Lecture 1 – Pathogenesis of Microbial Disease PDF

BIOL 2010 Lecture 1 – Pathogenesis of Microbial Disease CHAPTER 2 BAILEY AND SCOT T’S – CHAPTER 3 In this lecture 2.0 Pathogenesis of Infectious Disease 2.1 Discuss infection versus infectious disease 2.2 Discuss normal flora and their role in infectious disease 2.3 Describe primary and secondar...

BIOL 2010 Lecture 1 – Pathogenesis of Microbial Disease CHAPTER 2 BAILEY AND SCOT T’S – CHAPTER 3 In this lecture 2.0 Pathogenesis of Infectious Disease 2.1 Discuss infection versus infectious disease 2.2 Discuss normal flora and their role in infectious disease 2.3 Describe primary and secondary infection 2.4 Describe the phases of the infectious process 2.5 Explain the characteristics and pathogenesis of commonly encountered clinically significant microorganisms, including the most frequently isolated species by body system, under various groupings. 2.6 Discuss bacterial virulence 2.7 Discuss endotoxins and exotoxins Thought questions What makes some microbes pathogenic but others non-pathogenic? If microbes are ubiquitous, and we encounter them all the time, why don’t we develop more infections? Host-Microbe Relationships Symbiosis: two organisms living together Commensalism: Microorganism benefits while host is not harmed. Mutualism: Microorganism and host benefit Parasitism: Microorganism benefits while the host is harmed. Indigenous (normal) flora: Microorganisms commonly found on or in healthy persons Colonization: Refers to the growth of microbiota in or on a body site without causing damage or notable symptoms Resident Microbiota: or microorganisms that colonize an area for months or years Transient flora: Microorganisms temporarily colonizing a host Carrier state: Condition of hosts capable of transmitting the infection Host-Microbe Relationships Host-microbe relationship can be: Pathogenic: Organism causes a disease Ex. Salmonella Nonpathogenic: Organisms which don’t generally cause disease Ex. Corynebacterium species – indigenous flora of skin Opportunistic pathogen: Organisms which cause infections when one or more host defenses are compromised Ex. Indigenous flora Carriers: People can carry pathogens in body parts without it causing an infection/disease Ex. Many people carry Staphylococcus aureus in their nares, without experiencing an infection. If this gets passed to another person, they can cause severe infections. Terms The degree to which a microorganism can cause disease is called pathogenicity Pathogens are therefore highly pathogenic – they often damage the human host severely Non-pathogens have low pathogenicity This distinction is not always clear, as host factors can affect the development of infections and disease The degree of pathogenicity is called virulence Indigenous Microbiota in humans Host-Microbe Interactions Infection: growth and multiplication of microorganisms that result in damage to the host When infection produces notable changes in human physiology = disease occurs Disease which can be transmitted: Infectious Disease Host-Microbe Interactions For an infection to occur, a few things must occur (Image on right) Host factors, and an organism’s pathogenicity/virulence plays a role in the development of infection Host-Microbe encounter Recall: Microbes are everywhere! Hosts can encounter microbes in a variety of ways, based on Reservoirs: The origin of the etiologic agent or location from which it disseminates Mode of Transmission: The means by which etiologic agents are brought in contact with the human host Host-Microbe encounter RESERVOIR TRANSMISSION Humans Direct – host contacts microbial Indigenous flora reservoir directly Infected individuals Ex. birth, sexual contact, Animals Indirect – host encounters Ex. through eating meat, animal bites microbe through an agent Non-living – fomites Environment o How HAI are spread Ex. water, soil Living - vectors Host-Microbe encounter Colonization of host surfaces Colonization can be Harmless (i.e. become part of flora or transient colonizers) The last step in the establishment of a long-lasting, mutually beneficial (i.e., commensal) or harmless relationship between a colonizer and the human host. Entry, Invasion and Dissemination In most instances, to establish infection, microorganisms must penetrate or circumvent the host’s physical barriers (i.e., skin or mucosal surfaces); Overcoming these defensive barriers depends on both host and microbial factors  Skin Physical Barriers Against Initial Colonization Mucous = first line of membranes defense Organ specific defenses Overview of Host Barriers Phagocytes Coagulation System When microbes penetrate physical Inflammation barriers Cytokines Antibodies Host barriers Once a microbe attains contact with a human host, outcome is based on interaction with host and can lead to colonization Persistent survival of microbes on a surface of the human body Host has various defenses to prevent colonization Nonspecific, physical barriers: The first areas to encounter microorganisms, and offer first line of defense Physical surfaces like skin and mucus membranes Nonspecific barriers Nonspecific characteristics unique to specific organs Host barriers - Skin