know your enemies: bacteria and virusesdb.phm.utoronto.ca/dojo soeandy lecture 4.pdfmacrophages that...

Know your enemies: bacteria and viruses

Lecture 4- Dojo Soeandy’s section

1

Pathogens vs. antigens

• Pathogens: “non-self” infectiousagent like bacteria, viruses, parasites or fungi

• Antigens (antibody generator): molecules that can initiate an immune response, includes• proteins on the surface of pathogens • non-living substances like toxins,

chemicals, foreign particles (e.g. a splinter)

• autoantigens- a normal protein or complex of proteins (sometimes DNA or RNA) that elicit an immune response in autoimmune diseases

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Parasitic roundworm

Salmonella bacteria

Bacteria• Bacteria are single-celled pathogens

• No nucleus or membrane bound organelles (prokaryote instead of eukaryote)

• Genetic information is contained in a single loop of dsDNA, with some having an extra-genomic/choromosomal circular dsDNA called a plasmid. • Plasmid often contains genes that give

the bacterium some survival advantage.

• E.g. it may contain a gene that makes the bacterium resistant to a certain antibiotic.

• They can pass plasmid to daughter cells after mitosis and can also share this to other bacteria through “conjugation” 3

addgene.org

Al-Mohanna, 2016

Bacterial cell structure• Capsule:

• Outer most layer of the bacteria (extracellular)

• Usually composed of polysaccharide• Glycocalyx- when form loose meshwork of

fibrils extending outward from the cell• Slime layer- when masses of polymer that

formed appear to be totally detached from the cell, with the cell entrapped in it

• Provides protection in unfavourableenvironments

• Presence is important in disease causing ability of some bacteria. (e.g. The non-capsulated strains of Pneumococcus are destroyed by host phagocytes and are therefore not effective)

4Encyclopedia Brittanica

Bacterial cell structure• Flagellum:

• Long hair-like filaments extending from cytoplasmic membrane to exterior of the cell

• Used for locomotion/movement

• Fimbriae or Pili:• Extremely fine hair-like filaments (usually

on gram negative bacteria)• They are thinner, shorter and more

numerous than flagella and they do not function in motility.

• Function in adhesion (non-sex/common pili.

• Sex pili help in conjugation5

Bacterial cell structure

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Bacterial cell structure

• Cell wall: • Provides bacterial shape and rigidity

• Composed of peptidoglycan- i.e. alternating units of N-acetylglucosamine and N-acetylmuramic acid

• It is a primary target of antimicrobial therapy – because it is specific to prokaryotes

• Peptidoglycan e.g. destroyed by lysozyme

• Basis for bacterial classification by Gram stain

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Bacteria classifications• Gram stain:

• Discovered by H.C. Gram in 1884 it remains an important and useful technique

• Slides go through a sequence of staining with crystal violet, iodine, destained with alcohol and counter-stained with safranin

• Gram positive- stain blue-purple; larger peptidoglycan (cell wall) in Gram positive bacteria causes iodine and crystal violet to precipitate instead of getting eluted by alcohol (e.g. Staphylococcus epidermidis on skin)

• Gram negative- stain red; thinner cell wall, and so the crystal violet is readily eluted from the bacteria (e.g. Enterobacteriaceaelike E. Coli in digestive tract)• Another unique characteristic of Gram negative bacteria is the

presence of lipopolysaccharide (LPS) molecules on the outer membrane (an endotoxin)

• Some bacteria such as mycobacteria (the cause of tuberculosis) are not reliably stained due to the large lipid content of the peptidoglycan; so require other staining methods like Kinyoun or acid fast stain

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Bacteria classifications

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2bscientific.com


• Morphology/shape:• Cocci/coccus- spherical

• Streptococci: When they appear in chain form.

• Staphylococci: Arranged in irregular clusters like bunch of grapes.

