Chapter 15 Innate Immunity PDF

Chapter 15 Innate Immunity Suggestions to help you study:  Read and work through the power point (adjusting your notes as necessary)  Take note of any vocabulary words  Answer all embedded questions  Answers will be in the notes section under the slide  M...

Chapter 15 Innate Immunity Suggestions to help you study:  Read and work through the power point (adjusting your notes as necessary)  Take note of any vocabulary words  Answer all embedded questions  Answers will be in the notes section under the slide  Mark any questions or concerns you have and either email me or attend/request office hours  Objectives on the last slide are a good way to study and determine if you understand the material. They are not test questions.  Read any associated sections in the textbook.  Exam questions range from vocabulary to basic recall/identification to critical thinking and case study type questions. An Overview of the Body's Defenses  Pathogen can only cause disease if:  Gain access  Attach to host cells  Evade body's defense mechanisms  Humans have resistance to most plant and animal pathogens due to species resistance  Due to:  Incorrect chemical receptors on human cells  Conditions of host may be incompatible with pathogens  Examples: FIV, kennel cough, TMV Body’s Three Lines of Defense:  First line (Innate Immunity)  Skin  Mucous membranes  Their chemicals Non-specific  Second line (Innate Immunity) defenses  Specialized cells  Antimicrobials chemicals  Components of the blood  Inflammation, fever  Third line  Adaptive Immunity (Ch 16)  Body defense’s become more effective with subsequent exposure to the pathogen Innate Immunity  Composed of:  External physical barrier to a pathogen  Skin  Mucosal membranes  Internal defenses  Protective cells  Blood-borne chemicals  Inactivate/kill invading pathogens  Present at birth  Rapid  Works against a wide variety of pathogens  Humans are not naturally resistant to a number of pathogens The Body's First Line of Defense  Skin  Mucous membranes  Respiratory  Digestive  Urinary  Reproductive  Structures, chemicals, and processes that work to prevent pathogens entering the body  It is only when these defenses are damaged that they become portals of entry The Body's First Line of Defense: Skin NIH  The Skin is composed of two layers:  Epidermis  Multiple layers of tightly packed cells  Few pathogens can penetrate  Shedding removes microorganisms  Dendritic cells – phagocytic Figure 15.1 A scanning electron  Removal of pathogens micrograph of the surface of human skin.  Inform adaptive immunity of invaders  Dendritic cells also found in mucosal membranes  Dermis  Hair follicles, glands, nerve endings  Contains collagen fibers  Gives strength and viability to prevent Combination of barrier penetrating the dermis and introducing function, shedding, microbes phagocytic cells, strength and pliability allows skin to be a nonspecific defense The Body's First Line of Defense: Skin  The Role of Skin: Chemical  Sweat glands secrete perspiration  Salty How does this kill invaders?  Dermal cells secrete:  Antimicrobial peptides (Defensin)  Positively charged chains of amino acids What charge to cells  have? Dermicidin – Broad-spectrum antimicrobial (Who can it kill?)  Insensitive to salt and pH (Why important?)  Lysozyme  Destroys cells wall by breaking bond in peptidoglycan  Where else is lysozyme produced in the body?  Sebaceous (oil) glands secrete sebum  Helps keep skin pliable, less likely to break/tear  Lowers skin pH (pH 5) – Why is this important? The Body's First Line of Pharynx Tongue Defense: Larynx (voice box) Mucous Membranes  Line all of the body cavities open to the environment Trachea Bronchus  Nonspecific defense  Two distinct layers:  Epithelium  Thin, outer covering of tightly packed cells Figure 15.2 The structure of the  Living cells respiratory system, which is lined with a mucous membrane.  