MB - Pathogenesis

• Pathogenesis

  the process by which bacteria causes disease
• Major Mechanisms of Pathogenesis


  colonization, physical damage, toxins, inflammation
• Adherence


  ability of bacteria to attach to host cells or tissues in the process of infection and disease
• Tissue Tropism


  the preference of an organism toward a particular type of tissue
• Specificity


  the selectivity of pathogens for particular host cells, tissues, or receptors
• Adherence is mediated by...

  adhesins (bacterial surface structures) and receptors (host cell surface structures)
• Glycocalyx

  gel-like layer that surrounds some bacteria, non-covalent and non-specific
• Microbial Access Sites

  mouth, urogenital tract, invasion through epithelia caused by injury
• Measure of pathogenicity is expressed by its...

  virulence factor. The more virulent, the more equipped an organism is to cause disease. Some factors are required while others increase the likelihood.
• Attenuation


  the loss of virulence in an organism, often used in the creation of vaccines (cause immune response but no disease)
• Examples of virulence factors in Salmonella

  Type 1 fimbriae, cytotoxins, and flagellum cause adherence, enterotoxins and endotoxins cause damage, and VI and O antigens provide defense from the host cell
• Toxin groups

  Exotoxins and Endotoxins
• Differences in Exotoxins and Endotoxins

  protein vs LPS

  extracellular vs part of cell

  usually denatured vs not

  usually enzymatic activity vs none

  high potency vs low potency

  high specificity vs low specificity

  occasional pyrogenicity vs yes
• Exotoxins secrete...

  proteins
• Types of exotoxins


  A-B toxins, superantigens, cytolytic proteins
• A-B toxins


  A is the active portion which contains the toxic portion, B is the binding site which is responsible for transporting toxin. Examples include enterotoxins, diphtheria toxin, botulinum toxin, tetanus toxin
• Superantigen


  overstimulate immune system (toxic shock)
• Cytolytic proteins


  proteases, lipases, etc; breakdown cellular components
• Endotoxins


  lipopolysaccharides from outer-membrane of Gram-negative bacteria that release toxins when cell is lysed
• Pyrogenicity


  ability to cause fever in host cell
• Enterotoxins


  type of A-B exotoxin that affect the small intestine, result in loss of water from the body, Salmonella and E.coli are organisms that cause different entertoxins, ex. Cholera toxin
• Cholera toxin


  enters host through endocytosis and causes massive water movement to lumen
• Diphtheria toxin

  A-B exotoxin that enters host through endocytosis by attaching to mucous membranes and interfering with protein synthesis, primarily affects respiratory tract causing thick membrane and obstructing breathing
• Botulinum toxin


  A-B toxin that binds to receptors that release acetylcholine. When acetylcholine cannot be released, nerve-to-muscle communication is disrupted and temporary paralyzation occurs. However, it is sometimes used in the treatment of dystonia, chronic cramping, and plastic surgery.
• Tetanus toxin


  A-B toxin that blocks the release of GABA and glycine which usually inhibits excitatory neurons, this causes uncontrollable muscle contractions and spasms.
• Mechanism of superantigens


  causes excessive stimulation of T-cells (immune system cells). Once attached, the T-cells release excess immune signaling molecules called cytokines, leading to inflammation
• LPS of endotoxins

  provide information, Lipid portion A is what causes issues, had several targets (nonspecific), weakly toxic, and usually cause fever, diarrhea, and vomiting
• LPS targets and pathways examples

  interacting with immune system, increasing permeability of blood vessel, clotting
• Constitutive defenses

  general, nonspecific mechanisms common to healthy individuals (skin, tears, flushing of urinary tract, pH changes)
• Induced defenses


  induced by exposure, involve immune system mediated defense
• Factors that affect host defense

  age, stress, diet, hygiene
• Compromised Hosts

  hospital patients (transplants, surgery, anti-inflammatory drugs, invasive procedures), out of hospital (smokers, heavy drinkers, IV drug users, poor sleep, chronic infections), genetic predisposition
• Phagocytes 


  innate response cells that recognize patterns common to pathogens (PAMPs) and engulf them
• Phagosomes


  vesicles that capture pahtogens
• Phagolysosomes


  vesicles that capture pathogens and destroy them
• Escape of Host Defenses

  capsules, intracellular growth, antigenic variation, blocking immune system, degradative enzymes
• Phagocytes can present...


  antigens to T-cells to activate an adaptive response (immunity by antibodies or cell mediated)