Host Pathogen Interactions PDF

Host Pathogen interactions Innate Immune systems  Terminology Susceptibility Lack of resistance to a disease Resistance Ability to ward off disease Nonspecific resistance Defenses against any pathogen Specific resistance Imm...

Host Pathogen interactions Innate Immune systems  Terminology Susceptibility Lack of resistance to a disease Resistance Ability to ward off disease Nonspecific resistance Defenses against any pathogen Specific resistance Immunity, resistance to a specific pathogen Mechanisms of Pathogenicity Pathogenicity is the ability to cause disease Loading… Figure 15.9  Host Defense Mechanisms Defense mechanisms two broad groups – Innate or Non-specific Immunity – Adaptive or Specific Immunity Non-specific – Protect against most any disease agent – Variable Stress Age Diet  Host Defenses Loading… Complement Barriers and chemicals Receptors for Pathogen Specialized Cells: Recognition: Antigen or shape recognition TOLL-Like “learned” or adaptive Complement Intercellular – Humoral Pattern recognition Intracellular – Cellular Figure 16.1  First Line of Defense Physical barriers – Skin is most visible barrier – Covers majority of surfaces – Mucous membranes digestive tract respiratory tract genitourinary tract Skin, not just a covering for the juicy bits… – Provides the most difficult barrier to penetrate – Composed of two main layers Dermis – Contains tightly woven fibrous connective tissues » Makes extremely tough Epidermis – Composed of many layers of epithelial cells » As cells reach surface, they become increasingly flat – Outermost sheets of cells embedded with keratin » Makes skin water-repellent – Outer layers slough off taking microbes with it  Other Factors Mucous membranes and Secretions – Ciliary escalator: Microbes trapped in mucus are transported away from the lungs – Lacrimal apparatus: Washes eye – Saliva: Washes microbes off – Urine: Flows out – Vaginal secretions: Flow out – Defecation and vomiting  Normal Microbiota and the Host Microbial antagonism is a competition between microbes. Normal microbiota protect the host by: – Occupying niches that pathogens might occupy – Producing acids – Producing bacteriocins (Probiotics are live microbes applied to or ingested into the body, intended to exert a beneficial effect).  Normal Microbiota and the Host Transient microbiota may be present for days, weeks, or months. Normal microbiota Loading… permanently colonize the host. Symbiosis is the relationship between normal microbiota and the host. Figure 14.1c  Symbiosis In commensalism, one organism is benefited and the other is unaffected. In mutualism, both organisms benefit. In parasitism, one organism is benefited at the expense of the other. – Some normal microbiota are opportunistic pathogens. Representative Normal Microbiota Figure 14.1  Infection- a condition in which pathogenic microbes penetrate host defenses, enter tissues & multiply Disease – any deviation from health, disruption of a tissue or organ caused by microbes or their products  Who are these guys? includes bacteria, fungi, protozoa, viruses and arthropods Mosty in contact with the outside environment – large intestine has the highest numbers of bacteria internal organs & tissues & fluids are microbe- free – Presence of microbes indicate an infection  Physiological Barriers: Second line defenses Blood elements – PAMP recognition – Phagocytes – Complement proteins Inflammation response – Role of Inflammation Contain Damage Localize the response Restore function http://www.sabiosciences.com/pathwaymagazine/img/pathways7/page2b.jpg Innate Defense Phagocytosis Proteins in Blood part of “complement system” Recognitio n  Overview of Innate Defenses – Complement System – Acts in response to stimuli Activation sets off chain reaction that results in destruction or removal of invader The Complement System Figure 16.9  Effects of Complement Activation Opsonization or immune adherence: Enhanced phagocytosis Membrane attack complex: Cytolysis Attract phagocytes Figure 16.10 Complement membrane channel or MAC https://classconnection.s3.amazonaws.com/830/flashcards/1208830/png/screen_shot_2012-05-23_at_122743_am1337747276573.png  Next Time Adaptive Immune system Adaptive Immune Response (Acquired Immunity) PAMPs vs Antigens Innate vs Adaptive  The other Immunity Adaptive or specific immunity – Removes specific pathogens – Remembers pathogens in case… Division of labor – Humeral immunity – extracellular – Cellular immunity – intracellular Innate immunity: Defenses against any pathogen- PAMP recognition Adaptive immunity: Induced resistance to specific small shapes that make up a pathogen  Loading… http://textbookofbacteriology.net/cellsindefenses75.jpg  Phagocytic cells Non-specific – recognize PAMPs – multiple (Toll and Nod) – Some are Antigen Presenting cells Dendritic Cells and Macrophages Each cell – many receptors – any pathogen Specific – only one shape – T-cells – T cell receptor Only recognizes single antigen – B-Cells – Immunoglobulin receptor Only recognizes single antigen  Dual Nature of Adaptive Immunity T and B cells develop from stem cells in red bone marrow Humoral immunity – B cells mature in the bone marrow Loading… (Chickens: Bursa of Fabricius ) – Effect Due to antibodies Cellular immunity – T cells mature in the thymus – Effect Due to T cells Where have we been, Where are we going?  