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Pathogenicity
new
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Definitions
Pathogen
organism that can cause disease in a susceptible
host
Opportunistic pathogen
organism that causes disease only ifthere is a
significant change in the hosts immune system
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Iatrogenic infection
occurs as the resultof medical treatmentora
procedure
Nosocomial infection
infections acquired while in the hospital orother
medical institution
Definitions
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Kochs Postulates
German bacteriologist, who discovered anthrax,cholera,and tuberculosis-causing bacteria
Demonstrated the conditions which must be metbefore an organism is considered to be apathogen-1890
Postulates1. organism must be present in every case
2. organism must be isolated from diseased host3. same disease must be produced when a culture ofthe
organism is introduced intoahealthy host
4. same organism must be recovered fromexperimentally infected host
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How does an organism
establish an infectious disease?
Reachthe hostand find a portal of entry(colonization is 1st step)
Adhere tohost
Penetrate host defenses Proliferation
Organism reproduces and then competes with NF fornutrients
Damage host cells
Spread to distant sites via motility, destruction ofhostcells via enzymes orother factors
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Mode of transmission
Airborne (droplet nuclei)
Ingestion (fecal-oral route)
Zoonoses (animal reservoirs)
Arthropod vectors (living entity) Close contact (salivary orgenital)
Inanimate objects (fomites) Vehicles
Vertical transmission (motherto infant)
Endogenous infection (hosts normal flora)
Parenteral Route (IV,Puncture wound)
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Portals of Entry Mucus membranes
Respiratory tract*
Easiest portof entry (common cold, TB, pneumonia, flu,smallpox, measles, diphtheria, whooping cough)
Gastrointestinal tract
Food, fingers, feces, fomites
Polio, Hep A,typhoid fever, dysentery (amoebic orbacillary) cholera
Are eliminated in feces and therefore can be transmitted toothers
Genitourinary tract
STDs (HIV,Chlamydia,herpes, syphilis,gonorrhea)
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Portals of Entry
Skin orParenteral route
Hair follicles
Sweatgland ducts
Injections
Bites
Surgery Wounds
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Portal of Entry
Organisms have preferred portals of entry
Inhalation of strep may cause pneumonia but if
swallowed, may not cause disease
Infectious dose (ID50) varies accordingto
entry port
B. anthracis requires few bacterial spores to
produce cutaneous anthraxand many to producegastrointestinal anthrax
10-50 endospores vs 250,000-1,000,000
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Adherence
Organism must find appropriate nutrients
and environmental conditions
pH: 6.5-7.5
temperature: 35-37 degrees C
redox potential: aerobic oranaerobic
availability of nutrients
more nutrients available in damaged, necrotic
tissue
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Adherence
Adhesins or ligands (proteins) that bind specifically
with surface receptors on host cells
May be located on the cellsglycocalyx, pili, fimbriae,or
flagella
Biofilms, slime layers
Produced by masses oforganisms and bacteria
They multiply and secrete aglycocalyxto furtherattachthe
bacteriato eachotherand surfaces like teeth, catheters,stents,heartvalves,hip replacements and contact lenses
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Host defenses
Skin Outer layer is a physical/chemical barrierto bacteria
Continuous shedding dislodges bacteria
Dry and cool vs. moistand warm needed by bacteria
Normal skin colonizers (flora) preventgrowthofharmful bacteria competes fornutrients preventing colonization by other
organisms
Mouth
Protected by flow of saliva containingantimicrobial substances Colonization by normal flora which prevent invasion by harmful
agents
Normal flora competes with pathogens
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Host defenses Respiratory tract
lining is covered by nasal hairs and cilia which sweep
organisms/particles toward oropharynx
Gastrointestinal tract
Low pH = acid pH destroys most bacteria Stomach enzymes and bile salts destroy bacteria
peristalsis prevents attachmentto intestine
Heavy colonization by normal flora
Genitourinary tract cleansed by process ofvoiding
Low pH =acid pH (3.8-4.5)ofvagina inhibits many organisms
Heavy colonization with normal flora
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Host defenses
Mucus membranes
Sloughingoffof cells
Lubricates cells toavoid damage Trap bacteria
Contains specific antibodies
Antibacterial substances (non-specific)
Lysozymes, lactoferrin, lactoperoxidase
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Flora
Normal flora (resident flora) inhabits surfaces ofthe human body
competes withharmful organisms forspace and nutrients
fetus is in sterile environment; colonized duringthe first few days
afterbirth
Transient flora
survive in hosts environment, do not multiply and frequently shed
withhost cells
Carrier state
pathogenic organisms establishthemselves without causing
disease in the host
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Penetrate host defenses /
Invasion
Some orgare able to damage the surface of
tissues, but most must penetrate to cause
