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Borrelia recurrentis

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1

Borrelia recurrentis

-spirochetes

-Louse-borne relapsing fever

-transmitted to humans by the human body louse (lice)

-recurring episodes of septicemia and fever

-doxycycline or erythromycin -bull's eye rash

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Borrelia Ornithodorus

-spirochetes

-Tick-borne relapsing fever

-soft ticks

-ticks and rodents can be reservoirs

-recurring episodes of septicemia and fever due to body trying to remove the spirochetes

-doxycycline or erythromycin

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Leptospirosis interrogans

-found in wild and domestic animals (zoonotic) -grows in kidney tubules -enters cuts/abrasions in skin and mucous membranes -obligately aerobic bacteria -two axial filaments for movement

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Spirochetes group

-contracted via contact with infected urine or environment -can lead to kidney dysfunction if travels through bloodstream -found only in kidneys -antibody tests for diagnosis -eradication impractical due to the various animal reservoirs

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Vibrios group

-curved rods -darting motility -oxidase positive -polar flagellum for movement -found in water environments -most pathogenic strains prefer warm, salty, alkaline water and can survive in shellfish

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Vibrio cholerae

-can survive in freshwater -particularly O1 El Tor strain -can survive in shellfish -cholera toxin -adequate sewage and water treatment can limit spread -characteristic diarrhea symptoms -can lead to muscle cramping, kidney failure, coma, and death --“rice-water stool”; patient history -fluid and electrolyte replacement for treatment

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Vibrios parahaemolyticus

-results from ingestion of shellfish

-causes cholera-like gastroenteritis

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Vibrios vulnificus

-septicemia due to consumption of contaminated shellfish

-wound infections can result from washing wounds with contaminated seawater

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Campylobacter jejuni

-most common cause of gastroenteritis in the United States -slightly curved, oxidase positive, and motile

-microaerophilic: grows in low O2 and capneic: thrives in high CO2 (how it differs from vibrios)

-zoonotic disease --> poultry, cattle, dogs/cats -adhesins, cytotoxins, and endotoxins

  • self-limiting bloody and frequent diarrhea

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Helicobacter pylori

-slightly helical, motile -urease positive -colonizes in stomach -causes gastritis and most peptic ulcers --can lead to stomach cancer --gastric acid destroys epithelial cells and underlying tissue. -*proteins that inhibits acid production in stomach -flagella help the pathogen to burrow through the stomach lining -adhesins facilitate binding to gastric cells -exotoxins: cytotoxin-associated gene A product (CagA) -portal of entry: mouth -treat with antimicrobial drugs in combination with drugs that inhibit acid production

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Viruses (general)

-cannot carry out any metabolic pathway -neither grow nor respond to the environment

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intracellular state

-capsid removed -virus exists as nucleic acid -virus becomes active

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extracellular state

-called virion -protein coat (capsid) surrounding nucleic acid -nucleic acid and capsid also called nucleocapsid -some have phospholipid envelope -outermost layer provides protection and recognition sites that bind to host cells

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specific hosts

-only infect particular kind of cell in a particular host

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general hosts (generalists)

-infect many kinds of cells in many different hosts including bacteria, archaea, protozoa, fungi, plants, animals and humans. **ex: influenza virus, West Nile virus

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enveloped virion

-a virus with an outer envelope surrounding the capsid

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non-enveloped or naked virion

-virion without an envelope

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matrix proteins

-fill the region between capsid and envelope

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lysogeny

-modified replication cycle -infected host cells grow and reproduce normally for generations before they lyse -temperate phages or lysogenic phages -basically, it involves the incorporation of the viral genome into the host cell genome, infecting it from within

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attachment of animal viruses

-direct penetration -membrane fusion -endocytosis

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synthesis of animal viruses

-DNA viruses often enter the nucleus, except poxviruses -RNA viruses often replicate in the cytoplasm

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replication of dsDNA viruses

dsDNA --> mRNA --> viral proteins

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replication of ssDNA viruses

ssDNA --> dsDNA --> mRNA --> viral proteins

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replication of retroviruses

+ssRNA --> +ssRNA --> DNA --> viral proteins --> (acts as mRNA)

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assembly and release of animal viruses

-enveloped viruses cause persistent infections -naked viruses are released by exocytosis or lysis

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culturing viruses in the laboratory

  1. culturing viruses in mature organisms -lysis of bacteria produces plaques --allows estimation of phage numbers by plaque assay

  2. in embryonated chicken eggs -inexpensive, among the largest of cells, free of contaminating microbes, and contain a nourishing yolk

  3. culturing viruses in cell tissue -diploid cell cultures --created from embryonic plant, animal or human --do not last more than 100 generations -continuous cell cultures --longer lasting --derived from tumor cells (HeLa)

