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Chapter 25 Microbial Pathogenesis
micro final
47
Microbiology
Undergraduate 3
05/10/2011

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Term
Pathogenicity
Definition
the ability of a symbiont to cause disease
-symbiosis is the state in which two organisms coexist
-Because pathogens harm the host they are parasitic symbionts
Term
Pathogen
Definition
a pathogen is a microbial agent of disease
-it may be used synoymously with parasite
-Ectoparasite: lives on the surface of the host
Endoparasite: lives inside the host's body
*Infection does not always cause disease
Term
Primary pathogens vs. Opportunistic pathogens
Definition
Primary pathogen cause disease in healthy hosts
Opportunistic pathogens cause disease only in immunocompromised patients
Term
Virulence
Definition
is the measure of the degree or severity of disease
-a highly virulent pathogen is more likely to cause death
A pathogen can be highly infectious but not highly virulent, ex. common cold
-Depends on the invasiveness of the pathogen, or ability to proliferate in the host
-depends on the toxigenicity or the ability to produce toxins which injure the host tissure
Term
Infectiouis dose vs. Lethal dose
Definition
scientist can measure virulence by seing how much of an organism is required to kill 50% of the experimental hosts, thus finding the LD50 or its lethal dose
If the pathogen is not virulent, or simply colonizes but does not kill the host we can measure the infectious dose needed to colonize 50% of the hosts.
Term
Infection cycle
Definition
The infection cycle is the route the pathogen takes from one organism to another.
Horizontal transmission is when the pathogen goes from one member of a species to another, either through:
Formites- inanimate objects, such as a used tissure
Vectors- animals that carry the pathogen from host to host, such as mosquitoes or ticks
Vertical Transmission is from a parent to child
Acciental Transmission is when a host who is not part of the normal infectious cycle unintentionally encounters that cycle
Term
A Reservoir
Definition
is an animal, bird, or insect that normally harbors the pathogen
Term
Portal of entry
Definition
the way that a pathogen infects the host that is best suited to their mechanism of pathogenesis
Examples:
-Mouth: food-borne pathogens
-Respiratory tract: airborne pathogens
Term
Immunopathogenesis
Definition
when the immune system's response to an infection damages host cells or tissues
Term
Virulence Factors
Definition
are factors that allow or enhance the disease producing capability or pathogenicity of the pathogen.
They are encoded by virulence genes, and include toxins, attachment proteins, capsules, and other devices used to avoid the host's immune system
They are encoded by virulence genes that can be found in pathogenicity islands in the chromosome, on plasmids, or even on phage genomes.
Term
Pathogenicity Islands
Definition
These are clusters of genes that can be found in the chromosome that encode for virulence factors.
-many are originally inherited through horizontal transmission
-have a GC content different from the rest of the genome
-often flanked by phage or plasmid genes that can move the island from one organism to another
Term
Resistance: Nonspecific surface defenses
Definition
Structural defenses- epithelium
-skin, mucous membranes
Mechanical defenses
-movement of material through intestines
-mucociliary system, mucous production and ciliary movement in nasal cavity
-Movement of fluids- eyes are bathed in tears
Biochemical defenses
-lysozymes in tears and saliva
-fatty acids on the skin
-bile in the intestines
Term
Resistance: Nonspecific Interior defenses
Definition
Inflammation
-stimulates phagocytosis; bacteria engulfed and killed by phagocytes
-stimulates complement cascades; bacteria lysed by a membrane attack complex
Term
Resistance: Specific Interior Defenses
Definition
-activation of B and T cells
-production of antibodies and activation of cytotoxic T cells that can kill bacteria-infected cells
Term
Pathogens and disease
Definition
Overall ability of a pathogen to cause disease = V/R, where V= Virulence and R= resistance
or
= I x T/R, where I= invasiveness and T is toxigenicity
Toxins ability to cause disease= T/R
Certain pathogens can be toxic without actually infecting the host, the host can simply ingest it, example: botulism
Term
Entry
Definition
-break in epithelial layer
-specific adherence to an epithelial layer
-species specificity limits the species of host that can be infected
-tissue specificity limits the tissue which can be infected
-tissure specificity limits the tissue which can be infected
-specificity is mediated by macromolecules on both the surface of the host and pathogen
Term
Pathogen specificity
Definition
Fimbriae and pilli proteinaceous structures
Capsule-polysaccharides, proteins or glycoproteins
Capsules- can also protect pathogens from phagocytosis
Term
Adhesin
Definition
the general term for any microbial factor that promotes attachment
Term
Pili (fimbriae)
Definition
Many bacteria typically attach to host cells by hair-like appendages called pili (fimbriae):
Type I: adhere to mannose residues
-produce static attachment to host cell
-grow from outer membrane; new subunits are added at the base
-adding free mannose will inhibit attachment; mannose sensitive
Type IV- involved in "twitching motility"
-continually assemble and disassemble
-grow from inner membrane
Term
Non-pilus adhesions
Definition
Streptococcus pyogenes: M protein which binds to fibronectin and complement factor H
Bacteria can also attach to surfaces in bulk forming a biofilm.
