Pathogenesis Flashcards
Pathogen
microbe causes disease
Pathogenicity
ability of a microorganism cause disease to other organism
Opportunistic pathogen
cause disease by accessing to tissue or body sites where they are not usually found
True pathogen
cause disease by producing toxin or damaging compound
Virulence
Measurement of pathogenicity
High virulent, more likely to cause disease
Indicators of virulence
Median infectious dose (ID50)
Median lethal dose (LD50)
Median infectious does (ID50)
number of pathogen cells required to activate infection in 50% of inoculated animals
Median lethal dose (LD50)
number of pathogen cells required to kill 50% of infected animals
Steps of pathogenesis
- Entry: with number of invading microbes + adherence
- Penetration or Evasion of Host Defenses
- Damage Host cell
- Exit: usually same with entrance
Factors of virulence
Adhesion Colonization Toxigenesis Invasiveness Resistance and immune system evasion
Adhesion
Process that bacteria attach to cell, tissue, and biological subtances
Colonization
adherence, multiplication, and establishment of bacteria at entrance
Toxigenesis
ability to produce toxins
Invasiveness
ability to forcingly enter tissues
Resistance and immune system evasion
ability of bacteria to resist antimicrobial compounds or to escape containment of host immune system
Steps of immune system
- Innate immunity: rapid, halts infection, no memory
2. Adaptive immunity: slower, clears infection, memory
Antigen
Foreign particle elicit immune response
Epitope
A segment of antigen where antibody recognize and bind to.
How antibodies work?
Neutralization
Opsonization
Complement activation
Neutralization
Antibodies bind their target
Opsonization
Macrophage or neutrophil consume the target. When enough bacterial cells, antibodies will conjugate and form polymers to stick large amount of pathogen to prevent them from getting away and to localize them
Complement activation
Series of protein damages microbe
How are microbes digested?
- Phagosomes cover microbes.
- H+ pumps on phagosomes surface pump into phagosome mixture
- Lysosomes are activated by low pH and digest microbes.
Ways of invasion
Injecting multiple protein into host cell to disrupt, kill, or make the cell work differently.
Causing cytoskeletal reorganization which engulf the bacteria.
Disrupting intercellular attachment molecules.
Using surface protein to bind to host cell surface and induce its own endocytosis
How pathogen can survive from being digested?
Block lysosome
Stop the digestion by inhibiting enzyme or producing opposite phasing proton
Compare types of toxin
Lipopolysaccharides (LPSs): endotoxin Proteins: - Tissue sites - Extracellular diffusible toxins - Heat-labile
What include in the production of inflammatory cytokines?
Tumor necrosis factor (TNF)
Interleukin-1Beta (IL-1Beta)
Gamma interferon (IFNy)
Chemokines
What happen with overzealous production of inflammatory cytokines?
Lead to cytokine storm
Contribute to mortality consecutive to sepsis or toxic shock syndrome
What the production of inflammatory of cytokines do?
Guide anti-infectious innate immune response
Endotoxin
- Inflammatory bc they auto-amplificatory loops after monocytes activate
- Cell wall of Gram-negative
- Heat-stable
Why endotoxin is the most potent microbial mediator?
- Small does within a localized tissue space can make antimicrobial defense and stimulate bacterial clearance mechanism.
- Sudden release of large amount can release a massive, dysregulated, and potentially lethal inflammatory response such as endothelial injury, low blood flow, disseminated intravascular coagulation, low blood pressure
Exotoxin
- Gram-positive
- Cell lysis
How exotoxin work?
- Bacterium produces and release exotoxin
- B component binds host cell receptor
- A-B exotoxin enters host cell by endocytosis
- A-B exotoxin close pinched-off potion of plasma membrane during pinocytosis
- A-B exotoxin separate. A component inhibit protein synthesis and affect cell function. B component release from host cell
A-B exotoxin (binary toxin)
- 2-component protein complex secreted by pathogenic bacteria
- Comprise of heavy and light chain
- Connect by disulfide bond
- Ex: botulinum toxin
How botulinum toxin affect nerve cell function?
- Flaccid paralysis: neurological weakness, paralysis, reduce muscle tone (even breathing one)
- Reduce wrinkle
- Unsuccessfully used as bioterror agent
5 Types of botulism
- Foodborne
- Wound
- Infant
- Adult intestinal toxemia: rare
- Iatrogenic: too much botulinum toxin in cosmetic
Cholera
- Non-toxigenic: in water
- Toxin-producing: infected with ctx gene bacteriophage
Mechanism of cholera
- Catalytic portion find G-proteins of cellular signaling and attach ADP molecule to them
- G-protein convert into permanently active state to send never-ending signal
- The cell confuses and transports a lot of water and sodium to outside
- Intestine is flood
What CFTR do?
Movement of chloride ions in and out of cell