Pathogenesis

Question 1

Match the following terms to their definitions:

1) Primary pathogens
2) Opportunistic pathogens
3) Infection

A) Pathogen/parasite enters/begins to grow on a host. Does not necessarily imply overt disease

B) Cause disease in healthy hosts

C) Cause disease only in compromised hosts/following entry into unprotected sites

Answer 1

Primary pathogens: Cause disease in healthy hosts

Opportunistic pathogens: Cause disease only in compromised hosts/following entry into unprotected sites

Infection: Pathogen/parasite enters/begins to grow on a host. Does not necessarily imply overt disease

Question 2

(T/F) Some microbes can enter a latent state during infection. This infectious organism cannot be found by culture.

Answer 2

True!

Question 3

What is pathogenicity?

Answer 3

Organism’s ability to cause disease; it is defined in terms of:
1) Infectivity: how easily an organism causes disease

2) Virulence: how severe that disease is/the relative ability of a pathogen to cause disease

3) the specific GENETIC MAKEUP of the pathogen

Question 4

(T/F) Ebola is highly virulent, whereas rhinoviruses are not.

Answer 4

True!

Question 5

What is virulence?

Answer 5

The relative ability of a pathogen to cause disease.

Question 6

Match the following terms regarding measuring virulence:

1) ID50
2) LD50

A) the amount of an agent that kills 50% of the animals in a test group

B) number of pathogen cells/virions required to cause active INFECTION in 50% of inoculated animals

Answer 6

ID50: infectious dose - number of pathogen cells/virions required to cause ACTIVE INFECTION in 50% of inoculated animals

LD50: lethal dose - the amount of an agent that KILLS 50% of the animals in a test group

Question 7

If agent 1 has a LD50 of 10^4 and agent 2 has a LD 50 of 10^6, which agent is more virulent?

Answer 7

Agent 1 is more virulent!

Mortality is caused at a lower dose.

Question 8

What is immunopathogenesis?

Answer 8

It is the “friendly fire” by our immune system reacting to a pathogen that causes major tissue and organ damage.

The term applies when the immune response to a pathogen is a contributing cause of pathology and disease.

Question 9

To fully understand any infectious disease, researches must study both:

Answer 9

1) pathogenic mechanisms of the pathogen
2) disease symptoms caused by immunopathogenesis

Question 10

The _________ ______ describes the route of transmission of an infectious organism.

Answer 10

Infection cycle

Question 11

Discuss horizontal vs vertical transmission of a infectious organism:

Answer 11

Horizontal transmission: passage from one person or animal to another within the same generation. DIRECT/INDIRECT. Can be through fomites (inanimate objects) or through vehicles (ingested/inhaled materials).

Vertical transmission: passage from a mother to her fetus during pregnancy (transplacental) or brith (parturition)

Question 12

Describe the steps of the infection process of pathogenesis:

Answer 12

1) Exposure to pathogens
2) Adherence to skin/mucosa
3) Invasion through epithelium (BREAK IN BARRIER)
4) Multiplication: growth and production of virulence factors and toxins

Question 13

What is the disease process of the pathogenesis?

Answer 13

After multiplication (last step of the infection process), they can induce:
1) TOXICITY (toxins effects are local/systemic) or INVASIVENESS (further growth at original and distant sites)

which leads to:

2) Tissue or system damage

Question 14

What are 5 portals of entry for infectious agents to enter the body?

Answer 14

1) Mouth
2) Respiratory tract
3) Conjunctiva and mucous membranes
4) Wounds, injuries, and skin lesions
5) Parenteral route (into bloodstream)

*infectious agents can enter the body through one or more of these depending on whats best suited to their mechanisms of pathogenesis.

Question 15

To cause disease, all pathogens must:

How do they accomplish these goals?

Answer 15

1) Attach to our surfaces and tissues
2) Damage tissues to obtain nutrients and replicate
3) Avoid host immune responses

Pathogens employ VIRULENCE FACTORS, encoded by VIRULENCE GENES to accomplish these goals.

Question 16

What are virulence factors?

Answer 16

Virulence factors include toxins, attachment proteins, capsules and other devices.