• Baccili/baccilus- rod-shaped• Vibrios- comma-shaped• Spirilla- rigid spiral forms• Spirochetes- flexuous spiral forms• Actinomycetes- branching filamentous

bacteria• Mycoplasmas- bacteria that are cell wall

deficient and hence do not possess a stable morphology. They occur as round or oval bodies and as interlacing filaments. 11

Al-Mohanna, 2016

Bacteria classifications• Growth requirements:

• Gaseous: • Obligate aerobes- require oxygen and cannot grow in the

absence of O2 (e.g. Mycobacterium tuberculosis, the causative agent of tuberculosis and Micrococcus luteus, a gram-positive bacterium that colonizes the skin)

• Obligate anaerobes- can grow only in absence of Oxygen; O2can kill these bacteria (e.g. Bacteroidetes represent a large fraction of the microbes in the human gut)

• Facultative anaerobes- do not require O2 but can use it if available (e.g. some Staphylococci found on the skin and upper respiratory tract; E. Coli in digestive tract)

• Aerotolerant anaerobes- do not require O2 for growth but can tolerate the presence of O2 (e.g. some Streptococci found in the oral microbiota)

• Microaerophiles- grow under conditions of reduced oxygen and sometimes also require increased levels of carbon dioxide (e.g. Helicobacter pylori involved in stomach ulcers)

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Growth requirements (Gaseous):

lumenlearning.com


• Growth requirements:• Mode of nutrition:

• Phototrophs- gain energy from light (and use organic or inorganic compounds)

• Chemotrophs- gain energy from chemical compounds (organic or inorganic); cannot carry out photosynthesis

• Autotrophs- uses carbon dioxide as sole source of carbon to prepare its own food (may use light or chemical compounds as energy cource)

• Heterotrophs- most human pathogenic bacteria; use organic carbon as food

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• Growth requirements:• Temperature:

• Psychrophiles/cryophiles- optimum growth temperature of 15°C or lower; cannot grow in a climate beyond a maximum temperature of 20°C

• Mesophiles- bacteria that can grow best atmoderatetemperature (25-40°C) but optimum temperature for growth is 37°C; most applicable to disease-causing bacteria

• Thermophiles- heat loving microbes thriving at high temperature usually more than 45°C

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• Growth requirements:• Salt:

• Halophiles- require NaCl or another salt for growth (e.g. most in Vibrio family)

• Halotolerant- bacteria that do not require NaCl but can tolerate low concentration of NaCl in growth media (e.g. Vibrio Cholera)

• pH:• Acidophiles- bacteria that grow best at acidic pH

• Alkaliphiles- bacteria that grow best at alkaline/basic pH

• Neutriphiles- bacteria that grow best at neutral pH (6.5-7.5); most bacteria

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• Spore forming: • Some bacteria (usually gram positive) can form

spores, which are dormant structures that are extremely resistant to hostile physical and chemical conditions such as heat, UV radiation and disinfectants, and so they are very difficult to destroy.

• Many endospore-producing bacteria are nasty pathogens, for example Bacillus anthracis, which is the cause of anthrax.


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micro.cornell.edu

• Spore forming: • Specifically refer to endospores, consist of:

• Outer proteinaceous coat surrounding the spore-provides much of the chemical and enzymatic resistance

• Specialized peptidoglycan called the cortex- helps dehydrate spore, which aids in resistance to high temperature

• Germ cell wall peptidoglycan will become the cell wall of the bacterium after the endospore germinates

• Inner membrane- major permeability barrier against several potentially damaging chemicals

• The core- exists in a very dehydrated state and houses the cell's DNA, ribosomes and large amounts of dipicolinic acid

• Small acid-soluble proteins (SASPs) are also found in endospores- tightly bind and condense the DNA, and are in part responsible for resistance to UV light and DNA-damaging chemicals.


