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Describe the classification of viruses
- Type of nucleuic acid present: DNA, RNA, ss/ds, +/-
- Mode of replication
- Symmetry of virus particle: icosahedral, helical, or complex
- Presence or absence of external envelope
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Virus introduction (general information)
- Metabolically inert: must parasitize host to replicate
- Infect every form of life (not other viruses)
- Cause some of the most common AND most serious diseases
- Difficult targets for antiviral agents due to cell infection (vaccines are more useful)
- Obligate intracellular parasites
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Summary of infection of a host cell by a virus (very general)
- Attachment (highly specific)
- Penetration
- Uncoating
- Replication using host machinery
- Assembly of new virus particles
- Release of virus particles
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What are the four possible outcomes of a viral infection?
- Cell lysis (lytic infection): release of new viral particles by cell lysis
- polio and influenza
- Persistant infection: host cell may remain alive and continue to release virus particles by budding
- Infected person may act symptomless
- hepatitis B
- Latent infection: virus remains silent by putting their genetic material without replicating....
- in cytoplasm (herpesvirus)
- in genome (retrovirus, hep B)
- Transform the host cell into a tumor cell: may become cancerous
- may be benign growth (papillomaviruses)
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What are the most common forms of virus transmission (with example viruses)?
- Inhaled droplets (rhinovirus, influenza)
- Food or water (hepatitis A, noroviruses)
- Direct transfer from other infected hosts (HIV, hepatitis B)
- Bites of vector arthropods (yellow fever, West Nile virus)
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Describe viral specificity
- Viral attachment to a host cell depends on SPECIFIC INTERACTIONS between the virus and the receptor molecules of the host cell membrane
- molecules of nucleocapsid in naked viruses
- virus membrane in enveloped viruses
- eg. Influenza attaches by its hemagglutinin to sialic acid on cells of mucous membrane and on red blood cells.
- In this process the hemagglutinin binds to sialic acid, conformationally changes to bring the two membranes together, and then fuses them releasing the viral DNA into the cell.
- Only very specific animals (and often cells) are infected.
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Describe viral oncogenes
- Many transforming viruses carry "oncogenes" that cause transformation when incorporated into the host genome
- These have arisen from incorporation of HOST oncogenes into the viral genome during viral replication
- Many sequences are also found in normal human genes
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Generic fungi information
- Eukaryotes that are distinct from plants and animals
- Multinecleate or multicellular organisms with a thick carbohydrate cell wall containing glucans and chitin
- May grow as thread-like hyphae or single cell
- Normal flora (C. albicans) or local infection (skin, hair)
- Pathogenic fungi from the external environment can digest material and take up nutrients directly from host tissue
- Mycology: study of fungi
- Mycoses: fungal infection (plural)
- Mycosis: fungal infection (singular)
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Describe the major groups of disease causing fungi based on growth forms
- Filamentous: grows as the mass of hyphae (mycelium)
- Asexual reproduction results in spores which are a common cause of infection (after inhalation)
- vegetative mycelium - grows out
- aerial mycelium - grows up to release spores
- Yeast-like: grow as a single cell which reproduces by division
- Dimorphic: show both forms in their life cycle
- Many form hyphae at environmental temperatures, but occur as yeast in the host
- Candida is the reverse of the above (thrush is hyphae form)
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Describe the major groups of disease causing fungi based on the type of infection w/ examples
- Superficial mycoses: fungus grows on body surfaces (skin, hair, nails, mouth, or vagina)
- spread by person-to-person contact or from animal-to-human contact
- eg. tinea pedis (athlete's foot) and vaginal candidiasis (thrush)
- Subcutaneous mycoses: fungus infects via skin and grows in nails and deeper layers of skin
- eg. mycetoma (Madura foot) and sporotrichosis
- Systemic or deep mycoses: infects internal organs
- often result from the opportunistic growth of fungi in individuals with impaired immune competence
- primarily acquired via the respiratory tract
- eg. histoplasmosis (breathing in the spores of Histoplasma capsulatum) and systemic candidiasis
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What is a parasite?
