Host Pathogen Interactions Flashcards
What is the difference between a principal pathogen, an opportunistic pathogen and commensal organisms?
Principal pathogens: regularly cause disease in only a proportion of susceptible hosts with a normal immune system
Commensals: live on you and in you but don’t cause damage and actually maintain normal physiology
Opportunistic pathogen: don’t normally cause disease unless they have the “opportunity” to so, for example when you’re immune compromised
Koch’s postulates are to establish what?
Whether a specific organism causes disease
What are #Kochs_Postulates?
Koch’s postulates:
- Organism has to be in all cases of diseased folks (but not in healthy folks)
- Bug has to be isolated from the diseased folk and grown in culture
- Disease is reproduced in a new host when bug is inoculated in a susceptible host
- The bug has to be isolated from the newly infected host and cultured (and basically found to be the same one)
What are #Molecular_Koch’s_Postulates?
Factors to determine which specific factor contributes to a bug’s virulence
The 3 molecular Koch’s postulates are ___
- Gene encoding the phenotype should be ass’d with the pathogenic strain (and not in the non pathogenic strains)
- Inactivating the gene results in reduction of virulence
- Restoring the wildtype gene re-establishes virulence
The most common outcome of infection is ___
No #symptoms
Host factors that affect the emergence of new infections include changes in behavior, ___, ___, contamination of environment and food supply and ___
Host factors:
Changes in behavior: e.g. AC can lead to propagation of certain bugs as is the case of Legionella, or new eye infections with contact lenses
Expanding populations and increased travel: potential zoonotic transfer with folk going to new places and increasing travel allows for the easy propagation of these infections
Contamination of environment and food supply
Immunosuppression: one can be susceptible to infection if your immune system is dampened for whatever reason
What are some microbial factors that effect the emergence of new infections?
Short generation time: bacteria reproduce super quickly and new mutations produced with each generation can propagate quickly as well
Acquisition of new genetic material from other bacteria
Changes in vector distribution (like if you have a new vector for a particular bug, that might also affect the emergence of new infections)
The 3 ways bacteria can acquire new genetic material are by ___
Conjugation
Transformation
Transduction
Describe the 3 ways thru which bacteria can acquire new genetic material
Conjugation: exchange of dna between bacteria by direct contact (#bacteria_sex). Can also happen between unrelated bacteria
Transformation: transfer of “naked” dna >> basically one bacteria can release its dna into the cytosol and another bacterium can take that dna up
Transduction: transfer of dna mediated by a bacteriophage
What is the difference between commensals and pathogens if commensals follow the same steps as pathogens do in the infectious cycle?
Commensals do all of the steps in the infectious cycle EXCEPT cause damage (i.e. disease)
Two barriers for bugs to overcome as they try to enter the host are ___
What in the body serves as an ecological barrier to bug infection?
Entry into the host: barriers include the skin and mucosal surfaces
Overcoming barriers: overcoming anatomical barriers like the skin would normally require some kind of trauma to the barrier; ecological barrier = the host microbiome
The first step in establishment is ___
T/F: Bugs that don’t adhere are equally as virulent as those that do
The first step in establishment is adherence
Adherence is usually high avidity and over long distances to overcome electrostatic repulsion between the bug and the host cell surface
Adherence is also the result of adhesins on the surface of the bug, and receptors on the surface of the host cell
Mutants that aren’t adherent are typically avirulent
Describe the role of fimbriae/pili
Fimbriae/pili: rod like things that protrude from the bug’s cell surface. Proteins at the tip of these things actually mediate adherence
**note that the pilus rod provides the distance between the two negatively charged surfaces of the host cell and the bug cell to overcome electrostatic repulsion**
What is the significance of a #biofilm to bug adherence
Staph epidermidis can adhere to catheters via formation of a biofilm
Many bugs form biofilms on foreign surfaces
The biofilms are typically composed of polysaccharides and other things that not only help with adherence but are also resistant to anti-microbial treatment
3 ways thru which bugs can evade killing by the host immune system are complement evasion, ___ and ___
Complement evasion
Invasion and alteration of cell biology
Avoidance of phagocytosis
Other ways bugs can evade killing by the host immune system include ___
Survival in the phagocyte
Antigenic variation
Inactivation of antibodies
An example of bacteria escaping complement activation is #Neisseria infection
How does Neisseria evade killing by the complement system? How does this cause pathology in the host?
Neisseria meningitidis can bind Factor H on its surface (recall that Factor H is a complement inhibitor)
Binding factor H will allow the bacteria to inactivate complement on their surface.
Because there are many bacteria, the bacteria’s binding to Factor H reduced the functional level of Factor H for the host so the host actually has complement constantly activated which can lead to vascular damage
There’s also a polymorphism affecting expression of factor H that is ass’d with increased risk of N. meningitidis infection
Another way for a bug to evade killing by complement and antibodies is __
What are two example systems thru which a bug can achieve this?
Surviving inside the host cell is another way of getting inside the cell
On the slide: trigger mechanism = using the type 3 secretion system, and the zipper mechanism = using cellular receptors
What is a type III/IV secretion system?
One way that bugs alter host cell biology is through Type III secretion systems that can deliver virulence factors into the host cell cytoplasm and the factors cause changes that effect the host cell
(think of it like a delivery system except the package that the host cell is receiving is #virulence instead)
One way that bugs evade phagocytosis is by expressing what?
