Exam 2: Host-Parasite Relationships: Pathogenesis of Infections Flashcards
In any host-pathogen encounter, what are the 2 principal determinants of the outcome?
Virulence of the parasite
Resistance of the host
What are opportunistic pathogens?
Bacteria or fungi that are generally harmless in their normal habitat but can cause disease when they gain entrance to other sites or tissues
They have a low potential to cause disease, but once disease is established, they can be difficult to treat
What is an obligate pathogen?
Organisms that always cause disease when it encounters a host
What is pathogenicity?
The capacity of an organism to cause disease
What is virulence?
The measure of the degree of pathogenicity
What is infectivity?
The capacity of an organisms to become established in the tissues of the host
It involves the ability to penetrate the tissue, survive the host’s defenses, and disseminate within the animal
What is toxigenicity?
The ability of certain organisms to produce exotoxins
There are both toxigenic and nontoxigenic strains of Clostridium perfingens. Which has the ability to cause disease?
Toxigenic
What is virulence factor?
A bacterial product or strategy that contributes to its ability to cause infection
What is the classical method to definitively determine whether an agent is causing disease?
Koch’s postulates
What are Koch’s postulates?
The suspected agent is present in all cases of the disease
The agent is isolated from such disease and propagated serially in pure culture, apart from its natural host
Upon introduction into an experimental host, the isolate produces the original disease
The agent can be reisolated from this experimental infection
What are the 2 basic mechanisms that bacteria cause disease by?
Direct damage of host cells
Indirectly by stimulating exaggerated host inflammatory/immune response
What is involved with direct damage of host cells?
Extracellular pathogens
Intracellular pathogens
What are extracellular pathogens?
Secreted exotoxins or effector proteins cause damage
What do intracellular pathogens do?
Destruction of host cells or alteration of host cells’ function
What are the 2 categories of virulence factors?
Those that cause damage to the host
Those that do not directly damage the host but promote colonization and survival of infecting bacteria
What are exotoxins?
Protein molecule liberated from intact living and lysed bacteria
They are antigenic and can elicit protective antitoxic antibodies
What can many exotoxins be converted to?
Nontoxic immunizing agents termed toxoids by treatment with formalin
What are the 3 roles of exotoxins in disease?
Ingestion of preformed toxin (botulism)
Colonization of wound or surface followed by toxin production
Exotoxin produced by bacteria in tissues to aid growth and spread
What are the different types of exotoxins?
A-B toxins (intracellular acting)
Membrane disrupting (surface damaging)
Superantigens
Extracellular enzymes
What are A-B toxins composed of?
Two parts: A and B portions
What does the B portion of A-B toxins do?
The B potion mediates binding to a specific host cell receptor
What happens after the B part of A-B toxins bonds to the host cell?
The A portion is translocated into host cells and has biological activity against an intracellular target
What do membrane disrupting exotoxins do?
Cause damage or disruption of plasma membranes, which leads to osmotic lysis and cell death
What are many membrane disrupting exotoxins known to cause?
Damage to host tissues and contribute to virulence
What 3 types of membrane disrupting toxins?
Enzymes that hydrolyze phospholipids
Toxins with detergent-like surfactant activity that disrupt by membrane solubilization
Pore forming toxins
What are pore forming toxins?
Proteins that insert in the host membrane and form a hydrophilic pore
What are superantigens?
Toxins that bind directly to MHC II on macrophages and form a crosslink with T cell receptors
What does crosslinking with superantigens cause?
Stimulation of up to 1 in 5 T cells
What does excessive IL-2 production from superantigens result from?
The massive stimulation of T helper cells, which causes nausea, malaise, and fever
What does the stimulation of other cytokines by IL-2 with superantigens lead to?
Shock
What do extracellular enzymes do?
Break down host macromolecules
What do extracellular enzymes often play a role in?
Disease development by providing a source of carbon and energy or aiding in dissemination
What can extracellular enzymes cause?
Extensive tissue damage
How do some vaccines or bacterins elicit protective immunity from extracellular enzymes?
By neutralizing their activity
What is an endotoxin?
Lipopolysaccharide produced by pathogenic and nonpathogenic gram-negative bacteria
Describe lipopolysaccharide
Lipid A is the toxic portion
It is only release to exert its effect when bacteria lyse
What is released LPS bound by?
LPS binding proteins in plasma, which the binds CD14
What do CD14-LPS complexes bind?
Toll-like receptor 4 on macrophages and monocytes, which release cytokines causing prostaglandins and leukotriene release which activate complement and coagulation cascades
What happens in bacteria sepsis with endotoxins?
The inflammatory response is triggered throughout the body
When does septic shock (endotoxic shock) occur?
When bacterial products reach high enough levels in the blood to trigger complement activation, cytokine release, and coagulation cascade activation in many parts of the body
What can the amount of endotoxin be determined by?
The limulus amebocyte lysate assay, which can detect nanogram amounts
Describe limulus amebocyte lysate assay
Endotoxin reacts with proteins from horseshoe crab blood cells to produce a gel
In gram-positive bacteria, although they lack LPS, what is septic shock like?
It is very similar to those with LPS by it is triggered by TLR2 or TLR1
What does TLR2 bind?
Lipoproteins/teichoic acids
What does TLR1 bind?