Adaptive Response Stimulated by Antigens T-independent – Strong signal – Triggers B or T cells to proliferate and differentiate – Attack Pathogen T-Dependent – Weaker signal – Needs confirmation from Helper T-Cell – Helper T cell stimulates Proliferation and differentiation  Antigens Antigen = antibody generators Shape = conformations Antigens are mostly proteins, (few carbohydrates) – Small pieces, 5-9 amino acids – Secondary structures (especially for carbohydrates) Self Antigens – normal produced by body Non-self Antigens = foreign or exogenous  Antigen Presentation General Characteristics – During antigen presentation, antigen cradled in grove of major histocompatability complex molecule (MHC molecule) Two types MHC – MHC class I » Bind endogenous antigen – MHC class II » Bind exogenous antigen  Loading… From: "Making sense of mass destruction: quantitating MHC class I antigen presentation", Jonathan W. Yewdell, Eric Reits & Jacques Neefjes, Nature Reviews Immunology 3, 952-961 (December 2003) doi:10.1038/nri1250 Courtesy Eric Rei  In General Antigen = “antibody generator” All cellular proteins and some carbohydrates can potentially act as antigens Shape or conformation of protein that can bind to cell surface receptor of immune cells – Usually only few amino acids in length – Shape is it! – Each protein can have multiple shapes therefore can be more than one antigen  More on Antigens Self Antigens – Own proteins made by normal cellular metabolism – Sampled during processing by Golgi Apparatus – Presented on Cell Surface to Identify self from “non-self” (MHC I) External Antigen – (Foreign) Proteins and other “antigenic” molecules – Processed by phagocytic cells and presented on specialized receptors to activate Adaptive immunity (MHC II)  Stop and Catch up What is an antigen? How is this different than a PAMP? What is a self antigen? What is an exogenous antigen? Compare roles of MHCI to MHCII – What types of cells – What types of antigens  More in General Antigen Presenting Cells digest pathogens – Hydrolyze Their proteins into small pieces – The shapes (based on 2o structure) act as distinct patterns (Like keys) – “key holder” is MHCII Patterns Match receptors (like locks) – CD4 (Helper T-Cells) – CD8 (Cytotoxic T-Cells) – B-Cells (Humoral Response)  Immune cells “preadapted” recognize antigens (Bergstrom and Antia 2006).  Non-specific Phagocytosis Antigen Processing and presentation Activation of Activation of cytotoxic T cell Helper T cell C el Humoral Immunity lu la Intracellular Activation of Intercellular r Pathogens B-cells Pathogens I m  Overview of Immune responses Pathogen associated Molecular patterns Pattern Recognition molecules B cells bind soluble antigen With B cell receptor then Display antigen on MHCII For Th cell  Catch up Outline or explain the T-dependent Humoral response Which B cells are selected? What gives them the go ahead to clone and differentiate? What do they differentiate into? Humoral Response = B cells Chapter 21, Immune System 21 Figure 21.9  T Lymphocytes Cellular Immune Response General characteristics – Two major function T cell populations Cytotoxic T cells – Proliferate and differentiate to destroy infected or cancerous “self” cells – Have CD8 receptor – Recognize MHC class I Helper T cells – Multiply and develop into cells that activate B cells and macrophages – Stimulate other T cells; orchestrate immune response – Have CD4 marker – Recognize antigen display by MHC class II  T Lymphocytes Antigen Recognition and Response Functions of TH (CD4) cells – Orchestrate immune response Recognize antigen presented by MHC class II molecules – MHC class II molecules found only on APC If TH cell recognizes antigen, cytokines are delivered – Cytokines activate APC to destroy antigen  T Lymphocytes Antigen Recognition and Response  T Lymphocytes Antigen Recognition and Response Role of TH cells in B cell activation – If TH cell encounters B cell bearing peptide: MHC calls II complex TH cell responds by producing cytokines – B cell is activated in response to cytokine stimulation B cell proliferates and undergoes class switching Also drives formation of B memory cells Lymphocyte Development  T Lymphocytes Antigen Recognition and Response Functions of Tc (CD8) cells – Induce apoptosis in “self” cells Cells infected with virus or intracellular microbe Destroys cancerous “self” cells – Nucleated cells degrade portion of proteins Load peptides into groove of MHC class I molecule MHC class I molecule recognized by circulating Tc cell – Cell destroyed by lethal effector function of Tc cell Tc cells releases pre-formed cytokines to destroy cell  Natural Killer Cells Natural killer cells descend from lymphoid stem cells – They lack antigen specificity No antigen receptors Recognize antigens by means of Fc portion of IgG antibodies – Allow NK cells to attach to antibody coated cells Actions augment adaptive immune response – Important in process