Continual shedding  Dendritic cells below epithelium phagocytize pathogens  Goblet (mucus producing) and ciliated columnar (carry mucus + microbes) cells help remove invaders  Deeper connective layer that gives nutritional and mechanical support The Body's First Line of Defense: Mucous Membranes  Produce chemicals that defend against pathogens  Nasal mucous membrane  Lysozyme  Defensin The Body's First Line of Defense  Role of the Lacrimal Apparatus  Produces and drains tears  Tears contain the antimicrobial lysozyme  Bathe eye in tears and Nasolacrimal duct blinking to remove debris Paranasal Lacrimal Lacrimal sinus apparatus glands Lacrimal Pharynx gland duct Lacrimal canal Nasolacrima l duct Trachea Esophagus Anterior view Lateral view Figure 15.3 The lacrimal apparatus. The Body's First Line of Defense  Role of Normal Microbiota  Microbial Antagonism  Normal microbiota outcompete pathogens (microbial antagonism)  Typically live in the crevices around hairs or gland ducts  Microbiota  Consume nutrients  Change pH  Stimulate 2nd line of defense  Provide nutrient to host: vitamins, vitamin precursor The Body's First Line of Defense  Other first line defenses  Antimicrobial peptides – can be specific for Gram +/-What are some common  See Table 15.2 methods to remove or inhibit microbes?  Which statement best describes the environment of the skin and its effect on microbial growth? a) The skin is simply a physical barrier to keep microbes from entering the body. b) The skin's defenses are minimal, and it is a suitable environment for many microbes. c) Salt, defensins, enzymes, and a low pH make the skin inhospitable for all microbes. d) The skin is inhospitable for most microbes, but some normal microbiota are still present. Second Line of Defense  Comes into play after 1st lines of defense have been penetrated  No barrier system Areas of the first line of defense have now  Utilizes specialized cells, antimicrobial chemicals become portals of entry and specific processes  Can overlap with 1st line of defense  Defense components of the blood  Blood is liquid tissue composed of cells/portions of cells in plasma  Inflammation  Fever Second Line of Defense: Defense components of the blood  Plasma is mostly water with electrolytes, dissolved gas, nutrients and proteins  Inflammation  Blood clotting – prevents excess blood loss and decreases risk of inflection  Plasma without clotting factors = serum  We use serum as the media for coagulase test  Iron-binding proteins  Complement proteins  Antibodies – more in Ch 16 Second Line of Defense: Defense Components of the blood - Plasma  Iron-binding proteins  Example: Iron "tug of war"  Iron is important because:  S. aureus produces siderophores  Cytochromes in ETC (Fe-binding proteins that steal iron from host)  Enzyme cofactor  Body produces lactoferrin to take  Hemoglobin – oxygen carrying protein in RBC back the iron  S. aureus can have hemolysin that  Iron-binding proteins (transferrin) are defensive punches holes in RBC to release iron because sequester iron away from microbes  Ferritin if stored in the liver Some pathogens obtain iron by secreting iron-binding proteins called ________. a) siderophores b) lactoferrins c) transferrins d) hemoglobins Second Line of Defense: Defense components of the Blood  Hematopoiesis – blood stem Figure 15.4 A schematic representation of hematopoiesis. cells (bone marrow) produce: Blood stem cell in bone marrow  Formed elements – cells or fragments Erythroid Myeloid Lymphoid stem cell stem cell stem cell  Erythrocytes – carry oxygen and carbon dioxide  Platelets – blood clotting  Leukocytes – defensive Erythrocyte Platelets Basophil Neutrophil Eosinophil Monocyte Lymphocyte Clotting, Inflammation Phagocytosis inflammation Gas Innate immunity, second line of defense Adaptive immunity transportation Leukocytes  Second Line of Defense: Defense components of the Blood - Leukocytes The Granulocytes Basophils Eosinophils Neutrophils Eosinophils – Basophil Neutrophil Eosinophil phagocytic, Inflammation Phagocytosis diapedesis, secrete antimicrobial chemicals Basophils – can leave Neutrophils – phagocytic, the blood diapedesis, produce toxic oxygen (diapedesis), release species (H202 or O2-) to convert to inflammatory hypochlorite, nitric oxide Second Line of Defense: Defense components of the Blood - Leukocytes The Agranulocytes Lymphocytes MonocytesLymphoid stem cell