Skin as a barrier It is a non-specific defense Protective factors include: Dry, acidic, cool outer layer which acts as a physical barrier Production of antibacterial substances such as sebum and sweat Conjunctiva produces lysozymes in tears Indigenous flora may also secrete substances which deter growth of pathogens – microbial antagonism Skin-Associated Lymphoid tissue Host barriers – Mucus Membrane Mucus membranes as a barrier It is a non-specific defense – lines respiratory tract, GI tract and genitourinary tract Protective factors include: Rapid sloughing of mucosal cells Mucus (produced by goblet cells)– helps trap bacteria Production of antibacterial substances such as Lactoferrin, Lysozymes, Lactoperoxidase Mucosa-Associated Lymphoid Tissues (MALT) – consist of immune cells which respond to bacteria which have penetrated the membranes Host barriers – Mucus Membranes Summary of specific defenses in various parts of the body’s mucous membranes Host barriers – Other nonspecific barriers Specific characteristics which deter growth of pathogens Oral cavity consists of saliva, antibody (IgA), lysozymes and indigenous flora which confer protection Stomach has low pH and proteolytic enzymes Small Intestines have bile salts and resident microbiota Upper Respiratory tract have cilia Vaginal lining has a low pH, resident microbiota and a thick mucus plug Host Barriers - Phagocytes Host also has various defenses when microbes are successful in penetrating physical barriers Phagocytes are white blood cells which ingest and destroy bacteria and other foreign particles Process is called phagocytosis Main cells: Neutrophils or Polymorphonuclear Neutrophils (PMN) Monocytes/Macrophages Dendritic cells Note: Not all microbes can be targeted by PMNs Host Barriers - Phagocytes Host Barriers - Inflammation Inflammation is a broad term – includes cellular and biochemical components Manifestations of inflammation: Swelling, Redness, Heat, Pain Complement system Cascade which attracts and enhances the activities of phagocytes OR directly kills bacteria (via Membrane Attack Complex) Coagulation System Walls off the site of infection Cytokines Chemical messengers secreted by many immune cells which enhance immune response Host Barriers - Inflammation Host Barriers - Antibodies Antibodies are the central molecule of the immune system and highly specific Antibodies (or immunoglobulins) Secreted by Plasma cells (activated B cells) in response to a foreign substance Such as chemicals, toxins, components of organism’s structures Usually proteins or polysaccharides Protect the host if organism is encountered 2nd or 3rd time – has memory Circulate in the liquid portion of the host’s blood, as well as in secretions (ex. saliva) Overcoming Host Barriers Despite host barriers, microorganisms can overcome them to colonize body surfaces and/or cause infection Colonization can be Harmless Ex. Indigenous microbiota First step in the development of infection Overcoming Host Barriers How do microbes overcome host barriers? Microbes have defenses against ALL host barriers Defenses against first line of defense (ex. physical barriers) Virulence factors Biofilm Formation  Overcoming Host Barriers Some host factors can also break the barrier such as: Trauma Deep wounds, abrasions – including surgical wounds, needle sticks Burns Childbirth Inhalation Smoking, toxic gas inhalation Implantation of Medical Devices Overuse of Antibiotics Chronic diseases Previous infections Chronic diseases: ex. diabetes  Overcoming Host Barriers Microbial Strategies to overcoming first line of defenses: 1. Survival Against Environmental Conditions Localization in moist areas Protection in ingested or inhaled debris Expression of specific metabolic characteristics (e.g., salt tolerance) 2. Achieving Attachment and Adherence to Host Cell Surfaces Pili Adherence proteins Biofilms Various protein adhesins 3. Other Factors Motility Production of substances that compete with the host for acquisition of essential nutrients (e.g., siderophores to capture iron) Ability to coexist with other colonizing microorganisms Overcoming Host Barriers – Virulence Factors Virulence factors are characteristics which allow pathogens to cause damage to host. Most virulence factors protect organism against host attack or mediate damaging effects on host cells Virulence factors can be specific to certain pathogenic genera, species or strains Knowledge of a microorganism’s capacity to cause infections plays a major role in the development of clinical microbiology An organism can possess more than one virulence factor Overcoming Host Barriers – Virulence Factors Virulence factors can cause infection by aiding: Attachment Invasion Survival against Inflammation Ex. Capsules produced by Streptococcus pneumoniae Ex. Ability to live inside phagocytes by Mycobacterium tuberculosis Ex. production of toxins and enzymes which destroy phagocytes, complement proteins Toxin Production  Overcoming Host Barriers – Virulence Factors Toxins are biochemically active substances released by microorganisms that have a particular effect on host cells Endotoxin Exotoxin Mostly associated with gram-negative bacteria Mostly associated