of antibody dependent cellular toxicity Enable killing of host cells with foreign protein in membrane Natural killer cells recognize destroyed host cells with no MHC class I surface molecules – Important in viral infection Loading…  Fill in the Summary Table Cell Type MHC Receptor MHC Receptor Outcome of activation Presented? Recognized? Dendritic Cells Helper T-Cells (CD4) Cytotoxic T-Cells (CD8) Natural Killer Cells  What do you Remember? What is the difference between: – Humeral Immunity Humeral response video – Cellular Immunity – http://www.dnatube.com/video/194/Specific- Adaptive-immunity-humoral-and-cell-mediated – More Videos Humoral Response Cellular Response  Next Time – Microbes and Disease Over View  Consequences of Adaptive Response Humoral – B-cell activation – Antibody production to extracellular pathogens Loading… – Immune memory Cellular – Cytotoxic T-cell Activation – Migration – Immune memory Types of Immunity Loading… Host Microbe Interactions Introduction to disease  Principles of Infectious Disease Infection – colonization of host with microorganisms – Infection does not always lead to noticeable adverse effects – Infectious Disease – infection that results in disease – Disease – Deviation from normal health Usually due to damage or injury to host  Two Main Types of Infections Beneficial – normal flora – Microbes living on and in body – Over a trillion microbes associated human body – 500 to 1000 different species in gut alone – Outnumber all cells in your body 10:1 or more! Harmful – Pathogenic Microbes  Pathogenicity Pathogenicity – Ability to cause disease True Pathogens are organisms that can cause disease in otherwise healthy people That pathogen termed primary pathogen Opportunistic Pathogen - Microbes that cause disease when the body’s defenses are down May be part of normal flora or common in environment Mechanisms of Pathogenicity Virulence factors Figure 15.9  Virulence – Virulence is quantitative term referring to pathogen’s disease-causing ability – Measure of ability to cause disease Highly virulent organisms have high degree of Loading… pathogenicity – These organisms more likely to cause disease – Example: Streptococcus pyogenes » Causes disease from strep throat to necrotizing fasciitis  Virulence Factors Biotic factors that lead to increased virulence Often additive or synergistic – Morphological characters – Metabolic pathways (e.g. antibiotic resistance) – Toxins – Enzymes  Infectious Disease Characteristics of infectious disease – Disease that spreads from host to host termed communicable or contagious – Virulence or ease of spread reported as infectious dose Infectious dose is number of organisms required to establish infection Diseases with small infectious dose more easily spread than those requiring large numbers  How bad is the bug? Microbes – ID50: Infectious dose for 50% of the test population Toxins or poisons – LD50: Lethal dose (of a toxin) for 50% of the test population Smaller LD or ID more toxic or virulent  Bacillus anthracis Portal of entry ID50 Skin 10-50 endospores Inhalation 10,000-20,000 endospores Ingestion 250,000-1,000,000 endospores  Virulence Factors Virulence is determined by combination of factors Often additive or synergystic More factors = more virulent – Examples: Fimbriae Glycocalyx Enzymes Toxins Host  I. Adherence factors Adhesions/ligands bind to receptors on host cells Most adhesins – glyco- or lipoproteins – Glycocalyx Streptococcus mutans – Fimbriae Escherichia coli – M protein Streptococcus pyogenes Facilitate binding to host cells or tissues Figure 15.1a Figure 15.1b Figure 15.2  II. Exoenzymes/Proteins – Enzymes or proteins secreted by bacteria Digestive enzymes – Proteases, nucleases, lipases – Used to penetration/invasiveness – Used to degrade host defense proteins Antibodies Complement Cytokines Penetration into the Host Cell Figure 15.2  III. Toxins Toxin Substances that contribute to pathogenicity Toxigenicity Ability to produce a toxin Toxemia Presence of toxin the host's blood Toxoid Inactivated toxin used in a vaccine Antitoxin Antibodies against a specific toxin  Toxins Endotoxins – Found in cell walls or cells – Released after death – Examples?? Exotoxins – Secreted by organism – Highly toxic!! Endotoxin Figure 15.4b  Endotoxin Source Traditionally Gram – Metabolic product Lipopolysacharide cell wall (teichoic acids) Chemistry Carbohydrate and lipid Fever? Yes Neutralized by antitoxin no LD50 Large Exotoxins Figure 15.4a  Exotoxin Source Gram + and Gram – (most gram +) Metabolic product By-products of growing cell Chemistry Protein Fever? Depends on Toxin Neutralized by antitoxin Yes LD50 Small  IV. Metabolic Pathways Enzymes to degrade antibiotics – Beta-lactamases Export pumps for antimicrobials Loading… Glycogen degradation – Use intramuscular polysaccharides as carbon source  Summarize What are the 4 major factors that influence virulence Difference between Endotoxin and exotoxin Who makes them? Virulence Factors Toxins  Last time Virulence and Virulence factors – Adhesions – Exoenzymes (some of these act as toxins) – Exotoxins – Metabolic pathways  More About Exotoxins synthesized by specific