chapter_13_Infection and Infectious Diseases - Summer 2020.pdf

Chapter 13 Infection and Infectious Disease (Microbe-Human Interactions) Chapter 13 Topics - Human Host - Progress of an Infection - Epidemiology You’re never alone • From the moment of birth we begin to acquire bacteria • Our bodies house 800-1000 different species of bacteria. • Bacterial cel...

Chapter 13 Infection and Infectious Disease (Microbe-Human Interactions) Chapter 13 Topics - Human Host - Progress of an Infection - Epidemiology You’re never alone • From the moment of birth we begin to acquire bacteria • Our bodies house 800-1000 different species of bacteria. • Bacterial cells outnumber our own cells 10 to 1. • All this and you’re still healthy! What is healthy and what is disease? • Health – a stable state in which all the body’s systems function adequately. • Disease – is an unstable state, ending with either recovery or death. Any deviation from health. Healthy humans and bacteria • Normal flora, or biota, are the bacteria we coexist with in a stable relationship. • These bacteria inhabit the surfaces of our body -skin -conjunctiva -nasal cavity and nasopharynx -mouth and intestinal tract -vagina -urethra Symbiotic Relationships Between Microbes and Their Hosts • Normal Microbiota in Hosts – Also termed normal flora and indigenous microbiota – Organisms that colonize the body’s surfaces without normally causing disease – Two types • Resident microbiota • Transient microbiota © 2012 Pearson Education Inc. Figure 14.2 Normal microbiota of the human nasal cavity Table 14.2 Some Resident Microbiota • Resident biota – inhabit the body through out life, can be reduced but never eliminated • Transient biota – inhabit our bodies under certain circumstances and can be removed by cleansing • Opportunists are bacteria that cause disease when the hosts defenses are weakened, or normal flora is altered. –Broad spectrum antibiotics –Implantation of devices Acquire resident flora • Beneficial outcome – Removed by immune system – Microbial antagonism • Adverse effects – Escape immune system – Multiply and disrupt tissue Our normal flora changes over time. • 2 weeks general colonization of normal flora • 6 months – with teeth, Streptococci population increases, and Fusobacterium and Bacteroides colonize gumline. • With breast milk 90% of intestinal bacteria is Bifidobacterium. Once weaned her flora will resemble more adult intestinal flora. • Vaginal bacteria change with estrogen production. Increase estrogen increase lactobacilli (acidic), decrease estrogen, decrease lactobacilli (alkaline) Symbiotic Relationships Between Microbes and Their Hosts • Symbiosis means “to live together” • We have symbiotic relationships with countless microorganisms • Types of symbiosis – Mutualism – Commensalism – Parasitism © 2012 Pearson Education Inc. Symbiotic relationships • Commensalism – (+, 0) Healthy humans and their normal flora. • Mutualism – ( +, +) usually neither survives without the other. Ruminants and digestive bacteria. • Parasitism – (+, -) Pathogenic bacteria. BUT some commensals could be pathogenic under the right circumstances, this makes them opportunists • **Remember - the right bacteria, in the wrong place, at the right time = disease** Table 14.1 The Three Types of Symbiotic Relationships Basic defenses (an intro) • We have 3 general defenses – Structural – Mechanical – Biochemical More about these later Microbes have adapted to survive these defenses -ability to adhere Adhesins located on the cell surface, or on pili. Bind to complementary receptors on epithelial cells. • Adhesins are very specific to particular receptors. Usually only binding to one kind of epithelial cell in one kind of animal. • Other bacteria persist because they produce defensive toxins that inhibit their competition called bacteriocins. Progress of an Infection • • • • • • • Pathogenicity Portals of entry Attachment Surviving host defenses Causing disease Process of infections and disease Portals of exit Pathogenicity • True pathogens • Opportunistic pathogens • Virulence True pathogen • Cause disease in healthy individuals • Associated with a specific and recognizable disease Opportunistic pathogen • Cause disease in immune compromised host • Gain access (injury) to sterile regions Factors that predispose a person to infections. Table 13.4 