-play important roles in chronic infections
Bordetella pertussis: Pertactin which binds to integrni
Term
Colonization
Definition
Once the pathogen is binded to the target cell or tissue, there are a number of factors that determine if it can colonize
Colonization requires that the pathogen can grow
Factors effecting colonization include pH, redox potential, temperature, and supply of nutrients
Term
Invasion
Definition
once it begins colonizing, the pathogen can remain localize and act by liberating toxins or penetrate the epithelium or mucus membrane and grow in the submcuosa or spread to other tissues
Some pathogens release toxins while attached to the mucosa others are actively invasive
Term
Collagenase-proteolytic enzyme
Definition
this enzyme is capable of degrading the collagen network supporting host tissues
Term
Hyaluronidase
Definition
breaks down hyaluronic acid which is the basis of connective tissue
Term
Streptokinase
Definition
breaks down coagulated plasma and allows spread of pathogen
Term
Coagulase
Definition
allows fibrin clot to form around pathogen and protects pathogen from phagocytes in a localized infection
Term
Avoiding death inside the host cell
Definition
Cell ingests pathogens in phagosome
-some pathogens use hemolysin to break out ex. Shigella dysenteriae, Listeria monocytogenes
Phagosome fuses with acidic lysosome
-some pathogens secrete proteins to prevent the fusion ex. Salmonella, Chlamydia, Mycobacterium, Legionella
-some pathogens mature in acidic envirinment ex. Coxiella burnetii = Q fever
Term
How do Pathogens avoid death outside of host cell?
Definition
Complements, antibodies bind pathogen
-some pathogens secrete thick capsule ex. streptococcus pneumoniae, Neisseria meningitidis
-Some pathogens make proteins to bind antibodies
ex S. aurues cell wall Protein A
- Binds Fc fragment
-antibodies attach upside down
-prevents opsonization
Other pathogens can cause apoptosis of phagocytes
Others can alter surface antigen periodically
Term
How do bacteria recognize host environment?
Definition
-two component signal transduction
-detect magnesium concentration, pH
-both low in host cell vacuole
Quorum Sensing
-detects exotoxins made by other ells
-Delays toxin synthesis until many bacteria present
-may be a possible pathway for preventing pathogen growth?
Term
Induction of disease state
Definition
Happens in two ways:
1. thru sheer numbers pathogens block heart or lung function, the large inflammatory response to a huge number of bacteria can also harm the host
2. Many pathogens produce toxins which can harm host tissues
Term
Host Response
Definition
the hsot responds to infection or mechancial injury via the innate immune system (inflammatory response)
-Macrophages attack pathogens and signal for other responses; blood vessels dilate and become moe ermeable allowing neutrophils to extravasate
-Phagolysosomes kill bacteria in several ways
Term
Phagolysosomes
Definition
Lower pH by anaerobic fermentation to produce lactic acid
Produce hydrolytic enzymes that can degrade bacteria like lipases, proteases, and nucleases
Produce reactive O2 and N2 species that can damage bacteria, like singlet oxygen, hydrogen peroxide, hypochlorous acid, and nitrate
Function:
Bacteria binds to the surface of the phagocytic cell
-invagination of the membrane traps the organism inside the cell
-a lysosome binds to the phagosome inside the cell and deposits an enzyme that generates reactive O or N species that kill the bacteria
Term
Antigen presentation
Definition
Degraded pathogen macromolecules are displayed on cell surfaces of neutrophils and macrophages to intiate the produciton of antibodies
Term
Pathogens Respond
Definition
Many pathogens produce leukocydins which lyse phagocytes
S. aurues produce carotenoids which can inactivate singlet oxygen
Some pathogens escape from the phagosome into the cytoplasm
Term
Further host responses
Definition
Lysis of phagocytes releases histamines which increase inflammatory response
They also relesae endogenous pyrogen which induces fever
Slight increases in temperature accelerate phagocytic responses and antibody response
the higher temperature can also slow pathogen growth
Term
Adaptive Immunity
Definition
Lymphocytes produce antibodies to bacterial cell componenets and also to toxins.