A #polysaccharide capsule
An example of a bug surviving killing by phagocytosis is Listeria monocytogenes. Explain how this bug does this
Listeria monocytogenes escapes from the phagosome and goes into the cytosol as a way to evade killing by the host. It can also move around inside the cell and once it pops out of one cell, it can go right into another one (so it won’t be sensed by the host environment)
Listeria’s that ho that just keeps dude hopping
Some bugs evade phagocytic killing by inhibiting fusion of the phagolysosome. Who are these dudes?
Legionella pneumophila
Toxoplasma gondii
Histoplasma capsulatum
**borrowed from Yas
Ghandi didn’t believe that just coz you were a toxic (toxoplasma) person that you deserved to fry. He was all about keeping the lysosomes + phagosomes #separate to avoid the violence against toxoplasma that would happen
Something about him going down in HISTory (histoplasma capsulatum) not just in this legion of pneumophila (Legionella pneumophila) but around the world as well :/
In other cases, phagolysosomal fusion happens but the bug survives still. Who all are these folks that do this?
Leishmania
Coxiella burnetii
**this girl Coxie (lla) got some burns all over herself and then she went somewhere and got Leishmaniasis. How unfortunate**
What is antigenic variation and how does that help pathogens evade the host immune system?
Antigenic variation: changing the targets of antibodies
Neisseria gonorrheae expresses pili that are targets for antibodies. Problem is these bugs can actually change the targets of the antibodies, making the antibodies #useless
How does Staph inactivate antobodies?
What’s another example of antibody inactivation?
Some bugs also have ways to inactivate antibodies
Staph aureus expresses Protein A, which binds antibodies at the Fc region and not the Fab region, thereby rendering the antibody unable to perform its antibacterial function
Protein A can also cause B cell apoptosis, which further reduces the level of functional antibodies
Some mucosal pathogens secrete an IgA protease that degrades IgA (recall that IgA is your major antibody for mucosal defense)
A direct way that pathogens can cause damage to the host is thru secretion of (exotoxins/endotoxins)
Direct:
Exotoxins – proteins secreted by growing bacteria that cause damage to the host cell (the 1st ones discovered where tetanus and botulinim toxins)
Indirect ways that bugs can cause damage to the host include ___
Superantigens and endotoxin
Diptheria is an upper respiratory infection caused by ___ and is characterized by a ___
Upper respiratory infection by Corynebacterium diphtheriae
Dense white-grey pseudomembrane in swollen posterior pharynx
Listen , Cory’s bacteria causes diptheriae. The thing makes a fake blanket (membrane) over the back of the throat and makes it so big (swollen)
The pathogenesis of Diptheria is mediated by ___
How does this work?
Diptheria toxin
Diphtheria toxin is an A/B toxin
It has an active domain and a binding domain
The toxin enters the cell via receptor mediated endocytosis thru the B subunit
After acidification of the endosome, the B subunit changes conformation and forms a pore in the endosomal membrane
The A subunit (at this point has been clipped by the Furin host protease) then translocates across the pore of the B subunit and binds to ADP which ribosylates Elongation Factor 2, thereby inhibiting the cell’s protein synthesis and killing the cell
How does Shiga toxin cause damage to the host cell?
Name 2 organisms that make Shiga toxin
Shiga toxin is another A/B toxin that has one A subunit and 5 B subunits that are noncovalently attached
The subunits bind a cell surface receptor, are endocytosed and the A subunit ends up in the cytosol where it disrupts protein synthesis by depurinating the 28S ribosomal RNA
Shigella dysenteriae and some E. coli
How does Shiga toxin cause Hemolytic Uremia syndrome (typical)?
Shiga toxin is also important in kidney cells
Shiga toxin causes typical hemolytic uremic syndrome. The toxin can bind to microvessels in the kidney which leads to tissue and organ damage
2 examples of membrane damaging toxins include ___
Other toxins damage the membrane directly by forming elaborate pores in the host cell membrane thru multimerization
Other bacteria secrete phospholipases that digest the phospholipid bilayer
Explain how superantigens and LPS binding can cause damage to the host cell/are involved in damage mediated by host responses
Recall that superantigens damage the host cell by skipping binding to MHC and instead binds to the side and causes cytokine storms >> shock
Recall also that TLR4 binding causes inflammatory responses which can cause damage if there’s too much stimulation (this is a host cell indirect kind of disease)
Which of these features best distinguishes pathogens from commensals?
A.Ability to overcome anatomical barriers
B.Adherence to host cells
C.Damage to the host
D.Evasion of host immune responses
E.Transmission to susceptible hosts
C
Molecular Koch’s postulates can be used to determine
A.how a pathogen evades host immunity
B.how to isolate a pathogen from an infected animal
C.that a specific organism is the cause of a disease
D.whether a specific factor contributes to infection
D
Which of the following is not a mechanism used by pathogens to evade host immunity?
A.Binding of complement regulatory factors
B.Cleavage of MHC and TCR molecules
C.Production of a polysaccharide capsule
D.Survival inside host cells
E.Variation of surface antigens
B
Which of the following is a factor in the emergence of new infections?
A.Decontamination of the environment
B.Exchange of genetic material between bacteria
C.Long generation time of bacteria
D.Stability of human populations
B
•A 20-year-old admitted the day prior for fever and confusion and is now improving after prompt initiation of antimicrobial therapy. Neisseria meningitidis was cultured from his cerebral spinal fluid. The physician recommends that all members of his family receive prophylactic treatment with an antimicrobial. In the absence of such treatment, which of the following is the most likely outcome in the family members after household exposure to N. meningitidis from this patient?
A.Death
B.Meningitis
C.Mild headache
D.No symptoms
D