Factors that weaken host defenses and increase susceptibility to infections Portals of entry • Most pathogens have specific portals of entry – Skin – Gastrointestinal tract (mucous membrane) – Respiratory tract (mucous membrane) – Urogenital (mucous membrane) – Placenta – Inoculum size Figure 14.3 Routes of entry for invading pathogens Ear Broken skin Insect bite Conjunctiva of eye Nose Mouth Placenta Vagina Anus In males: Penis Urethra The Skin • 2 functions – protect interior tissues, regulate temp. Microbial environment - very dry, any moisture comes from perspiration and oil. - fatty acids can be inhibitory - lysozyme in sweat - salt can be inhibitory Best examples of skins usefulness are burn victims. Burn victim with a pseudomonas infection Pseudomonas shows up as a greenish tinged bacteria. The skin cont. • Normal flora Keep skin healthy by occupying space. - Staphylococcus sp. - diptheroids - fungi - mites *10,000 bacteria per square centimeter of dry skin!* Diphtheroids – - wide range of bacteria from genus Corynebacterium. - examples: cutaneous diphtheroids, anaerobic diphtheroids (most common in areas rich in sebaceous glands). - Corynebacterium acnes originally used to describe skin anaerobic diphtheroids, now use Propionibacterium acnes and as P. granulosum. Bacteroides – - genus of gram negative, bacillus bacteria - Bacteroides species are non-endospore forming, anaerobes that may be motile or non-motile, depending on the species. Staphylococcus species • Staph. aureus 5-10% of people, and epidermidis ubiquitous. facultative anaerobe, very hardy. • aureus is most pathogenic, but epidermidis causes most wound/procedure site infections. Diptheroids (gram + rods) • Propionibacterium acnes – lives deep in hair follicles, feeding on sebum. • “Coccal people” vs “diphtheroid people” Skin • Staphylococcus aureus – Boils • Haemophilus aegyptius – Pinkeye Post surgical MRSA The Conjunctiva • Protected by the bathing of the tears from the lacrimal gland down to the nasolacrimal duct. • Few bacteria are found here – Staphylococcus and diphtheroids The Movement of Microbes into Hosts: Infection • Portals of Entry – Mucous membranes • Line the body cavities that are open to the environment • Provide a moist, warm environment hospitable to pathogens • Respiratory tract is the most common site of entry – Entry is through the nose, mouth, or eyes • Gastrointestinal tract may be route of entry – Must survive the acidic pH of the stomach © 2012 Pearson Education Inc. The Nasal cavity and Nasopharynx • Average adult inhales 10,000 microorganisms a day! • Warm moist environment • Thank your ciliary escalator! • Problems with cilia = infections – Cystic fibrosis – Smoking Normal flora • Staphs and Streps are present • Lactobacillus is present • Some gram (–) pathogens are present – Moraxella catarrhalis – middle ear infections – Haemophilus influenzae Respiratory tract • Streptococcus pneumoniae – Sore throat, meningitis • Fungi – Cryptococcus – pneumonia The Mouth • One of the first places to be colonized • Warm, moist, perfect mode of entry. – Violent! Talking chewing swallowing dislodge bacteria! – Saliva (lysozyme) constantly washing out mouth. Normal flora • 80 different species – Streptococcus spp. Most are harmless, but mutans causes tooth decay – Staphylococcus spp. Widespread – Moraxella, Haemophilus, lactobacilli, and diphtheroids are present. – Anaerobes are present beneath the gumline, Bacteroides spp, Fusobacterium spp. – Candida albicans – yeast, thrush The Intestinal Tract • The esophagus, stomach, and upper small intestine, too harsh. - stomach acid, bile salts, peristalsis all inhibit bacteria - The large intestine moves more slowly and houses a lot of bacteria - about 1/3 dry weight of feces is bacteria Normal flora • Hundreds of species live in the large intestine. • Vast majority are anaerobes, Bacteroides, Bifidobacterium, Fusobacterium and Clostridium make up 90% of all bacteria. • Many are facultative anaerobes, and fairly common. • Most inhibit the growth of competing organisms, pathogens or not. Gastrointestinal tract • • • • Salmonella, Shigella, Vibrio Viruses – polio, hepatitis A Protozoan – Giardia lamblia Enter via ingestion or the anal route Urogenital • Numerous sexual transmitted diseases (STDs) • Virus – human papillomavirus – Genital warts • Protozoan – Trichomonas – trichomoniasis • Bacteria – Neisseria gonorrhoeae – Gonorrhea • Acquire by intercourse or intimate contact The Vagina • Warm moist environment, only low pH and few nutrients stop bacteria from growing. • Mostly Lactobacilli keep the pH acidic. • A few other bacteria are present, but also Candida albicans, the yeast. The Urethra • The majority of the urethra is free of microorganisms. Only the area closest to the outside has bacteria. • Urethral epithelium are packed closely together and resist adherence. • The urine is very effective in keeping the area flushed of any bacteria. • In fact urine can be used as excellent growth media. Common STDs which include viruses, protozoan, fungi, and bacteria. Placenta • Some bacteria can penetrate the placenta barrier – Syphilis spirochete • Birth canal – Herpes simplex virus Microorganisms and Human Interaction Part II How do infections occur? • Microbes must be able to overcome our defenses and cause disease. • Disease causing capabilities are called virulence factors • Infection – growth of the pathogen in the body • Disease – the consequence of infection 7 easy steps to becoming successful pathogen! • You must: 1. Maintain a reservoir (a place to live before and after infection) 2. Leave the reservoir and enter a host 3. Adhere to the surface of the host 4. Invade the body of the host 5. Evade the body’s defenses 6. Multiply within the body 7. Leave the body and return to its reservoir or enter a new host Reservoirs • Carriers • Vectors • Nonliving Maintaining a reservoir • These are the places microbes exist when they are not infecting humans. – Ebola virus infects humans and gorillas. • If the reservoir is eliminated, the pathogen is eliminated. Human reservoirs • Humans are the only reservoirs to many pathogens that are too fragile to live outside the body. (several STD’s gonorrhea, syphilis, and common cold) – Someone serving as a reservoir is called a carrier • Seemingly healthy people who are infected but have not developed symptoms are Incubatory carriers. (HIV vs AIDS) • Chronic carriers have harbored a pathogen for months or years even. (Typhoid Mary and Salmonella typhi) Carriers • • • • • Asymptomatic Incubation Convalescent Chronic Passive Examples of different types of carriers. Fig. 13.12 Carriers • Human diseases that have an animal reservoir are called zoonotic – Rabies is a mammalian disease – Animal reservoirs can profoundly affect human disease patterns. • Influenza recombination • Yellow Fever in Cuba and Panama Zoonotic infections are caused by vectors and animal reservoirs spreading their own infections to humans. Table 13.10 Common zoonotic infections Nonliving Reservoirs • Soil – Transmit bacteria, protozoa, helminths, fungi – Transmit spores, cysts, ova, larvae • Water – similar to soil – Other pathogens survive in water, soil, house dust. • Versatile pathogens, C. tetani, V. cholerae, S. typhi Getting to and Entering a Host • Disease transmission – pathogen leaves the reservoir and enters the host – Critical phase – Bordetella pertussis transmitted by respiratory droplets. • Portal of entry – where it enters the hosts body, usually where we find normal flora. – The nose is the portal of entry for B. pertussis. – May change depending on point of contact. • The likelihood of infection depends on how many cells enter. • Infectious dose, (ID 50)- the number of organisms needed to establish infection in 50% of test animals. • Lethal dose, (LD 50) – the number of organisms needed to cause death in 50% of test animals. Inoculum size • Infectious dose (ID) – minimum number of bacteria required to cause disease – Low ID = high virulence Modes of transmission • 3 Basic types; – Human contact (direct or indirect) – Vehicles (inanimate objects) – Vectors (living transmitters, arthropods) Human Contact (horizontal) • Respiratory droplets – Sneezing, coughing, laughing, speaking – Most common method of transmitting disease. – Last only a brief time, but very efficient A sneeze can release enormous amounts of moist droplets, and the dry droplets form droplet nuclei. • Direct body contact – Touching, kissing, sexual intercourse – STD’s spread by direct mucous membrane contact • Very fragile pathogens • Nonsexual means, herpes simplex one, contact or exchange of saliva. • Vertical transmission is transmission from mother to