Virulence factors are bacteria-associated molecules that are required for a bacterium to cause disease.

Question 17

Virulence in salmonella is through pathogenicity islands and _________ plasmids.

Answer 17

Resistance

(genes that direct invasion & promote systemic disease are on the islands)

Question 18

REVIEW: How do we know that most pathogenicity islands have been horizontally transmitted via conjugation/transduction?

Answer 18

1) Unique GC/AT ratio
2) Codon bias
3) Flanked by inverted repeats
4) Found in only certain strains of species

Question 19

What do microbes use for MICROBIAL ATTACHMENT?

Answer 19

1) Adhesins
2) Capsules
3) Fimbriae and pili
4) Flagella

Question 20

Adhesins are ___proteins or ____proteins found on the ________’s surface that enable it to bind to the host cells.

Answer 20

Glyco; Lipo

Pathogen

*there are many different receptors coating both the pathogen and tissues where the bacteria/virus bind.

Question 21

(T/F) Fimbriae pili are the same as conjugation/sex pili used for gene transfer. They also help bacteria to attach to specific host cells.

Answer 21

False!

Fimbriae pili are not the same as conjugation/sex pili used for gene transfer.

Fimbriae pili are hairlike appendages that bacteria use to attach to specific host cells.

Question 22

Match the different types of pili to their definition:

1) Type I
2) Type IV

A) Involved in “twitching motility”. Produce a DYNAMIC attachment via assembly/disassembly. Grow from INNER MEMBRANE of many gram-NEGATIVE bacteria.

B) Adhere to carbs on host membranes. Produce a STATIC attachment and grow from OUTER MEMBRANE of gram-NEGATIVE bacteria.

Answer 22

Type I: Adhere to carbs on host membranes. Produce a STATIC attachment and grow from OUTER MEMBRANE of gram-NEGATIVE bacteria.

Type IV: Involved in “twitching motility”. Produce a DYNAMIC attachment via assembly/disassembly. Grow from INNER (& cross outer) MEMBRANE of many gram-NEGATIVE bacteria.

Question 23

(T/F) Bacteria also possess adhesins that are not pili.

Answer 23

True! They’re AKA nonpilus adhesins.

Question 24

Why are some people susceptible to certain infections, whereas others are not?

Answer 24

1) Immunocompetence (capacity to see and eliminate danger)
2) Receptor availability (capacity to adhere to host cells)

Question 25

Pathogens rely on __________ to recognize and attach to appropriate host cells.

Answer 25

Receptors (specific surface structures)

Question 26

Is person-to-person differences in receptor structures possible? If so, give an example.

Answer 26

Yes! Example: HIV binds C-C chemokine receptor type 5 (CCR5); individuals with a CCR5 mutation are resistant to HIV infection!

Question 27

The bacterial ________ forms a thick coating outside the plasma membrane and cell wall.

Answer 27

Capsule

Question 28

What are the two important functions that bacterial capsule serve in bacterial pathogenecity?

Answer 28

1) Facilitates attachment on host tissues (capsule is sticky + has specific receptors) 2) Inhibit opsonization (protect the bacteria from phagocytosis) *human immune cells use opsonins to tag pathogens for elimination by phagocytosis

Question 29

(T/F) Often, without a capsule, the bacterial strain is not pathogenic.

Answer 29

True!

Question 30

Other than blocking opsonization, how do capsules prevent phagocytosis (and hide the bacteria)?

Answer 30

1) Block antibody/complement 2) Reduce entry into endocytic pathway to lessen antigen presentation 3) Mimics "self" molecules, preventing stimulation of antibody/complement responses.

