Bacterial Pathogenicies and Host Interactions Lecture Sep 10

Question 1

What is the LD50?

WHat is the ID50?

Answer 1

LD50 – number of bacteria necessary to kill half the host

ID50 – number of bacteria necessary to cause infection in half the hosts

Question 2

WHat are the 8 stages of bacterial pathogenicity?

Answer 2

1. TRansmission from an external source into the body
2. Evasion of initial host defense
3. Attachment to mucous membranes
4. Colonization at attachment site
5. Sometimes spread and reattach in new locations
6. Disease symptoms cuased by toxins or tissue invasion followed by inflammation
7. Nonspecific and specific immune host repsonses
8. Progression or resolution of the disease

Question 3

What are the three general mechanisms of bacterial disease?

Answer 3

1. tissue invasion followed by inflammation
2. toxins (exotoxin and endtoxin)
3. Immunopathogenesis (like rheumatic fever)

Question 4

GIve an example of disease caused by toxin only–the bacteria doesn’t even need to multiply in the body.

Answer 4

This is the case in food poisoning where the bacteria replicated in the food and secreted toxin. We eat the toxin-containing food and develope disease.

Question 5

What are the main branches of transmission mechanisms?

Answer 5

Human to human

Direct contact (like infectious mono)

Non-direct contact (fecal oral)

Transplacental

Transferred blood products or contaminated needles

Non-human to human

Contaminated soil (tetanus)

Contaminated water (legionnaries’ disease)

Direct from animals (cat scratch fever)

Insect vectors (lyme disease)

Question 6

WHat are the 4 main portals of entry in the order of most common to less common?

Answer 6

1. Respiratory tract
2. GI tract
3. Skin
4. Genital tract

Question 7

What are 6 examples of bacterial STRUCTURAL virulence factors?

Answer 7

1. Pili for attachment (N. gonorrhea to urinary tract epithelium(
2. Capsule (strep pneumonia)
3. Glycocalyx (strep viridans on heart valves)
4. Endotoxin (gram negative bacteria)
5. Biofilms (pseudomonas in cystic fibrosis patients)
6. Bacterial Secretion Systems (T3SS in Salmonella typhimurium)

Question 8

What are 4 examples of secrete enzymes as virulence factors?

Answer 8

1. Coallagenase and hyaluronidase (strep pyogenes cellulitis)
2. Coagulase (helps coat staph aureus with fibrin to help protect from phagocytosis)
3. Immunoglobulin A protease (degrades IgA allowing strep pneumonia to adhere to mucous membranes)
4. Leukocidins (destroy neutrophilic leukocytes and macrophages in staphylococci and group A streptoccocci)

Question 9

WHat does M-protein do for a bacteria?

Answer 9

It is an antiphagocytic proteins produced by strep pyogenes

Question 10

What does protein A do for a bacteria?

Answer 10

It binds to IgG and prevents activation of complement

Question 11

What do invasins do for a bacteria?

Answer 11

Invasins are bacterial proteins which promtoe bacterial entry or contact with host cells (e.g. heliobacter pylori)

Question 12

What are pathogenicity islands?

Answer 12

PAIs code for groups of virulence factors.

THis is often in gram negative bacteria.

In gram negative bacteria that have PAIs, all of their virulence factors tend to be on the PAI except for the endotoxin.

So if you find a way to get rid of the PAI, the bacteria loses its ability to cause disease

Question 13

What are toxoids? How are they made?

Answer 13

A toxoid is an exotoxin that has been treated with formaldehyde and/or heat to be used in protective vaccines

Question 14

What is the general composition of exotosin?

Where are they encoded?

Answer 14

Exotoxins are polypeptides secreted by bacteria

They frequently have an A-B subunit structure with A having the toxic activity and the B protion involved in binding to cells

Exotoxins are coded for on the bacterial chromosome, plasmid, or a phage in the host cell

Question 15

What are the five biological efects of exotoxin?

Answer 15

ALl exotoxins have at least one of the following effects:

1. alter cellular components (clostridium perfringens produces alpha toxin which is a PLP to hydrolyse phosphorylchlorine in the membrane so the membrane breaks down and the cell lyses, causing death. Staph aureus produces an alpha toxin that causes potassium pores leading to a loss of nutrients and cell death)
2. are superantigens
3. inhibit protein synthesis (c. diphtheriae produce an AB toxin that inactivates elongation factor 2 to prevent protein synthesis by the ribosome)
4. increase synthesis of cAMP (vibrio cholerae has a multiunit toxin that increases adenylate cyclase activity leading to an increase in cAMP which triggers the excretion of ions into the lumen the gu leading to diarrhea)
5. Alter nerve impulse transmission (clostridium tetani produce a toxin that blocks inhibitory transmitter release, so you get continuous stimulation by an excitatory transmitter) (Clostridium botulinum blocks the release of ACh from vessicles)

Question 16

For what types of bacteria/toxins would antibodies specific for a toxin NOT be effective?

