Bacterial Pathogenesis Lec 3 (2024-2025) PDF

Bacterial Pathogenesis Lec3 (2024-2025) Done by: Dr. Zainab Jumaa Qasim PRINCIPLES OF PATHOGENESIS: A microorganism is a pathogen if it is capable of causing disease; however, some organisms are highly pathogenic (i.e., they often cause disease). Opportunistic pathogens are those tha...

Bacterial Pathogenesis Lec3 (2024-2025) Done by: Dr. Zainab Jumaa Qasim PRINCIPLES OF PATHOGENESIS: A microorganism is a pathogen if it is capable of causing disease; however, some organisms are highly pathogenic (i.e., they often cause disease). Opportunistic pathogens are those that rarely, if ever, cause disease in immunocompetent people but can cause serious infection in immunocompromised patients. These opportunists are frequent members of the body’s normal flora. Virulence is a measure of a microbe’s ability to cause disease (i.e., a highly virulent microbe requires fewer organisms to cause disease than a less virulent one).  The infectious dose of an organism required to cause disease varies greatly among the pathogenic bacteria. For example, Shigella and Salmonella both cause diarrhea by infecting the gastrointestinal tract, but the infectious dose of Shigella is less than 100 organisms, whereas the infectious dose of Salmonella is on the order of 100,000 organisms. The infectious dose of bacteria depends primarily on their virulence factors (e.g., pili, exotoxins or endotoxins, a capsule, they can survive various nonspecific host defenses such as acid in the stomach). WHY DO PEOPLE GET INFECTIOUS DISEASES? People get infectious diseases when microorganisms overpower our host defenses (i.e., when the balance between the organism and the host shifts in favor of the organism). From the organism’ perspective, the two critical determinants in overpowering the host are: 1. The number of organisms to which the host, or person, is exposed 2. The virulence of these organisms. however, that a small number of highly virulent organisms can cause disease just as a large number of less virulent organisms can.  Many infections are asymptomatic or inapparent because our host defenses have eliminated the microorganism before it could multiply to sufficient numbers to cause the symptoms of disease. The term infection has two meanings: (1) the presence of microbes in the body (2) the symptoms of disease. The presence of microbes in the body does not always result in symptoms of disease TYPES OF BACTERIAL INFECTIONS Bacteria cause disease by two major mechanisms: (1) toxin production (2) invasion and inflammation. Three epidemiologic terms are often used to describe infections: Endemic infections are those that occur at a persistent, usually low level in a certain geographic area, Epidemics are those infections that occur at a much higher rate than usual, Pandemics are those infections that spread rapidly over large areas of the globe.  many infections are inapparent or subclinical and can be detected only by demonstrating a rise in antibody titer or by isolating the organism. Some infections result in a latent state (organism stop growth, no symptoms), after which reactivation of the growth of the organism and recurrence of symptoms may occur. Certain other infections lead to a chronic carrier state, in which the organisms continue to grow with or without producing symptoms in the host. Chronic carriers are an important source of infection of others and hence are a public health hazard. STAGES OF BACTERIAL PATHOGENESIS A generalized sequence of the stages of infection is as follows: (1) Transmission from an external source into the portal of entry. (2) Evasion of primary host defenses such as skin or stomach acid. (3) Adherence to mucous membranes, usually by bacterial pili. (4) Colonization by growth of the bacteria at the site of adherence. (5) Disease symptoms caused by toxin production or invasion accompanied by inflammation. (6) Host responses, both nonspecific and specific (immunity), during steps 3, 4, and 5. (7) Progression or resolution of the disease.  DETERMINANTS OF BACTERIAL PATHOGENESIS 1. Transmission An understanding of the mode of transmission of bacteria and other infectious agents is extremely important from a public health perspective, because interrupting the chain of transmission is an excellent way to prevent infectious diseases. The modes of transmission of microbes include human-to human (via airborne respiratory droplets or fecal contamination of food and water, sexual contact, urine, skin contact, blood transfusions, contaminated needles, or biting insects. The transfer of blood, either by transfusion or by sharing needles during intravenous drug use, can transmit various bacterial and viral pathogens. The main “portals of entry” into the body are the respiratory tract, gastrointestinal tract, skin, and genital tract.  