and coordinate various defense mechanismsTypes of leukocytes:A. Granulocytes (visible granules)1. Neutrophils-aka PMNs(polymorphonuclear leukocytes)-3 to 5 lobed nuclei-highly mobile and phagocytic-first to arrive at injury or infection-dominate during initial stages of infection or injury-often dominate during bacterial infection2. Basophils (blood)= Mast cells (tissue)-not phagocytic-release histamine: triggers inflammation and allergyAmy Warenda Czura, Ph.D.7SCCC BIO244 Chapter 16 Lecture Slides3. Eosinophils-motile-slightly phagocytic-produce toxins to fight multicellularparasiteinfectionsB. Agranulocytes (granules not visible)1. Monocytes (blood) =Macrophage (activated, in tissues)-highly phagocyticA. Fixed macrophages / histiocytes-remain in certain tissue/organs toscreen for pathogens & remove damaged cells (e.g. Kupffer cell (liver), microglia (CNS),Alveolar macrophages (lung)Amy Warenda Czura, Ph.D.8SCCC BIO244 Chapter 16 Lecture SlidesB. Wandering/Free Macrophage-move from blood to injury or infection-arrive after neutrophils-phagocytose dead cell debris-dominate in later stages of infection or injury repair-dominate during fungal or viralinfectionC. Dendritic cells-located in epidermis, mucous membranes & lymphoid tissues-initiate adaptive immune responses2. Lymphocytes = T, B, & NK cellsT cells: cell mediated immunityB cells: antibody mediated immunityNK cells: non-specific, target infected or cancerous cellsrelease perforin & granzymeshttp://pathmicro.med.sc.edu/lecture/dendritic-cell.gifAmy Warenda Czura, Ph.D.9SCCC BIO244 Chapter 16 Lecture Slides-specialized cells-not phagocytic-in lymphoid tissues and blood-B & T cells involved in specific resistance-B & T cells respond to specific antigensphagocytes = leukocytes specialized to endocytose microbes & cell debrisneutrophils, macrophages, eosinophilsMechanism of phagocytosis (on handout)http://pathmicro.med.sc.edu/lecture/dendritic-cell.gifAmy Warenda Czura, Ph.D.10SCCC BIO244 Chapter 16 Lecture Slides1. Chemotaxis and AdherenceChemotaxis = chemical attraction of phagocyte to microbe; attracted by microbial products, damagedcells, cytokines, and/or complementAdherence = attachment of plasma membrane of phagocyte to microbe; Toll-like receptors (TLRs) onphagocyte membrane bind to pathogen-associated molecular patterns (PAMPs) on microbeAdherence made easier by opsonizationOpsonization = coating of the microbe with antibodies or complement proteins2. Ingestion: phagocyte extends pseudopods around microbe3. Phagosome formation: fusion of pseudopods around the microbe encloses it in a phagocytic vesicle called a phagosome which now floats in the cytoplasm4. Phagolysosome formation: the phagosome fuses with a lysosome creating a phagolysosome putting themicrobe in contact with digestive enzymes and bacteriocidal substances5. Digestion: most microbes are killed and hydrolyzed in 10-30 minOxidative burst kills the microbe: toxic oxygen radicals (superoxide, hydrogen peroxide)Enzymes and acids hydrolyze the microbe into component organic molecules6. Formation of the residual body: useful small organic molecules are absorbed into the cytoplasm and theacids and enzymes are neutralized. Residual body = all remaining undigested material in a vesicle7. Exocytosis: residual body contents are discharged outside the cellPhagocytosisAmy Warenda Czura, Ph.D.11SCCC BIO244 Chapter 16 Lecture SlidesMicrobial Evasion of Phagocytosis:1. Inhibit adherence or engulfment-M protien: Streptococcus pyogenes-Capsules: Streptococcus pneumoniae-Biofilms: prevent detachment2. Survive phagocytosis-Leukocidins: Staphylococcus