infant. – Prenatal, across the placenta. Syphilis and HIV. – Perinatal,during or after birth. Gonorrhea, herpes, or HIV. Vehicles (inanimate objects) • Fomites – Inanimate objects such as eating utensils, towels, bedding, handkerchiefs that transmit disease. • Depends on portal of entry, utensils are likely fomites for intestinal pathogens, entry is mouth. • Not a reservoir, little survival. – Hand washing can break the cycle of transmission. • Or disinfection of fomites can be helpful as well • Example: common cold Vectors • Biological – Participates in the pathogen’s life cycle – Infected with the pathogen – Transmit by bites, defecation • Mechanical – Not part of pathogen’s life cycle – Not infected with the pathogen Vectors (living transmitters) • Arthropod vectors – Can carry pathogens on their bodies (mechanical vector) most flies. – Are an essential link in transmission by being part of the life cycle of the microorganism. (biological vector) fleas, ticks, mosquitoes Other “combined” modes of transmission • Fecal – oral route – Pathogens transmitted from infected feces to mouth of new host – Direct hand to hand (poor hygiene) – Hand to mouth by vehicles such as water, food and fomites – Vectors (flies to food) – V. cholerae is a good example • Parenteral transmission – Microorganisms are deposited directly into blood vessels or deep tissue (AIDS, Malaria, elephantiasis) – Biological vector bites through skin – Intravenous drug users share needles – Deep wounds or puncture wounds allowing anaerobic pathogens to enter. • Airborne transmission – Organisms that can survive in the air are inhaled. – Can survive for long periods, and transmitted across distances. May settle in dust. M. tuberculosis Attachment • Adhesion – Binding between specific molecules on both the host and pathogen • Structures – Capsules – Pili or fimbriae – Hooks Example of how fimbriae and capsules are used to adhere to the host cell. Fig. 13.5 Mechanisms of adhesion by pathogens Adhering to body surface • Pathogens like normal flora use adhesins to stick to body surfaces. – Tissue trophism (which cells or tissues a pathogen attacks) depends on the adhesins and receptor sites of the target cells. – Most pathogens produce several types of adhesins. B. pertussis – filamentous hemagglutinin (FHA) binds to sulfatide on cilia of respiratory cells. Examples of different microbes, the disease they cause, and the structures used for adhesion. Table 13.6 Adhesion properties of microbes. Invading the body • Most pathogens are invasive, entering host cells and/or tissues. A few are noninvasive, remaining on the surface. – Invasive pathogens that must enter host cells to live are intracellular pathogens, the cell is a nutrient rich, safe environment. • Some trigger phagocytes to engulf them and survive in the phagolysosome (M. tuberculosis, Listeria monocytogenes) • Others have invasins and trigger non phagocytic cells. Salmonella and Shigella • Some stay in cells, others move on to deeper tissue Evading the bodies defenses. Tricky pathogens! • Keeping phagocytes from actually having direct contact. – Capsules: S. pneumoniae without capsules are avirulent (harmless), those with thickest capsules are the most virulent. – Surface proteins keep phagocytes at bay. S. pyogenes has M proteins • Notice the very thick capsule around the diplococcus, S. pneumoniae Pathogens challenge the specific immune system • Pathogens that make it past nonspecific defenses run up against the specific immune system. • However they can evade our immune system by changing their surface antigens (antigenic variation) thus they “look” different. N. gonorrhoeae • Some attack antibodies with IgA proteases. N. gonorrhoeae Multiplying in the host • How do pathogens damage tissue? – Production of toxins (poisonous products that harm tissue) The Nature of Infectious Disease • Virulence Factors of Infectious Agents – Pathogenicity • Ability of a microorganism to cause disease – Virulence • Degree of pathogenicity • Virulence factors contribute to virulence – – – – – © 2012 Pearson Education Inc. Adhesion factors Biofilms Extracellular enzymes Toxins Antiphagocytic factors Figure 14.8 Relative virulence of some microbial pathogens More virulent Francisella tularensis (rabbit fever) Yersinia pestis (plague) Bordetella pertussis (whooping cough) Pseudomonas