Chapter 16 Lecture Outline-1 PDF

Chapter 16 Innate Immunity: Non-Specific Defenses of The Host 1 The Concept of Immunity W AR IN THE BODY:HUMANS VS PATHOGENS ----IF PAGHOGEN W INS IT W ILL LEAD TO A DISEASE. Immune system - protects the human host GET RID OFF Immunity - ability to fight-off pathogens & prevent disease HOST NO DISEA...

Chapter 16 Innate Immunity: Non-Specific Defenses of The Host 1 The Concept of Immunity W AR IN THE BODY:HUMANS VS PATHOGENS ----IF PAGHOGEN W INS IT W ILL LEAD TO A DISEASE. Immune system - protects the human host GET RID OFF Immunity - ability to fight-off pathogens & prevent disease HOST NO DISEASE HOST HAVE DISEASE Resistance (host having immunity) vs Susceptibility (host lacking immunity) TO PATHOGENS TO PATHOGENS LACK RESISTANCE Host defenses - ability of host to remove pathogen(s) in order to prevent disease If host defenses are successful  the host has immunity! HAVE RESISTANCE If host defenses are NOT successful  the host becomes diseased! SUSCEPTABLE HAVING HOST DEFENSES IS THE SAME AS HAVING IMMUNITY. SAME AS HAVING RESISTANCE. 2 2 TYPES 2 TYPES OF IMMUNITY Host Defenses: Innate Immunity vs Adaptive Immunity HOST DEFENSES Innate Immunity: Immunity or resistance to any pathogen ALL AND ANY PATHOGENS AKA “Non-specific” immunity DOES NOT DISCRIMINATE AGAINST PATHOGENS IT' S NOT PICKY,GETS RID OF EVERYTHING HOST DEFENSES Adaptive Immunity: Immunity or resistance to a RIDS CERTAIN PATHOGENS, specific pathogen ONLY SPECIFIC. EX:MAYBE ONLY GRAM POSITIVE,BUT NOT GRAM NEGATIVE. VIRUS, BUT NOT FUNGUS. AKA “Specific” immunity DISCRIMINATES AGAINST PATHOGENS. IT IS PICKY. 3 Innate Immunity MEANS NEW BORN IMMUNITY ARE BORN W ITH HOST DEFENSE;GETS RID OF Host defenses that are present at birth YOU EVERYTHING,NOT PICKY. AKA “Non-specific” Defenses of the Host FOR SURVIVAL OF A NEW BORN No specific recognition of microbes involved No immunological memory response BC AS A NEW BORN YOU HAVENT ENCOUNTERED PATHOGENS YET Rapid immune response Composed of 1st & 2nd Lines of Host Defenses 3 TOTAL LINES OF HOST DEFENSES FRIST 2 BELONG TO INNATE IMMUNITY 4 Adaptive Immunity YOU ARE NOT BORN W ITH IT,IT DEVELOPS LATER IN LIFE,AND IT W ILL HANDLE ONLY SPECIFIC MICROBES. Host defenses that develop later to handle a specific microbe AKA “Specific” Defenses of the Host Specific recognition & response to a specific microbe Has immunological memory HAS ENCOUNTERED SAME PATHOGEN PREVIOUSLY Slower immune response (slower than innate immunity) NOT SLOW ,JUST SLOW ER THAN INNATE Composed of 3rd Line of Host Defenses 5 An Overview of Host (Body’s) Defenses HOST HAS 3 LINES OF "HOST DEFENSE" FIRST 2 BELONG TO INNATE,3RD BELONGS TO ADAPTIVE BORN W ITH Innate Immunity (Non-specific Host Defenses) 1st Line of Defense 2nd Line of Defense DEVELOP LATER IN LIFE Adaptive Immunity (Specific Host Defenses) 3rd Line of Defense 1. Physical Barriers (5) 1. Formed Elements 1. Humoral Immunity 2. Chemical Barriers (4) 2. Phagocytosis 2. Cell-Mediated Immunity 3. Biological Barriers (1) 3. Inflammation 4. Fever 5. Antimicrobial Substances (2) IF THE PATHOGEN GETS THROUGH ALL 3 DEFENSES,HOST GETS A DISEASE. 6 An Overview of Host (Body’s) Defenses 1ST LINE BELONGS TO 2ND LINE OF DEFENSE 2ND LINE 3RD LINE HOST 7 1st Line of Host Defense: Physical Barriers 1. Intact skin NON-BROKEN SKIN (NO CUTS,NO INJURIES) 2. Mucous membranes 3. Ciliary escalator LINE BODY CAVITIES W ITH MUCOUS INVOLVE RESPIRATORY TRACT 4. Lacrimal apparatus INVOLVES EYES 5. Saliva, urine & vaginal secretions 8 NON BROKEN SKIN,NO INJURIES Intact Skin FLAT CELLS Closely packed epithelial cells SQAMOUS CELLS Continuous layering MULTIPLE LAYERS OF THE CELLS Keratin protein in top layer PROTECTING UNDERLYING LAYERS. REINFORCES THE SKIN. Dryness BACTERIA PREFERS MOISTURE,SO DRY SKIN IS GOOD. Shedding of top layer Figure 