Lecture Exam 4

• Share the same 5 stages as lytic bacteria

• There are some changes because many animal viruses are enveloped

• There are some differences between DNA and RNA viruses

Attachment

• Animal viruses do not have tail fibers. Instead they use glycoprotein spikes to attach to host cells

Entry and Uncoating

• There are three methods for viruses to enter animal cells

• Direct Penetration – done by some naked viruses

  • Has correct type of spike proteins to bind with receptors

  • Can inject genome into the cell

• Membrane fusion – phospholipid of the viral envelope fused with host cell

  • Because they are enveloped, they can bind onto the cell

• Endocytosis – when the virus trigger receptors on the cell surface to engulf the entire virion

  • Triggers macrophages to eat it because it is not recognized by the cell

  • Virus infects the cell that engulfs it

  • Happens with HIV (macrophages, helper cells, lymphocytes)

Bacteriophages inject DNA into the host cell, whereas animal viruses enter by endocytosis or membrane fusion

• Similar to replication of normal cellular DNA and translation or proteins

• Replication usually happens in the nucleus

• Animal cells do not use ssDNA

• When a ssDNA virus enters a cell, the host will synthesize a complementary strand of DNA to viral genome

• Then replication and protein synthesis will proceed

• Ribosomes of the host cell directly translate proteins using the codons of these types of viruses

• Codes for proteins allowing the viruses to remake its capsid

• Essentially the +ssRNA viruses as a mRNA recognized by the cell

• Makes a complimentary strand of –ssRNA

  • Then if it keeps making copies of negative sense of RNA then it can continue to propagate

• poliovirus is a common example

• Do not use their genome as mRNA

• Instead they use reverse transcriptase to create a new strand of cDNA the cell will then use

• The newly made DNA serves as a template to make more of the retrovirus and as the template for genome of the virus

• HIV is the most well-known retrovirus

• Host ribosomes cannot translate a -RNA strand

• A positive sense strand looks exactly like mRNA

  • Negative sense are just opposite direction

• These viruses carry RNA dependent RNA transcriptase in their capsids

• The enzyme then creates +RNA strands which can serve as mRNA for creating more of the virus’ genomes as well as proteins

• A very common disease is influenza

• the +RNA strand can act directly as mRNA

• The -RNA strand can be transcribed into +RNA and then translated

• Certain rotaviruses have this type of genome which causes gastroenteritis

the breakdown of a cell caused by damage to its plasma (outer) membrane

many enveloped viruses incorporate phospholipid membranes from their host cells as they are released

can cause the phenotype of the bacterium to change from harmless into pathogenic

• Viruses are thought to cause some 20-25% of human cancers

• The most well-known is cervical cancer caused by HPV (Human Papilloma Virus)

• Protooncogenes – are genes in a host cell involved in normal cell division.

Two Hit hypothesis

• a virus inserts a promotor that converts a protooncogene into an oncogene

• Often this first hit doesn’t cause cancer, but if a second hit damages the downstream repressor gene, \n then the oncogene disrupts cell division and causes cancer

• Using live organisms create ethical difficulties

• Cell cultures are costly

• Look to see if virus eats through it

• To estimate phage numbers, you assume that each plaque corresponds to a single phage in the original bacterium/virus mixture

• Bovine Spongiform Encephalopathy (BSE)

• Chronic Wasting Disease (CWD)

  • in deer and elk

• vCJD – variant Creutzfeldt Jacob Syndrome

  • in humans

• Scrapie

• Kuru

Proteinaceous infectious particles

• In human prion diseases a normal PrP protein’s structure becomes altered and begins to affect other \n PrP proteins around it

• As more of the altered PrP proteins aggregate it causes neurons to die and leave holes in the brain

• Diseases caused by prions are called spongiform encephalopathies

• Ingestion of injected tissue, transplants of infected tissue or contact between infected tissues and \n mucous membranes can transmit prion diseases

• in animals they kill the entire herd

• They are not removed through normal autoclaving or decontamination processes

• Sustained heat for several hours at extremely high temperatures (900°F and above) will reliably destroy a prion

1. mutualism

2. commensalism

3. amensalism

4. parasitism

• The microbe benefits without affecting the host – many types of gut bacteria

• These may be mutual and we just haven’t figured it out yet

• Both host and microbe benefit from the interaction

• The relationship is beneficial to both, but not necessary

• When one symbiont is harmed a second symbiont, while the second is neither harmed or helped by the first

• E.g. – Pencillum fungus makes the antibiotic penicillin which inhibits nearby bacteria, but the bacteria have no effect on the fungus

• The parasite gets benefit from the host while causing it harm or disease

• Any parasite that causes disease is called a pathogen

• Which type of parasites would be most effective?

