1. Asymptomatic—90-95% 2. Minor illness—4-8% 3. Non-paralytic aseptic meningitis—1-2% 4. Paralytic poliomyelitis—0.1-0.5%

Lecture 20: Pathogenesis Flashcards by Cagn Walker

Pathogenesis

The steps that are involved in the origin and development of a disease

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Pathogenicity

The ability of an organism to cause disease or induce damage to the host

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Virulence

The degree of pathogenicity

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Steps of bacterial pathogenesis

Source or Reservoirs
Entry into the host
Attachment & colonization
Invasion of Host Tissues/ Evading Host defenses
Growth and multiplication
Leaving the host
Enter into new host

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Modes of microbial transmission

Inhalation/ Repiratory
-Cold and Flu
Ingestion of contaminated food/water
-Rotaviruses
Blood or bodily fluids
-HIV and Hepatitis
Through insect bite-arbovirus
-West Nile, Lyme, EEE

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Zoonosis or zoonose

Any infectious disease that can be transmitted from non-human animals, both wild and domestic, to a human

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How do pathogens cause disease?

Cell lysis
Cell dysfunction
Immune responses-Inflammation
Immunodeficiency
Cancer
Produce toxins (Bacteria)

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Cell lysis example

Poliovirus

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Poliovirus

-Tropism for motor neurons in spinal cord -Enteric virus in the Picornaviridae family
-Soon to be eradicated

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Poliovirus outcomes

Asymptomatic—90-95%
Minor illness—4-8%
Non-paralytic aseptic meningitis—1-2%
Paralytic poliomyelitis—0.1-0.5%

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Polio transmission

Fecal-oral
GI track—>Lymphatics—>Blood (viremia)—>CNS

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Ebola virus

•Filoviridae family
•1976 outbreak
•Spread by body fluids
•Fruit bat—>great apes—>human

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Ebola virus disease

•Dysfunction and inflammation work together
•Cytokine production and virus attachment to blood vessels lead to a loss in vascular integrity
•No coagulation (damage to liver)
•Hypovolemic shock

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Inflammation

•Immune system can cause damage when trying to control infection
•Immune response causes disease
-Influenza and COVID
-Cytokine storm

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Inflammation& the brain: meningitis

•The swelling and irritation (inflammation) of the membranes covering the brain and spinal cord
•can be bacterial, fungal, or viral

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Pelvic inflammatory disease

•Usually due to chronic infection of:
-Chlamydia trachomatis
-Neisseria gonorrhoeae

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Immunodeficiency ex. HIV

•Human Immunodeficiency Virus (Lentivirus family)
•HIV infects helper T cells, dendritic cells , and macrophages
-Kills helper T cells and causes them to undergo apoptosis

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•Immunodeficiency ex.
Measles

-5-6th leading cause of death in children
-“Immune Amnesia” lasts for 2 years or more
—Increase in secondary infections
—Diminishes prior immunity to past infections

How do some microbes cause cancer

Uncontrolled growth of abnormal cells in the body due to increased cell proliferation, decreased apoptosis, and metastasis

Mechanism of oncogenecity

Direct—Introduction of new “Transforming gene” into the cell
Indirect—Alteration of expression of pre-existing cellular gene
Leadings to:
-Loss of normal growth regulation processes
-Affection of DNA repair mechanisms
-Genetic instability
—Mutagenic phenotype

Oncogenic bacteria

•Heliobacter pylori—Stomach cancer
•Salmonella typhi—gall-bladder cancer
•Streptococcus bovus—Colon cancer
•Chlamydia pneumonias—lung cancer
•Bartonella—vascular tumors
—15% of cancer cases were attributed to a carcinogenic infection

Dr. Peyton Rous

• Won Nobel prize for showing that viruses can cause cancer
-Chickens grow a tumor called fibrosarcoma
-Rous ground up these sarcomas, centrifuged them to remove the solid material, and injected the remaining liquid into chicks
-The chicks developed sarcomas
-The purified oncogenic virus called Rous sarcoma virus (RSV)

Oncogene

Some pathogens have oncogenes
•A mutated gene that promotes cell proliferation and blocks apoptosis
—Proto-oncogenes are healthy genes that enhance cell growth, division, and survivability
•Ex: v-Sec in Rous Sarcoma Virus (RSV)

Tumor suppressor genes

Some pathogens have a protein that blocks a Tumor suppressor gene
•Tumor suppressors are genes that block cancer progression
—found in host cells
—Surveillance
—p53 is an example

How can Bacterial or viral genes alter host cell behavior

•Host cell cell cycle—proliferation •Cause or block apoptosis •Cell adhesion/attachment •Activate cell signaling pathways for migration •Increasing cell turnover—> more spontaneous mutations •Chronic inflammation —> DNA damage due to ROS

HPV

•A few types of HPVs are associated with 82% of the cervical cancers •Cervical cancer: 2nd largest cause of female cancer mortality worldwide •Major cause of throat and esophageal cancer

Heliobacter pylori

•H. Pylori in 1/3 of all adults in the US, causes inflammation of the mucous membrane of the stomach -In 20% of infected persons, H. pylori induces gastric ulcers -60-90% gastric cancers caused by H. pylori -Increases risk of developing gastric cancer by 6x -CagA in some strains of H. pylori

Hepatitis C virus

•Cells stop regenerating -Cirrhosis •Increase chance of mutation -Cancer

How do chronic infections cause cancer (Hep C/H. pylori)

Chronic lytic infections increase cell death and cell turnover. Greater cell division to compensate for cell loss can lead to more DNA mutations

Chronic infections lead to …

Chronic inflammation

Chronic inflammation causes..

•Reactive oxygen species (ROS) -Cell proliferation -Apoptosis -Signal transduction -DNA damage •Reactive nitrogen species •Inflammatory cytokines cause cell proliferation

Burkitt’s Lymphoma

•Genomic instability •Epstein Barr virus (Herpesvirus) infects B cells •Integrates genome which make double-stranded breaks in DNA •Chromosome translocation occurs: -Now human Myc gene (oncogene) is controlled by an active promoter that controls antibody production

Bacterial toxins

•Endotoxin •Exotoxin

Endotoxin

Structural components of gram- cell walls •Lipopolysaccharide -Released when bacteria break down or divide -Endotoxins do not cause cell damage on their own, but stimulate immune system —shock-like symptoms…chills, fever, weakness, fatigue, small blot clots

Exotoxins

Secreted toxins

Exotoxins ex. Staphylococcus toxins

Leucocidin-Leukocyte lysis Hemolysis-Red blood cell lysis Coagulate-Fibrin clotting

Streptokinase exotoxins

Streptococci (Gram positive) produces streptokinase-the clot buster enzyme

Type of exotoxin

AB toxins (active/binding) •Cholera toxin •Anthrax toxin •Tetanus toxin

Botox (Botulinum toxin)

Botox injection inhibits release of acetylcholine (ACh) -Muscles are in relaxed state and cannot contract

Tetanus toxin

-Clostridium tetani Toxin prevents release of inhibitory neurotransmitter: GABA and glycine=Muscle spasm

Different toxins-Same environment-different outcomes example

Small intestine -Shiga toxin (E. Coli): Epithelial and endothelial cell lysis-bloody diarrhea -Cholera toxin: Water release into gut-Rice-water stool

Cholera toxin

Cholera toxin influences chloride channels in the cells that line the gut causing these cells to release water into the small intestines

How does E. coli deliver toxin

E. Coli can attach and deliver toxins -Shiga toxin can block protein synthesis which leads to immediate death of cells and breakdown of the IT barrier