Mechanisms of Pathogenicity

What type of microbes does normal biota (normal flora) include

bacteria, fungi, protozoa, & viruses

Normal biota (normal flora)

large & diverse collection of microbes living in & on the body

Normal flora is best described as….

large & diverse

Microbiome

all the genes found in one’s microbiota

Microbiota

all microbes that live in & on an organism

Holobionts

hosts & microbes live together & evolve together

each microbial niche is related to a variety of factors such as…

body location, age, sex, diet, & environment

Sites definitely known to harbor microbiota

• skin & adjacent mucous membranes

• upper respiratory tract

• outer urethra

• external genitalia

• vagina

• external ear canal

• external eye

Antagonism

effect of “good” microbes against intruder microbes

• prevent overgrowth of intruder microbes

• often “normal flora”

What did we learn from the Human Microbiome Project?

• we have a lot of microbes in areas we thought were sterile

• all healthy people harbor potentially dangerous pathogens, but in low numbers

Additional sites now thought to harbor at east some microbiota

• lungs (lower respiratory tract)

• bladder & urine

• breast milk

• amniotic fluid & fetus

Sites which DNA from microbiota has been detected

• brain

• bloodstream

What can makeip of intestinal biota influence?

makeup of your intestinal biota can influence many facets of your overall health

Differences in the gut microbiome have been associated with differences in the risk for:

• heart disease

• asthma

• autism

• rheumatoid arthritis

• mental illness/mental health disorders

What causes endogenous infections? How can it occur?

• caused by biota inside the body

• can occur when normal flora is introduced to a site where they aren’t naturally occurring

  • C. diff infections or E. coli entering the bladder, causing UTI

infection

a condition in which pathogenic microbes penetrate host defenses, enter the tissues, & multiply

pathologic state

• cumulative effects of infection damage

• disruption of tissues & organs

• results in disease

disease

any deviation from health

what factors cause disease?

infections, diet, genetics, aging

infectious disease

disruption of tissues or organs caused by microbes or their products

What does a pathogen result in? What relationship does a pathogen have with its host?

• results in infection & disease

• has parasitic relationship with host

What does type and severity of infection depend on?

pathogenicity of the organism & condition of the host

pathogenicity

describes an organisms potential to cause infection or disease

True pathofens

capable of causing disease in healthy persons with normal immune defenses

When do opportunistic pathogens cause disease?

• when host defenses are compromised

• when the become established in a part of the body that is not natural to them

  • Candida albicans

What is virulence?

the relative severity of the disease caused by a particular microbe

Virulence factor

structures, products or capabilities that allow a pathogen to cause infection in the host. Adaptations microbe uses to invade & establish in host

What do virulence factors determine?

degree of tissue damage that occurs

What must a pathogen do in order to cause a disease?

pathogen must contact a host & survive within it

extracellular pathogens

remain in tissues & fluids but never enter host cells during disease

intracellular pathogens

grow & multiply within host cells

facultative intracellular pathogens

can live & multiply both inside host cells & in the extracellular environment, allowing them to hide from the immune system during infection

obligate intracellular pathogens

only grow inside host cells

Course of infectious disease (4)

incubation period, prodromal stage, illness period, convalescence

incubation period

time between pathogen entry & development of signs & symptoms

Prodromal stage

mild, non-specific signs & symptoms

illness period

disease is most severe & display signs/symptoms

convalescence

recovery stage

What resources does the host provide the pathogen?

protection, nutrients, energy

What 3 factors affect the success of transmission?

1. virulence of organism

2. # of invaiding organisms

3. presence of adhesion & invasion factors

Organism outcompetes the resident microbiota for _____ & survive host _____ ______

resources, defense mechanisms

When does disease occur?

when organism produces molecules that directly damage host cells or stimulate host immune cells to destroy infected tissue

Sources of pathogens

animate, inanimate, vector, reservoir

Reservoir

natural environment

How does pathogen transmission occur?

directly or indirectly

What are some examples of direct transmission?

horizontal contact, airborne droplets, vector, vertical contact

What are some examples of indirect transmission?

contact, food, water, biological products

4 main routes of transmisson

airborne (droplets), contact, vehicle, vector-borne

vertical transmission

pregnant women can pass a pathogen to their unborn child

contact transmission

• host touching source or reservoir of the pathogen

• direct contact (physical interaction)

• indirect contact (involves fomite that transfers infectious agents between hosts)

vehicles

• materials that indirectly transmit pathogens

• surgical instruments, drinking vessels, food, water, biological materials (food/water), air

a single source containing pathogens can ______ a common vehicle that causes multiple infections

contaminate

vector

living organism that can transmit a pathogen (most are arthropods or vertebrates)

How does a pathogen benefit from vector-borne transmission

due to extensive reproduction & spread between hosts

Do important pathogens harm their vectors?