  • ones that keep host alive

Human microbiome/normal flora/microbiota

• Strep is a large member of the upper respiratory tract

• Most of the fungal members are candida

  • Candida albicans has colonized pretty much everyone

  • Doesn’t really cause any issues unless the pH changes or immunocompromised

Oral cavity

• Streptococcus

• Lactobacillus

  • Probiotic yogurts

• Treponema

  • Spirochetes

  • Palladium – syphilis

Small intestine

• Lactobacillus

• Enterococcus

Large intestine

• Dense and diverse microbial population

  • Klebsiella

  • Enterococcus

  • Fecal coliforms

Primarily vaginal canal

• Lactobacillus

• Staphylococcus

• Streptococcus

• Candida

Babies born vaginally are colonized with other microorganisms that those delivered by caesaria

Primarily populated with gram positive organisms

• Staphylococcus

• Streptococcus

• Corynebacterium

• Propionibacterium

Most are commensals

• Things we pick up from environment around us and other people

• Found in same places as resident bacteria

  • Until dislodged by competition

  • Discovered by immune system

  • If causing disease immune system will pick it up

• Best way to get rid of them is washing hands

• Begins at birth

• Axenic environment – completely free of bacteria

  • Moms' womb

• Initially colonized when we pass through the birth canal

• Breastfeeding introduces bacteria that will become gut bacteria

1. introduction of normal microbiota into an unusual site in the body

   1. E coli introduced from the digestive tract into the urethra can cause UTIs

2. Immune Suppression

   1. Anything that suppresses the normal immune response of our body

   2. Post surgery/injury

   3. Steroids work to hurt the injury cascade

      • Why c. diff. Is common

3. Changes in the normal microbiome

   1. Normal microbiota provide a competitive environment for incoming pathogens

   2. antibiotics can allow transients to get a foothold

4. Stressful conditions

   1. Emotional or Physicals stressors can allow pathogens to have a competitive advantage

   2. Can allow pathogens to get a competitive advantage

      • Cold sores, candida

Animals

• Zoonoses

• Hard to eradicate because there are so many ways in which we interact with animals (food,

  waste processing, pets, etc.)

Human Carriers

• Can be asymptomatic for years

• Typhoid Mary

Nonliving Reservoirs

• Soil, water, food

• The presence of microbes in the body

• Can have no effect

• They can become part of our normal flora.

• Remain as transients for a time

• Become pathogens

• When the pathogen overwhelms the body’s defenses

• Some infections do not cause disease

• skin

• mucous membrane

  • MAIN PORTAL OF ENTRY

• placenta parenteral route

• Stratum corneum helps prevent many infections, but only as long as it remains intact

• Other pathogens can enter through natural openings: hair follicles, sweat glands

• Anything that opens the skin can lead to infection

• Sweat glands, oil glands

• MAIN PORTAL OF ENTRY

• The epithelial lined body cavities that are open to the environment

• This is the major portal for most microbe entry

• GI tract, Respiratory, Urinary, Reproductive and the conjunctiva

• The most common portal is the respiratory system

• List some pathogens that enter via the respiratory route below

• Only a few types of pathogens can directly cross the placenta

• In the small percentage that do, there can be severe consequences to the embryo, fetus, or mom

• E.g. – If measles is able to cross the placenta it can cause fatal encephalitis in the fetus

• This is not a traditional route of entry, but a way in which pathogens are deposited directly into tissues

• needle sticks, thorns or stepping on rusty nails

• Cut in the skin

• Viruses and bacteria most commonly use lipoprotein or glycoprotein ligands that allow them to \n attach to receptors on the host cells

• The specific interaction of adhesions to their host cells often determines which types of hosts they \n can infect

• Some pathogens only have one type, others can have multiple

• Some are able to change their adhesions over time to evade the host’s immune system

• If a virus or bacteria loses the ability to make a specific adhesion protein it will become avirulent

• many organisms only cause disease when they are in biofilm form

  • Some bacteria will change their phenotype drastically when in a biofilm

When a pathogen invades a host

When the injury caused by the pathogen is significant enough to interfere with normal functioning of the host

the condition of suffering from a disease or medical condition

the ability to cause disease

the degree of pathogenicity and is enhanced by virulence factors

• More subjective

• Pain

• Nausea

• Headache

• Sore throat

• Fatigue

• Itching, cramps etc.