• Flagella:• Monotrichous - single flagella on one

end of cell (e.g. Vibrio cholera)

• Lophotrichous - bundle of flagella on one end

• Amphitrichous - single or cluster of flagella at both ends of cell

• Peritrichous - flagella all over the cell surface (e.g. E.coli, Salmonella)

• Atrichous – no flagella (e.g. Shigella)

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biologydiscussion.com

Bacteria and their relationships with humans• Symbiotic relationships:

• Mutualism- two species benefit from each other• E. coli relies on intestinal contents for nutrients, and humans

derive certain vitamins from certain strains of E. coli, particularly vitamin K, which is required for the formation of blood clotting factors.

• Commensalism- one organism benefits while the other is unaffected• Staphylococcus epidermidis uses the dead cells of the human skin

as nutrients. We don’t usually get any immediate effects from this.

• Parasitism- one organism benefits while harming the other• The relationship between humans and many pathogenic bacteria

can be characterized as parasitic because these organisms invade the body, producing toxic substances or infectious diseases that cause harm.

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Bacterial disease example: Tuberculosis

• Caused by bacteria called Mycobacterium tuberculosis

• Types of tuberculosis infection:• Latent (LTBI)- (90%) infected with the

bacterium, but the disease does not develop and no symptoms are experienced (can remain dormant for years)

• Active- (10%) TB disease and associated symptoms

• Symptoms: long-enduring cough (more than 2 wks), presence of blood or sputum (thick, cloudy mucus) in cough, fever, night sweats, tiredness, weightloss, etc.

• Diagnosis: tuberculin skin test, blood/sputum test (to check for bacteria), chest x-ray

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Dubey, Rath, Sahu, et al. 2012


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museumofhealthcare.cabchdmi.org

Tuberculin skin test Chest xray

medscape.com

Bacterial disease example: Tuberculosis• Pathogenesis:

1. Tubercle bacilli dispersed in the air from a patient with active pulmonary TB reach the alveoli of the host.

2. Mtb is quickly phagocytized by professional alveolar macrophages that most often can kill the entering bacteria.

3. If this first line of defence fails to eliminate the bacteria, M. tuberculosis invades the lung interstitial tissue, either by the bacteria directly infecting the alveolar epithelium or the infected alveolar macrophages migrating to the lung parenchyma.

4. Adaptive immune system kicks in; form a granuloma. Fibrotic components cover granuloma and can overtime calcify so that the bacilli remain encapsulated inside —latent TB.

5. The bacteria replicate within the growing granuloma. If the bacterial load becomes too great, the granuloma will fail to contain the infection — the infected host is now infectious, symptomatic and is said to have active TB disease.

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24Pai et al. 2016

Bacterial disease example: Tuberculosis• Treatments: it is very important that the medicine is finished and that

the drugs are taken exactly as told. It takes at least six months and possibly as long as one year to kill all the TB germs. If drugs not taken correctly, can get resistant strains.• isoniazid (INH)- prodrug and must be activated by bacterial catalase.

Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. Usually bactericidal.

• rifampin (RIF)- inhibits bacterial RNA polymerase, the enzyme responsible for DNA transcription

• ethambutol (EMB)- inhibits arabinosyl transferases which is involved in cell wall biosynthesis

• pyrazinamide (PZA)- has no or little activity against growing tubercle bacilli and is primarily active against non-growing persisters. prodrug that is converted to the active form pyrazinoic acid by bacteria. Through a process involving efflux and influx of the molecule based on pH, it can cause cytoplasmic acidification. Result in inhibition of vital enzymes, affect membrane transport, inhibit protein and RNA synthesis, etc.

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Bacterial disease example: Lyme disease

• Caused by Borrelia burgdorferi that is spread through the bite of infected ticks

• In most cases, the tick must be attached for 24 hours or more before the Lyme disease bacterium can be transmitted.

• The nymphal stage typically occurs during the summer months and is the stage most responsible for human infections. This is due to their very small size (less than 2 mm) which prevents people form noticing them on their body.