bacteria toxin genes plasmids or prophage among the most lethal substances known – Small LD50 Loading… are highly immunogenic – can stimulate production of neutralizing antibodies (antitoxins) – inactivated to form toxoids Passive immunity in form of antitoxin can be given as treatment  Damage to the Host Exotoxins – Can be grouped into functional categories Neurotoxins – Cause damage to nervous system – Major symptom is paralysis Tissue Specific – Enterotoxins » Damage to intestines and tissues of digestive tract Cytotoxins – Damage to variety of cells or general tissues – Damage caused by interference with cell function or cell lysis  Exotoxins Released extracellularly May travel far from focus of infection Three main modes of action – Cytolytic toxins Attack cell components causing lysis Loading… – A-B toxins (site specific, membrane disrupting) Two subunits B = binds to cell surface A = damages cell – Superantigen toxins Stimulate large immune response and subsequent inflammation  Cytolytic Toxins Two main types: – Lipases Phospholipases Lecithinases – Pore forming leucocidins streptolysins  Other cytolytic toxins Membrane-damaging toxins (enzymes) – Phospholipases are group of potent membrane-damaging toxins Remove polar heads of phospholipid Destabilizes membrane Example: Clostridium perfringens Figure 33.6 (b)  Pore-forming exotoxins (examples) leukocidins – kill phagocytic leukocytes hemolysins – kill erythrocytes, leukocytes, and many other cells – e.g., streptolysin-O (SLO) oxygen-sensitive – e.g., streptolysin-S (SLS) oxygen stable – e.g. Staphylococcus aureus produces toxin Figure 33.6 (a)  Hemolytic reactions beta-hemolysis – complete lysis – observed as zone of clearing around colony on blood agar alpha-hemolysis Loading… – partial lysis – observed as greenish zone around colony on blood agar Beta: complete lysis Alpha: partial lysis  More Damage to the Host A-B toxins – Toxins consist of two parts A subunit – Toxic or active part B subunit – Binding part » Binds to specific host cell receptors – Structure offers novel approaches to development of vaccine and other therapies Use toxin structure as binding a delivery system  A-B toxins Example = Diphtheria toxin – Corynebacterium diphtheriae – Rats/mice resistant, humans susceptible – Single toxin molecule needed to kill a cell Fragment B – Promotes binding to host cell and allows entry of Fragement A Fragment A – blocks translation – Prevents tRNA binding to ribosomes – Prevents protein synthesis  Other Examples of A-B toxins Clostridium toxins – Clostridium tetani – tetanus toxin – Clostridium botulinum – botulinum toxin Release toxins from site of wound – Influence muscle contractions – Botulinum toxin prevents muscle contraction – Tetanus toxin prevents muscle relaxation  Compare and explain Compare notes with your neighbor on the actions of the two examples of exotoxins Cytolytic A-B toxins Give examples of the modes of action of each  Superantigen Toxins – Elicit very strong immune response – Induce extensive release of cytokines – Systematic inflammatory response Vomiting Diarrhea Fever Systemic shock – Superantigens also suspected in contributing to autoimmune disease  Superantigens Examples: – Toxic shock syndrome toxin Staphylococcal and Streptococcal – Staphylococcal enterotoxin A Staphylococcus aureus – Scarlet Fever Toxin Streptococcus pyogenes  Superantigens Trick T cells – think they have been activated by specific antigens – Bridge MHCII of APC to CD4-T cell – T – Cell release cytokines – Activate large number of T-Cells (up to 30%) Over stimulates immune system – Systemic inflammation – Capillary leakage – Shock Some synergistic with endotoxin  Immune Responses Damaging effects of the immune response – Damage associated with antibodies Antigen-antibody complexes – Complexes form and settle in joints and kidneys » Causes destructive inflammation – Cross-reactive antibodies Some antibodies produced in response to infection bind to body’s own tissues – Promotes autoimmune response – Streptococcus pyogenes - rheumatoid arthritis  Endotoxins Gram neg bacteria Lipopolysaccharide layer on envelope – Lipid A Releases when cells are lysed Endotoxin symptoms – Fever – cause release of pyrogens – Diarrhea – Inflammation  Damage to the Host Endotoxins – Endotoxins are LPS of gram negative cell wall Toxin fundamental part of gram negative organism – Endotoxins are heat stable and therefore not suitable for use as toxoids – Lipid A responsible for toxic properties – Symptoms associated with vigorous immune response – Toxin responsible for septic shock a.k.a endotoxic shock  More about Endotoxins heat stable toxic (nanogram amounts) weakly immunogenic generally similar, despite source Responsible for “injection fevers” Used rabbits as an assay – Rabbit test or pyrogen test Endotoxins…Exogenous Pyrogens usually capable of producing general systematic effects – fever – shock – blood coagulation – weakness – diarrhea – inflammation – intestinal hemorrhage – fibrinolysis  Damage to the Host Other bacterial cell wall components – PTG and other cell wall components can elicit symptoms similar to those seen with endotoxic shock (PAMP) – These include Fever Drop in blood pressure  How do they compare? Endotoxins less toxic than exotoxins Mouse LD50 endotoxin 200-400 ug/kg Mouse LD50 exotoxin 25 pg/kg 1,000,000 pg in a ug Even though less toxic than exotoxins still toxic enough to cause major clinical problems! Presence of endotoxin can enhance sensitivity to TSS toxins up to Million fold!  