• Objective signs of disease that are measurable

• Swelling

• Rash or redness

• Vomiting

• Diarrhea

• Fever

  • Recommended treatment is above 100.5

• Increase or decrease in WBC’s

• Increase or decrease in HR

• Increase or decrease in BP

• A group of signs and symptoms that characterize a disease

• AIDS – hallmarks are malaise, decrease in T4 cells, diarrhea, weight loss, pneumonia, other rare

• Fungal infections and cancers

• Lack observable signs or symptoms

• May still be detected by proper testing

• Some types of herpes virus infections are asymptomatic

• Person may be able to transmit disease to others

The cause for a disease

• Some conditions are named for the disease and not the specific pathogen

• the gold standard for determining infectious disease

• The suspected agent must be present in every case of the disease

• The agent is isolated and grown in pure culture

• The cultured agent must cause disease when inoculated into healthy host

• The same agent should be found in the diseased host

• Must be followed in order. – E.g., Haemophilus influenzae

• Some pathogens cannot be grown in lab

• Some diseases are caused by a combination of pathogens

  • Some are polymicrobial

    • Combination of pathogens working together

    • Like some are only infectious when they form biofilms

• It is unethical to test human diseases using Koch’s postulates

• Some diseases are named for what they affect rather than a specific pathogen

• extracellular enzymes

• endotoxins

• exotoxins

• things that block phagocytosis

• Hyaluronidase – destroys hyaluronic acid, a key substance in ground substances of CT

• Collagenase – destroys collagen allowing bacteria to spread.

• Coagulase – causes blood clotting (coagulase test)

  • Staph aureus and strep are known to do this

  • Clots protect the bacteria

• Kinases (Streptokinase, Staphylokinase) – digest blood clots and release bacteria

  • Allows them to spread through the body

• Only produced by gram negative cells

• The lipid A component of a gram-negative cell wall

  • Most common

  • Released when cells die

  • endCan cause fever, hemorrhage, inflammation

• Released when the cells die or are destroyed by the host

• Can cause – fever, inflammation, diarrhea, hemorrhage, shock, coagulation

• can be produced by gram negative and positive bacteria

• produced and released by the bacteria

  • Cytotoxins

    • Kill cell membranes

  • Neurotoxins

    • Nervous tissue

    • Botulinum

      • Damages synaptic transmission (nerve to nerve and nerve to muscle)

  • Enterotoxins

    • GI tract

• Our bodies can produce antibodies that will neutralize exotoxins before they make us sick

• Vaccines that look for exotoxins are looking for a certain protein signature

Exotoxins are more serious than endotoxins, but if a large number of gram-negative cells die then endotoxins can cause disease

• Need smaller number of exotoxins to cause disease

• Onset of disease from exotoxin is more rapid and severe right off the bat

• For endotoxins they take longer to cause disease

1. incubation period

2. prodromal phase

3. illness period (climax)

4. decline

5. convalescence

   You can be infectious at any stage

• Capsules – are composed of the same things as body cells

  • Can evade detection for longer

  • Some capsules also make the bacteria very slippery and had to grab

• Antiphagocytic Chemicals – chemicals produced by bacteria that prevent lysosomes in the phagocytes from attaching to the bacteria and allows them to survive inside the phagocytes

  • E.g. – M factor produced by Strep pyogenes

the time between entry of the microbe and symptom appearance

• Many infectious agents this is between 1-7 days

• Depends on virulence of microorganism and infective dose

• State and health of host (faster infection if immunocompromised)

• Site of infection

a time of mild signs or symptoms

• Mild signs and symptoms

• Some infectious diseases that can skip the prodromal phase (GI bugs)

known as climax

• when signs and symptoms are most intense

  • Most severe part

  • When you feel the worst

  • The hosts immune system has not responded adequately yet or it is completely overwhelmed

  • Often but not always the most infective stage

As signs and symptoms subside

• Immune system starts to recover or when antibiotics or antiviral meds kick in

• When fever goes away but still sick

The body systems return

• Length depends upon same factors that cause disease (no co-morbidities)

Airborne

• When it is small enough to be picked up in air currents

• Much more common occurrence with dental and surgical drills

Waterborne

• Can act as a reservoir as well

• Fecal-oral route

Foodborne

• Another fecal-oral route

• From improper food handling

Bodily fluids

• Considered underneath water transmission

• Can be a form of direct contact

• Blood or semen come in contact with open cut

• Should always be treated as if they contain pathogens

Biological

• Bites

• Insects

• Mosquito is most common

Mechanical

• Indirect transmission

• e.g., fly walks on sandwich

Direct

• Bodily contact

• Touching, kissing, sex,

• Biting or scratching in zoonoses

• Vertical transmission

• Mom passes it to the baby via placentas

Indirect

• Fomites – inanimate objects that are capable of transferring pathogens

• e.g., toothbrush, medical equipment, money

Droplet

• Droplets of mucous propelled out of nose or throat when talking, sneezing, coughing