An organism (animal) that lives in or on a host organism and gets food from or at the expense of its host
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What are the three main classes of pathogenic parasites in humans with a brief description?
- Protozoa: microscopic, single-celled organisms that can be free-living or parasitic in nature
- Transmission is fecal-oral route (intestinal protozoa) or via arthropod vector (blood/tissue protozoa)
- Helminths: Large, multicellular, parasitic worms
- Microscopic at larval stage, macroscopic at adult stage
- Can be either free-living or parasitic in nature
- Arthropods (ectoparasites): important as vectors of many different pathoges
- blood-sucking arthropods (mosquitos, fleas, ticks, lice, mites) attach or burrow into the skin and remain there for long periods of time
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General information about protozoa
- Single-celled animals, ranging in size from 2-100nm
- Many species are free-living, but others are important parasites of humans
- Protozoal infections are most prevalent in tropical and subtropical regions, but can occur in temperate regions (global warming)
- May cause disease directly (eg. rupture of red cells in malaria), but typically the pathology is caused by host-response
- Malaria presents the most severe global problem of all parasites (>1.5 million deaths each year)
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Intracellular protozoa information + strategies to avoid host responses
- Infects a wide variety of cells (red blood cells, macrophages, epithelial cells, brain, muscle).
- Plasmodium (malaria) and Leishmania (Leishmaniasis) are insect-transmitted
- Toxoplasma (Toxoplasmosis) can be aquired by ingestion of feces from contaminated cat OR from mother in utero
- Antigens of intracellular parasites may be presented at the surface of the host cell, which can then be a target for cytotoxic T cells or TH1 helper cells
- Survival within cells, especially macrophages (Leishmania, Toxoplasma), requires devices to evade/inactivate intracellular enzymes or reactive oxygen and nitrogen metabolites
- eg- Leishmania is covered in lipophosphoglycan to protect against digestion
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Extracellular protozoa information + strategies to avoid host responses
- Lives in the blood, intestine, or genitourinary systemMany are transmitted by ingestion of contaminated food/water
- Trichonomas vaginalis is transmitted through sexual activity
- Trypanosomes are transmitted by insect vectors (T. brucei [sleeping sickness] by Tsetse flies)
- Try to survive by avoiding immune recognition of their plasma membrane by host
- eg - Trypanosomes undergo repeated antigenic variation of surface antigens
- eg - Malaria parasites show polymorphisms in dominant surface antigens
- eg - Amebae can consume complement at the cell surface
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Describe the transmission of helminths
- Swallowing infective eggs or larvae via the fecal-oral route
- Swallowing infective larvae in the tissues of another host
- Active penetration of the skin by larval stages
- The bite of an infected blood-sucking insect vector
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What are the three main groups of human parasitic helminths (w/ examples)?
- Flatworms (platyhelminths): the trematodes (flukes) and cestodes (tapeworms)
- Thorny-headed worms (acanthocephalins): reside in the gastrointestinal tract
- Roundworms (nematodes): reside in the gastrointestinal tract, blood, lymphatic system, or subcutaneous tissues
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General information about helminths
- Greater frequency in tropical and subtropical regions that favor fecal-oral contact, poor practices in food preparation and consumptions, and the availability of suitable vectors
- Greater frequency in children and individuals closely associated with domestic animals
- Many helminths live in the intestine
- Some live in deeper tissues where they actively feed on host tissues or intestinal contents
- For majority sexual reproduction results in the production eggs, which are released from the host in fecal material
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General information about tape worms
- Acquired by eating undercooked or raw meat containing larval stages
- Frequently infect humans
- Relatively harmless despite potential for great size
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General information about schistosomes
- AKA blood fluke
- Most important species of fluke
- Cause of schistosomiasis (disease in millions)
- Three main species - S. haematobium, S. japonicum, S. mansoni
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What are the two ways that arthropods can cause disease?