Limulus test Limulus amebocyte lysate (LAL) Limulus is genus of horseshoe crab – Amebocytes – “white blood cells” of crab – Have no advanced immune system – Blood or lysate clots in response to pathogens (endotoxins) – Used as presumptive test for endotoxin  Endotoxemia Examples – Bacterial infection – Burns and severe wounds Significance Loading… – 20 to 30% of intensive care patients – 100,000 to 200,000 deaths a year in NA alone Young L, Glauser M, editors. Gram-negative septicemia and septic shock. Philadelphia: WB Saunders; 1991. Limulus Amebocytes  Limulus Test Problems – Can’t discriminate between live and dead cells – Can’t discriminate toxins of different species  Explain What is an endotoxin? What group of bacteria produce this? What are the symptoms What is an assay for the presence of endotoxin Skin Infections Chapter 34  Normal Flora of the Skin Large numbers of microorganisms live on or in the skin Numbers of bacteria are determined by location and moisture content Skin flora are opportunistic pathogens Most skin flora can be categorized in three groups: – diphtheroids – staphylococci – yeasts  Normal Flora of the Skin Diphtheroids – – nondiptherial corynebacteria – Named for their resemblance to Corynebacterium diphtheriae Loading… – Gram-positive bacteria with varied shape and low virulence – Non-toxin producers like C. diphtheriae – Responsible for body odor Odor caused by the bacterial break-down of sweat – Common diphtheroid is Propionibacterium acnes  Normal Flora of the Skin Staphylococci – Gram-positive, salt-tolerant organism – Relatively avirulent Can cause serious disease in immuno- compromised people – Principle species is Staphylococcus epidermidis – Functions on the skin to prevent colonization of pathogenic flora – Maintains balance among microbial skin flora  Normal Flora of the Skin Fungi (yeast) – Tiny lipophilic yeast universally found on normal skin Loading… Usually from late childhood throughout life – Fungi shapes vary among strains Usually round or oval; however can be short rods – Fungi found on skin are generally harmless Can cause skin conditions such as rash, dandruff or tinea versicolor  Staphylococcal Infections Causative Agent – Most hair follicle infections are caused by Staphylococcus aureus More virulent than more common staphylococci found on the skin This bacterium is a significant pathogen and is responsible for numerous medical conditions  Staph Infections Epidemiology – S. aureus is found primarily in the nostrils – Nearly everyone carries it at one time or another 20% of healthy adults carry it continuously 60% will be colonized at some point in a given year – Transmission is usually on hands – Individuals with staphylococcal skin infections shed large numbers of bacteria – Sources of staphylococcal epidemics are difficult to identify precisely  Staphylococcal Wound Infections Causative Agent – Staphylococci Gram-positive cocci in clusters Grow aerobically or anaerobically (facultative) Salt tolerant – Allows survival in numerous foods Most important species are S. aureus and S. epidermidis – Both survive well – Easy to transfer from person to person  Hospital Acquired MRSA Most common form of MRSA Usually after surgery or other invasive procedure Nasal Carriers have higher incident rates Health care workers that are nasal carriers are reservoirs  Community Acquired MRSA Found in general population Usually associated with people who have not been in hospital recently Associated with – Skin to skin contact – Fomites – Cuts or abrasions – Poor hygiene  Clinical characteristics May present as any of the following skin infections: Boils, abscesses, furuncles, folliculitus cellulitis. May have the appearance of a spider bite. Loading… Cutaneous lesions 5 cm or larger in diameter are not uncommon for this infection. Pain and erythema that seem out of proportion to the severity of the cutaneous findings. Necrosis is a strong indicator of infection with CA-MRSA  Diagnosis Incision & drainage (I&D) of the abscess. Culture the contents of the abscess. If I&D is not performed consider culture of draining wounds or aspirate or biopsy of central area of inflammation. Culture exudates from infected site for positive identification of the organism and antibiotic susceptibilities.  