16.1 BLOOD VESSEL W HEN TOP LAYER SHEDS IT TAKES PATHOGENS W ITH IT. 9 Mucous Membranes & Ciliary Escalator Mucous Membranes Epithelial layer that lines gastrointestinal, respiratory & genitourinary tracts THICK MUCUS TRAP PATHOGENS Secrete viscous fluid called mucus GETS RID OF THEM Ciliary Escalator MOVES IN ONE DIRECTION TOW ARDS Epithelial cells of lower respiratory tract have cilia CILIA THE THROAT,HAS MUCUS ON TOP OF IT. Cilia move together and sweep the mucus up & out of body YOU CAN SW ALLOW OR SPIT IT OUT 10 Lacrimal Apparatus & Saliva, Urine, Vaginal Secretions Lacrimal apparatus PROTECTS THE EYE BY FLASHING AW AY PATHOGENS IN THE EYE. Protects the eyes Tears - continuous washing action Saliva, Urine & Vaginal Secretions Flushing mechanism Washes away pathogens FROM THE MOUTH,URITHRA,GENETAL URINATION TRACT 11 1st Line of Host Defense: Chemical Barriers PRODUCED IN THE BODY TO PROTECT THE HOST 1. Chemical factors of the skin 2. Lysozymes ENZYMES 3. Gastric juices 4. Blood transferrins CIRCULATING PROTEINS FOUND IN BLOOD 12 Chemical Factors of Skin & Lysozyme Chemical factors in and on the skin pH of skin - slightly acidic BACTERIA PREFERS NEUTRAL ENVIRONMENT Salinity MOST BACTERIA IS NOT HALOPHILES Sebum W AXY LIPID TENDS TO LOW ER pH OF SKIN, BACTERIA DOESNT LIKE ACIDITY Lysozymes Enzymes found in body secretions (sweat, tears, saliva) Break chemical bonds in peptidoglycan  destroys bacterial cell wall 13 Gastric Juices & Blood Transferrins Gastric juices Produced by stomach Contains enzymes & acid HCL W ILL DESTROY MOST BACTERIA,AXCEPT FOR H. PYLORY (ACIDOPHILES) BLOOD PROTEINS ANY AVAILABLE IRON THEREFORE NO IRON Blood transferrins REMOVES AVAILABLE FOR BACTERIA. BACT NEEDS IRON (MICRONUETRIENT) Proteins that bind to iron Iron is necessary for bacterial growth 14 1st Line of Host Defense: Biological Barriers Normal Microbiota MICROBES THAT DONT HARM HOST AND CAN BE USEFUL TO THE HOST. Commensal microbes vs beneficial microbes Competitive exclusion 15 Normal Microbiota BENEFICIAL TO THE HOST,LIKE MAKING VITAMINS ETC DOESNT HARM HOST,BUT DOESNT DO ANYTHING FOR HOST Commensal microbes Beneficial microbes One organism benefits while other organism (host) is unaffected Ex - microbes on skin and in gastrointestinal tract Microbes provide something to the host Ex - vitamin K-producing bacteria in gastrointestinal tract VS. E. COLI NOT NORMAL MICROBIOTA Opportunistic microbes IF REMOVED FROM THEIR NORMAL HABITAT HAVE THE POTENTIAL TO HARM THE HOST. EX:E. COLI IN THE URETHRA = UTI)  Microbes that act as pathogens under certain circumstances 16 Normal Microbiota !!ITK!!! Competitive Exclusion NORMAL MICROBIOTA OUTCOMPETES INVADING PATHOGENS AKA “microbial competition” Normal microbiota compete with pathogens (invading microbes), leading to decreased populations of pathogenic bacteria How do normal microbiota defeat invading pathogenic bacteria?  Take-up all the nutrients NO NUTRIENTS FOR PATHOGENS  Take-up all the space for growth LEAVE NO ROOM FOR PATHOGENS HARMFUL FOR PATHOGENS,NOT  Produce substances harmful to invading pathogens ONLY THE HOST 17 INNATE IMMUNITY,NON-SPECIFIC 2nd Line of Host Defense 1. Formed Elements in the blood 2. Phagocytosis 3. Inflammation 4. Fever 5. Antimicrobial Substances 18 Formed Elements in Blood CLEAR PART OF BLOOD Cells and cell fragments suspended in plasma CELLS FRAGMENT 1. Erythrocytes RBC CONTAIN HEMOGLOBIN (BIND O2,CO2) 2. Leukocytes W BC IMMUNE REPONSE BLOOD CLOTTING PLATELETS UPON INJURY 3. Thrombocytes not cel l ,i t' sa fragment STEM CELL,CAN BECOME ANY CELL HEMATOPOIESIS Created in red bone marrow stem cells via hematopoiesis Hematopoiesis 19 Formed Elements in Blood: Leukocytes Leukocytes have granul es,butnotvi si bl e vi si bl e granul esundermi croscope abri vi tate BEN Granulocytes Basophils Eosinophils Agranulocytes