3. Pathogenesis and Virulence Factors (Nicole) Flashcards
infections of animals are related to
pathogen and host related determinants
whether or not an animal displays clinical disease is dependent on
modifying factors
examples of modifying factors
stress, tissue damage, host immunity, barrier damage (gut, skin), immune status
examples of pathogen related determinants
virulence, stability in environment, route of entry, infective dose, tissue tropism, susceptibility to host defence
host related determinants examples
species, breed, age, sex, genetic factors, physiological factors, immune competence
a pathogen is
a microorganisms, that is able to cause disease
pathogenicity is the ability of
a microorganism to cause disease in another organism, namely the host
virulence is
the degree of pathogenicity
opportunistic pathogens are bacteria that
do not need to cause disease to facilitate their own transmission
- can cause disease in an immunocompromised host
-may be able to survive in environment
obligate pathogens require a
host for survival and transmission. Infection with these organisms usually results in disease
barriers to bacteria
IgA/antibodies, lysozyme/other enzymes, antimicrobial peptides, microbiome/commensal organisms, complement, tight junctions, peristaltic movement, ciliary movement, tight junctions
virulence factors are
mechanism to circumvent host defences and multiply
- bacteria may have single or multiple virulence factors
two broad qualities of pathogenic bacteria underlie the means by which they cause disease:
invasiveness and toxigenesis
what is invasiveness?
the ability to invade tissues
2 steps of invasiveness
-mechanisms for colonization: adhesions, invasins
-ability to overcome host defence mechanisms
what is toxigenesis
the ability to produce toxins
endotoxins are released from
bacterial cells and may act at tissue sites removed from the site of bacterial growth
endotoxins are
a bacterial cell-associated substance. When released from cells (due to lysis, antibiotics, etc) they may be transported by blood and lymph and cause cytotoxic effects at tissue sites REMOTE from the original point of invasion or growth
exotoxins are produced inside mostly ______ __________ bacteria as part of their growth and metabolism. They are then secreted or released following lysis into the surrounding medium
gram positive
endotoxins are part of the outer portion of the cell wall of ____ __________ bacteria. They are liberated when the bacteria due and the cell wall breaks apart
gram negative
bacterial protein toxins (exotoxins) differentiate
virulent strains from non-virulent strains
many protein toxins are basically
enzymes
why are protein toxins basically enzymes?
-denatured by heat, acid, proteolytic enzymes
- have a high biological activity (most act catalytically)
- exhibit specificity of action; highly specific
example of skin exotoxins
staphylococcus pseudointermedius exfoliating toxin - causing pyoderma in dogs
example of enterotoxigenic enteritis
E. coli enterotoxins activate ion and water pumps causing loss of fluid and electrolytes from cells
- binds to and colonizes microvilli of small intestines
when bacteria release toxins, what is needed in the host?
the correct receptors for that toxin to take effect.
also important tot note that toxins act in a number of different ways to disrupt regular cell functions
LPS and virulence of gram-ve bacteria - toxicity is associated with
the lipid component
LPS remains associated with the cell wall until
disintegration of the bacteria (autolysis, external lysis, phagocytic digestion)
LPS results in wide spectrum of pathophysiological reactions related to inflammation such as
fever
changes in WBC counts
DIC
hypotension
shock
death
pathogenesis step 1
establish infection - stick, enter, and grow (aka colonization)
establish infection (stick) step - where do bacteria enter
urogenital tract
digestive tract
resp tract
conjunctiva
stick step - adherence to a eukaryotic cell or tissue surface requires a
receptor and a ligand
receptor needed stick step
specific CHO or peptide residues on the eukaryotic cell surface
stick step- the bacterial ligand is called an
adhesion, and is typically a macromolecular component of the bacterial cell surface
specific adherence of bacteria to cell and tissue surface - 3 reqts
- tissue tropism
- species specificity
- age specificity
example of how understanding bacteria virulence mechanisms has helped us prevent disease
breed pigs to not have an F4 receptor or vaccination of F4 receptor-positive piglets
(against F4 positive ETEC)
establish infection - enter step - bacteria use
invasins - virulence factors that enable internalization of the bacteria into tissues
what are type 3 secretion systems
machinery possessed by many gram negative bacteria to deliver effector proteins - as a result, hijack host-cell signalling
example of enter step type 3 secretion system
salmonella typhimurium: delivers effectors (invasions) that manipulate the host’s acton cytoskeleton -> uptake in membrane vacuoles
what are spreading factors
bacterial enzymes that affect the physical properties of tissue matrices and intercellular spaces, thereby promoting the entry/spread of the pathogen
pathogenesis step 2 - evasion of host defences -
resist innate immune mechanisms, phagocytic defences, resist specific adaptive immune mechanisms
examples of innate immune mechanisms
complement, antimicrobial peptides, phagocytic defenses
3 ways to evade complement
1-capsules
2-lipopolysaccharides (LPS)
3 - destruction of complement component
how bacteria evade complement - capsules
polysaccharide capsules can hide bacterial components
some bacterial capsules can inhibit formation of complement
LPS - how they evade complement
LPS is the principal targets of complement on gram -ve bacteria
- LPA modification by attachment of silica acid residues to the LPS antigen –> prevents effective MAC killing
evading complement - destruction of complement component
eg - pseudomonas aeruginosa produces an extracellular elastase enzyme
4 steps of phagocytosis
1 - find & engulf
2 - phagosome formation
3 - lysosome fusion
4- lyse & digest
avoiding step 1 of phagocytosis (avoiding contact with phagocytes) - how do bacteria do it?
-remain confined in regions inaccessible to phagocytes (oral cavity, luminal surfaces of GI tract etc)
- hide the antigenic surface of the bacterial cell
- inhibit phagocyte chemotaxis
how do bacteria avoid step 2 of phagocytosis (inhibition of phagocytic engulfment?)
antiphagocytic substances on the bacterial surfaces
ex - polysaccharide capsules of S. pneumoniae and Klebsiella pneumoniae
ways bacteria avoid step 3 of phagocytosis (lysosome fusion)
-inhibition of phagosome-lysosome fusion
- survival inside phagolysosome (resistant to inhibition and killing)
- escape from phagosome
ways bacteria avoid step 4 of phagocytosis (lyse/digest)
killing phagocytes before ingestion
killing phagocytes after ingestion
how to bacteria kill phagocytes before ingestion
hemolysins: extracellular enzymes secreted by many gram +ve bacteria
streptolysins: secreted by pathogenic streptococci –> lysosomal grabulaes in neutrophils expose, releasing their contents into the cell cytoplasm
killing phagocytes after ingestion
many intracellular pathogens eventually destroy macrophages, but mechanisms not well understood
examples of resistance to antibody-dependent defences (im gonna be honest guys idk if any of these are right)
proteinases, actue attacks, cell wall proteins, peptidoglycans, hiding intracellularly, antigenic mimicry, binding host proteins, super antigens, divert productive immune response
damage to host used by 2 mechanisms
toxin induced damage
inducing host immune responses
toxin induced damage can include
CV/NS disturbances, destruction of blood vessels, diarrhea, plasma membrane disruption, inhibition of protein synthesis, shock
inducing host immune responses: damage caused by
reactive oxygen and nitrogen species
inflammation
septic shock