No, they don’t want to kill the host

Is vertical transmission more or less common than horizontal transmission?

vertical transmission is less common than horizontal transmission

babies born with an infectious disease are said to have a ______ infection

congenital (Gonorrhea, syphilis, herpes, german measles, toxoplasmosis)

infectious dose 50

number of microbes required to cause disease in 50% of inocluated hosts

• varies among pathogen

lethal dose 50

dose that kills 50% of a group of experimental hosts within a specific period

what can influence LD₅₀ ?

influenced by the susceptibility of the host

• immune system, nutrition, hygiene, emotional health

5 steps of infection

1. portals of entry

2. attaching to the host

3. surviving host defenses

4. causing disease

5. portals of exit

portal of entry

a characteristic route taken by microbe to initiate infection

exogenous

originating from outside the body

endogenous

already existing in the body

What are the sites of entry of the skin?

abraisions, punctures, conjunctiva (eyes)

Can microbes easily penetrate skin?

intact skin is a tough barrier that few microbes can penetrate

What microbes can penetrate through skin?

• some helminths (hookworm)

• some microbes can enter skin thru insect, tick, or animal bites

Entry by GI tract occurs through…

food, drink, ingested substances

What is unique about microbes that enter through the GI tract?

they are adapted to survive digested enzymes & disrupt pH changes

What are the gateways to the respiratory tract?

oral & nasal cavity

What microbes are often transferred from one site to another?

• bacteria

• viruses

• fungi

what does the continuous mucous membrane cover?

upper respiratory tract, sinuses, auditory tubes

What infects the urogenital tract?

STIs - pathogens transmitted by seuxal means

What are the entry points (skin/mucosa) of the urogenital tract?

penis, external genitalia, vagina, cervix, urethra

What is TORCH? What does each letter stand for?

TORCH - common infections of the fetus & neonate

• Toxoplasmosis

• Other diseases (syphilis coxsackievirus, AIDs, chlamydia)

• Rubella

• Cytomegalovirus

• Herpes simplex virus

What 3 things impact the outcome of infection?

• preferred portal of entry

• number of invading microbes

• adherence

what is adhesion?

a process where microbes gain a more stable foothold on host tissues

What is adhesion dependent on?

The binding between specific molecules in the host & pathogen

Why are particular pathogens limited in adhesion?

some pathogens are limited to only those cells & organisms to which it can bind

what can happen once a pathogen ia attached to a cell?

it can invade body compartments

phagocytes

WBCs that engulf and destroy pathogens by means of enzymes & antimicrobial chemicals

antiphagocytic factors

virulence factor that helps pathogen avoid getting engulfed

• circumvent some part of the phagocytic process

Examples of antiphagocytic factors (3)

• strep & staph produce substances that kill WBCs

• some microbes secrete slime or the capsule can make it hard for phagocytes to engulf

• some bacteria can survive inside phagocytes (hide, grow, spread)

virulence factors

structure, products, or capabilities that allow a pathogen to cause infection in the host

• adaptations microbe uses to invade & establish itself within the host

what do virulence factors determine?

the degree of tissue dammage

What are exoenzymes? What are they secreted by? What do they do?

• extracellular enzymes

• secreted by pathogenic bacteria, fungi, protozoa, & worms

• break down & inflict damage on tissues

• dissolve host defense barriers & promote spread of microbes into deeper tissue

toxin

specific chemical product of microbes, plants, & some animals that is poisonous to other organisms

Exotoxin

produced by a living bacteria & released into the extracellular environment

• made of proteins

• many types

What causes symptoms of disease?

Exotoxins

Antitoxins

antibodies produced against exotoxins

What secretes exotoxins? where does it go?

secreted by a living bacterial cell to the infected tissues

How are endotoxins produced? What are they made of?

They are shed from the outer membrane, lipopolysaccharide of cell wall

• They are not actively secreted

• shed during death

LPS

outer membrane contains lipoproteins, phospholipids, & lipopolysaccharides

what bacteria do endotoxins occur in?

gram-negative only

Compare the toxicity of exotoxins & endotoxins

exotoxins are toxic in minute amounts, endotoxins are toxic in high doses

Septic shock (Describe the 2 steps)

1. Gram-negative bacteria to produce endotoxin that cause phagocytes to secrete tumor necrosis factor (TNF)

2. TNF causes damage to capillaries resulting in loss of fluid resulting in shock

What causes the shock in septic shock?

the endotoxin

when does pyrogenic response occur?

when a gram negative bacteria is ingested by a macrophage

What happens in pyrogenic response?

as bacteria is degraded, LPS factor is released, LPS endotoxins cause cytokines to be produced

Where do cytokines travel?

hypothalamus