Nonhuman-to-human processes. Nonhuman sources include animals, soil, water, and food. Animals to human : animals are the reservoir for infection are called zoonoses. from mother to offspring, a process called vertical transmission. (across the placenta, birth canal during birth, and via breast milk). Some infections are not communicable or not contagious (i.e., they are not spread from host to host). For example, botulism is not communicable, because the exotoxin produced by the organism in the contaminated food affects only those eating that food.  2. Adherence to Cell Surfaces: These adherence mechanisms are essential for organisms that attach to mucous membranes; mutants that lack these mechanisms are often nonpathogenic. (E.g., Pili. And Glycocalyx) 3. Invasion, Inflammation, & Intracellular Survival One of the two main mechanisms by which bacteria cause disease is invasion of tissue followed by inflammation. The other main mechanism, toxin production, and a third mechanism, Immunopathogenesis (is the process of disease development involving an immune response. Several enzymes secreted by invasive bacteria play a role in pathogenesis: For example, hyaluronidase degrades hyaluronic acid in the subcutaneous tissue, allowing the organism to spread rapidly.  Toxins fall into two general categories: exotoxins and endotoxins. Exotoxins are polypeptides released by the cell, whereas endotoxins are lipopolysaccharides (LPS), which form an integral part of the cell wall. Endotoxins occur only in gram-negative rods and cocci, are not actively released from the cell, and cause fever, shock (hypotension + disseminated intravascular coagulation), and other generalized symptoms. Both exotoxins and endotoxins by themselves can cause symptoms; the presence of the bacteria in the host is not required. Exotoxins Exotoxins are secreted by certain bacteria that alter specific cell functions resulting in the symptoms of disease. They are produced by both gram- positive and gram-negative bacteria. Exotoxins are antigenic and induce antibodies called antitoxins. Exotoxins can be modified to form toxoids (treated with formaldehyde), which are antigenic but not toxic. Toxoids, such as tetanus toxoid, are used to immunize against disease. Exotoxins have different mechanisms of action and different targets within the cell and therefore cause a variety of diseases with characteristic symptoms. Some exotoxins act by proteolytic cleavage of a cell component, whereas others act as superantigens, causing the overproduction of cytokines. Some are neurotoxin causes paralysis, Enterotoxin cause diarrhea, hemolysin (RBC lysis) Many exotoxins have an A–B subunit structure in which the A subunit is the active (toxic) one and the B subunit is the one that binds to the cell membrane and mediates the entry of the A subunit into the cell. Endotoxins Lipid A is the toxic component of LPS. It induces the overproduction of cytokines such as tumor necrosis factor, interleukin-1, and nitric oxide, from macrophages, which causes the symptoms of septic shock, such as fever and hypotension. In addition, LPS activates the complement cascade resulting in increased vascular permeability, and the coagulation cascade, resulting in increased vascular permeability and disseminated intravascular coagulation DIC Endotoxins are poorly antigenic, do not induce antitoxins, and do not form toxoids.  TYPICAL STAGES OF AN INFECTIOUS DISEASE A typical acute infectious disease has four stages: (1) The incubation period, which is the time between the acquisition of the organism (or toxin) and the beginning of symptoms (this time varies from hours to days to weeks, depending on the organism). (2) The prodrome period, during which nonspecific symptoms such as fever, malaise, and loss of appetite occur. (3) The specific-illness period, during which the overt characteristic signs and symptoms of the disease occur. (4) The recovery period, also known as the convalescence period, during which the illness abates and the patient returns to the healthy state. After the recovery period, some individuals become chronic carriers or latent infection or subclinical. In subclinical infections and after the recovery period is over, the presence of antibodies is often used to determine that an infection has occurred. The END