9-4 IMM Microbial Pathogenesis and Mechanism of Virulence Flashcards
Pathogen definition
organism that can cause disease
Pathogenesis definition
process resulting in disease
Virulence definition
degree of damage or disease resulting from infection
Infectivity definition
likelihood of causing infection/disease with exposure to a particular dose
How infectious is E. Col?
ID50 ranges from 10^1 to 10^3 colony forming units for different strains
Rhinovirus
- common cold
- high infectivity, low virulence
Influenza virus
- moderate infectivity, greater virulence, host dependent
Ebola virus
- causes hemorrhagic fever
- high infectivity, high virulence
Fomite disease transfer
From inanimate object
Microbial virulence factors (3)
1) structures involved in attachment, adherence and invasion
2) toxins involved in cell or tissue damage
3) processes involved in immune avoidance
Bacterial pili (fimbriae)
- filamentous structures extending from the bacterial surface
- important for adherence to host cell
- can be homo or heterodimers
Type IV pili
- can extend, bind, retract
- promotes surface motility, microcolony and biofilm formation, adherence to host cell and immune evasion
Pili vs flagella
Pili: shorter, thinner, more numerous and usually for attachment
Flagella: longer, thicker, fewer and for locomotion
Gram - bacteria use type __ (3 types) to inject substrates into other cells
Type III, IV and V
Viral attachment for naked viruses
- done by capsid proteins on naked virus
- virus enters via endocytosis
- example: adenovirus
Viral attachment for enveloped viruses
- done by glycoprotein spikes on enveloped virus
- virus enters via membrane fusion or endocytosis
- example: HIV
HIV attachment
- 2 part glycoprotein spike (GP120 and GP41)
- GP120 binds to CD4 on human T cell
- GP41 can then bind and initiates viral envelope fusion with host cell
Cholera toxin
- A subunit activates adenylate cyclase, increases cAMP, promotes secretion of electrolytes and fluid by intestinal cells = profuse watery diarrhea
Anthrax toxin
- A subunits Edema Factor (EF) and Lethal Factor (LF)
- EF activates adenylate cyclase
- LF cleaves cellular kinase leading to altered signaling and cell death
Diphtheria
- A subunit inhibits protein synthesis
Tetanus
- A subunit inhibits neurotransmitter release from inhibitory neurons in CNS resulting in spastic paralysis
Pertussis (whooping cough)
- A subunit inhibits adenylate cyclase, increases cAMP in neutrophils and macrophages, decreases phagocytosis
Example of pore-forming toxin
S. aureus
Superantigen definition
bypasses antigen specificity of receptor
Polysaccharide capsules
- extracellular, attached to gram - or + bacterial surface
- defines different serotypes of pathogen
- avoids phagocytosis and immune recognition
- common feature of pathogens that can disseminate via bloodstream to CNS
Antigenic variation
- during infection, pathogens express different versions of key antigens so antibodies made against one version don’t recognize later versions
- Examples: trypanosoma brucei protozoan (sleeping sickness)
Ways of avoiding immune surveillance
- biofilms
- mycobacterium tb induces formulation of “granulomas,” slowly replicating bacteria inside aggregates of dead cells
- Herpes virus travels from periphery to dorsal root ganglia and lay dormant in sensory neurons
- treponema pallidum produces very few surface proteins - teflon pathogen of syphillis
Supressing immune system
- HIV destroys CD4+ cells
- M. tuberculosis prevents fusion of phagosomes and lysosomes in macrophages
- staphylococcal protein A binds IgG by the Fc region
