Pathogenesis Flashcards
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
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
(T/F) Some microbes can enter a latent state during infection. This infectious organism cannot be found by culture.
True!
What is pathogenicity?
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
(T/F) Ebola is highly virulent, whereas rhinoviruses are not.
True!
What is virulence?
The relative ability of a pathogen to cause disease.
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
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
If agent 1 has a LD50 of 10^4 and agent 2 has a LD 50 of 10^6, which agent is more virulent?
Agent 1 is more virulent!
Mortality is caused at a lower dose.
What is immunopathogenesis?
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.
To fully understand any infectious disease, researches must study both:
1) pathogenic mechanisms of the pathogen
2) disease symptoms caused by immunopathogenesis
The _________ ______ describes the route of transmission of an infectious organism.
Infection cycle
Discuss horizontal vs vertical transmission of a infectious organism:
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)
Describe the steps of the infection process of pathogenesis:
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
What is the disease process of the pathogenesis?
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
What are 5 portals of entry for infectious agents to enter the body?
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.
To cause disease, all pathogens must:
How do they accomplish these goals?
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.
What are virulence factors?
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.
Virulence in salmonella is through pathogenicity islands and _________ plasmids.
Resistance
(genes that direct invasion & promote systemic disease are on the islands)
REVIEW: How do we know that most pathogenicity islands have been horizontally transmitted via conjugation/transduction?
1) Unique GC/AT ratio
2) Codon bias
3) Flanked by inverted repeats
4) Found in only certain strains of species
What do microbes use for MICROBIAL ATTACHMENT?
1) Adhesins
2) Capsules
3) Fimbriae and pili
4) Flagella
Adhesins are ___proteins or ____proteins found on the ________’s surface that enable it to bind to the host cells.
Glyco; Lipo
Pathogen
*there are many different receptors coating both the pathogen and tissues where the bacteria/virus bind.
(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.
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.
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.
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.
(T/F) Bacteria also possess adhesins that are not pili.
True! They’re AKA nonpilus adhesins.
Why are some people susceptible to certain infections, whereas others are not?
1) Immunocompetence (capacity to see and eliminate danger)
2) Receptor availability (capacity to adhere to host cells)
Pathogens rely on __________ to recognize and attach to appropriate host cells.
Receptors (specific surface structures)
Is person-to-person differences in receptor structures possible? If so, give an example.
Yes!
Example: HIV binds C-C chemokine receptor type 5 (CCR5); individuals with a CCR5 mutation are resistant to HIV infection!
The bacterial ________ forms a thick coating outside the plasma membrane and cell wall.
Capsule
What are the two important functions that bacterial capsule serve in bacterial pathogenecity?
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
(T/F) Often, without a capsule, the bacterial strain is not pathogenic.
True!
Other than blocking opsonization, how do capsules prevent phagocytosis (and hide the bacteria)?
1) Block antibody/complement
2) Reduce entry into endocytic pathway to lessen antigen presentation
3) Mimics “self” molecules, preventing stimulation of antibody/complement responses.
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)
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
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:
1) Facilitating their invasion/propagation
2) Enhancing their capacity of evading the host immune system
__________ requires a pathogen break down host tissues. This is often done with __________ that attack host cells.
Invasiveness; enzymes
HYALURONIDASE breaks down host tissues.
How does hyaluronidase break down host tissues?
Hyaluronidase producer attaches to epithelia, leading to the production of hyaluronidase, which results in pathogen invading deeper tissue.
The other enzymes involved in tissue invasion are Coagulase and Streptokinase. What are their functions and how do they work?
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.
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
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
Bacterial toxins can be divided into two main types:_________ and ___________.
Briefly describe both.
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
What are the three categories of microbial exotoxins?
1) Membrane disruptors (cytolysins)
2) AB-type toxins (two subunits)
3) Transport disrupting toxin
Two types of exotoxins disrupt host cell membranes (cytolysins):
______________ _____ insert themselves into membranes by binding cholesterol and membrane receptors.
____________ _____ hydrolyze phospholipids into fatty acids.
Pore-forming proteins
Phospholipase enzymes
Briefly give an example of a pore-forming protein and how it works.
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
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
Hemolysins; leukocidins
Some membrane-disrupting exotoxins function as both!
AB exotoxins consist of two subunits called A and B and they work together to ________ _____ ________ _________.
A subunit:
B subunit:
Disrupt host cell functions
A subunit: toxicity associated factor
B subunit: binds host cell, delivers “A” subunit
(T/F) AB5 exotoxins consist of five “A” subunits arranged in a ring with a singular “B” subunit nestled in the center.
False!
AB5 exotoxins consist of five “B” subunits arranged in a ring with a singular “A” subunit nestled in the center.
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?
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.
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
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.
Briefly describe DIPHTHERIA EXOTOXIN.
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.
What are the two neurological exotoxins? What are they also?
1) Botulinum toxins
2) Tetanus toxins
These are the two-subunit AB exotoxins.
Both toxins are also TRANSPORT DISRUPTERS.
What does the A subunit of botulinum toxin do?
Destroys snare proteins which are responsible for acetylcholine release into motor neurons. Without acetylcholine, muscles are in constant state of relaxation.
(T/F) Tetanus toxin is an AB protein neurotoxin, acts in the similar manner as the botulinum toxin.
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.
What is the lipopolysaccharide (LPS) composed of?
Lipid A (endotoxin)
Core glycolipid
O antigen (polysaccharide chain)
LPS if found in gram ________ bacteria.
Negative
(form the outer leaflet of the gram - outer membrane)
How does LPS cause its toxic effects?
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.
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.
3!
Endotoxins less toxic than exotoxins.
vaccines can be made for exotoxins
Besides PAMPs (pathogen-associated molecular patterns), what else can induce SEPTIC SHOCK?
Exotoxins, superantigens, secreted enzymes & highly immunogenic PAMPS
What is the end result of a septic shock?
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
(T/F) Gram +, gram -, viruses, fungi and protozoa infections can all result in septic shock under the right conditions.
True!
Describe the differences between endotoxins and exotoxins regarding:
1) Source
2) Composition
3) Effect on host
4) Heat stability
5) LD50
6) Enzyme activity
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
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.
same; different
plasmids, transposons, genome of temperate (lysogenic) phages + pathogenicity islands.
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
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
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
Two! Each secretion system is a large complex of proteins that forms channels through the membrane.
What does the type II secretion system do?
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.
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.
T3SS
How does the type III secretion system work?
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.
T3SS genes are usually located within ___________ ________ inherited via _________ gene transfer.
Pathogenicitiy islands; horizontal
What do T3SS inject into the host cell?
EFFECTOR PROTEINS: have a function that will help the bacteria manipulate the host to its advantage (invasion, immune evasion).
The T4SS is an evolutionary modification of a conjugation ______ that secretes _____ only, or _______ plus ______.
It allows them to secrete these directly from their _________ or ________.
pilus; proteins; proteins; DNA
cytoplasm; periplasm
