1. 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
  2. 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
  3. 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
  4. 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)
  5. 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)
  6. 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.
  7. 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
  8. 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)
  9. 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)
  10. 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
  11. 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
  12. 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
  13. 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)
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. What are the two ways that arthropods can cause disease?
    • Directly by their feeding (blood and tissue fluids)
    • Indirectly my transmitting infections
  22. 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.
  23. 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
  24. 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)
  25. 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
  26. 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
  27. 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
  28. 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)
  29. 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)
  30. 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
  31. 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
  32. 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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