Lesson 13: Pathogenesis

Pathogens need to

be able to adhere to the hsot cell

host cell has mechanisms to try and remove it

What are the two processes of pathogenesis

The infection process

the diseases process

Describe the infection process (4 steps)

Exposure (to pathogens)

Adherence (of the pathogen to the skin or mucosa)

Invasion (through epithelium)

Multiplication (growth and production of virulence factors and toxins)

What are the three steps/sections of the disease process

Toxicity (toxin effects are local or systematic)

Invasiveness (further growth at original and distant sites)

They both lead to tissue or systemic damage

What are the three structures pathogens use for adhereance

Capsules, fimbriae, pili

What are capsuels

extracellular polysaccharide

What are Fimbriae

Short, abundant filaments

What are pili

long retractable filaments

What must an infection evade and how does it do so

evade immune system

one mechanimsm is the capsule

another is toxins - kill the thing that kills it

What are three factors that make a hospitable envrionment

pH

temperature

oxygen level

What is nutrional immunity?

Pathogens have to acquire nutrients. nutrional immunity is when the host detects the pathogen/infection, and then the hsot reduces the total amount of nutirents so the pathogen has less as well

What to transerrin and lactoferrin do

they are human proteins that tightly bind to Fe so bacteria can’t get to it

How can bacteria overcome transferrin? (2 ways)what is an example?

some bacteria can bind to these hosts proteins and acquire the iron

Neisseria makes a transferrin receptor protein

Some bacteria ,ake their own chelators (siderophores) to trap the limiting iron

• e.coli makes aerobactin (type of chelator) that binds iron and returns it to the cell

What does LD50 mean

Lethal dose 50

What does LD50 measure

the number of pathogen cell per host required to kill 50% of the host

What does LD50 depend on (3 major groups/things)

pathogen species + strain

Host species, age, sex, physical condition

Route of infection

What are the three main types of routes of infection? which one can trgger a stronger reaction? what deos that mean for LD50?

Oral

intravenous (triggers stronger rnxs so LD5 reached at lower inocculation numbers)

inhale

What are virulence factors

things produced by the pathogen that increase its ability to cause disease

What are the two groups of toxins

Non-protein toxins

protein toxins

What type of toxin(s) are in non-protein tox

Endo toxin

WHat is endotoxin? wat does it cause

the LPS is the gram negative outermembrane

causes fever, diarrhea, cytokine relase, inflamation

What type of toxin(s) are in protein tox?

Exotoxins

Enterotoxins

What are exotoxins? what do they cause

Proteins released from the pathogen cell that can travel within the host and cause damage elsewhere

What are enterotoxins? what do they cause

A particular class of exotoxin protein that acts in the small intestine, henerally causing fluid release (discharge)

What are two examples of endo toxins

Hemolysin and neutroxins

What is hemolysin? what does it do> how does it work?

Exotoxin, protein, that causes the lyses of red blood cells, so they can steal iron from them

• (but can lyse other as well)

Act by:

cleaving the host cell membrane lipids (lipases_

forming pores in the host cell membran e

What are two different examples of neurotxoins> What type of toxin are they

they are exotoxins

c. botulism toxin blocks nerve stimulation of mucle contraction: botulism, muscles can’t work

C. tetani toxin causes constant nerve stimulation of muscle contraction: tetnus ex. lockjaw

What are enterotoxins

Class of exotoxin that affects the small intestine

causes diarrhea

Describe enterotoxin process, what is an example (5 steps)

1) normal ion movement, Na+ from lumen of sall intestine to blood, no net Cl- movement

2) Infection and toxin production from V. Cholerae. Cholera toxin AB form from Vibrio cholerae cell

3) activation of epitheleal adenylate cyclase by cholrea toxin A subunit:

the A subunit is able to go into the host cell, while the B subunit attaches to the host cell/identifies cell. Now that the A subunits are in the cells, there is an overproduction of cAMP.

4) elevated cAMP blocks Na+, causes net anion movement to intertinal lumen. co Cl- and Hco3- are trying to get into small intestine

5) as water follows carged molecules, massive water movement to lumen + ion loss trigger cholera symptoms

What are the difference in the chemical proerties of exo vs. endo toxins (what are they made of, where do they come from, how they handle heat)

Exotoxins: proteins excreted by ceertain gram positive or gram negative bacteria, geneally heat-labile

Endotoxins: lipopolysaccharide-lipoprotein complexes, released on cell lysis as part of the outer membrane if gram-negative bacteria; extremely heat-stable

What is the difference in the mode of action;symptoms between exotoxins and endotoxins

Exotoxins: Specific, usually mind to a specific cell receptors or structures, eiter cytotoxin, enterotoxin, oe neurotoxin with defined speicifc acion on cells or tissues

Endotoxins: general, fever, diarrhea, vomitting

Difference between toxicity of exotoxins and endotoxins

Exotoxins: often highly toxic, sometimes fatal

Endotoxins: wealky toxic, rarely fatal

Describe difference in immunogenicity response of exotoxins and endotoxins

Exotoxins: highly immunogenic, stimulate the production of neutralizing antibody

Endotxoins: relatively poor immunoge; immune response not sufficient to neutralize toxin

Describe toxoid potential between exotoxins and endotoxins

treatment of toxin with formaldehyde will destroy toxicity, but treated toxin (toxoid) remains immunogenic

Endotoxins: none

Describe the fever potential in exotoxins vs endotoxins

exotoxin: does not produce fever in host

Endotoxin: odten induces fever (think about how they are heat stable)

What are siderophores

small high affinity iron chelating compounds made by microorganisms

What are streptococcus (gram result, morphology, where they can be found in body, what do the pathogenic strains do)

Gram positive cocci

common member of normal flora of upper respiratory tract

pathogenic strains generally produce capsule (so smooth colony)

What are 7 common streptococcus diseases and what are they.what do they affect

• Pharyngitis (strep throat)

• otitis media (ear infection)

• mastititis (mammary glands)

• erysipelas (very red skin)

• Scarlet fever

• Necrotizing fasciitis (rare, flesh eating bacteria)

• Rheumatic fever (auto immune reaction against heart valves)

What are characteristics of neisseria meningitdis

Gram negative

diplococci

What are two diseases n. meningitidis scan cause

Bacteremia

meningitis

Describe bacteremia

Invasion of blood stream

toxin cause coagulation and blocks flow to extremities

Describe meningitis

Inflammation of the membrane around the central nervous system

rapid progression

10% mortality rate

commin in college student populations

What are characteristics of Borrelia burgdorferi

Gram negative spirochete

Where does B. burgdorefi come from and how is it trasnfered to humans

grows in many wild animal mammals without clear diseases

transferred from resevoir wild animals to humans by deer ticks

Where is lyme diseases common? Why have lyme diseases cases been increasing

Common in northeast adn upper midwest

iincreasing due to

• increased reporting

• increases temperatures

• increased deer populations

• increased human/tick contact

What are symptoms of lyme disease

no toxins, just inflammation

initial symptom: erthema migranes spreads from bite over days: bull’s eye rash

headache, chills fatigue

trateable with antibiotics

What can untrested lyme diseases cause

arthiritis as bacteria goes to joins

invasion of neurosystem

• palsy, facial ticks, weakness