Peptidoglycan
What is host damage caused by during invasion?
Direct disruption of function
An exaggerated immune response that compromises tissue function or homeostasis
What are the invasive bacteria classified as?
Facultative Intracellular parasites
Obligate intracellular parasites
Extracellular parasites
Describe facultative intracellular parasites
Not confined to cells
Some can multiple in professional phagocytic cells
What happens with facultative intracellular pathogens when a balance is established between the bacterium and phagocyte?
The bacteria may survive in this intracellular state of relative equilibrium for months or years
Describe obligate intracellular parasites
Can only propagate inside host cells
Describe extracellular parasites
Cause tissue damage while they are outside phagocytes and other cells and do not have the ability to survive long periods in cells
What are the steps in bacterial invasion?
Motility
Adherence
Invasion of host cells
Manipulation of host cell functions
What is the best characterized thing for motility?
Flagella
What is flagella adapted for?
Low viscosity fluids
What are other types of motility?
Corkscrew type (spirochetes) Gliding motility
What is the corkscrew type motility best in?
Viscous solutions
What is gliding motility?
Movement over solid surfaces
What is chemotaxis?
Directional swimming using a gradient
How does chemotaxis occur?
1: Bacteria senses the concentration gradient of the attractant and move through the medium in the direction of the attractant
2: When moving to an area of higher concentration, the peritrichous flagella twist together and the bunched flagella rotate as one in a counterclockwise direction
3: When rotating in a clockwise direction, the flagella spread apart. The force of many flagella on the cell causes a tumbling motion to occur
What are the 2 common strategies of adherence?
Fimbriae and monomeric protein adhesins
Describe fimbriae
Receptors are usually carbohydrate residues of glycoproteins or glycolipids
Attachement is more fragile
Highly specific binding, often mediated by adhesins, can be blocked by antibodies, often specific for host tissue type/location
What are the 2 types of bacterial-mediated invasion?
Zippering
Triggering
What is zippering?
Bacteria present ligands on their surface allowing them to bind to host cells and initiate the entry process
What is triggering?
Bacteria inject effectors into host cells via T3SS to regulate phagocytosis
What happens following attachment to host cells?
Pathogens cause changes in host cell cytoskeleton that cause the pathogen to be internalized
What can some pathogens utilize to move through host cells?
Actin fiber intracellularly
What may invasins do?
Mediate uptake of bacteria into professional phagocytic cells in a way that bypasses normal phagosome formation
What can bacterial pathogens do to host cell functions?
They are often very manipulative of them
Both extracellular and intracellular pathogens will cause host cells to perform functions favorable to the pathogen
What does a type III secretion system that some bacterial pathogens have do?
Forms a needle-like structure that injects effector proteins directly into the host cell cytoplasm
What can the effector proteins injected by T3SS do?
Serve as receptors in the host membrane for bacterial attachment
Mobilize cytoskeleton to cause phagocytosis
Can induce or prevent apoptosis
What must bacteria be able to do during infection?
Obtain all of their essential nutrients
What is a very nutrient rich environment?
Host cytoplasm
How do extracellular pathogens obtain nutrients?
They often lyse cells
How do intracellular pathogens obtain nutrients?
They either escape from phagosomes to enter the nutrient rich cytoplasm or modify the vacuole so they can get nutrients from cytoplasm
What are host tissues very low in iron?
Because it is bound to transferrin, lactoferrin, ferritin, and heme
What are the bacterial strategies for obtaining iron?
Siderophores
Direct binding of host transferrin, lactoferrin, ferritin, or heme by bacteria surface receptors
Exotoxins that lyse host cells
What are siderophores?
Low MW compounds that chelate iron with very high affinity
Secreted and taken up by bacteria surface receptors
What is serum resistant to?
Complement
What is serum resistance defined as?
The ability to prevent bacterial lysis by the C5b-CP MAC
How does capsule mediate serum resistance to complement?
Preventing C3b binding
Promoting C3bH complex formation instead of C3bBb
How can O polysaccharide mediate serum resistance to complement?
Having sialic acid attached to promote C3bH formation
Having long O polysaccharide side chains that prevent MAC killing after C5b binds
What allows for resistance to opsonization/phagocytosis?
Capsule
LPS O polysaccharide if it has sialic acid
S-layer
Extracellular products
What are the extracellular products that contribute to resistance to opsonization/phagocytosis?
Enzymes that inactivate C5a chemoattractant
Toxins that kill phagocytes
Inhibit migration
Reduce oxidative burst
What are strategies for surviving phagocytosis?
Escape from phagosome before fusion with lysosome
Prevent phagosome-lysosome fusion
Express factors that allow survival in harsh phagolysosome conditions
How does evading antibody response occur?
sIgA proteases
Phase variation or antigenic switching
Masking
Describe virulence gene regulation
Regulon-coordinated control of group of virulence factors that are activated or deactivated in response to environmental signal
Allows bacterial pathogen to adapt to varying host conditions
What can virulence gene expression be triggered by?
When a pathogen senses environmental cues from the host environment
What is virulence gene expression triggered by?
Quorum sensing
What is quorum sensing?
When a pathogen detects sufficient bacterial numbers are present
What can mutations in regulatory genes do?
Either deactivate multiple virulence genes or cause inappropriate expression
