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Transcript
College of Medicine Microbiology Microbiology Dr.Jawad K. Tarrad Microbial Pathogenesis and infection: Dr. Bara H. Hadi ----------------------------------------------------------------------------------------Infection is presence and multiplication of pathogenic microbe within human body, and cause symptoms of infection. The infection differs from other diseases is that caused by living microbial pathogens. The infection does not arise in vacuum. It results from interaction of several factors include mainly three factors: a. Pathogenic microbe. b. Susceptible host. c. Environmental factors Infection (or not) is determined by balance between number and virulence of microbe and competency of that host defense. If microbes are overcome, the disease results. Outcome of most host-parasite relationship is dependent on three main factors ; a. Number of pathogenic microorganism infecting the host(dose). b. Degree of pathogenicity of organism(virulence). c. Degree of host defense (resistance). The infectious disease equation: Number of organisms(dose) x Virulence = Infectious Disease Host resistance Stages of microbial pathogenesis: 1. Encounter of microbe with susceptible host. 2. Entry and adhere to susceptible host tissues. 3. Multiply and spread to target cells inside human body. 4. Evade host defense mechanism. 5. Damage the host tissues and disease symptoms. 6. Progression or resolution of the disease. 7. Shedding of microbial pathogen into environment. 1 Sources of infection: 1. Human : is common source of infection from patients or carriers. The carrier is person recovered from disease but harboring pathogenic organism in his body. Fomites are inanimate objects of patients that may be contaminated and serves as source of pathogenic organisms. The infectious agent is transmitted from person to person by various ways such as direct contact, kissing, inhalation of aerosols, fecal-oral, venereal contact, blood transfusion and insect bite. 2. Animals ; are important source of pathogenic organisms that infect human. The animals can be serve either the source (reservoir )or made transmission (vector)of certain organism. The organisms can be transmitted from infected animals to human when direct contact with animals, and handling or consumption of their products , also transmitted indirectly by bite of vectors( insect). 3. Food: the foods are most important media for surviving and transporting the infection eg. food poisoning. Transmission of organisms from food to human during feeding or food handling. 4. Water: many pathogenic microbes are found in water. The infectious agents are transmitted to human by consumption of water or when swimming in it. 5. Soil: it serves as source of infection for many pathogenic organisms or spores of some bacteria and fungi. The infectious disease agents are transmitted to human through direct work with soil that contain infectious agents or inhalation of dust . Portals of entry(routes of infection) : Major: 1. Respiratory tract(nose). 2. GIT(mouth). 3. Skin, non-intact. 4.Genital tract(vagina). Minor : 1. Eye. 2. Anus 3. Ear canal 4. Urethral canal. Mode of transmission: Horizontal transmission: Inhalation: the pathogenic agents may be transmitted by inhalation of respiratory secretions of infected patients, or by inhalation of contaminated dust with pathogenic bacteria . Ingestion: the infectious agents can be transmitted by consumption of contaminated water or food. Skin : any small break, abrasion, and wound in skin that permit initial entry. The transmission may occur through direct contact(such as handshaking, kissing)with infected person or infected animal or during handling of fomites of patients, or the organism is transmitted indirectly by vector bite . Injection of needles during intravenous drug use or indwelling catheter, have role in transmission. Blood transfusion: some pathogenic microorganisms can be transmitted by blood transfusion. Sexual intercourse: certain pathogenic microorganisms can be transmitted by sexual contact in homosexual or heterosexual persons. 2 Vertical transmission: The pathogen can transmitted from infected mother to her fetus ; Across the placenta (prenatal) ,or At time of delivery from birth canal (perinatal), or During breast feeding (postnatal) . Adherence of microbe to host cell: The microbes tend to exhibit cell and organ specificities dependent on : 1. Adherence factors of microbe interact with specific cellular receptors on surface of target cell. 2. Environmental factors such as physical barriers, local temperature, pH, oxygen tension and others are very important in initial infection. The presence of cellular receptors and environmental factors as well as initial location and other conditions on tissue can determine which part of human body is infected . Multiplication of pathogen: The microbes can be multiplied by growing at site of adherence and form colonization. Colonization means establishment of a site of microbial multiplication in the host. The pathogen must multiply to sufficient number in host tissues to cause the symptoms of disease. The period between entry pathogenic organism and beginning of symptoms known as incubation period. Invasion of host tissues: The invasiveness is ability of microorganism to spread into host tissues. Some bacteria are non-invasive, but multiply at site of adherence. Invasive bacteria secrete several invasive factors (spreading factors) that result in degrading tissue and facilitate the pathogen spreading through human body. Evasion of host defense: Generally, Some mechanisms that play important role in resistance of pathogenic organism to host defenses: Certain bacteria have capsule that prevent the phagocytosis. Certain bacteria secrete enzymes(eg. IgA protease) that destroy antibody IgA. Certain bacteria produce toxin(such as leucocidin) that lead to destroy the immunity cells. Change in genetic materials lead to antigenic variation. Certain pathogens able to survive and grow intracellular. Pathogenesis (mechanism of damage and death of cell): In general, the pathogenic microbes cause damage of tissue by three main mechanisms of pathogenesis: 1. Production of toxins and enzymes. 2. Immunopathiesl reactions . 3. Mechanical effects. Toxin production(toxigenicity): the ability of pathogen to produces toxin that damage the host tissue and produce disease. Bacterial pathogens produce two types of toxins; exotoxin and endotoxin. Exotoxin(protein) is produced by Gram positive and Gram negative bacteria . In contrast, endotoxin(LPS) is produced by only Gram negative bacteria. 3 Exotoxins produce various effects by different mechanisms in host body. For example, Diphtheria toxin cause cell death by inhibition of protein synthesis. Enterotoxins cause watery or bloody diarrhea by stimulation of adenylate cyclase. Tetanus toxin cause paralysis by effect on neurotransmitters, and so on. Endotoxins less potent than exotoxins and produce similar effects on host such as fever , hypertension, DIC and shock. Immunopathies reaction : Microbial pathogens may stimulate the immune system to attack the host tissue because it carries antigens that resembled those of host. It may be appears as autoimmune response(the immune system fails to distinguish between self and non-self, and attacks part of the body) or as crossreaction between antigens of pathogenic microbes and antigenic components of human body. Some diseases also might be due to hypersensitivity reaction. Tuberculosis is a good example of involvement of hypersensitivity reaction in disease. Mechanical effect causes of disease: Mechanical obstruction results from pathogen such as many Ascaris can occlusion of intestine lumen. A single worm may migrate to bile duct and obstruct the passage of bile. Mechanical obstruction results not from microbe but from response of inflammatory host such as infection of prostate can obstruct flow of urine from bladder. Outcome of infection: If microbial pathogens overcome the defenses of infected individual, the disease resulted and may cause death of infected host, while the host defenses overcome in first step, the disease is not occurring. If the host defenses overcome the virulent microbe after infection, this lead to repair and healing, and recovery from infection. If the host defense is failure to eliminate the microbe from the body, the infection may become persistent infection for long period. Types of Persistent infection: 1. Chronic infections: some patients who have infected with some microbes continue to multiply and produce significant symptoms of disease for long period. 2. Latent infection: some patients recover from initial infection and microbe production stops. However, the patients harboring the microbe in their bodies (remain as carriers) without significant symptoms. Microbes shedding: The last stage in pathogenesis is the shedding of infectious microbes. The microbial pathogens leave the host and shed back into environment or return to reservoir or enter a new host. 4