- Directly by their feeding (blood and tissue fluids)
- Indirectly my transmitting infections
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Describe the arthropods that transmit disease directly by their feeding
- feed on human blood and tissue fluids
- Blood feeders include mosquitoes, midges, biting flies, bugs, fleas, and ticks
- Contact may be temporary or permanent
- Mosquitoes are temporary ectoparasites, feeding for only a few minutes
- Scabies mite Sarcoptes scabiei lives permanently on humans, burrowing into superficial layers of skin to feed and lay eggs. Heavy infections can build up causing a severe inflammatory condition.
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Describe the arthropods that transmit disease indirectly by transmitting infections
- Transmit a wide variety of pathogens (from viruses to worms)
- The ability to transmit infections acquired from animals to humans poses a constant threat of acquiring zoonoses
- Zoonosis: any infectious disease that can be transmitted between species (from animals to humans)
- Reverse zoonosis: from humans to animals
- 61% of pathogens were found to be zoonotic
- Mosquito-transmitted West Nile Virus has become a significant threat in the USA
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General information about prions
- Everyone has the normal form of the prion protein PrP
- It is found on the surface of the brain
- Begins to aggregate when it changes to its misfolded form, interrupt normal brain functions
- Infection occurs when a small amount of misfolded protein is accidentally ingested or introduced into the blood
- Papua New Guinea - devastation due to cannibalism
- Recent concern about the prions that cause mad cow disease infecting humans (cow and human PrP are very similar)
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What characteristics do prions have?
- Small, proteinaceous infectious particles (filterable)
- Extreme resistance to heat, disinfectants, and irradiation
- Susceptible to high concentrations of phenol, periodate, sodium hydroxide, sodium hypochlorite
- Diseases have long incubation period, appear late in life
- Cannot be cultured in vitro (protein)
- Does not elicit immune or inflammatory responses
- Resistant to Proteinase K and detergent insolubility
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What are spongiform encephalopathies? Give examples
- Prion diseases that develop large vacuoles in the CNS
- humans: Kuru ("to shake") and Creutzfeldt-Jakob diseases (CJD)
- cattle: bovine spongiform encephalopathy (BSE)
- sheep: scrapie
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Describe scrapie in detail
- Host-derived glycoprotein termed PrPsc
- derived from natural prion protein PRPc
- Association results from conformational conversion from α-helices to β-sheets
- The PrPsc aggregates into amyloid fibrils and plaques
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Development and transmission of prion diseases in humans
- Origin in human prion diseases may arise from spontaneous mutations
- However, most require exposure to infective agent
- Eating contaminated food material
- Use of contaminated medical products (blood, hormone extracts, transplants)
- Use of contaminated instruments during surgical procedures (prions bind strongly to metal surfaces)
- Possibility of mother-fetus transmission during pregnancy (unconfirmed)
- Eating brains of dead, infected, humans (kuru)
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Describe prions crossing species boundaries
- More effective between the same species, but CAN occur between different species
- eg - cattle with BSE to humans through consumption of meat resulted in vCJD outbreaks
- BSE is a result of transfer from sheep with scrapie to cows
- Human vCJD and BE were caused by the same prion strain
- The number of human infections "Likely" to arise from the BSE cattle in UK is controversial (long incubation time)
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What lessons were learned from/about Kuru?
- Kuru is a disease (shaking, paralysis, death) which was identified with cannabalistic behavior (undercooked brains of relatives) in Papa Nuew Guinea
- More than 2700 infections between 1957-2004
- Incubation time estimated at 50+ years
- Fatality rate fell from 200+/year to 6/year after prohibition of cannibalistic ritual
- Most patients with kuru were heterozygous at codon 129
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Why are prion diseases difficult to diagnose?
- Cannot be cultured
- No immune response
- Early stages CANNOT be diagnosed
- Clinical appearances (memory loss, personality changes, hallucinations, and speech impairment) indicate probability, but CANNOT be confirmed until post-mortem, histology
- A recent test, a conformation-dependent immunoassay, makes use of the abnormal prion RESISTANCE to protease digestion, is more accurate
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Are prion diseases are curable?
- There is no treatment OR vaccine
- Understanding of the nature of the interactions between PrPsc and PrPc may eventually offer hope of regulating/mitigating PrPsc
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