aeruginosa (infections of burns) Clostridium difficile (antibiotic-induced colitis) Candida albicans (vaginitis, thrush) Lactobacilli, diphtheroids Less virulent Bacterial toxins • Exotoxins – Gram positive and Gram negative cells – Excreted (ex. Hemolysins) – Highly toxic in small amounts • Endotoxins – Gram negative cells – Membrane associated • Lipopolysaccharide (LPS) – Fever associated Exotoxins are released by the bacterium and directly affect different host organs, while endotoxins are released after the bacterium is lysed. Fig. 13.7 The origins and effects of circulating exotoxins and endotoxins. • Toxins – Exotoxins released outside the cell. - AB toxins, composed of two protein subunits. A active, B binding. Work in tandem to alter or inactivate cellular components or enzymes. Ptx interrupts cellular communication. – Proteolytic toxins, attack host proteins and split them – Pore forming toxins, form pores that essentially cause host cells to “leak” – Enzymatic activity is the reason these toxins are so potent. 130 micrograms of tetanus toxin is enough to kill an adult. • Exotoxins often enter the blood stream and do damage across the body. • We can fight exotoxins with certain antibodies. From here we developed toxoid vaccines. • Toxins may alter the growing environment for the bacteria • Toxins may be ingested with food, these are called poisonings not infections. • Other toxic proteins; Toxic extracellular enzymes – Cytolysins- attack cell membranes – Hemolysins – lyse red blood cells – Leukocidins – lyse white blood cells – Hyaluronidase – breaks down the cementing matrix that holds tissues together – Collagenase - degrades collagen in connective tissue – Coagulase – causes fibrinogen to form fibrin clots – Kinases – dissolves fibrin clots Leaving the body • When the pathogen leaves the host body it exits through the portal of exit. – Respiratory exit is same as entrance, the nose. – Gastrointestinal entrance is mouth, exit is anus. - diarrhea causing pathogens especially – STD pathogens will exit the body the same way they entered across mucous membranes – Parenterally by arthropods leave as they came in a drop of blood. Portal of exit • Enables pathogen to spread to other hosts – – – – – – Respiratory Salivary Skin Fecal Urogenital Blood Figure 14.11 Portals of exit Ear (earwax) Eyes (tears) Nose (secretions) Broken skin (blood) Mouth (saliva, sputum) Skin (flakes) In females: Mammary glands (milk, secretions) Vagina (secretions, blood) Anus (feces) Seminal vesicles (semen and lubricating secretions) Urethra (urine) A sneeze can release enormous amounts of moist droplets, and the dry droplets form droplet nuclei. Representation of the different portals of exit. Fig. 13.9 Major portals of exit of infectious diseases. Epidemiology • The study of disease in populations – Frequency data – Distribution data • Center for Disease Control and Prevention (CDC) Epidemiology – Statistics – Strategies – Reservoir – Carriers – Vectors – Acquisition and transmission – Nosocomial – Koch’s postulates Koch’s postulates • Method used to determine the etiologic agent • Ex. Toxic shock syndrome, AIDS, Lyme disease, Legionnaires Figure 14.7 Koch’s postulates Agent not typically found in healthy subjects The suspected agent must be present in every case of the disease. Diseased subjects Healthy subjects Petri plate Bacterial colonies The agent must be isolated and grown in pure culture. Streaked plates Injection The cultured agent must cause the disease when it is inoculated into a healthy, susceptible experimental host (animal or plant). The same agent must be reisolated from the diseased experimental host. The Nature of Infectious Disease • Causation of Disease: Etiology – Exceptions to Koch’s postulates • Some pathogens can’t be cultured in the laboratory • Diseases caused by a combination of pathogens and other cofactors • Pathogens that require a human host – Difficulties in satisfying Koch’s postulates • Diseases can be caused by more than one pathogen • Pathogens that are ignored as potential causes of disease © 2012 Pearson Education Inc. Nosocomial infections • Infectious diseases that are acquired or developed from a hospital stay – Urinary tract infections – Respiratory infections – Surgical incisions The most common nosocomial infections. Fig. 13.16 Most common nosocomial infections.