microbial pathogenesis

Question 1

five steps required for a pathogen to cause disease

Answer 1

1- host entry
2- attachment and colonization
3- avoidance of host immunity
4- host damage
5- host exit

Question 2

virulence factors

Answer 2

traits that enhance a pathogen’s ability to cause disease

Question 3

horizontal gene transfer

Answer 3

major mechanism in which bacteria acquire new virulence factors (conjugation, transformation, transduction)

Question 4

genomic island

Answer 4

integration of foreign DNA into the host chromosome

Question 5

pathogenicity island

Answer 5

look different, flanked by phage or plasmid genes, and contain virulence factors

Question 6

what determines if a particular genomic island is a pathogenicity island?

Answer 6

the DNA increases the fitness of a microbe within its host

Question 7

what virulence factors are required for attachment

Answer 7

adhesions

Question 8

why is attachment required for all microbes to colonize the host?

Answer 8

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

Question 9

pilin

Answer 9

protein that forms pilus/pili

Question 10

pilus/pili

Answer 10

product of pilin assembly (an adhesion)

Question 11

which region of the pili is assembled first?

Answer 11

the tip

Question 12

which region of the pili interacts with the host receptors?

Answer 12

adhesion protein

Question 13

type I pili

Answer 13

static, hairlike appendages, for attachment adhesion only

Question 14

type IV pili

Answer 14

dynamic, thin, and flexible for twitching adhesion AND motility

Question 15

pili are an example of adhesion molecules what should we appreciate about them?

Answer 15

different adhesions on bacteria will determine host species and cell types that these bacteria will attach to and colonize

Question 16

how do bacteria colonize the body do so?

Answer 16

biofilms

Question 17

biofilm attach to

Answer 17

organic (tissue and organs) and inorganic (implants) materials

Question 18

biofilms vs planktonic cells

Answer 18

cells within biofilms (planktonic cells) have differences in the expression of surface molecules, antibiotic resistance, nutrient use, and virulence factors

Question 19

quorum sensing

Answer 19

the cell to cell communication that occurs between cells in a biofilm

Question 20

how do biofilms lead to chronic infections and chronic inflammation?

Answer 20

their presence chronically activates toll-like receptors and triggers chronic inflammation due to cytokines and the biofilm not clearing up

Question 21

appreciate the steps of bacterial pathogenesis in order, what type of bacteria does this apply to?

Answer 21

1) entry into the body
2) adhesion to host cell surface
3) colonization
4) biofilm development
APPLIES TO: extracellular bacteria

Question 22

how do intracellular pathogens’ pathogenesis differ?

Answer 22

1) adhesion
2) entry
3) colonization
4) biofilm
intracellular pathogens may enter cells after adhesion but before colonization and biofilm development

Question 23

assume a pathogen gets to the colonization step, is it at risk of being sensed/removed from the immune system?

Answer 23

YES! It is after colonization that bacteria will be sensed/removed. pathogens must evade or counteract the immune system to develop disease

Question 24

how do pathogens sense they are in our bodies?

Answer 24

by using mechanisms to sense environmental conditions

Question 25

when are virulence factors expressed?

Answer 25

when environmental cues are sensed

Question 26

what are the 6 mechanisms extracellular bacteria use to avoid being sensed/removed by the immune response?

Answer 26

1- capsule 2- vary antigen structure 3- sequester antibodies 4- secrete fake cytokines 5- manipulate host cytokine production 6- control virulence factor synthesis

Question 27

how does a capsule benefit bacteria?

Answer 27

coats bacterial cell walls that mask PAMPS (pathogen-associated molecular patterns) and antigens, prevents phagocytes from binding

Question 28

how does varying antigen structure benefit bacteria?

Answer 28

on the cell surface to avoid immune detection

Question 29

how do sequester antibodies benefit bacteria?

Answer 29

cell surface proteins like Protein A bind the Fc region

Question 30

how does secreting fake cytokines benefit bacteria?

Answer 30

influences the immune system

Question 31

how does manipulating host cytokine production help benefit bacteria?

Answer 31

manipulates immune cells

Question 32

virulence factor synthesis is?

Answer 32

induced by biofilm quorum sensing

Question 33

what are the two classes of intracellular pathogens? which class would be most likely to spread from person to person?

Answer 33

(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

Question 34

what is something to appreciate about intracellular bacteria in relation to extracellular bacteria?

Answer 34

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

Question 35

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*

Answer 35

(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

Question 35

what is an endotoxin and what types of bacteria express it?

Answer 35

an important virulence factor common to all gram-negative cells

Question 35

why is it called an endotoxin?

Answer 35

is it within the cell and is toxic once the cell (in this case gram-negative cells) dissinegrate

Question 36

(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?

Answer 36

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

Question 37

what is the role of endotoxins in driving sepsis?

Answer 37

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

Question 38

exotoxins

Answer 38

secreted by bacteria to alter host cell function, disrupt the immune system, or outright kill the host cell to obtain nutrients, *exotoxins are secreted*

Question 39

list the 9 exotoxin modes of action

Answer 39

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-?

Question 40

which membrane are exotoxins transported across in gram-positive cells? gram-negative?

Answer 40

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

Question 41

what type of bacteria uses specialized type II, III, and IV secretion systems?

Answer 41

gram-negative

Question 42

mechanisms of the general secretion pathway. secrete outside of the cell or exotoxin directly to target?

Answer 42

Gram-positive bacteria use general to transport proteins outside of the cell and into the periplasm *secrete outside of the cell

Question 43

mechanisms of specialized secretion type II. secrete outside of the cell or exotoxin directly to target?

Answer 43

piston mechanism, push proteins out of the cell *secrete outside of the cell

Question 44

mechanisms of specialized secretion type III, secrete outside of the cell or exotoxin directly to target?

Answer 44

needle mechanism, inject proteins into the host cell *directly to target (cell-cell contact)

Question 45

mechanisms of specialized secretion type IV. secrete outside of the cell or exotoxin directly to target?

Answer 45

modified conjunction sex pilus mechanism, transport toxins *directly to target (cell-cell contact)

Question 46

remember the definition of viruses

Answer 46

obligate, intracellular parasites *all viruses are pathogens in their host and all pathogens are parasites

Question 47

what happens to a virus outside of the host cell

Answer 47

it is completely inert (inactive)

Question 48

what are the main ways (3 examples) viruses have immune avoidance (changing the way they look to the immune system)

Answer 48

antigenic variation 1-serotypes 2-antigenic drift 3-antigenic shift

Question 49

serotypes

Answer 49

same species but antigenically distinct enough to generate a unique immune response

Question 50

antigenic drift

Answer 50

small; mutations cause slightly different forms

Question 51

antigenic shift

Answer 51

big; reassortment of genome segments from a viral strain with segments that infect one species with strains from a different species

Question 52

why is influenza more pathogenic than rhinovirus?

Answer 52

-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

Question 53

(1) what strategies of viral pathogenesis are used by HPV and (2) how do the effects on the host cell benefit the virus?

Answer 53

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

Question 54

(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

Answer 54

1- Herpres virus has a latency period 2- reactivation

Question 55

In what 3 ways does HIV contribute to immunosuppression

Answer 55

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