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Vibrio cholera

-can survive in freshwater -causes cholera (particularly O1 El Tor strain) -can survive in shellfish -cholera toxin -adequate sewage and water treatment can limit spread -characteristic diarrhea symptoms -can lead to muscle cramping, kidney failure, coma, and death --“rice-water stool”; patient history -fluid and electrolyte replacement for treatment

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Vibrios vulnificus

-septicemia due to consumption of contaminated shellfish -wound infections can result from washing wounds with contaminated seawater

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Vibrios parahaemolyticus

-results from ingestion of shellfish -causes cholera-like gastroenteritis

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Campylobacter jejuni

-most common cause of gastroenteritis in the United States -slightly curved, oxidase positive, and motile -microaerophilic: grows in low O2 and capneic: thrives in high CO2 (how it differs from vibrios) -zoonotic disease --> poultry, cattle, dogs/cats -adhesins, cytotoxins, and endotoxins

  • self-limiting bloody and frequent diarrhea

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Helicobacter pylori

-slightly helical, motile -urease positive -colonizes in stomach -causes gastritis and most peptic ulcers --can lead to stomach cancer --gastric acid destroys epithelial cells and underlying tissue. -*proteins that inhibits acid production in stomach -flagella help the pathogen to burrow through the stomach lining -adhesins facilitate binding to gastric cells -exotoxins: cytotoxin-associated gene A product (CagA) -portal of entry: mouth -treat with antimicrobial drugs in combination with drugs that inhibit acid production

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intracellular state

-capsid removed -virus exists as nucleic acid -virus becomes active

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extracellular state

-called virion -protein coat (capsid) surrounding nucleic acid -nucleic acid and capsid also called nucleocapsid -some have phospholipid envelope -outermost layer provides protection and recognition sites that bind to host cells

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enveloped virus

-a virus with an outer envelope surrounding the capsid

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non-enveloped or naked virion

-virion without an envelope

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matrix proteins

-fill the region between capsid and envelope

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lysogeny

-modified replication cycle -infected host cells grow and reproduce normally for generations before they lyse -temperate phages or lysogenic phages -basically, it involves the incorporation of the viral genome into the host cell genome, infecting it from

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38

synthesis of animal virus

-DNA viruses often enter the nucleus, except poxviruses -RNA viruses often replicate in the cytoplasm

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replication of dsDNA viruses

dsDNA --> mRNA --> viral proteins

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replication of ssDNA viruses

ssDNA --> dsDNA --> mRNA --> viral proteins

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replication of retroviruses

+ssRNA --> +ssRNA --> DNA --> viral proteins --> (acts as mRNA)

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42

assembly and release of animal viruses

-enveloped viruses cause persistent infections -naked viruses are released by exocytosis or lysis

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43

culturing viruses in the laboratory

  1. culturing viruses in mature organisms -lysis of bacteria produces plaques --allows estimation of phage numbers by plaque assay

  2. in embryonated chicken eggs -inexpensive, among the largest of cells, free of contaminating microbes, and contain a nourishing yolk

  3. culturing viruses in cell tissue -diploid cell cultures --created from embryonic plant, animal or human --do not last more than 100 generations -continuous cell cultures --longer lasting --derived from tumor cells (HeLa)

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DNA viruses (except poxviruses) often enter/replicate...

in the nucleus

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RNA viruses often replicate..

in the cytoplasm

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viroids

-extremely small, circular pieces of RNA that are infectious and pathogenic in plants -similar to RNA viruses, but lack capsid -may appear linear due to hydrogen bonding within the molecule

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prions

-poteinaceous infectious agents first described by Stanley Prusiner in 1982 –lack nucleic acid -prion prp converts cellular prp (alpha helices) into beta-sheets

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prion diseases

-fatal neurological degeneration, fibril deposits in brain, and loss of brain matter -large vacuoles form in brain -characteristic spongy appearance ---spongiform encephalopathies – bovine spongiform encephalopathy, creutzfeld jakob disease, scrapie, kuru -transmitted by ingestion, transplantation, or contact of mucous membranes with infected tissues -prions only destroyed by incineration or autoclaving in 1 N NaOH or by prionzyme -no treatment

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Poxviridae group

-dsDNA -complex capsids and envelopes -largest human pathogenic viruses; infects mammals -species specific -infection through close contact (inhalation)

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Smallpox (variola)

-virus moves via the blood to the skin, where it produces

-scars result on the skin, especially on the face (lesions)

-infects internal organs, causing fever, malaise, and delirium

  1. macule

  2. papule

  3. vesicle

  4. pustule

  5. crust

  6. scar

-the first human disease to be eradicated

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Factors that enabled the eradication of smallpox