with gram-positive bacteria o Composed of the lipopolysaccharide portion of cell Produced and released by living bacteria; do not require envelope bacterial death for release o Released when a gram-negative bacterial cell is Effects are specific to host cells destroyed The type of toxin varies with the bacterial species Effects on host are generalized and can include: Effects can: o Disruption of clotting, causing clots to form throughout o Kill host cells and help spread bacteria in tissues the body (i.e., disseminated intravascular coagulation o Destroy or interfere with specific intracellular activities [DIC]) o Ex. Botulism toxin interferes with neuromuscular o Fever functions o Activation of complement and immune systems o Ex. Diphtheria toxin inhibits protein synthesis o Circulatory changes that lead to hypotension, shock, and death Overcoming Host Barriers – Pathogenicity Islands Pathogenicity Islands are genomic regions of pathogens which encode for virulence factors May be acquired mobile genetic elements PAIs facilitate the dissemination of virulence capabilities among bacteria Ex. Antimicrobial resistance genes PAIs are widely disseminated among medically important bacteria Ex. E. coli, Pseudomonas aeruginosa, Salmonella spp., Neisseria spp. Overcoming Host Barriers – Biofilms A biofilm is an accumulation of microorganisms embedded in a complex matrix composed of proteins, polysaccharides, extracellular DNA (eDNA), and other molecules Can be monomicrobic or polymicrobic population of organisms that Biofilms provide a protective environment for the resident microbes Clinical relevance: Biofilm formation on medical implants and prosthetic devices Biofilms are resistant to treatment Clinicallly relevant organisms which form biofilms include: Staphylococcus aureus, Pseudomonas aeruginosa Aggregatibacter spp Candida albicans Outcome of Infectious Diseases Outcomes depend on: State of host’s health Virulence/Pathogenicity of the pathogen Whether host can clear pathogen Types of infections: Acute – develops rapidly Chronic—Develops slowly (insidious) Latent—Silent phase with no symptoms Localized – infection in one site Systemic – infection has spread 35 Outcome of Infectious Diseases 36 Outcome of Infectious Diseases A symptom of a disease is defined as some evidence of a disease that is experienced or perceived by the patient—something that is subjective. Examples: ache or pain, a ringing in the ears (tinnitus), blurred vision, nausea, dizziness, itching, and chills. A sign of a disease is defined as some type of objective evidence of a disease. Examples: hepatomegaly, splenomegaly, abnormal heart or breath sounds, blood pressure, pulse rate, and laboratory results as well as abnormalities that appear on radiographs, ultrasound studies, or computed tomography scans. Signs and symptoms reflect the stages of infection. 37 Outcome of Infectious Diseases One infectious disease may commonly follow another, in which case the first disease is referred to as a primary infection and the second disease is referred to as a secondary infection. Example: During the primary infection, a virus causes damage to the ciliated epithelial cells that line the respiratory tract – this causes coughing While coughing, the patient may inhale some saliva, containing an opportunistic bacterial pathogen, such as Streptococcus pneumoniae or Haemophilus influenzae. Because the ciliated epithelial cells were damaged by the virus, they are unable to clear the bacteria from the lungs. The bacteria then multiply and cause pneumonia. In this example, the viral infection is the primary infection, and bacterial pneumonia is the secondary infection. 38 Stages of Infectious Diseases 39  Outcome of Infectious Diseases - stages 1. Incubation period: time that elapses between arrival of the pathogen and the onset of symptoms. The length is influenced by many factors such as: overall health and nutritional status of the host, the immune status of the host, virulence of the pathogen, and number of pathogens that enter the body. 2. Prodromal period: the time during which the patient feels “out of sorts” but does not yet experience actual symptoms of the disease. Patients may feel like they are “coming down with something” but are not yet sure what it is. 3. Period of illness is the time during which the patient experiences the typical symptoms associated with that particular disease (e.g., sore throat, headache, and sinus congestion). Communicable diseases are most easily transmitted during this third period. 4. Convalescent period: time during which the patient recovers. For certain infectious diseases (Ex. viral respiratory diseases), the convalescent period can be quite long. Permanent damage may be caused by destruction of tissues in the affected area even after recovery. Ex. brain damage may follow encephalitis or meningitis Ex. Paralysis may follow poliomyelitis Ex. deafness may follow ear infections. Thought questions - revisiting You should be able to add to your answers from earlier What makes some microbes pathogenic but others non-pathogenic? If microbes are ubiquitous, and we encounter them all the time, why don’t we develop more infections?