Answer 16

WHen the bacteria has a type III cytotoxin that is being injected into the cell through an injectosome. The antibodies never have access because the toxin is never in the extracellular space.

Question 17

What to superantigens trigger? WHat is the result?

Answer 17

Superantigens cause the massive release of cytokines, resulting in systematic inflammation, hypotension and shock.

Question 18

Describe endotoxin.

Where are they located? on what bacteria?

Can toxoids be maid?

Answer 18

Endotoxins are integral parts of the cell wall of gram negative rods and cocci.

This is the lipid A component of LPS

It cannot be made into toxoids for vaccines because it is only weakly antigenic (just very toxic)

Question 19

What are the biological effects of endotoxin?

Answer 19

1. Induce the release of endogenous pyrogens–fever
2. increase vascular permeability
3. imitate complement and blood coagulation cascades
4. cause fever, hypotension, disseminated intracellular coagulation and shock

Question 20

What is the difference between innate immunity and adaptive/acquired immunity?

Answer 20

Innate immunity is the macrophages (for phagocytosis) and complement (for lysis) which are in our systems all the time–they’re innate.

Acquired immunity is immunity our body learns. It involves antibodies that learn to recognize specific antigens (cytolytic, neutralizing, opsonins) and cytotoxic T cells to kill antibody-coated bacteria and virus-infected cells.

Question 21

What is the difference between passive and active immunity?

Answer 21

Passive immunity is when the body doesn’t have to learn its own response. It coems from administration of preformed antigen-specific antibodies to help protect from disease (like the human rabies immune globulin)

Active immunity is when the body still has to learn its own repsonse even though it’s helped a long a bit. This is the administration of specific antigens to stimulate an individual tod evelop immunity to help protect from a disease (like the influenza vaccine).

Question 22

What are some main live vaccines?

What are some main killed vaccines?

Which tends to be more effective?

Answer 22

Live/attenuated:

HPV vaccine, MMR, polio, varicella, yellow fever, small pos, influenza (cold adapted–in the nose spread)

Killed:

Hepatitis A, Influenca (whole virus injected), polio (salk), rabies, japanese encephalitis, cholera (diptheria toxoid), pertussis, plague, typhoid

Live vaccines are more effective

Question 23

What are some main diseases we can provide immunoglobulins for (either human Ig or horse Ig)?

Answer 23

CMV, HepB, Rabies, Tetanus, Smallpox, Varicella-zoster,

Botulism, Dipheria (from horses)

Question 24

What are the three general bacterial strategies tod eal with phagocytic cells?

Answer 24

1. Avoid contact with phagocytes
2. Inhibition of engulfment
3. Survival within the phagocyte

Question 25

What are three ways a bacteria can avoid contact with phagocytes?

Answer 25

1. reside in a niche not patrolled by phagocytes
2. suppress inflammation and/or chemotaxis so the phagocytes don’t even come
3. coat itself with host proteins to camouflage

Question 26

WHat are three ways bacteria can inhibit engulfment by phagocytes?

Answer 26

1. Many bacterial capsules are anti-phagocytic
2. Some surface polysaccharides (such as those that aid in biofilm structure) are antiphagocytic
3. Some bacteria produce specific antiphagocytic products

Question 27

What two things can capulses inhibit?

Answer 27

Phagocytosis and complement activation.

The combination fo the two is what’s necessary to lyse the cells.

Question 28

What three ways can bacteria deal with the phagosome after being engulfed?

Answer 28

1. escape the phagosome (shigella, lysteria)
2. Adapt to the phagosome (coxiella, leishmania)
3. Modify the phagosomal compartment (Salmonella, legionella, mycobacteria)

Question 29

How does LPS block phacotytosis?

Answer 29

The LPS O-antigen blocks macrophage access

Question 30

What do complement component peptidases do for a bacteria?

Answer 30

Destroys the complement components which inactivates the components AND stops complement activation

Question 31

What does antigenic variation do for a bacteria?

Answer 31

Some bacteria are able to spontaneously change the profile of the surface proteins that they express.

Antibodies are formed inr esponse to specific antigens on the bacteria

After a while, the bacteria is able to use a different cassette and present different surface proteins that the antibodies won’t recognize, thus allowing the bacteria to stay one step ahead of the immune response

Trypanosome variant specific glycoprotein (VSG) cassettes in B. recurrentis and neisseria are examples of this

Question 32

What are two things a bacteria can coat itself in to use as camouflage? What proteins are required for this?

Answer 32

Some will use coagulase and clumpting factor (staph auerus) to coat themselves with fibrin on the bacterial surface.

The treponema pallidum parasite does something similar

Staphyloccoci with protein A are able to bind IgG antibiodies backwards to camouflage themselves.

Question 33

What issue does pseudomonas cause in cystic fibrosis patients?

Answer 33

They create biofilm infections in the lungs