  1. Inexpensive, stable, and effective vaccine

  2. No animal reservoirs

  3. Obvious symptoms allow for quick diagnosis and in quarantine

  4. Lack of asymptomatic cases

  5. Virus is only spread via close contact

  6. Stocks of the virus are maintained in laboratories in the U.S. and Russia

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Molluscum Contagiosum (Molluscipoxvirus)

-skin disease characterized by pearly white to light pink, smooth, waxy papules (appear tumor-like)

-typically on face, trunk, and external genitalia

-spread by children, sexually active ppl, or ppl AIDS

-treatment by removing nodules

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Herpesviridae group

-enveloped polyhedral capsids and linear dsDNA -viral envelope fuses with the cell membrane to facilitate entry into cell -latent --virus enters sensory nerve cells and remains inactive inside infected cells --reactivation causes recurrence of the disease manifestations

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Human Herpesviruses 1

-typically occur via casual contact in children -often result in slow-spreading skin lesions -oral herpes

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Human Herpesviruses 2

-infections occur between ages of 15 and 29 from sexual activity -often result in slow-spreading skin lesions -genital herpes

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Infections of Human Herpesviruses 1 and 2

-infected cells fuse with neighboring uninfected cells to form syncytium which helps in cell to cell spread -after a primary infection, viruses remain latent in ganglia -ocular condition -whitlow (inflammation of blisters) -neonatal condition -treatment: nucleoside analogs (not a cure)

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Human Herpesvirus 3 (Varicella-Zoster Virus)

-causes chicken pox, found in children

-or causes shingles in adults

-chicken pox is highly infectious disease

-virus enters skin through the respiratory tract or eyes

-characteristic skin lesions (dew drops on rose petals)

-characteristic localization of shingle lesions along a band of skin, called a dermatome

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Human Herpesvirus 4 (Epstein-Barr Virus) (EBV)

-transmission occurs via saliva

-large lobed B lymphocytes with atypical nuclei and neutropenia are characteristic features of infection

-causes:

-oral hairy leukoplakia,

-burrito's lymphoma,

-nasopharyngeal cancer,

-chronic fatigue syndrome,

-Burkitt's lymphoma: swollen jar

-infectious mononucleosis: swollen lymph nodes

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Human Herpesvirus 5 (Cytomegalovirus) Infections

-infected cells become abnormally enlarged (owl’s eye)

-transmission occurs through bodily secretions

-requires close contact and a large exchange of secretion

--(sexual intercourse, in utero exposure, vaginal birth, blood transfusions, and organ transplants)

-complications in fetuses, newborns, and immunodeficient patients

-treatment: Fomiversen for eye infections

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Human herpesvirus 6 (HHV-6)

-causes roseola

-characterized by pink rash on face, neck, trunk, and thighs

-may be linked to multiple sclerosis

-can cause mononucleosis-like symptoms

-may make individuals more susceptible to AIDS

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Human herpesvirus 8 (HHV-8, Rhadinovirus)

-associated with Kaposi’s sarcoma, a cancer often seen in AIDS patients

-it is a rare and malignant neoplasia of blood and blood vessels

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Papillomavirus

-causes warts

--seed warts, plantar warts, flat warts, genital warts (condylomata acuminata)

-genital warts associated with an increased risk of cancer

-transmitted via direct contact and via fomites

-diagnose cancers by inspecting genitalia and by a PAP smear

-gardasil vaccine (three doses for all females 11-26 yrs of age) effective against most strains of cervical cancer

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Polyomavirus

-capable of causing tumors in animals and humans

--BK virus: potentially severe urinary tract infections can develop

--JC virus: can cause progressive multifocal leukoencephalopathy in which viruses can infect and kill oligodendrocytes of CNS

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Adenoviridae group

-contain single, linear dsDNA genome contained in a naked polyhedral capsid with spikes

-one of many causative agents of the “common cold”

-respiratory infections

-infection of the intestinal tract can produce mild diarrhea

-infection of the conjunctiva can result in pinkeye

-gamma interferon treatment

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Hepadnaviridae group

-invade and replicate in liver cells -unique genome that is composed of both single’ and double-stranded DNA -replicates through an RNA intermediary by using reverse transcriptase enzyme

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Hepatitis B

-causes hepatitis (inflammation of the liver)

-the only DNA virus that causes hepatitis

-jaundice, a yellowing of the skin and eyes, occurs when bilirubin accumulates in blood

-liver cells continually release virions into the blood

-virions are shed into saliva, semen, and vaginal secretions

-transmitted when infected body fluids contact breaks in the skin or mucous membranes

-can lead to liver cancer

-virus spread through infected needles, sex, and passage to babies

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Hepatitis B (2)

