Micro 4: Microbial Pathogenesis

Question 1

What is a pathogen?

Answer 1

a microbe capable of causing disease, especially in immunocompetent people

Question 2

What is pathogenesis?

Answer 2

the mechanism of disease development

Question 3

What is virulence?

Answer 3

a measure of a microbe’s ability to cause disease

Question 4

What is a virulence factor?

Answer 4

any number of products produced by pathogens that allow the microbe to invade, evade host defense, and/or cause disease

Question 5

What is colonization?

Answer 5

the presence and multiplication of microorganisms with tissue invasion or damage

Question 6

What is infection?

Answer 6

colonization that generally leads to disease

Question 7

What is an epidemic?

Answer 7

a disease that rapidly affects many people in a fixed period of time

Question 8

What is a pandemic

Answer 8

a disease that affects people worldwide

Question 9

What is an endemic?

Answer 9

a disease that is constantly present at a low level in a certain population

Question 10

What are primary (frank) pathogens?

Answer 10

microbes that are always associated with disease, regardless of whether the host is immunocompetent or compromised

Question 11

What are opportunistic pathogens?

Answer 11

pathogens that only cause disease in immunocompromised patients. While the symptoms may appear severe, these pathogens are actually less virulent that primary pathogens because they can only affect compromised individuals

most bacteria fall somewhere in between frank and opportunistic pathogens

Question 12

What are some of the determinants of infection?

Answer 12

1. Number of microorganisms present (innate)
2. Virulence of microbe
3. Immune status of host (innate)
4. Past immune history of the host (adaptive)

Question 13

What is the initial phase of pathogenesis?

Answer 13

The incubation phase, which consists of the time from the initial contact until the presentation of symptoms of an infection occur. This stage includes: Transmission, in which the host comes into contact with the microbe. This microbe must evade host defenses to colonization and potentially initiate an infection, and many times adherence is a requirement. The localized followed by systemic spread of the infection is the final stage of this phase

Question 14

What is the difference between prodromal and specific symptoms of an infection?

Answer 14

prodromal symptoms are nonspecific to a particular pathogen and typically precede the presentation of the pathogen induced (specific- i.e. unique to that pathogen) symptoms following infection

Question 15

What is the most common route of infection for viruses?

Answer 15

respiratory, maybe less so with bacteria. Very hard to control- easy transmission

Question 16

What are the most common portals of entry for microorganisms into the body?

Answer 16

sites where skin and mucous membranes meet- respiratory, GI, and GU tracts

Question 17

T or F. Viruses are obligate intracellular pathogens

Answer 17

T.

Question 18

How do microbes get into cells?

Answer 18

Bacteria and other microbes enter cells through a receptor-mediated endocytosis event. Under normal circumstances, endocytosed material merges with an intracellular phagosome and is transported to lysosomes for breakdown. Pathogens, on the other hand, have evolved mechanisms to evade their destructions. The mechanisms include:

1. escape from the phagosome prior to lysosome intervention
2. Inhibition of phagosome-lysosome fusion
3. blockage of acidification of the enzymes designed to degrade them

Question 19

What is a Type III secretion system?

Answer 19

exclusive to pathogenic microbes, this system allows the bacterium to introduce its own receptors onto the surface of the target cell, and can then attach to that receptor to mediate its own entry into the cell

Question 20

What is transcytosis?

Answer 20

a type of transcellular transport in which various macromolecules are transported across the interior of a cell. Macromolecules are captured in vesicles on one side of the cell, drawn across the cell, and ejected on the other side (ex. M cells). This allows bacteria to gain access to subepithelial layers to allow them to enter cells that may not have a receptor on the surface and to spread systemically within the host

Question 21

Systemic dissemination (spread) of infection commonly occurs through what three routes?

Answer 21

blood, lymph, and CSF. Sometimes, distal damage following systemic spread can be attributed to toxin dissemination rather than the actual spread of the bacteria itself

Question 22

What are some non-toxin virulence factors used by bacteria to evade phagocytosis and initiate/spread infection?

Answer 22

1. capsules
2. collagenase and hyaluronidase
3. coagulase
4. IgA protease
5. Protein A

Question 23

How does the presence of a capsule help pathogenic bacteria evade destruction and promote infection?

