microbial pathogenesis Flashcards
five steps required for a pathogen to cause disease
1- host entry
2- attachment and colonization
3- avoidance of host immunity
4- host damage
5- host exit
virulence factors
traits that enhance a pathogen’s ability to cause disease
horizontal gene transfer
major mechanism in which bacteria acquire new virulence factors (conjugation, transformation, transduction)
genomic island
integration of foreign DNA into the host chromosome
pathogenicity island
look different, flanked by phage or plasmid genes, and contain virulence factors
what determines if a particular genomic island is a pathogenicity island?
the DNA increases the fitness of a microbe within its host
what virulence factors are required for attachment
adhesions
why is attachment required for all microbes to colonize the host?
it is step one for successful disease and is required to cause disease. Pathogens must overcome barrier methods that the body has in place to resist pathogens
pilin
protein that forms pilus/pili
pilus/pili
product of pilin assembly (an adhesion)
which region of the pili is assembled first?
the tip
which region of the pili interacts with the host receptors?
adhesion protein
type I pili
static, hairlike appendages, for attachment adhesion only
type IV pili
dynamic, thin, and flexible for twitching adhesion AND motility
pili are an example of adhesion molecules what should we appreciate about them?
different adhesions on bacteria will determine host species and cell types that these bacteria will attach to and colonize
how do bacteria colonize the body do so?
biofilms
biofilm attach to
organic (tissue and organs) and inorganic (implants) materials
biofilms vs planktonic cells
cells within biofilms (planktonic cells) have differences in the expression of surface molecules, antibiotic resistance, nutrient use, and virulence factors
quorum sensing
the cell to cell communication that occurs between cells in a biofilm
how do biofilms lead to chronic infections and chronic inflammation?
their presence chronically activates toll-like receptors and triggers chronic inflammation due to cytokines and the biofilm not clearing up
appreciate the steps of bacterial pathogenesis in order, what type of bacteria does this apply to?
1) entry into the body
2) adhesion to host cell surface
3) colonization
4) biofilm development
APPLIES TO: extracellular bacteria
how do intracellular pathogens’ pathogenesis differ?
1) adhesion
2) entry
3) colonization
4) biofilm
intracellular pathogens may enter cells after adhesion but before colonization and biofilm development
assume a pathogen gets to the colonization step, is it at risk of being sensed/removed from the immune system?
YES! It is after colonization that bacteria will be sensed/removed. pathogens must evade or counteract the immune system to develop disease
how do pathogens sense they are in our bodies?
by using mechanisms to sense environmental conditions
when are virulence factors expressed?
when environmental cues are sensed
what are the 6 mechanisms extracellular bacteria use to avoid being sensed/removed by the immune response?
1- capsule
2- vary antigen structure
3- sequester antibodies
4- secrete fake cytokines
5- manipulate host cytokine production
6- control virulence factor synthesis
how does a capsule benefit bacteria?
coats bacterial cell walls that mask PAMPS (pathogen-associated molecular patterns) and antigens, prevents phagocytes from binding
how does varying antigen structure benefit bacteria?
on the cell surface to avoid immune detection
how do sequester antibodies benefit bacteria?
cell surface proteins like Protein A bind the Fc region
how does secreting fake cytokines benefit bacteria?
influences the immune system
how does manipulating host cytokine production help benefit bacteria?
manipulates immune cells
virulence factor synthesis is?
induced by biofilm quorum sensing
what are the two classes of intracellular pathogens? which class would be most likely to spread from person to person?
(1) facultative intracellular pathogens- can invade host cells but can also survive outside the cell *** more likely to spread from person to person because more adaptive to different modes of transmission due can survive and replicate outside of the cell
(2) obligate intracellular pathogens- invade and reproduce inside the cell only
what is something to appreciate about intracellular bacteria in relation to extracellular bacteria?
intracellular bacteria will be inherently more hidden from most innate and immune cells than extracellular bacteria are but they can still be detected and removed
what are the 3 mechanisms that intracellular bacteria can use to survive within cells when they are endocytosed/phagocytosed consider how these fates benefit the bacteria or hide them from the immune system
(1) Survive and replicate within phagolysosomes
(2) prevent lysosome fusion and persist in phagosome
- exocytosis can expel bacteria into extracellular space
-phagocytes can inject pathogens and deliver them to the lymph node
(3) can break out of the phagosome and move throughout the cytoplasm and adjacent cells
what is an endotoxin and what types of bacteria express it?
an important virulence factor common to all gram-negative cells
why is it called an endotoxin?
is it within the cell and is toxic once the cell (in this case gram-negative cells) dissinegrate
(1) which component of the LPS acts as an endotoxin? (2) In what situation do immune cells recognize it? and (3) what senses it and what is the result?