Wound Infections Disease production in infected wounds depends on – How virulent infecting organisms are? – How many organisms infect the wound? – Is the host immunocompetent? – Nature of the wound does it contain crushed material or foreign material – Such wounds do not heal until foreign material is removed Most all wound infections Polymicrobial  Common Bacterial Wound Infections Most wounds infections are poly-microbial Common bacterial wound infections include – Staphylococcal wound infections – Group A Streptococcal wound infections – Pseudomonas aeruginosa infections Consequences of wound infection include – Delay in healing – Formation of abscess – Extension of bacteria or their products to adjacent tissues or bloodstream  Staphylococcal Wound Infections Staphylococci are leading cause of wound infections Bacteria commonly present in nose and on skin More than 30 recognized strains – Two account for most human infections S. aureus S. epidermidis  Staphylococcal Wound Infections Symptoms – Bacteria are purulent Produce pus – Infection causes Inflammation Fever in cases where infection has spread – Some strains produce toxic shock syndrome  Staphylococcal Wound Infections Causative Agent – S. aureus Virulence due to the production of extracellular products and antibiotic resistance – Coagulase » Causes blood clotting to evade phagocytosis – Clumping factor » Aids in bacterial wound colonization – Protein A » Hide bacteria from phagocytic cells – toxin » Produces hole in host cell membrane  Staphylococcal Wound Infections Causative Agent – S. epidermidis Bacteria have little or no invasive ability – Maintained on skin surface – Introduced into body from wound » Example: surgical incision – Internalized strains bind and allow colonization of indwelling devices » Colonization produces biofilm which protects organism from phagocytosis  Group A Streptococci Causative Agent – Many cases including epidemics are caused by Streptococcus pyogenes – S. pyogenes is a Gram-positive, β hemolytic cocci Often referred to as Group A, β hemolytic S. pyogenes – Due to presence of group A cell wall polysaccharide Streptococcus species also form the characteristic chain formation  Group A Streptococci Two main Types of Strep Infections – Non-invasive Pharyngitis, Impetigo, erysipelas, puerperal fever – Invasive necrotizing (subcutaneous) fasciitis [NF], streptococcal toxic shock syndrome [STSS], cellulitis, bacteremia, pneumonia, puerperal sepsis  Other Strep Problems… Primary Infections – Suppurative Sequelae – Nonsuppurative – scarlet fever, rheumatic fever, acute glomerulonephritis and erythema nodosum.  Group A Streptococci Pyoderma infection – Characterized by pus production Pyodermas can result from insect bites, burns and scrapes – Such injuries can be so slight that they miss detection Impetigo is most common type of pyoderma  Streptococcal Impetigo Pathogenesis – Infection established through scratches and minor injuries Allows bacteria into deeper layers of epidermis – Bacteria produce destructive enzymes Proteases – degrade skin proteins Nucleases – degrade nucleic acid – Bacteria surface components interfere with phagocytosis  Group A Streptococcal Infections Causative Agent – S. pyogenes (GAS) Β hemolytic, Gram-positive cocci in chains Group A Lancefield cell wall polysaccharide Some strains cause invasive infection – These are more virulent than strains that do not Two extracellular products are responsible for virulence – Pyrogenic exotoxin A » Acts as a superantigen and causes streptococcal toxic shock – Exotoxin B » Destroys tissue through protein breakdown Pseudomonas aeruginosa Infections P. aeruginosa is an opportunistic pathogen Major cause of nosocomial infections – Occasional cause of community acquired infections Pseudomonas aeruginosa Infections Community acquired infections include – Rash and external ear infections Obtained from contaminated swimming pools and hot tubs – Infection of foot bones – Eye infections – Heart valve infections – Lung biofilms Nosocomial infections include – Lung infections – Burn infections Pseudomonas aeruginosa Infections Symptoms – Change in tissue color P. aeruginosa releases pigments that often Loading… color tissues green – Chills, fever, skin lesions and shock Caused by bacterial infection in bloodstream Pseudomonas aeruginosa Infections Causative Agent – Pseudomonas aeruginosa Gram negative rod Motile by means of single polar flagellum Generally aerobic – Can grow anaerobically in the presence of nitrate Produces numerous water soluble pigments – Pigments combine to produce color change in tissues  Chickenpox Varicella-zoster virus (human herpesvirus 3) Transmitted by the respiratory route Causes pus-filled vesicles Virus may remain latent in dorsal root ganglia Prevention: Live attenuated vaccine Breakthrough varicella in vaccinated people Figure 21.11a  Shingles Reactivation of latent HHV-3 releases viruses that move along peripheral nerves to skin Postherpetic neuralgia – sequelae nerve damage. Prevention: Live attenuated vaccine Acyclovir may lessen symptoms Figure 21.11b  Herpes Simplex Human herpesvirus 1 (HSV-1) and 2 (HSV-2) Cold sores or fever blisters (vesicles on lips) Herpes gladiatorum (vesicles on skin) Herpetic whitlow (vesicles on fingers) Herpes encephalitis HSV-1 can remain latent in trigeminal nerve ganglia Cold Sores Caused by Herpes Simplex Virus Figure 21.12 HSV-1 in the Trigeminal Nerve Ganglion Figure 21.13  Herpes Simplex HSV-2 can remain latent in sacral nerve ganglia HSV-2 encephalitis: 70% fatality Encephalitis treatment: Acyclovir  Next Time Respiratory Tract Infections Examples of Respiratory Diseases  Respiratory