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Bacterial Pathogenesis Outline Bacterial Pathogenesis • • • • Introduction Host Susceptibility Pathogenic Mechanisms Virulence Factors Introduction of Bacterial Pathogenesis • Infection: growth and multiplication of a microbe in or on the body with or without the production of disease. • The capacity of a bacterium to cause disease reflects Its relative “Pathogenicity.” • Virulence is the measure of the pathogenicity of a microorganism. • Pathogenesis refers both to the mechanism of infection and to the mechanism by which disease develops. Host Susceptibility • Susceptibility to bacterial infections =>Host Defenses vs Bacterial Virulence • Host Defenses: Barriers (skin & mucus)–first line Innate Immune Responses (complement, macrophages & cytokines)–the early stage Adaptive Immune Responses (Ag-specific B & T cells)–the later stage • Host defenses can be comprised by destructing barriers or Defective immune response. Pathogens • Strict pathogens Are more virulent and can cause diseases in a normal person. • Opportunistic pathogens Are typically members of normal flora and cause diseases when they are introduced into unprotected sites, usually occur in people with underlying conditions. Entry into the human body • The most frequent portals of entry - Mucus - -Skin • Routes: Ingestion, inhalation, trauma ,needles, catheters, arthropod bite, sexual transmission Characteristics of Pathogenic Bacteria 1. Transmissibility 2. Adherence to host cells 3. Invasion of host cells and tissue 4. Evasion of the host immune system 5. Toxigenicity Abacterium may cause diseases by 1. Destroying tissue (invasiveness) 2. Producing toxins (toxigenicity) 3. Stimulating overwhelming host immune responses Pathological Mechanism of Bacterial Infections • Bacteria-mediated Pathogenesis • Host-mediated Pathogenesis • Bacterial virulence Factors =>bacterial factors causing diseases Bacterial virulence Mechanisms • Adherence • Invasion • • • • • • • • • • By products of growth (gas,acid) Toxins Degradative enzymes Cytotoxic protiens Endotoxin Superantigen Induction of excess inflammation Evasion of phagocytic and immune clearance Capsule Resistance to antibiotics Virulence Factors virulence factors help bacteria to • (1) invade the host (2) cause disease (3) evade host defenses. The following are types of virulence factors: • Adherence Factors: Many pathogenic bacteria colonize mucosal sites by using pili (fimbriae) to adhere to cells. • Invasion Factors: Surface components that allow the bacterium to invade host cells can be encoded on plasmids, but more often are on the chromosome. • Capsules: Many bacteria are surrounded by capsules that protect them from opsonization and phagocytosis. • Endotoxins: The lipopolysaccharide endotoxins on Gram-negative bacteria cause fever, changes in blood pressure, inflammation, lethal shock, and many other toxic events. • Exotoxins: Exotoxins include several types of protein toxins and enzymes produced and/or secreted from pathogenic bacteria. Major categories include cytotoxins, neurotoxins, and enterotoxins. • Siderophores: Siderophores are iron-binding factors that allow some bacteria to compete with the host for iron, which is bound to hemoglobin, transferrin, and lactoferrin Adhesion • Adherence of bacterium to epithelial or endothelial Cells allow them to colonize the tissue. • Common adhesins: pili(fimbriae), slime, lipoteichoicacid, surface proteins or lectins. • Biofilm , formed on a surface by the bacteria that are bound together within a sticky web of polysaccharide, is a special bacterial adaptation that facilitates colonization on the surgical appliances (e.g. artificial valves or indwelling catheters) and dental plaque. It can protect the bacteria from host defenses and antibiotics. The bacteria may invade via the M cells