Bacterial Virulence and Host Defense-Felton

Question 1

What are the 4 possible outcomes which can occur from the infection of a susceptible host by a pathogenic microorganism?

Answer 1

The majority of the population does not experience the same severity of the disease.

1. Usually no symptoms. The only evidence is seroconversion = the production of antibodies to the infecting pathogen.
2. 2nd sub-population will have mild, non-specific disease, w/ malaise, fever, nausea or flu-like symptoms.
3. 3rd smaller sub type will have more severe and more specific disease.
4. 4th even smaller sub type will have very severe and specific disease, sometimes resulting in death.

Question 2

Why are there different responses to bacterial infection?

Answer 2

1. Differences in the infecting dose.
2. Differences in virulence among infecting strains.
3. Differences in the effectiveness of peoples’ immune systems.
   •MHC (major histocompatibility complex): genetically polymorphic among individuals.
   •Toll-like receptors (TLR): involved in innate immunity. Also vary.

Question 3

In reference to the host-parasite relationship, why are less virulent strains selected for? What are the 2 exceptions?

Answer 3

There tends to be a selection to less virulence in pathogens so as not to kill the host before the bacteria can produce.
Exceptions:
1. Situations in which hosts are abundant and abnormally crowded, and hygiene is poor (like in prison or refugee camps). In these situations, a pathogen can race thru the population w/o running out of hosts. If it lasts long enough, greater virulence would be selected for.
2. Emerging disease, where the pathogen has jumped to humans from other species.The pathogen might not be as well adapted to humans and may be extra virulent in the beginning. Over time they would become less virulent though.

Question 4

What are the 2 routes of infection? Define them.

Answer 4

1. Endogenous: acquired from our own microbial flora which leaves its normal location and is introduced into an area where it causes harm.
2. Exogenous: acquired from other people, animals or environment.

Question 5

What are the 6 portals of entry for exogenous infections?

Answer 5

1. gastrointestinal tract
2. respiratory tract
3. genitourinary tract
4. ocular mucosa
5. wounds
6. arthropod bites

Question 6

What are the 6 routes of transmission of exogenous infections?

Answer 6

1. direct contact
2. airborne
3. fomites
4. food and water (e.g. fecal-oral)
5. traumatic injury
6. arthropod vector
   Infections that originate in animals may be transmitted via direct contact with a pet, through the food supply, from well water that is contaminated with fecal runoff from a pasture, from the bite of a rabid bat, or by a flea that had previously bitten a rat infected with plague.

Question 7

What are the 4 steps of the pathogenic sequence?

Answer 7

Adherence and colonization → invasion → disruption or avoidance of host defenses → production of damage to the host.

Question 8

Describe adherence and colonization for gram (-) and gram (+) bacteria. What role do the glycocalyx and siderophores play?

Answer 8

• Gram- bacteria have adhesins on the tips of pili extending from the outer membrane.
• Gram+ bacteria have proteins attached to outer surface of cell wall peptidoglycan.
• Glycocalyx is also used for adherence.
• Siderophore: used to sequester iron for nutrients.

Question 9

Invasiveness: What do gram (-) bacteria use to invade host cells? Describe invasion at the cellular level. Describe gross destruction at the macroscopic level (what are the 4 types of enzymes responsible?).

Answer 9

•Gram- bacteria have Type III and IV secretion systems to infect bacterial effector proteins into the host cells.
Invasion at cellular level:
•Bacteria cross membrane and gains entry into host cell.
•Uses invasins (cell surface proteins) and the two secretion systems.
Gross destruction at macroscopic level:
•Secretion of histolytic enzymes like phospholipase, hyaluronidase, collagenase and other proteases.

Question 10

What are the 3 mechanisms for overcoming host defenses?

Answer 10

1. Avoiding/surviving Phagocytosis
2. avoiding complement-mediated lysis
3. avoiding adaptive immunity

Question 11

What are the 4 methods bacteria use to avoid/survive phagocytosis?

Answer 11

1. Bacterial capsules and some Gram + cell wall proteins are antiphagocytic.
2. Prevent acidification of the phagosome.
3. Prevent phagolysosomal fusion
4. Escape from phagosome into cytoplasm of macrophage.

Question 12

How do bacteria avoid complement-mediated lysis? Do these mechanisms protect against opsonization?

Answer 12

•O-antigen of LPS protects Gram (-) bacteria against complement MAC.
•Polysaccharide capsule also shows protection.
*These mechanisms DO NOT provide any protection against opsonization by C3b.

Question 13

How do bacteria defend themselves against adaptive immunity?

Answer 13

• IgA protease: degrades IgA.
• Antigenic variation: numerous pilus genes.
• Leukocidins (toxins): lyse and kill WBCs including phagocytes and lymphocytes.
• Superantigens: non-specifically over-activate helper T cells response in an antigen-independent manner. Results in overproduction of cytokines.

Question 14

What are the 2 kinds of toxins used to damage the host? Define them.

Answer 14

1. Exotoxins: secreted proteins

2. Endotoxins: LPS or LOS from Gram- outer membrane.

Question 15

Describe the features (4) of exotoxins. Give 3 examples that use them. How does the structure contribute to the toxin?

Answer 15

1. High toxicity.
2. Antigenic.
3. Not heat stable
4. Can be quite variable.
   Examples: tetanus, botulinum and diphtheria.
   Structure: A-B
   •A subunit has toxic activity. Some A subunits have ADP ribosyltransferase activity leading to activation of adenylate cyclase and cAMP.
   •B subunit binds to the receptor on target tissue.

Question 16

Describe the features (6) of endotoxins.

Answer 16

1. Lipoteichoic acid can act like an endotoxins sort of.
2. Not secreted.
3. Low variability but multiple activities (fever, hypotension, complement activation, coagulation).
4. Has low toxicity.
5. Poorly antigenic.
6. Heat stable.

Question 17

How does hypersensitivity damage the host? (What mediates the response? What do they bind to? What are they part of? What do they induce production of?)

Answer 17

•TLR (toll-like receptors) located on macrophages, B cells and other cell types.
-Bind to LPS, peptidoglycan, bacterial flagellins, prokaryotic methylation patterns in DNA, lipoteichoic acid, porins, etc.
-Part of the innate response.
-They induce production of cytokines like TNF, IL-1 and synthesis of NO which leads to inflammation, fever, hypotension and sometimes septic shock.
•Damage to the host caused by out-of-control defense mechanisms.