System Infections Encompass enormous variety of illnesses – Trivial to fatal – Usually transmitted by aerosols Divided into infections of – Upper respiratory Head and neck Uncomfortable but generally not life threatening – Lower respiratory Chest More serious Can be life threatening  Common Cold Symptoms – Malaise – Scratchy mild sore throat – Runny nose – Loading… Cough and hoarsness – Nasal secretion Initially profuse and watery Later, thick and purulent No fever – Unless complicated with secondary infection – Symptoms disappear in about a week  Common Cold Causative Agent – 30% to 50% caused by rhinovirus More than 100 serotypes of rhinovirus Member of picornavirus family Small Non-enveloped Single-stranded RNA genome  Common Cold Pathogenesis – Virus attach to specific receptors on respiratory epithelial cells and multiply in cells Large number of viruses released from infected cells Loading… – Injured cells cause inflammation which stimulates profuse nasal secretion, sneezing and tissue swelling – Infection is halted by inflammatory response, interferon release, and immune response Infection can extend to ears, sinuses and lower respiratory tract before stopping  Common Cold Prevention Treatment – No vaccine – Antibiotic therapy is Too many different types of ineffectual rhinovirus – Certain antiviral medications – Makes vaccination show promise impractical Must be taken at first onset of – Prevention directed at symptoms Hand washing – Treatment with over-the- Keeping hands away from counter medications may face prolong duration due to Avoiding crowds during inhibition of inflammation times when colds are prevalent  Diphtheria Symptoms – Usually begins with mild sore throat and slight fever, fatigue and malaise and dramatic neck swelling – Swollen Lymph nodes in neck – Whitish membrane forms on tonsils, or in nasal cavity Pseudomembrane – Most strains release diphtheria toxin – Production of toxin requires lysogenic conversion of causative agent  Diphtheria Causative Agent – Corynebacterium diphtheria – Variably shaped – Gram-positive – Non-spore forming – Certain strains produce diphtheria toxin  Diphtheria Pathogenesis – Little invasive ability Exotoxin released into bloodstream – Results in damage to heart, nerves and kidneys – Diphtheria toxin Released from bacteria in inactive form Cleaved into A and B chains – B attaches to host cell membrane and enters through endocytosis – A chain becomes active enzyme that inhibits proteins synthesis – Small amount of enzyme inactivates large population of cells which explains potency  Diphtheria Epidemiology – Humans are primary reservoir – Spread by air Acquired through inhalation – Sources of infection include Carriers who recovered from infection Asymptomatic cases People with active disease Contaminated fomites – Bacterium can be carried in chronic skin ulcer Cutaneous diphtheria  Diphtheria Prevention Treatment – Disease results primarily from – Effectiveness depends on toxin absorption early antiserum treatment Not microbial invasion Delay in treatment may be – Prevention directed at fatal immunization Loading… DPT - Neutralize toxin (not available in US) – Antibiotics are given to eliminate bacteria – Immunity wanes after childhood Penicillin and erythromycin Booster immunization should Stops transmission of disease be given every 10 years – No effect on absorbed toxin – Even in presence of treatment 1 in 10 patients die  Pertussis Causative Agent Bordetella pertussis – Gram neg Bacteria – Small, aerobic – Fastidious  Pertussis Pathogenesis – Little invasiveness – Attaches to ciliated epithelial cells in URT – Potent AB toxin Inhibits intracellular signaling Inhibit function of cillia Inflammation  Pertussis Prevention Treatment – Disease results primarily from – Effectiveness depends on toxin absorption early antiserum treatment Not microbial invasion Delay in treatment may be – Prevention directed at fatal immunization – Antibiotics are given to DPT - Neutralize toxin eliminate bacteria – Immunity wanes after erythromycin or childhood azithromycin Stops transmission of disease – Many adults susceptible – No effect on absorbed traveling toxin  Streptococcal Pharyngitis Symptoms – Characterized by Difficulty swallowing Fever Red throat with pus patches Enlarged tender lymph nodes – Localized to neck – Most patients recover uneventfully in approximately a week  Streptococcal Pharyngitis Causative Agent – Streptococcus pyogenes Gram-positive Coccus in chains β hemolytic – Complete hemolysis of red blood cells Commonly referred to as group A streptococcus – Due to group A carbohydrate in cell wall – Basis for identification from other organisms  Streptococcal Pharyngitis Pathogenesis – Causes a wide variety of illnesses Due to numerous virulence factors – Bacteria produces enzymes and toxin that destroy cells – Complications of infection can occur during acute illness – Examples include scarlet fever and quinsy Scarlet fever – superantigen toxin Quinsy – inflammation of tonsil – Post Streptococcal sequelae Acute glomerulonephritis (nephritogenic strains) Acute rheumatic fever  Streptococcal Pharyngitis Epidemiology – Spread readily by