Answer 23

capsules are antiphagocytic. There are, however, vaccines that target capsule components in order to break them down and allow for opsonization

Question 24

What are three examples of pathogenic bacteria that are very dependent on their capsules to initiate an infection?

Answer 24

Str. pneumoniae, H. influenzae, and N. meningitidis

Question 25

What is the purpose of coagulase in bacteria like Stahpylococcus aureus?

Answer 25

coagulase accelerates clot formation around the bacteria which allows the bacteria to be antiphagocytic

Question 26

What kinds of bacteria have IgA protease?

Answer 26

Str. pneumoniae, H. influenzae, and N. gonorrhea. This IgA protease cleaves the hinge region of the antibody

Question 27

What is Protein A and what bacteria produce it?

Answer 27

It is produced by Stap. aureus only and it binds to the IgG Fc which prevents binding of complements

Question 28

Damage is the result of which three activities associated with bacterial infections?

Answer 28

inflammation, toxin production, and immune cross-reactivity

Question 29

What are the two types of inflammation and their associated effector cells?

Answer 29

pyogenic (pus-producing)- neutrophils

granulomatous- macrophages

Question 30

What are the two main types of toxins?

Answer 30

endotoxins and exotoxins

Question 31

T or F. The symptoms associated with most viral infections are due to our immune response

Answer 31

T. Viruses don’t have that many virulence factors that directly do damage, most is the result of our own immune trying to clear the infection

Question 32

How does endotoxin Lipid A of the LPS layer of gram-negative bacteria lead to whole-body sepsis? Draw the flowchart

Answer 32

major cause of sepsis

Lipid A activates:

1. macrophages which cause:
   a) IL-1 to be expressed leading to fever
   b) TNF causing fever and hypotension
   c) nitric oxide causing hypotension
2. complement which causes:
   a) C3a leading to hypotension and edema
   b) C5a leading to neutrophil chemotaxis (the movement of an organism in response to a chemical stimulus)
3. activates tissue factor leading to the coagulation cascade

Question 33

T or F. Exotoxins are polypeptides that are secreted by both G+ and G- bacteria

Answer 33

T. They are antigenic and induce antibodies (aka antitoxins) that can be used to prevent or treat some infections.

Question 34

What are toxoids?

Answer 34

inactivated forms of toxins that can be activated to develop antitoxins

Question 35

How do A-B exotoxins work?

Answer 35

they consist usually of a single A subunit, which is the effector part of the toxin, and multiple B subunits which are responsible for binding the exotoxin to a host cell. When B subunits bind, the whole complex is endocytosed and inside the cell the A subunit dissociates from the B subunit and begins to work

Question 36

What are the common mechanisms of action of the A subunit of A-B exotoxin?

Answer 36

the often ADP-ribosylate G proteins which inactivates or activates them depending on their purpose. Others alter or cleave ribosomes to disrupt protein synthesis

Question 37

What are metalloproteases? Give two examples.

Answer 37

These are A-B exotoxins which act to cleave Snares, blocking neurotransmitter delivery

Botulism- flacid paralysis by blocking inhibitory mediators
Tetanus- results in tightening of muscles (lock-jaw)

Question 38

What is an example of a pore-forming exotoxin and how does it work?

Answer 38

Hemolysins work by punching holes in the membranes, depolarizing them and allowing leakage

Question 39

What are superantigens?

Answer 39

exotoxins that bind directly to class II MHCs on APCS. The binding results in a large number of T cell releasing cytokines, initiating a “cytokine storm”.

Question 40

What are some examples of superantigens?

Answer 40

Staph aureus and group A streptococci (GAS)

Question 41

T or F. Many infections will be asymptomatic and will resolve on their own

Answer 41

T. Especially true of viral infections. In these cases, the best course of action is to treat the SYMPTOMS and not the infection itself. Many resolved infections lead to lifelong immunity

Question 42

What are some of the causes of recurrent infection?

Answer 42

poor immune response, antigenic variation, many serotypes

Question 43

What are the two types of persistent infection?

Answer 43

chronic- there is chronic low level detection of the microbe where there has been an impasse between the immune system and the growth of the bacterium so that it is still present

latent- the microbe goes undetected for long periods of time but remains in the body and can come back (especially viral infections like herpes)

Question 44

Can cancer be caused by microbes?

Answer 44

Few and rare but H. pylori can cause GI tumors

and oncogenic microbes can