Fami l y Lymphocytes Neutrophils B cel l T cel l B Lymphocytes* T Lymphocytes* adapti ve i mmuni ty * These cells are part of “Adaptive Immunity” adapti ve i mmuni ty Fami l y Monocytes/ Macrophages NK Cells 20 Formed Elements in Blood: Leukocytes Granulocytes: leukocytes with granules in their cytoplasm that are visible with a light microscope granul es 1. Basophils: release histamine; involved al l ergysymptoms in allergic responses 2. Eosinophils: toxic against parasites and worms engul f phagocyte 3. Neutrophils: phagocytic; work in early a fi rstresponder; stages of infection ak fi rstphagocyte to arri ve atthe si te ofi nfecti on; i ndi catesrecent/new i nfecti on. Table 16.1 21 Formed Elements in Blood: Leukocytes Agranulocytes: leukocytes with granules in their cytoplasm that are not visible with a light microscope 1. Monocytes: travel in blood & will mature into macrophages in tissues where they become phagocytic cells willengulfpathogensin TISSUE 2. Lymphocytes: T cells* partof3rd l i ne Adapti ve B cells* NK cells * T cells & B cells play a role only in adaptive immunity Table 16.1 22 23 l eukocytes Differential White Blood Cell Count Abundance of each type of white blood cell in a sample of 100 white blood cells (in a normal state) Serum G N N G G Al l ergy Neverl etmonkeyseatbananas 24 Phagocytosis engul fmentofsol i d Phagocytosis: ingestion of microbes or other substance by a phagocyte INNATE Immuni ty Phagocyte: non-specific host cell capable of phagocytosis engulfanypathogen Ex - Neutrophils, Macrophages, Dendritic Cells BELONG TO HOST,al l3 neutrophi l 1stresponder Macrophage i n ti ssue Mature monocyte i n bl ood Dendri ti ccel lfound i n ski n cel l 25 IN ORDER The Mechanism/Phases of Phagocytosis 1. Chemotaxis Release of chemical signals (cytokines) by pathogen  attract phagocytes 2. Adherence Attachment of phagocyte to surface of the pathogen 3. Ingestion vesi cl e wi th pathogen i nsi de Endocytosis of pathogen  form a phagosome  merges with lysosome  form a phagolysosome inside phagocyte di gesti ve enzymes 4. Digestion Pathogen is digested inside a phagolysosome byl ysosome 26 The Phases of Phagocytos is Figure 16.8 27 Microbial Evasion of Phagocytosis How do pathogens (microbes) evade phagocytosis?  Capsule - pathogen too big to be engulfed  Ex - Streptococcus pneumoniae make a hol ei n the cel lmembrane ofphagocyte  Leukocidins - a pore-forming toxin capable of killing phagocytes  Ex - Genus Staphylococcus i n bactcel lwal l  Mycolic acid - a waxy lipid ; inhibits lysosome enzymes of phagocyte  bacteria multiply inside phagocyte & hide from immune system  Ex - Genus Mycobacterium can lead to TB 28 Inflammation goali sto getri d ofpathogen due to pathogen,notphysi cal Due to injury and infection Signs & symptoms: cytoki nesdamage nerve endi ngs,causi ng pai n cytoki nes 1. Pain - due to release of certain chemicals by leukocytes 2. Redness (erythema) - blood goes to affected area bri ngi ng neutrophi l sand monocytesto the affected area 3. Immobility - from local loss of function in severe inflammation 4. Swelling (edema) - due to accumulation of fluids 5. Heat - increased blood flow to affected area 29 The Process of Inflammation 1. Tissue or cells get damaged bypathogen/infection 2. Damaged cells release chemicals such as cytokines 3. Cytokines promote chemotaxis of phagocytes neutrophi l s& monocytes 4. Phagocytes squeeze through blood vessel & move to site of tissue injury 5. Phagocytosis of invading pathogens begins 6. Tissue gets repaired Figure 16.9 30 Fever goali sto getri d ofpathogens 1. Toxins are released by bacteria  induces cytokine release from phagocytes body' sthermostat;regul atesbodytemp 2. Cytokines bind to hypothalamus receptors  increases set point for body temperature bcnew setpoi nti shi gherthan currentbodytemp 3. The “new” set point now makes person feel cold (chills) & person increases their body temperature 4. Once “new” set point is reached, person experiences abnormally high body temperature (fever) 5. As pathogens are eliminated  toxins & cytokines get eliminated 6. Body thermostat is reset  body temperature falls  decline of fever is called “crisis” i fthere are no pathogens,no toxi nsproduced. No toxi nsproduced,no cytoki nes produced. Ifno cytoki nesproduced the bodytemp goesbackto normal. 