• Early detection and removal of ticks is important in the prevention of Lyme disease: remove the tick with fine-tipped tweezer or finger, being careful not to crush/squeeze it

26cdc.gov

Bacterial disease example: Lyme disease• Symptoms usually begin 3 days

to 4 weeks after a bite, and include:• Fever and chills• Headache• Stiff neck• Muscle and joint pains• Fatigue• Circular rash (also known as a bull’s

eye rash or erythema migrans). This rash occurs in 70 to 80 per cent of people who get Lyme disease

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James Gathany, Center for Disease Control and

Prevention

Bacterial disease example: Lyme disease

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Robert Lochhead for Medical College of Wisconsin

Bacterial disease example: Lyme disease• Pathogenesis

29Kumar, Risto, Shi, et al. 2015

Antibiotics Antibiotic classes/types: An antibiotic class is a grouping of different drugs that have similar chemical and pharmacologic properties. Their chemical structures may look comparable, and drugs within the same class may kill the same or related bacteria.

• Penicillin (beta-lactam antibiotics)• Penicillins work by preventing the cross linking of amino

acid chains in the bacterial cell wall. • This does not affect pre-existing bacteria, but newly

produced bacterial cells have weak cell walls that easily rupture.

• Includes drugs like amoxicillin, ampicillin, etc.

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Antibiotics • Tetracycline

• Bind 30S ribosomal subunit and block incoming tRNA from binding to the ribosome acceptor site; ultimately inhibiting protein synthesis.

• Primarily bacteriostatic which means that they prevent bacteria from multiplying but don't necessarily kill them.

• Increased bacterial resistance against them overtime though

• Include doxycycline, omadacycline, etc.

• Aminoglycosides• Inhibit bacterial synthesis by binding to the 30S

ribosome and act rapidly as bactericidal antibiotics (killing the bacteria).

• Used mainly in the treatment of aerobic gram-negative bacilli infections, although they are also effective against other bacteria.

• Often used in combination with other antibiotics.

• Include gentamicin, amikacin31

antibiotics-info.org

Antibiotics • Quinolones

• Also known as fluoroquinolones• Interfere with bacterial DNA synthesis by inhibiting topoisomerase

proteins, and so block the relaxation of supercoiled DNA for normal transcription and duplication, or block separation of replicated chromosomal DNA during cell division.

• Usually bactericidal• The FDA has issued several strong warnings about this class due to

potential disabling side effects, so should only be considered when treatment with other, less toxic antibiotics, has failed, or if they are unusual like anthrax or plague.

• Include moxifloxacin, levofloxacin, etc.

• Sulfonamide• Interfere with the synthesis of folic acid in bacteria, which is essential for

nucleic acid formation and ultimately DNA and RNA• Bacteriostatic on its own, but often combined with trimethoprim to make

them bactericidal (kill bacteria), because trimethoprim acts on a different enzyme in the folic acid synthesis pathway

• Include sulfamethoxazole and trimethoprim, sulfasalazine, etc.32

Viruses

• Obligate intracellular parasites• They fully depend on the complicated biochemical

machinery of eukaryotic or prokaryotic cells. • Are inert outside the host cell.• Are unable to generate energy

• Virion: a fully assembled infectious virus. Composed of• Nucleic acid: single- or double-stranded RNA or DNA and a

protein coat• Capsid: protein shell (encoded in virus genome) to protect

the viral genome from nucleases, and during infection, attaches the virion to specific receptors exposed on the prospective host cell (for unenveloped virus)

• May sometimes contain coat/envelope: lipid bilayer derived in part from modified host cell membranes. Contain viral glycoproteins necessary for entry into cells 33

ck12.org

Viral classification• Viruses are classified by factors such as capsid

structure, presence of outer envelope, their core content (DNA/RNA) and mode of replication.

• Capsid: generally divided into helical, polyhedral/icosahedral, or complex shaped

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lumenlearning.comOpentextbc.ca

Viral classification

• Envelope: presence or absence around capsid. No defined shape.