Lymphocytes are small and nucleated Involved in adaptive immunity Includes natural killer lymphocytes Monocyte Lymphocyte Monocytes are large, Phagocytosis nucleated. Innate immunity, second line of Adaptive immunity Can leave blood and defense Leukocytes mature into macrophages Macrophages are phagocytic Second Line of Defense: Defense Components of the Blood  Lab analysis of leukocytes  Differential WBC count can signal disease  Increased eosinophil  Indicate allergies or parasitic worm infection  Increased leukocyte and neutrophils  Bacterial diseases  Increased lymphocytes  Viral infections Second Line of Defense: Phagocytosis 1. Chemotaxis Use pseudopods to crawl toward infection Attracted by: microbial component secretions damaged tissues WBC chemotactic factors defensin complement peptide chemokine – release by leukocytes at site of infection Second Line of Defense: Phagocytosis  Phagocytosis – kills pathogens upon ingestionPhagocytos is 2. Adherence – bind through 2a.More easily engulfed if covered complementary chemicals on in antimicrobial proteins membrane (glycoproteins) (complement) or antibodies Chemotaxis 1 phagocyte of Virulence factors can inhibit/hinder Coating – opsonization using to microbes Microbes opsonins 2Adherence Pseudopods move (chemotaxis) Ingestion 3 of microbes 3. Ingestion – internalization by phagocytes within vesicle called phagosome Fusion 4 of a series of vessicles, 4. Fusion of vesicles to make Phagosome including lysosomes phagolysosome Killing of 5. Phagolysosome contains toxic Golgi body 5 Lysosome microbes by oxygen species, low pH 5.5, enzymes and Nucleus other chemicals enzymes (lipase, protease, Phagolysosome nuclease) Destroys microbes in 30 mintes Residual body Pseudopod 6. Elimination by Elimination 6 Phagocyte (exocytosis) exocytosis Second Line of Defense: Non-Phagocytic Eosinophil Killing  Can phagocytose (not the norm)  Secrete antimicrobial chemicals  Helminth infections – eosinophilia (an abnormally high eosinophil count)  LPS release triggers eosinophil to eject mtDNA  mtDNA + eosinophil secreted proteins = physical barrier that binds and kills bacteria  Natural killer lymphocytes  Secrete toxins with viral-infected cells or neoplasms (tumor)  Neutrophil  Create toxin oxygen species that can be converted to hypochlorite  Make nitric oxide to induce inflammation Second Line of Defense: Nonspecific chemical defenses  Augments phagocytosis  Defensive chemicals:  What is lysozyme? Lysozyme – typically first line of defense  What is defensin? Defensin – typically first line of defense  Toll-like receptor (TLR)  NOD  Interferon  Complement Second Line of Defense: Nonspecific chemical defenses  Toll-like Receptor (TLR)  Integral protein in plasma membrane of phagocytic cell  Early warning system against pathogen associated patterns (PAMPs)  Peptidoglycan, LPS, flagellin, dsRNA  PAMPs bind to TLR to initiate a defense response  Apoptosis (cell suicide)  Secretion of inflammatory molecules or interferons  Stimulate adaptive immunity (Ch 16)  If TLR fails:  Much of the immune response collapses Second Line of Defense: Nonspecific chemical defenses Interferon  Chemicals against viral pathogens  Interferon – proteins released by host to nonspecifically inhibit the spread of viral infection  Cause malaise, fever, chills, headache Viruses use the host's metabolic machinery Second Line of Defense: Nonspecific chemical defenses  Type I Inteferon (INF-α, INF-β)  INF-α – produced by infected monocyte, macrophage, lymphocyte  INF-β – produced by infected undifferentiated cells of cartilage, tendons, bone  Do not protect cells that secrete them  Activate NK lymphocytes to protect uninfected cells  Produce antiviral protein (AVP) to bind dsRNA  Binding destroys protein production of the cell but prevents viral replication  Typically 3-4 days, short enough to not kill cell MidlandsTech Second Line of Defense: Nonspecific chemical defenses  Complement (or Classical pathway Alternative pathway Lectin pathway Antigen C3b Mannose Complement System) Endotoxin and  Serum proteins glycoproteins Lectins Antibody C3b Factors B,  Initially act as opsonins and D, and P chemotactic