Pathogenesis Flashcards
when are we colonized
at birth
our microbiome protects us from
disease
how does our microbiome protect us from disease
produces inhibitory substances
stimulates appropriate immunity responses
stimulates antibodies
generate essential nutrients
what essential nutrients does our microbiome produce
vitamin K production in the colon by E.Coli
and fermenting fiber
types of disease
infectious: caused by a pathogen
communicable: transmit between organisms indirect or direct
non-communicable: does not transmit between hosts
contagious: easily spread
iatrogenic: caused by medical procedure
nosocomial: acquired in hospital
zoonotic: human infected by animal
reverse zoonotic: human infecting animal
pathogen
an organism that can produce disease
primary pathogen
infect any host
establish in a niche, occupied by commensal microbial populations
cross anatomic barriers or overcome other host defenses that limit commensals
opportunistic infections
infection when normal host defenses are diminished
weakened immune system: HIV, cancer, chemotherapy
dysbiosis
disruption of physical barriers
caused by primary pathogen or normal commensal bacteria: E.coli is commensal in intestine but can cause UTIs
periods of disease
incubation: pathogen has entered the host and multiplies but too few organisms are present to cause disease
prodromal: pathogen continues to multiply, non-specific signs and symptoms of illness, immune activation
illness: pathogen continues to multiply, signs and symptoms are obvious
decline: decrease in pathogen numbers of signs and symptoms of illness
convalescence: return to normal function
virulence
the degree that an organism is pathogenic
median infectious dose ID50
number of viable organisms required to infect 50% of subjects
if infectious dose is low, it can be difficult to
identify the source
koch’s postulates for virulent organisms
-bacteria must be present is diseased individuals but not healthy ones
-bacteria must be isolated from host with disease and grown in pure culture
-specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host
-bacteria from original host and new host must be identical
shortcomings of Koch’s postulates
-some disease can be commensals: H. Pylori
-many bacteria cannot be grown in pure cultures: Chlamydia
-not all hosts are equally susceptible to infection: SARS-CoV-2
-ethical issues, some pathogens can only infect humans
falkow’s molecular koch’s postulates: virulence genes
-phenotype of the disease should be associated only with pathogenic strain of species
-inactivation of the genes associated with pathogenicity should reduce virulence
-reversion of the mutation, or allelic complementation must restore virulence
virulence genes
help pathogens survive and proliferate
adherence/colonization factors
exotoxins
enzymes
immune evasion
adherence/colonization factors
bind to host cells
-fimbriae
-afimbrial adhesions
-capsule
exotoxins
secrete proteins to effect host function
-activated by heating
enzymes
degrade host structures
-proteases: degrades connective tissue
-lipases: lyse host cell membranes
immune evasion
hide from the immune system
-protective structurers: capsules, antigenic variation
-suppress immune responses
-physically hide from the immune system: bladder, or inside a cell
common exotoxins
botulism: blocks acetylchonline release, stops muscle contraction
tetanus: prevents release of glycine and GABA, prevents muscle relaxation
how does the bacteria know when it is in the host
quorum: when bacteria reach a required density - S. Aureus
temperature: 37 C
pH: stomach <3, stimulates gene expression in H. pylori
oxygen tension: normal atmospheric oxygen ~21%, human tissue 3-10%
expression of virulence genes is often _____
coordinated
genes are co-regulated in response to environmental cues
lateral gene transfer
spreads virulence factors
help bacteria adapt to new environment
selective pressure
plasmids: large, found in Shigella, Yersinia
phage: smaller pieces of DNA encoding few genes, found in Cholera, STEC