Question 31

Match the following terms to their definition regarding invasion and systemic infection: 1) Colonization 2) Invasiveness 3) Bacteremia 4) Septicemia A) ability of pathogen to grow in host tissue at densities that inhibit host function B) bloodborne systemic infection that can lead to massive inflammation, septic shock + death C) growth of microorganisms after they've gained access to host tissues D) the presence of bacteria in the bloodstream, not always harmful (vigorous toothbrushing can cause it)

Answer 31

Colonization: growth of microorganisms after they've gained access to host tissues Invasiveness: ability of pathogen to grow in host tissue at densities that inhibit host function Bacteremia: the presence of bacteria in the bloodstream, not always harmful (vigorous toothbrushing can cause it) Septicemia: bloodborne systemic infection that can lead to massive inflammation, septic shock + death

Question 32

As the microorganisms adhere, invade + proliferate, some can have features to cause disease in the host. These features can be beneficial to the microorganisms by:

Answer 32

1) Facilitating their invasion/propagation 2) Enhancing their capacity of evading the host immune system

Question 33

__________ requires a pathogen break down host tissues. This is often done with __________ that attack host cells.

Answer 33

Invasiveness; enzymes HYALURONIDASE breaks down host tissues.

Question 34

How does hyaluronidase break down host tissues?

Answer 34

Hyaluronidase producer attaches to epithelia, leading to the production of hyaluronidase, which results in pathogen invading deeper tissue.

Question 35

The other enzymes involved in tissue invasion are Coagulase and Streptokinase. What are their functions and how do they work?

Answer 35

Coagulase: forms clots Streptokinase: breaks down clots If there is a cut, bacteria (staphylococci) enter in the cut and produce COAGULASE to produce a clot that blocks access to immune system cells. After, STREPTOKINASE dissolves clot and releases pathogen to bloodstream and deeper tissues.

Question 36

Match the enzymes used as virulence factors to their function: 1) Glycohydrolases 2) Nucleases 3) Phospholipases 4) Proteases A) degrades phospholipid bilayer of host cells, causing cellular lysis, and degrade membrane of phagosomes to enable escape into the cytoplasm. B) degrades hyaluronic acid that cements cells together to promote spreading through tissues C) degrades collagen in connective tissue to promote spread D) degrades DNA released by dying cells (bacteria + host) that can trap bacteria, thus promoting spread

Answer 36

Glycohydrolases: degrades hyaluronic acid that cements cells together to promote spreading through tissues Nucleases: degrades DNA released by dying cells (bacteria + host) that can trap bacteria, thus promoting spread Phospholipases: degrades phospholipid bilayer of host cells, causing cellular lysis, and degrade membrane of phagosomes to enable escape into the cytoplasm. Proteases: degrades collagen in connective tissue to promote spread

Question 37

Bacterial toxins can be divided into two main types:_________ and ___________. Briefly describe both.

Answer 37

Exotoxins - proteins produced + secreted by bacteria - kill host cells + unlock nutrients - AB toxins, cytolysins + superantigens Endotoxins - LPS of -, lipoteichoic acid of + - hyper activates host immune systems to harmful levels

Question 38

What are the three categories of microbial exotoxins?

Answer 38

1) Membrane disruptors (cytolysins) 2) AB-type toxins (two subunits) 3) Transport disrupting toxin

Question 39

Two types of exotoxins disrupt host cell membranes (cytolysins): ______________ _____ insert themselves into membranes by binding cholesterol and membrane receptors. ____________ _____ hydrolyze phospholipids into fatty acids.

Answer 39

Pore-forming proteins Phospholipase enzymes

Question 40

Briefly give an example of a pore-forming protein and how it works.

Answer 40

Alpha toxin of staphylococcus aureus 1) S.aureus secretes alpha-toxin monomer. 2) Monomer binds to membrane receptor. 3) Additional monomers bind and oligomerzie 4) Conformational change and insertion of hydrophobic segments into membrane forms a pore

Question 41

Some exotoxins disrupt host cell membranes by forming pores that cause LEAKAGE of cell constituents (host cell lysis). ____________ lyse red blood cells ____________ lyse white blood cells

Answer 41

Hemolysins; leukocidins Some membrane-disrupting exotoxins function as both!

Question 42

AB exotoxins consist of two subunits called A and B and they work together to ________ _____ ________ _________. A subunit: B subunit:

Answer 42

Disrupt host cell functions A subunit: toxicity associated factor B subunit: binds host cell, delivers "A" subunit

Question 43

(T/F) AB5 exotoxins consist of five "A" subunits arranged in a ring with a singular "B" subunit nestled in the center.