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Viral classification• Core content and mode of replication (Baltimore

system)

36opentextbc.ca

Viral classification• Core content and mode of replication (Baltimore

system)

37microbenotes.com

Viral disease example: rhinovirus• Among the most common causes of infection: most common

cause of the common cold• Single-stranded positive sense RNA (group IV), not enveloped

and are icosahedral in structure• Belong to the family Picornaviridae (picornavirus).• Types: HRV-A, HRV-B, HRV-C (HRV= human rhinovirus)• The virus is thought to be transmitted to the upper respiratory

tract by airborne droplets. • After an incubation period of 2 to 5 days, the acute stage of the

illness lasts 4 to 6 days.

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Peter Jordan for The Guardian Opentextbc.ca

Viral disease example: rhinovirus• Pathogenesis:

1. Rhinovirus bind to receptors on epithelial cells that line the upper respiratory tract: ICAM-1 (major group); LDLR (minor group)

2. Inside endosome: drop in pH leads to viral uncoating

3. RNA genome crosses the endosome membrane into the cytosol and begin viral replication

4. Epithelial cells release cytokines and activate the immune system

• Increased in mucus secretioncaused by: neutrophil elastase, cytokines, tight junction disruption, etc.

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Kelly & Busse, 2008

Viral disease example: rhinovirus• Symptoms usually include:

• sore throat• runny nose• coughing• sneezing• headaches• body aches

• Prevention:• Wash your hands often with soap and water. Wash them for >20 seconds• Stay away from people who are sick or if you’re sick• Avoid touching your eyes, nose, and mouth with unwashed hands• Cover your mouth and nose when coughing or sneezing

• Treatments: No cure• lots of rest and drink plenty of fluids• over-the-counter medicines (pain relievers, cough/cold medicines) may

help ease symptoms but will not make your cold go away any faster.• don’t use antibiotics!

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cdc.gov

Viral disease example: influenza virus

• Multiple segments of single stranded negative-sense RNA, enveloped

• There are three main types of influenza (flu) virus that affect humans: types A, B and C.• Human influenza A and B viruses cause seasonal epidemics of disease

almost every winter in the United States. • The emergence of a new and very different influenza A virus to infect

people can cause an influenza pandemic (because they can use other animals as hosts too e.g. H1N1 and swine flu)

• Influenza type C infections generally cause a mild respiratory illnessand are not thought to cause epidemics.

41scientificanimations.com

Viral disease example: influenza virus• Symptoms:

• In general, flu is worse than the common cold, and symptoms are more intense.

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Viral disease example: influenza virus• Inserted into the lipid membrane are ‘spikes’ –

glycoproteins– known as HA (hemagglutinin) and NA (neuraminidase), which are important in influenza pathogenesis

• They are also important in host immune response: antibodies are often generated against these molecules.

43scientificanimations.com


• Influenza viruses are constantly changing. They can change in two different ways:• Antigenic Drift- small changes in the genes of influenza

viruses that happen continually over time as the virus replicates. But these small genetic changes can accumulate over time and result in viruses that are antigenically different. When this happens, the body’s immune system may not recognize those viruses.

• Antigenic Shift- abrupt, major change in the influenza A viruses, resulting in new hemagglutinin and/or new hemagglutinin and neuraminidase proteins in influenza viruses that infect humans. Usually emerge from an animal population that the resulting subtype is so different that most people do not have immunity to the new (e.g. novel) virus.

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Pathogenesis:

1. Binding of haemagglutinin (HA), expressed on the surface of the influenza virion, with sialic acid residues linked to host cell surface glycans induces binding and fusion of the virion with the plasma membrane of the target cell

2. Drop in pH in endosome due to lysosome leads to membrane fusion and release of ribonucleoprotein (RNP)

3. These are transported to the nucleus where viral RNA replication occurs

4. Other protein and glycoproteins synthesis occur outside the nucleus

5. During budding, new virions are linked to the plasma membrane by HA/sialic acid interactions; cleavage of sialic acid residues by neuraminidase (NA) releases the viral progeny so they are then free to infect other cells

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Antiviral drugs: influenza virus• Antiviral drugs are not a substitute for getting a flu vaccine.