respiratory droplets Especially in range of 2 to 5 feet – Infect only humans under natural conditions – Nasal organism spreads more effectively than pharyngeal carriers Anal carriers not common – Dangerous source of nosocomial infections – Peak incidence occurs in winter or spring Highest in grade school children  Streptococcal Pharyngitis Prevention Treatment – No vaccine available – Confirmed strep throat New possibilities on treated with 10 days of horizon antibiotics – Adequate ventilation Penicillin or erythromycin – Avoid crowds are drugs of choice – Eliminates organisms in – Sore throats in presence 90% of cases of fever should be cultured for prompt treatment Prompt treatment is essential to prevent complications  Think About it What are the dangers of an untreated Strep throat infection? Why treat if most patients recover in less than two weeks with or without antibiotics? What is a sequelae? Does strep have any? How is a sequelae differ from a secondary infection?  Bacterial Pneumonias Pneumococcal Pneumonia – Streptococcus pnuemoniae Gram-positive Diplococci Thick polysaccharide capsule 30% healthy adults carriers Klebsiella Pneumonia – Klebsiella pneumoniae Gram-negative Bacillus Encapsulated Redish Sputum Mycoplasma pneumoniae  What do you remember? What were three types of pneumonia? How can you tell them apart? Why wouldn’t penicillin be a good choice for treating mycoplasmal pneumonia? The Influenza Virus  Orthomyxoviruses enveloped, segmented ssRNA 2 types of envelope glycoprotein spikes – Hemagglutinin (HA) – binds to host cells – Neuraminidase (NA) – hydrolyzes mucus & assists viral budding & release genome constantly changes – Antigenic shift - major alteration occurring when segments recombine – Antigenic drift – minor change caused by mutations  Influenza Epidemiology – Highly contagious – Transmitted person to person aerosols – Reservoir humans, birds, swine – Sometimes referred to as zoonotic disease of birds Humans alternative host – Causes periodic pandemics  Influenza Pathogenesis – Inhalation of aerosolized droplets or secretions – Infected cilliated epithelial cells die – Destroys cilliary escalator – Lowers immune defense – Recovery usually week Complete recovery cilliated cells may be 2 months – Can cause death even in normal people – Secondary infections Pneumonia Staph, Strep or Haemophilus influenzae  Influenza Treatment – Vaccines 80-90% effective at prevention – Attenuate virus of epidemic strains – New vaccine each year Medications – Amantadine and rimantadine – Zanamivir (relenza) oseltammivir (Tamiflu) Neuraminidase inhibitors The Influenza Virus Loading… The Incidence of and Percentage of Deaths from Influenza in the United States  Influenza Virus cont. – Antigenic shift - major alteration occurring when segments recombine A person infected with human strain becomes infected with animal strain New virus emerge with combination of animal and human strains Bird flu example right now! – Antigenic drift – minor change caused by mutations  2009 A(H1N1) Swine flu Unique Version Genes from three different species Four different types Symptoms Sore throat, muscle aches ect… vomiting and diarrhea Genetic analysis used for diagnosis Garten et al. SCIENCE10 JUL 2009 : 197-201  Explain to your neighbor How do you identify different strains of flu? What is antigenic drift? What is antigenic shift? Why are cases of bird or swine flu in humans such a big deal?  Tuberculosis Symptoms Causative Agent – Chronic illness – Mycobacterium tuberculosis – Symptoms include Gram-positive cell wall type Slight fever with night sweats Slender bacillus Progressive weight loss Acid fast due to mycolic acid Chronic productive cough in cell wall – Sputum often blood Slow growing streaked – Generation time 12 hours or more Resists most prevention methods of control  Tuberculosis Pathogenesis – Usually contracted by inhalation of airborne organisms – Bacteria are taken up by pulmonary macrophages in the lungs – Resists destruction within phagocyte Organism prevents the fusion of phagosome with lysosomes; allows multiplication in protected vacuole  Tuberculosis Pathogenesis – Organisms are carried to lymph nodes – About 2 weeks post infection intense immune reaction occurs Macrophages fuse together to make large multinucleated cell Macrophages and lymphocytes surround large cell – This is an effort to wall off infected tissue – Activated macrophages release into infected tissue Causes death of tissue resulting in formation of “cheesy” material  Tuberculosis Epidemiology – Estimated 10 million Americans infected Rate highest among non- white, elderly poor people – Small infecting dose As little as ten inhaled organisms – Factors important in transmission Frequency of coughing, adequacy of ventilation, degree of crowding  Tuberculosis Epidemiology – Tuberculin test used to detect those infected Small amount of tuberculosis antigen is injected under the skin Injection site becomes red and firm if infected Positive test does not indicate active disease  One minute summary What causes TB? How is it transmitted? How do you diagnose? How do you treat?  Next Time Digestive System Diseases