Lecture 3: microbial pathogenesis Flashcards
Koch’s postulates
- suspected germ must be present in every case of disease
- germ must be isolated and grown in pure culture
- cultured germ must cause disease when inoculated into a healthy host
- same germ must be reisolated from the diseased experimental host
gold standard in establishing cause of infection
PCR
- identifies cause of disease using a single copy of DNA or RNA
- potential problems due to normal flora
colonization
- involves a transient or permanently established microbial growth
- NO interference with normal body function
Infection
- involves a transient or permanently established microbial growth
- may manifest disease
disease
- abnormal condition of body structures and function
- occurs when interaction leads to pathogenesis
- CAN occur without presence of microbe
- toxins from microbes can cause intoxications
how can different organisms lead to disease with similar signs and symptoms
due to similar pathogenicity mechanisms
- ex: conjunctivitis
how can the same organims lead to disease with different signs and symptoms
- due to different pathogenicity mechanisms
stages of disease: incubation (preclinical) stage
- pathogen has entered body
- no signs or symptoms
- innate immune system has not been activated
- not contagious
stages of disease: Prodromal (warning) stage
- appearance of signs and symptoms (non specific)
- activation of innate immune system
- pathogen numbers increase
- easily transmitted even before person realizes they are sick
stages of disease: acute stage; clinical illness
- most severe time of illness
- characteristic signs and symptoms
- acquired immune system has been activated
- pathogen numbers are stationary
- communicable diseases are easily transmitted
stages of disease: decline stage
- illness is still apparent but signs and symptoms dwindle
- immune system activity is reduced (Antibodies formed)
- pathogen cleared from host
- can be contagious if individual becomes carrier
stages of disease: convalescent stage
- patient returns to full health
- signs and symptoms end
- no immune system activity
- not contagious
mechanisms of bacterial virulence
- metabolites
- invasins
- adhesins
- toxins
mechanisms of bacterial virulence: tissue damaging metabolites
- acids, gases, or other byproducts of metabolism formed during bacterial growth
- serve to directly damage host tissues
- ex: strep mutans produces lactic acid which results in dental caries
mechanisms of bacterial virulence: invasins or “spreading factors”
- proteins or enzymes that act locally to damage host cells
- affect tissue matrices and intracellular spaces
- allow for spread and replication of bacterium
mechanisms of bacterial virulence: adhesins
- bind pathogens to receptors on host cells and tissues
- most bind to glycoproteins
name 3 types of adhesins
- glycocalyx material
- capsule and slime layers
- fimbriae and pili
- attach to specific host molecules
- afimbrial adhesins
- proteins associated with cell envelope (wall/membrane)
mechanisms of bacterial virulence: toxins
proteins with high activity and specificity and are heat labile
exotoxins are found in gram cells
both gram negative and positive cells
exotoxins
- proteins taht are toxic to cells, usually direct in action
- secreted into the extracellular fluid or assocaited with the bacterial cell surface
- bind host cell receptors
enterotoxins
exotoxins that cause GI signs and symptoms
what are the two main categories of exo/enterotoxins
A-B exotoxins
function of A and B in A-B exotoxins
- A- Attacks cells
- B- binds toxin to host receptor
- after binding, A is transported into cell
- can form toxoids
toxoids
inactivated toxins
superantigens
- toxins
- activate up to 40% T cells in absense of antigen
- result in massive release of cytokines
name three membrane active exotoxins
- proteases
- destroy protein in host cell (cell membrane)
- lipases: destroy lipids in cell membranes
- hemolysins: form pores in RBC and phagocytes
Name endotoxin of gram negative organisms
- LPS (not very toxic until released)
- O antigen
- Lipid A
virulence mechanisms: encapsulation
blocks phagocytosis
- ex: S. pneumoniae capsule
virulence mechanisms: inactivation of antibody
- S. pneumoniae secretes IgA degrading proteases
- S. aureus binds to Fc region of IgG
virulence mechanisms: intracellular growth
- escape detection so host can’t initiate an immune response
virulence mechanisms: antigenic variation
- ability of a microbe to
- change epitopes
- present new antigens to immune system
- initiates new cycle of disease
Antigenic drift
- accumulation of genetic mutations
- alters protein products
- leads to variability in population
- form antigenically distinct strains
Antigenic shift
- reassortment of viral genome
- in cell infected by 2 strains of influenza A
- produces a new subtype of virus
- can create flu pandemics
Antigenic switching
- can result from genetic conversion/shuffling
- due to recombination within group of genes
- results in new surface antigen, but no change in biological function