damage dothis by havinga capsule Capsules
always virulence factor,acapsularorgare avirulent
Prevent phagocytosis,resisthost defenses,org
hides within the capsule
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Penetrate host defenses /
Invasion
Cell wall components
M protein: mediates attachment, causes
production ofantibodies
Fimbriae/ Pili/ Opa: facilitate attachmentand
uptake of bacteria (for intracellularorganisms like
GC)
Waxes (mycolic acids) ofM
Tb cell wall resistdigestion,allow orgto multiply inside phagocyte
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Penetrate host defenses /
Invasion
Enzymes Coagulasesmost notably by STA
Coagulates fibrinogen
Protects the bacterium from phagocytosis
Isolates from otherbody defenses
Kinases to break down fibrin/ dissolve clots spread infection
Hyaluronidase, collagenase Dissolve connective tissue
aids the organism in spreading
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Penetrate host defenses /
Invasion
IgA proteases
IgA majorsecretory immunoglobulin
IgA formed to preventadherence of pathogens to
mucosal surfaces
Attack the IgA antibodies formed by the body
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Penetrate host defenses /
Invasion
Antigenic variation
Organisms are able to change theirsurface
antigens
By the time antibodies are produced,the
pathogen has already altered its antigens and is
unaffected by the antibodies
Seen withN
. gonorrhea andInfluenzavirus
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Penetrate host defenses /
Invasion
Host cell penetration
Actin is in host cell oforganism is used by
bacteriato invade host cells
Invasins (surface proteins) rearrange actin
filaments
Used by Shigella and Listeriato propel through
the host cell cytoplasm and from one host cell toanother these are intracellularparasites
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Host defenses
Mucus
Traps bacteria before they reachoutercell
surface
Lubricates cells to prevent damage which could
promote bacterial invasion
Specific responses:
Antibodies: IgG,IgM,IgA Cell mediated immunity: B cells activated for
intracellularparasites!
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Host defenses
Non-specific defenses
Neutrophils and macrophages p phagocytosis doesntalways
work
Lysozymes: break down the peptidoglycan layeroforganismscell wall-found in tears, saliva, sweat, phagocytes,PMNs
Inflammation:
Activates complement,attracts phagocytes, kills bacteria
Coagulation: attracts phagocytes, increases blood flow, walls off
infection to contain it
Cytokines: various effects, but enhances specific and non-specific
responses
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Damage/ dissemination
Toxins may be transported by blood and
lymphto cause cytotoxic effects atremote
sites from the original pointof entry
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Damage/ dissemination Exotoxins: protein toxins secreted by bacteria
produced mostly by Gram positives butalso by Gram
negatives
Protein in nature = heat labile
action is specific and limited, depends on organism and type
of exotoxins
can cause disease even in the absence of bacteria
can be used to immunize (body produces antitoxin antibody
to preventadherence tohost cell membrane)
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Damage/ dissemination Examples of exotoxins
1) Toxic shock syndrome toxin-1 produced by S. aureus
2) Pertussis exotoxin produced by Bordetella pertussisinterferes withhost protein contributes to coughing
and mucous production3) Gas gangrene resultof several toxins (alphatoxin)
produced by Clostridium perfringens
4) Tetanus (tetanospasmin) and Botulism which interfere
with neuromuscular function
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Damage/ dissemination
Examples of exotoxins
Enterotoxin
Neurotoxin affects nerves Leukocidin
Hemolysin (Streptolysin 0)
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Damage/ dissemination
Endotoxins: play role in complications of sepsis
Lipid A (endotoxin) found in LPS, partofthe cell wall ofGram negative organisms
lipid in nature = heat stable
When released in large amounts, contributes toanexcessive inflammatory response
causes fever,qBP,tissue destruction,DisseminatedIntravascularCoagulation, decrease in neutrophilfunction, shock, lethality
cannot be used to immunize
example: septic shock caused by Gram negativeorganisms
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Exotoxin-Endotoxin
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Signs of infection
Local signs dolor: general or localized aches and pains
calor: heat
rubor: redness orrash
tumor: swelling (lymph nodes)
functio laesa: loss of function Nausea,vomiting, diarrhea (GI)
Congestion, sore throat, coughing, sneezing (resp)
Systemic orgeneral signs acuteacute: fever, chills,vasodilation,o pulse rate chronic: intermittent low-grade fever, weight loss, lethargy,
malaise
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Signs of infection
Toxic reactions skin reactions, neuromuscular, cardiorespiratory orgastrointestinal
signs
Radiographic signs pulmonary infiltrates,thickeningof cavity linings,gas in soft
tissues,accumulation of fluid in organs and cavities
Laboratory values o sed rate, WBCs,gammaglobulins
production oftype specific antibodies
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Outcomes
Pathogen: Leave the host
Destroy host
Latent stage: examples: (TB, syphilis)
Is destroyed by host bestoutcome
Patient:
Full recovery Chronic Infection
Death