factors Complement  Indirectly triggers proteins inflammation and fever 1, 2, 4 Complement cascade  React with one another in Activation Opsonization (C3 C3a + C3b) Inflammation an amplifying sequence = cascade C5 convertases Inflammation C5 C5a + C5b  Three pathways Membrane attack complex and cell lysis Second Line of Defense: Figure 15.9 The classical pathway and the complement cascade. Nonspecific chemical defenses  Classical Pathway  Proteins "complement"/act in Membrane attack complex (MAC) conjunction with antibodies  Complement enzymes cleave other Antigen inactive complement proteins to form C1 becomes an active Antibody Enzymatic C1 C5b combines with C6, C7, C8, enzyme when it binds to active fragments and several molecules of C9 to antibody-antigen complexes. form a membrane attack complex (MAC). A MAC drills a circular hole in the pathogen's cytoplasmic membrane,  1. C1 becomes active when bind to leading to lysis of the cell. antibody-antigen complex  2. C1 cleaves C2 and C4 Enzyme C1 splits molecules Triggers inflammation Third enzyme cleaves C5 into C5a and C5b. of C2 and of C4.  3. C2/C4 cleave C3 Triggers inflammation Second enzyme Enzyme  4. C2/C4/C3 form enzyme Fragments of C2 and C4 combine C3b combines with the to form a second enzyme that second enzyme to form splits C3 into C3a and C3b. a third enzyme.  5. Cleaves C5 Acts as opsonin  6. C5 helps form MAC Triggers inflammation Second Line of Defense: Compleme nt Nonspecific chemical defenses  Classical Pathway C3b combines with the remaining fragments of C2 and C4 to form a  C3a and C3b function as Fragments of C2 third enzyme. and C4 combine opsonins to form a second enzyme that splits C3 into C2a C4b C3a and C3b.  Function? Enzyme C3 C3a C3b  MAC (Membrane attack complex) forms a hole in the membrane C3 Causes chemotaxis of phagocytes C3a C3b Acts as opsonin and triggers inflammation  Causes lysis of bacteria or Membrane attack complex eukaryotes  Gram negatives are very sensitive  Why?  Gram positives are resistant  Why? Second Line of Defense: Nonspecific chemical defenses  Alternative Pathway  Independent of antibodies  Cleavage of C3 to C3a and C3b occurs naturally at a slow rate in the plasma  C3b binds to microbes  Factor B adheres, Factor D cleaves B to Bb  Create C3b+Bb enzyme  Stabilized by factor P (properdin)  Cleaves C3  Aid in the formation of MAC http://faculty.ccbcmd.edu/ courses/bio141/lecguide/unit5/  Useful in early stages of infection before adaptive innate/images/activation%20of %20C3_alternative.jpg immunity creates antibodies Second Line of Defense: Nonspecific chemical defenses  Lectin Pathway  Lectins are chemicals that bind to polysaccharides (mannose) in pathogens  Mannose is rare in mammals  Lectin bound to mannose cause C2 and C4 to be cleaved – activate classical pathway  Inactivation of Complement  Body's cells withstand complement cascade  Break down activated complement proteins before damage occurs While they start at a different place in pathway, all three complement systems end with opsonization (C3b), direct attack (MAC), and recruitment of phagocytes (C3b, C5b). Second Line of Defense: Complement Animations Complement: Activation Which of the following is NOT an outcome of the activation of the complement system? a) opsonization of microbes b) inflammation c) lysis of the microbe d) prevention of infection by microbes What is the term for the process in which pathogens are coated with antimicrobial proteins to increase the likelihood of phagocytosis? a) opsonization b) chemotaxis c) diapedesis d) endocytosis A patient has a genetic disorder that makes it impossible to synthesize complement protein 8 (C8). Classical pathway Alternative pathway Lectin pathway Antigen C3b Mannose Is her complement system Endotoxin and Lectins nonfunctional? glycoproteins Antibody C3b Factors B, D, and P Complement What major effects could still proteins be produced? 