Answer 43

False! AB5 exotoxins consist of five "B" subunits arranged in a ring with a singular "A" subunit nestled in the center.

Question 44

Briefly answer the questions regarding cholera toxins: 1) What kind of toxin is the cholera toxin? 2) What does its "B" subunit do? 3) What does its "A" subunit do? 4) Why does this disease cause diarrhea?

Answer 44

1) AB5 exotoxin (disrupts signaling functions) 2) B subunit binds to intestinal cell membranes and trigger endocytosis of cholera toxin complex 3) A subunit: ADP-RIBOSYLATES A HOST CELL TARGET that leads to a sharp increase in cAMP levels. 4) cAMP activates ion transporters that cause water to leave the cell, causing diarrhea.

Question 45

Match the steps of the cholera toxin: 1) Step 1 2) Step 2 3) Step 3 4) Step 4 5) Step 5 6) Step 6 A) the phagosome containing CT is taken to the ER B) cyclic AMP levels rise and activate ion transport systems, causing an electrolyte imbalance. Water from the cell follows the ion, causing diarrhea. C) the 5B:1A toxin complex binds the ganglioside GM1 on host membrane lipid rafts D) the A1 peptide attaches an ADP-ribose to an amino acid within the host G protein and that regulates adenylyl cyclase E) the toxin is endocytosed F) the A1 subunit is removed from the B subunits and exported into the cytoplasm

Answer 45

Step 1: the 5B:1A toxin complex binds the ganglioside GM1 on host membrane lipid rafts Step 2: the toxin is endocytosed Step 3: the phagosome containing CT is taken to the ER Step 4: the A1 subunit is removed from the B subunits and exported into the cytoplasm Step 5: the A1 peptide attaches an ADP-ribose to an amino acid within the host G protein and that regulates adenylyl cyclase Step 6: cyclic AMP levels rise and activate ion transport systems, causing an electrolyte imbalance. Water from the cell follows the ion, causing diarrhea.

Question 46

Briefly describe DIPHTHERIA EXOTOXIN.

Answer 46

DIPHTHERIA EXOTOXIN is an AB exotoxin that BLOCKS protein synthesis. The toxin destroys healthy tissues in the RESPIRATORY SYSTEM. Within 2-3 days, the dead tissues form a thick, gray coating that can can build up in the throat/nose, makes it HARD TO BREATHE + SWALLOW. The toxin can also get into the blood stream and damage the heart, kidneys + nerves.

Question 47

What are the two neurological exotoxins? What are they also?

Answer 47

1) Botulinum toxins 2) Tetanus toxins These are the two-subunit AB exotoxins. Both toxins are also TRANSPORT DISRUPTERS.

Question 48

What does the A subunit of botulinum toxin do?

Answer 48

Destroys snare proteins which are responsible for acetylcholine release into motor neurons. Without acetylcholine, muscles are in constant state of relaxation.

Question 49

(T/F) Tetanus toxin is an AB protein neurotoxin, acts in the similar manner as the botulinum toxin.

Answer 49

False! Tetanus toxin is an AB protein neurotoxin but its actions are opposite to the botulinum toxin, where muscles are kept in a CONSTANT STATE OF CONTRACTION.

Question 50

What is the lipopolysaccharide (LPS) composed of?

Answer 50

Lipid A (endotoxin) Core glycolipid O antigen (polysaccharide chain)

Question 51

LPS if found in gram ________ bacteria.

Answer 51

Negative (form the outer leaflet of the gram - outer membrane)

Question 52

How does LPS cause its toxic effects?

Answer 52

As bacteria die, they release endotoxin, a MICROBE-ASSOCIATED MOLECULAR PATTERN (MAMP) molecule that bind to receptors on macrophages or B cells. Receptor binding triggers a massive cytokine release (cytokine storm) that can trigger fever, inflammation, shock, and death.

Question 53

Which one of the statements is false about endotoxin (LPS)? 1) It is less immunogenic than exotoxins (can't use for vaccines) 2) Generally local infections (diarrhea, vomiting and fever) 3) It is just as toxic as exotoxins 4) It is immunopathogenic and can lead to a toxic shock if systemic infections occur.