• Most travel 1m or less

• Distance

• Aerosols/airborne remain suspended in the air

• By taxonomic group

• By body system affected

• Longevity and Severity

• Symptoms develop rapidly and runs its course quickly

• e.g., influenza, rotavirus, strep throat

• Disease with usually mild symptoms that develop slowly and a long time

• e.g., COPD (Chronic Obstructive Pulmonary Disease), cancer, mono

• Disease whose time course and symptoms range between acute and chronic

• e.g., COVID

• disease that appears a long time after infection

• e.g., Proin diseases, Cold sores

• infection only in a specific area of the body

• e.g., Tick bite

Able to be transmitted from one host to another

disease not passed from person to person

communicable disease that is easily spread

• The study where, when, and how diseases occur

• How diseases affect the population

  • Can be applied to chronic diseases not just acute

• number of new cases that are appearing in a specific time

• Better for ongoing outbreak

• the total number of cases appearing in a specific time

• Better for the burden of disease

• naturally occurring in a population/normally around

• Common cold

• few cases of diseases that pop up

• Can be related or unrelated

• large new emergence of disease in an area

• More cases than normally predicted for a given region

• Continued or sustained spread of disease

• Different than outbreak

  • Outbreaks are limited

  • Not enough momentum or population to keep the outbreak going

    • Outbreak of food poisoning

worldwide epidemic

Descriptive

• Early studies

• Trying to figure out what the cause it

• What the reservoirs are

• Index case – person who is the original host or reservoir

Analytical

• Used to try to find associations between risk factors and behavior patterns of disease

• Often retrospective studies (after the fact)

Experimental

• Highest level of epidemiological studies

• Hypothesis generating and testing experimental studies based upon previous information

Types of HAIs

• Exogenous – picked up in a healthcare setting

• Endogenous – opportunists because of treatment

• Iatrogenic – caused by things like catheters, surgery, wrong antibiotics

Handwashing protocols can reduce infection by more than 50%

• Presence of microbes in the hospital setting

• Immunocompromised patients

• Transmission of pathogens between staff, and patients

adaptive

• Humoral – B-cell mediated

• Cell based – T-cell mediated

innate

• Mechanical

• Cells

• Chemicals

• Inflammation

  • Major component of immune response

  • Does not know the difference between sprain or bacteria

keep pathogens out

• Skin

• Secretions

  • Oils on skin

  • Sweat

• Tears

• Saliva

• Mucosa

• Made of about 20 proteins that are activated when exposed to bacterial antigens

• For generalized bacterial infections

• Series of proteins found in our blood

• Some are part of the hemoglobin molecule

Classical Pathway

• Stimulation by antigen-antibody complex

Alternate Pathway

• Stimulation by microorganism cell wall

• Literally pokes a hole in the wall of pathogens

• Part of non-specific immune response

• Generalized viral infections

• Infected cell (host 1) will die, but interferon will cause neighboring cells to produce protective anti-viral protein coats

• IFN’s used to treat some forms of Herpes and Hepatitis

• Also used for autoimmune disorders

  • MS

• Cells can produce interferon

• Moves to neighboring cells and telling it to protect themselves

• Integral proteins found on the cell membrane of phagocytes

• Trigger your body’s responses to a number of various bacterial and viral pathogens

• There are 10 different TLR’s found on human phagocytes

• Binding of Pathogen Associated Molecular Patterns (PAMP) triggers infected cells to do things \n like: apoptosis, initiate the inflammatory mechanism, or stimulate the adaptive response

• phagocytes – about 126 billion/day produced

• Usually the first WBC to make it to an infection

• 1 time use (like a honeybee stinger)

• Pus =dead neutrophils, microbes, pathogens

• monocytes in blood, macrophages in tissue

• Leave blood and increase numbers at site of infection

• They are the cleanup crew

• Include many different types – dendritic cells, microglia, alveolar, hepatic

• mobile

• Release factors which attract more WBC’s (chemotactic factors)

• nonmobile

• Are found near sites of possible pathogen influx

• Release chemotaxic factors

• Can also phagocytose bacteria

Act as moderators of inflammatory response and kill parasites by releasing enzymes all over them