Antitoxins directly inactivate toxins while antibodies stimulate phagocytosis of pathogens that escaped phagocytosis of the innate response
Term
Endotoxins
Definition
the LPS layer of Gram negative bacteria is toxic when released from the cell via lysis
-heat stable
-not extremely immuniogenic or toxigenic
-all endotoxins work by same mechanism
Term
Exotoxins
Definition
are toxic proteins released form a pathogen as it grows; usually secreted
-is a protein
-can be from gram pos or gram neg
-highly toxic and immunogenic
-heat labile, usually destroyed by boiling
-acts by binding to taret cell of host and disrupting specific cellular function
-Toxins can be coded by chromosome, plasmid, or temperature phage; meaning non virulent strains can become virulent by phage infection, plasmid transfer, or even transposition even of transposon
-can act at targets removed from focus of infection
Lipid A is relesaed as bacteria die
-causes massive release of cytokine from host cells
-can trigger fever, shock, and death
Term
Type I Exotoxin: Superantigens
Definition
Activate the immune response by binding to a large percentage of T cells and class II MHC molecules on antigen presenting cells
T cells are stimulated to grow and divide, machrophages, and phagocytes are activated and mass inflammatory response occurs which causes a disease state.
Found in S. aureus food poisoning and toxic shock syndrome
Found in S. pyogenes induced scarlet fever
Term
Cytolytic toxins
Definition
Phospholipases breakdown cell membranes
-pore forming toxins form a pore in the host cell membranes causing lysis
"cell membrane distrupter"
Term
Alpha toxin
Definition
produced by s. aureus
-forms a transmembrane, seven-member pore in target cell membranes
also a "cell membrane disrupter"
Term
AB toxins
Definition
Consist of two differen subunits
-toxic activity is in subunit A
-subunit B binds to host cell receptors
-many AB toxins have 5 B subunits and a single A subunit
The A subunit enters the host cel and alters the host metabolism
Some toxic activities of subunit A:
ADP-ribosyltransferase
-Diphtheria toxin
-Cholera toxin
Term
ADP-Ribosylating Toxins
Definition
Diphtheria toxin
-made by Corynebacterium diphtheriae
-ribolysates elongation factor 2
-blocks ribosome function; cell dies
-forms pseudomembrane over trachea
Cholera toxin
- made by Vibrio cholerae
-Ribosylates to overactivate adenylate cyclase
-cAMP activates ion transport; water follows
-Uncontrollable diarrhea
Term
Anthrax toxin
Definition
Made by Bacillus anthracis
Has two active toxins:
Edema factor raises cAMP levels
-causes fluid secretion, tissue swelling
Lethal factor cleaves protein kinases
-blocks immune system from attacking
Term
Protein Type II secretion
Definition
similiar to type IV pilus, just modified to secrete proteins
-can extend and retract
-proteins to be secreted first make their way to the periplams
-are then folded before secretion
Term
Protein type III secretion
Definition
use a molecular syringe to inject proteins from the bacterial cytoplasm directly to the host cell
-similar to flagellum
-genes on pathogenicity island
-found in salmonella, Yersinia, and shigella
Term
Protein Type IV secretion
Definition
Similar to conjugation pilus
-modified to secrete proteins only or proteins plus DNA
-can secrete proteins from cytoplasm or periplasm
-found in Agrobacterium tumefaciens and Bordetella pertussis
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