1B Pathogenicity Handouts

8/9/2019 1B Pathogenicity Handouts

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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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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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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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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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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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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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Examples of exotoxins

Enterotoxin

Neurotoxin affects nerves Leukocidin

Hemolysin (Streptolysin 0)


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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

1B Pathogenicity Handouts

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