1- Lipid A on the outer membrane
2- when gram-negative cells die they release lipid A and
3- toll-like receptors of the immune system recognize it which leads to a dramatic release of proinflammatory cytokines
what is the role of endotoxins in driving sepsis?
this release of pro-inflammatory cytokines causes a “cytokine storm” which can contribute to the signs/symptoms of sepsis (fever, activation of clotting factors, activation of complement, vasodilation -> low BP -> shock and death
exotoxins
secreted by bacteria to alter host cell function, disrupt the immune system, or outright kill the host cell to obtain nutrients, exotoxins are secreted
list the 9 exotoxin modes of action
1-plasma membrane disruption
2-cytoskeleton alterations
3-protein synthesis disruption
4-cell cycle disruption
5-signal transduction disruption
6-cell-cell adhesion disruption
7-blockage of exocytosis
8-redirection of vesicle traffic
9-superantigens that cause immunopathology
acronym-?
which membrane are exotoxins transported across in gram-positive cells? gram-negative?
gram-positive: cytoplasmic membrane
gram-negative: both the outer membrane and cytoplasmic membrane (have outer membrane)
BOTH use general secretion systems to transport proteins across the cytoplasmic membrane
what type of bacteria uses specialized type II, III, and IV secretion systems?
gram-negative
mechanisms of the general secretion pathway. secrete outside of the cell or exotoxin directly to target?
Gram-positive bacteria use general to transport proteins outside of the cell and into the periplasm
*secrete outside of the cell
mechanisms of specialized secretion type II. secrete outside of the cell or exotoxin directly to target?
piston mechanism, push proteins out of the cell
*secrete outside of the cell
mechanisms of specialized secretion type III, secrete outside of the cell or exotoxin directly to target?
needle mechanism, inject proteins into the host cell
*directly to target (cell-cell contact)
mechanisms of specialized secretion type IV. secrete outside of the cell or exotoxin directly to target?
modified conjunction sex pilus mechanism, transport toxins
*directly to target (cell-cell contact)
remember the definition of viruses
obligate, intracellular parasites
*all viruses are pathogens in their host and all pathogens are parasites
what happens to a virus outside of the host cell
it is completely inert (inactive)
what are the main ways (3 examples) viruses have immune avoidance (changing the way they look to the immune system)
antigenic variation
1-serotypes
2-antigenic drift
3-antigenic shift
serotypes
same species but antigenically distinct enough to generate a unique immune response
antigenic drift
small; mutations cause slightly different forms
antigenic shift
big; reassortment of genome segments from a viral strain with segments that infect one species with strains from a different species
why is influenza more pathogenic than rhinovirus?
-influenza replicates more easily at body temperature (37 degrees Celsius)
-PAMPs from influenza trigger proinflammatory cytokines in the lower and upper respiratory tracts
-patients from influenza are more likely to have secondary infections due to the immunopathology (damage from disease) in the respiratory tract
(1) what strategies of viral pathogenesis are used by HPV and (2) how do the effects on the host cell benefit the virus?
1- antigenic variation- 100s of serotypes. Also the proteins expressed during HPV increase host cell division of virus infected cells
2- these transformed host cells become immortal and replicate uncontrollably which can lead to cancer
(1) what type of virus infection has a stage that does not cause disease and (2) what process allows these viruses to replicate and cause disease
1- Herpres virus has a latency period
2- reactivation
In what 3 ways does HIV contribute to immunosuppression
1- depletes helper T cells by attachment proteins binding to CD4 and CDR5 on T helper cells
2- inhibits apoptosis of virus-producing cells while also initiating the death of healthy cells
3- HIV downregulates CD4 and MHC-1 to hide from CD8 cytotoxic T lymphocytes