1, 2, 4 Complement cascade Activation Opsonization (C3 C3a + C3b) Inflammation C5 convertases Inflammation C5 C5a + C5b Membrane attack complex and cell lysis Second Line of Defense: Nonspecific chemical defenses  Inflammation  General, nonspecific response to tissue damage  Signs and symptoms are the same  Redness in light skin (Rubor)  Localized heat (calor)  Edema (swelling)  Pain (dolor)  Two types:  Acute  Chronic Inflammation: Overview Second Line of Defense: Nonspecific chemical defenses  Inflammation  Acute Inflammation  Develop quickly  Short lived  Beneficial  Important defense:  Increase dilation and permeability of blood vessels  Diapedesis of WBC  Tissue repair  Chronic Inflammation  Damage or death of tissue  Result in disease Second Line of Defense: Nonspecific chemical defenses Inflammation C3a Bacteria C5a C3a C5a Granule containi A cut penetrates the ng chemical epidermis barrier, and s bacteria invade. Inflammatory mediators Damaged cells release prostaglandins, Blood clotting release leukotrienes, and inflammation histamine (shown in mediators green here). Histamine release in response to complement cascade Second Line of Defense: Nonspecific chemical defenses Inflammation Increased blood flow Increased oxygen, nutrients to site of injury Increased number of phagocytes to the area Prostaglandins and leukotrienes make vessels more permeable. Histamine causes vasodilation, increasing blood flow to the site. Macrophages and neutrophils squeeze through walls of blood vessels (diapedesis). Second Line of Defense: Nonspecific chemical defenses Inflammation Signs of Inflammation: Edema -swelling Rubor - redness Why do you have Dolor – pain pain? Calor - heat Swelling Heat Increased permeability allows antimicrobial chemicals and clotting proteins to seep into damaged tissue but also results in swelling, pressure on nerve endings, Nerve endin g and pain. Second Line of Defense: Nonspecific chemical defenses Inflammation Blood clot forms. More phagocytes migrate to the site and devour bacteria. Accumulation of Pus can erupt or form damaged tissue and an abscess (isolated leukocytes forms pus. site of infection) Undifferentiated stem If the site cannot be cells repair the damagedcompletely repaired - tissue. Blood clot is scar absorbed or falls off as a scab. Inflammation: Steps Second Line of Defense: Nonspecific chemical defenses  Fever Hypothalamus  Body temperature over 37º 2Hypothalamus secretes prostaglandin,  Augments the beneficial effects of inflammation which resets hypothalamic thermostat.  Side effects – malaise, body aches, tiredness 1Chemicals secreted  Results from presence of pyrogens by phagocytes travel in blood to hypothalamus.  Pyrogens are bacterial toxins, antibody-antigen 3Nerve impulses complexes, or released phagocytosed products cause shivering, higher metabolic rate, inhibition of sweating,  Triggers a reset of body temperature (higher) and vasoconstriction.  Causes vasoconstriction, increases metabolic rate 4 These processes increase body  Continues as long as pyrogen present Wound temperature to the point set by the hypothalamic thermostat.  Fever beaks: cool by perspiring, lower metabolic rate, dilate blood vessels Second Line of Defense: Nonspecific chemical defenses  Fever  High temperature thought to enhance  Interferons  Inhibit microbial growth  Enhance phagocytosis and tissue repair  Too high temperature  Protein denaturation  Cause hallucination, coma, death Should you take fever-reducing drugs or let a fever run its course? In order for a pathogen to cause disease, what 3 things must happen? Objectives:  Know all vocabulary  Describe the three lines of defense in the human body  What is species resistance?  What physical and chemical properties of the skin and mucosal membranes enable it to prevent pathogen entry?  What role do tears/saliva/defensin play in preventing infection?  How do the normal microbiota help prevent infection?  How does the blood/blood components function to defend the body?  Describe a macrophage’s role in preventing disease.  Describe the six stages of phagocytosis.  What pathogenic features prevent phagocytosis? What can the cell produce to overcome this?  What are PAMPs, TLRs, and interferons role in immunity?  Describe the complement system (three pathways). How do they interconnect?  What are the pros and cons of inflammation?  What are the pros and cons of fever?