31 Consequences of Fever Increases metabolic rate i ncrease i n cel l ul arrespi rati on,i ncrease ofATP producti on Enhances immune response phagocyte activity--phagocyteslooking forpathogens producti on Induces antimicrobial substances protei nsrel eased bycertai n cel l s 32 Antimicrobial Substances 1. Complement System 2. Interferons 33 Compl ementprotei n enhancesi mmune system Complement System Cal l ed compl ementprotei n Serum proteins (complement proteins) that enhances the immune system in destroying pathogens Complement proteins act in a cascade manner in a process called complement activation Exampl e: Compl ementprotei nsexi sti n 2 forms:Acti ve and Inacti ve C.P#1 (i nact)getsconverted to C.P#1 (acti ve). C.P#1 W i l lacti ve C.P#2(i nacti ve)to CP#2 (acti ve) 34 Outcomes of Complement Activation 1. Opsonization meansto coatthe surface ofsomething Complement proteins coat surface of pathogen Promotes attraction/attachment of phagocyte to pathogen 2. Inflammation contai n hi stami ne hi stami ne rel eased when mastcel lcoated wi th comp protei n Complement proteins bind mast cells Mast cells release histamine  increase blood vessel permeability makesbl ood vessel spermeabl e so monocytesand neutraphi l scan getto i nfected ti ssue Chemotactic attraction of phagocytes 3. Cytolysis Complement proteins create a membrane attack complex (MAC) MAC creates a hole/channel in pathogen’s cell wall/cell membrane  fluid enters the pathogen  pathogen bursts! 35 Outcomes of Complement Activation MAC Figure 16.12 COATING MAST CELLS 36 Microbial Evasion of the Complement System Capsule production Bactwi th capsul esi sVerydangerousbc:no phagocytosi s,no compl ementaryprotei n bi nds, capsul essti ckto ti ssue easi l y. Complement proteins cannot bind easily Inhibition of MAC formation Enzymes from bacteria prevent MAC assembly Inactivation/destruction of complement proteins Bacteria produce protease enzyme thatdestroysprotei ns EX:destroyscompl ementprotei ns 37 Interferons (IFNs) i nterfere wi th vi ral(Ani malcel l s)i nfecti ons VIRUS ONLY,notforbacteri a oranythi ng el se Small proteins produced by some animal host cells upon animal viral infection Antiviral action  Cause neighboring cells to heighten their anti-viral defenses al ertsUNINFECTED nei ghbori ng cel l sofnearbyvi rus,so theyhave ti me to protectthemsel ves 38 Mechanism of Action of Interferons 1. Animal virus enters animal host cell and multiplies when ani malhostcel lgetsi nfected,the i nfected cel lwi l lproduce IFNsto al ertofa potenti alvi rali nfecti on 2. Animal host cell produces IFNs (will serve as signal to uninfected neighboring animal cell for potential virus infection) 3. IFNs released by virus-infected animal host cell  binds to cell membrane of uninfected neighboring animal cell  it makes anti-viral proteins (AVPs) 4. Newly released viruses that infect neighboring animal cell has AVPs waiting to destroy virus (pathogen) 39 Mechanis m of Action of IFNs Ani mal Infected Ani mal HostCel l MakesIFNs Uni nfected nei ghbori ng Ani malHostCel l MakesAVP for protecti on 40 Flow Chart : Overview of Innate Immunity Innate i mmuni ty BIO Chem Physi cal FEVER Pl atel ets Infamati on Phagocytosi s RBC INFs B E N Lymphocytes Opso * B cells & T cells are part of 3rd Line Host Defenses (Adaptive Immunity) Cyto Infl amati on 41