Second line of defense that can be used to treat flu

• Four FDA-approved antiviral drugs:• oseltamivir phosphate (available as a generic version or under

the trade name Tamiflu®)- pill or liquid suspension• prodrug of oseltamivir carboxylate, which is an inhibitor of

neuraminidase- glycoproteins found on the virion surface

• zanamivir (trade name Relenza®)- inhaled• inhibition of influenza virus neuraminidase

• peramivir (trade name Rapivab®)- intravenous• cyclopentane analogue that competitively binds to the active site of the

influenza virus neuraminidase

• baloxavir marboxil (trade name Xofluza®)- pill• CAP endonuclease inhibitor, blocking the transcription of mRNA and

inactivate the influenza virus

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Vaccine: influenza virus

• Getting a flu vaccine can protect against flu viruses that are the same or related to the viruses in the vaccine.

• Traditional flu vaccines (called “trivalent” vaccines) are made to protect against: Influenza A (H1N1), A (H3N2), and one influenza B.

• Most vaccines in 2019-2020 will be quadrivalent (four-component) flu vaccines, composed of trivalent components + one extra influenza B.

• The seasonal flu vaccine does not protect against influenza C viruses.

• Additionally, flu vaccines will NOT protect against infection and illness caused by other viruses that also can cause influenza-like symptoms.

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medscape.com

Vaccine: influenza virus

• Options for flu vaccines include: inactivated influenza vaccine, recombinant influenza vaccine, or live attenuated influenza vaccine.

• Different vaccines are licensed for different age groups, and some vaccines are not recommended for some groups of people. For example• A high-dose trivalent flu shot or a trivalent flu shot made

with adjuvant are approved for people 65 years and older.

• A quadrivalent live attenuated influenza nasal spray vaccine is approved for use in people 2 years through 49 years of age.

• A recombinant quadrivalent flu shot is approved for people 18 years and older.

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medscape.com

Viral disease example: HPV• HPV is a very common virus. Some doctors think it’s almost as

common as the cold virus.

• Human Papillomavirus (HPV) are circular double-stranded DNA viruses, non-enveloped with an icosahedral capsid

• Infect mucosal and cutaneous epithelia and induce cellular proliferation.

• Some HPV types cause papillomas (warts), which are non-cancerous tumors. But some (at least 14) types of HPV are known to cause cancer.

50advanceddermspecialists.com

Viral disease example: HPV

• Mucosal (genital) HPV is spread mainly by direct skin-to-skin contact during sexual activity (not spread through blood or body fluids).

• It can be spread even when an infected person has no visible signs or symptoms.

• You DO NOT get HPV from:• Toilet seats

• Hugging or holding hands

• Swimming in pools or hot tubs

• Sharing food or utensils

• Being unclean

51health.harvard.edu

Viral disease example: HPV• Diagnosis:

• Evidence of genital warts; acetic acid placed on the skin turns the warts white.

• Anoscopy – An instrument called an anoscope may be inserted into the anus to visualize warts beyond visible skin.

• Colposcopy – An instrument called a colposcope is used to magnify and inspect possible warts in the vagina and on the cervix.

• Tissue biopsy – A small piece of tissue is removed and examined in a laboratory.

• Papanicolaou (Pap) smear – cells from your cervix are collected to test for cell changes indicative of cervical cancer in women. Recommendations:• (At the very least) ages 21 to 29- every 3 years• Ages 30 to 65- every 3-5 years

• HPV DNA test – test for the HPV virus (high-risk or carcinogenic types) that are most likely to cause cervical cancer by looking for pieces of their DNA in cervical cells

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Viral disease example: HPV• Pathogenesis:

• The HPV life cycle is closely linked to epithelial differentiation.

• Normal squamous human epithelia grow as stratified layers where only cells in the basal layers are able to actively divide.