Answer 53

3! Endotoxins less toxic than exotoxins. *vaccines can be made for exotoxins*

Question 54

Besides PAMPs (pathogen-associated molecular patterns), what else can induce SEPTIC SHOCK?

Answer 54

Exotoxins, superantigens, secreted enzymes & highly immunogenic PAMPS

Question 55

What is the end result of a septic shock?

Answer 55

1) Over activation of coagulation (DIC) 2) Over action of inflammation (fever, cytokine/chemokine production, cell death) 3) Vasodilation leading to hypovolaemia 4) Organ failure 5) Death

Question 56

(T/F) Gram +, gram -, viruses, fungi and protozoa infections can all result in septic shock under the right conditions.

Answer 56

True!

Question 57

Describe the differences between endotoxins and exotoxins regarding: 1) Source 2) Composition 3) Effect on host 4) Heat stability 5) LD50 6) Enzyme activity

Answer 57

Endotoxins 1) Source: gram - 2) Composition: lipid A (10kDA) 3) Effect on host: systemic symptoms of inflammation + fever 4) Heat stability: heat stable 5) LD50: high (need more to get sick) 6) Enzyme activity: no Exotoxins 1) Source: gram + 2) Composition: protein (50-1000kDA) 3) Effect on host: specific damage to cells dependent upon receptor-mediated targeting of cells + specific mechanisms of action 4) Heat stability: most heat labile 5) LD50: low 6) Enzyme activity: often

Question 58

Depending on what virulence factors they possess, the different strains of the _____ species will cause _________ diseases. The different virulence factors are encoded on: These transferable genetic elements may or may not be present in any single bacterium, which accounts for the ability to cause different diseases.

Answer 58

same; different plasmids, transposons, genome of temperate (lysogenic) phages + pathogenicity islands.

Question 59

Match the following secretion systems to their homologous structures: 1) Type II secretion (T2SS) 2) Type III secretion (T3SS) 3) Type IV secretion (T4SS) A) homologous to conjugation B) homologous to type IV pilus biogenesis C) homologous to flagellar synthesis

Answer 59

Type II secretion (T2SS): homologous to type IV pilus biogenesis Type III secretion (T3SS): homologous to flagellar synthesis Type IV secretion (T4SS): homologous to conjugation

Question 60

Which one of the statements regarding secretion systems is false? 1) They facilitate cellular activities (symbiosis, biofilm formation, enzyme secretion, DNA transfer, antibiotic release, protein delivery) 2) Each secretion system is a large complex of proteins that are located on the outer membrane. 3) They secrete proteins directly outside the cells into the environment or inject proteins into a host cell

Answer 60

Two! Each secretion system is a large complex of proteins that forms channels through the membrane.

Question 61

What does the type II secretion system do?

Answer 61

Secrete structures that extend and retract, just like pili. The proteins that get secreted first enter the periplasm, then they get folded and secreted via an OUTER MEMBRANE PORE.

Question 62

Some microbes do not rely on the natural array of host receptors for attachment, instead they use a _______ to insert their own receptors into target cells.

Answer 62

T3SS

Question 63

How does the type III secretion system work?

Answer 63

The T3SS is a reengineered flagellar synthesis mechanism that uses a MOLECULAR SYRINGE to inject proteins from the bacterial cytoplasm directly into the host cell. Secretion is triggered by cell-cell contact between host + bacteria.

Question 64

T3SS genes are usually located within ___________ ________ inherited via _________ gene transfer.

Answer 64

Pathogenicitiy islands; horizontal

Question 65

What do T3SS inject into the host cell?

Answer 65

EFFECTOR PROTEINS: have a function that will help the bacteria manipulate the host to its advantage (invasion, immune evasion).

Question 66

The T4SS is an evolutionary modification of a conjugation ______ that secretes _____ only, or _______ plus ______. It allows them to secrete these directly from their _________ or ________.

Answer 66

pilus; proteins; proteins; DNA cytoplasm; periplasm