• After division of basal cells, one of the daughter cells migrates upward and begins to undergo differentiation while the other remains in the basal layer.

• HPV infection occurs at the basal cell layer of stratified squamous epithelial cells (the deepest epidermal layer).

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• It is thought that HPV is able to enter cells because during wound repair basal cells upregulate α6ß4 integrin which interacts with L1, a capsid protein found on the surface of the HPV virion.

• During HPV infection, viral proteins override the normal cell cycle exit that occurs in differentiating cells in order to allow for the production of viral progeny.

Hebner & Laimins, 2006

Viral disease example: HPV• Pathogenesis:

• E5, E6 and E7 viral proteins allow HPV to stop infected cells from exiting the cell cycle • The presence of E7 leads to a characteristic retention of nuclei throughout all layers of

infected epithelia.• Expression of E5 in the stratum basale and spinosum would lead to sustained cell

proliferation, but extinction of its expression in the more superficial layers would permit cell differentiation and virion production

• The E6 and E7 proteins of high-risk HPV types act as viral oncoproteins.• High-risk HPV infections that progress to cancer typically integrates their viral DNA into

the host genome often resulting in the loss of E5 genes.• E6 binds to the p53 tumor suppressor gene product, which results in the premature

degradation of the p53 protein.• E7 protein binds to a tumor suppressor protein—the retinoblastoma protein—and

inhibits its function.

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Hebner & Laimins, 2006


• Pathogenesis: • Finally as the keratinocyte reach its terminal

differentiation (the stratum corneum), late viral protein expression (capsid proteins) and virus assembly occurs.

• Thereafter, as the outermost layer of epithelial cells are shed, virus is shed at the same time.

55Hebner & Laimins, 2006


• Immune evasion strategies:• As this is not a cytolytic virus, there is no viraemia and no

initiation of inflammation and subsequent activation of the immune system.

• E6 and E7 oncoproteins interfere with type 1 interferon responses preventing the initiation of intracellular antiviral cascades.

• Lack of inflammatory cytokine release from infected keratinocytes limits the activation of resident skin Langerhan’s cells which are required for induction of adaptive immunity.

• The E5 proteins promote entrapment of peptide-loaded MHC class I receptors in the Golgi body and there is thus a downregulation of it on the cell surface. This lack of surface expression allows escape from virus-specific CD8+ cytotoxic T cell detection.

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Viral disease example: HPV• Treatment:

• There’s no treatment for the virus itself. Most genital HPV infections can be dealt by the person’s immune system.

• The cell changes (warts) caused by an HPV infection can be treated (although it is common for them to return):• liquid nitrogen (cryotherapy) - freeze the tissue and make warts

disappear.• laser treatment• surgical removal• medication that you can apply to the warts at home (maybe in

conjunction with use of protective coating of petroleum jelly on delicate surrounding tissue)

• Pre-cancer lesions: WHO recommends the use of cryotherapy and Loop Electrosurgical Excision Procedure (LEEP)

• Invasive cervical cancer: treatment depends on the stage of the disease (include surgery, radiotherapy and chemotherapy, etc.)

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Vaccine: HPV• 3 vaccines protect against both HPV 16 and 18, which are

known to cause at least 70% of cervical cancers.

• Third vaccine protects against three additional oncogenic HPV types, which cause a further 20% of cervical cancers.

• However, the vaccines that only protect against HPV 16 and 18 also show cross-protection against other less common HPV types which cause cervical cancer, so WHO considers the three vaccines equally protective against cervical cancer.

• E.g. Gardasil vaccine contain purified inactive proteins from HPV types 6, 11, 16, and 18

• HPV vaccines work best if administered prior to exposure to HPV; WHO recommendation: vaccinate girls aged between 9 and 14 years. (Some countries have also vaccinated boys.)

• The vaccines cannot treat HPV infection or HPV-associated disease, such as cancer.

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know your enemies: bacteria and virusesdb.phm.utoronto.ca/dojo soeandy lecture 4.pdfmacrophages that...

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