-diagnose by detecting presence of viral antigens

--dane, spherical, and filamentous particles for diagnosis

-alpha-interferon treatment

-liver transplant required for end-stage chronic disease

-3 doses of vaccination

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Parvoviridae group

-only human pathogen with a ssDNA genome

-smallest of the DNA viruses

-B19 virus is the primary parvovirus of humans

--causes erythema infectiosum

-results in a reddening of the skin beginning on cheeks

-also called fifth disease or slapping disease

-the other four diseases that cause rashes are scarlet fever, rubella, roseola, and measles

-sunlight aggravates condition

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many RNA viruses

have a segmented genome: more than one molecule of RNA

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Picornaviridae group

-naked, +ssRNA viruses

-smallest of the animal viruses

-comprises of several genera: enterovirus, hepatovirus and rhinovirus

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rhinoviruses

-cause most cases of the common cold (along with adeno-, corona-, reo-, & paramyxoviruses)

-infections limited to the upper respiratory tract (33°C)

-a single virus is often sufficient to cause a cold

-pleconaril can reduce the severity and duration of colds

-handwashing!!

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enteroviruses

-transmitted via the fecal-oral route -ingestion of contaminated food or water -infect the pharynx and intestine -cytolytic -three main viruses: --polioviruses, coxsackieviruses, and echoviruses

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polioviruses

-causes poliomyelitis

--asymptomatic infections (almost 90%)

--minor polio (5%): fever, headache, sore throat

--nonparalytic polio (2%)

--paralytic polio (less than 2%)

---bulbar poliomyelitis (brain stem and medulla are infected)

--postpolio syndrome 2 vaccines:

-inactivated polio vaccine (IPV)

-oral polio vaccine (OPV)

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Hepatitis A

-naked, +ssRNA virus

-noncytolytic picornavirus

-transmitted through the fecal-oral route

-signs and symptoms: fever, nausea and jaundice are due to the patient’s immune response

-does NOT cause chronic liver disease

-enteric: contaminated food/water/etc

-two doses are recommended for all children and adults

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Caliciviruses and Astroviruses

-naked, +ssRNA virus

-star-shaped polyhedral capsids

-causes acute gastroenteritis

-outbreaks in day care centers, schools, hospitals, cruise ships

-best known virus is: Norovirus --causes diarrhea, nausea and vomiting

-incubation period is 24 hrs

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Hepatitis E

-naked, +ssRNA virus

-also known as enteric hepatitis

-fatal in 20% of pregnant women

-prevent by interrupting the fecal-oral route of transmission

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Togaviridae and Flaviviridae group

-enveloped, +ssRNA virus

-designated as Arboviruses (Arthropod-borne)

-mosquitoes and ticks transmit arboviruses among animal hosts causing zoonotic diseases

-arthropod vectors remain infected

-most infections result in mild, flu-like symptoms

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Togavirus

-enveloped, +ssRNA virus

-equine encephalitises

-eastern equine encephalitis (EEE)

-western equine encephalitis (WEE)

-venezuelan equine encephalitis (VEE)

-viral replication occurs in horses and humans

-normal host is a bird or rodent

-mosquitoes are vectors

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Rubella virus (Togaviridae)

-enveloped, +ssRNA virus

-also called “German measles” or “three day measles” (mild)

-one of the five childhood diseases that produces skin lesions (other four are measles, roseola, chickenpox, fifth disease)

-infection begins in respiratory system but spreads throughout the body

-rash of flat, pink to red spots

-not serious in children, but adults can develop arthritis or encephalitis

-infection of pregnant women can cause congenital defects

-vaccination

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Flavivirus

-enveloped, +ssRNA virus

-causes West Nile Encephalitis

-flu-like symptoms and encephalitis after being bitten by mosquitoes

-Aedes mosquito transmits virus that causes dengue fever

-first phase of high fever and severe pain in head, neck and muscles (breakbone fever)

-second phase: return of fever and bright red rash

-reinfection causes dengue hemorrhagic fever

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Yellow fever virus (Flaviviridae)

-involves degeneration of the liver, kidneys, heart and massive hemorrhaging resulting in “black vomit”

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Chickengunya virus (Flaviviridae)

-rash, nausea, joint pain

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Zika virus (Flaviviridae)

-fever, rash, joint pain, microencephaly

-diagnosis by serological tests like ELISA and agglutination test

-prevention by vaccination for Yellow fever

-no vaccine

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Hepatitis C (Flaviviridae)

-enveloped, +ssRNA virus

-spread through needles, organ transplants, and sexual activity but not by arthropod vectors

-chronic infection with few if any symptoms

-severe liver damage and liver failure can occur over time

-sofosbuvir (inhibits protease) cures most people within 12 weeks

-no vaccine

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Coronaviridae group

-enveloped, +ssRNA virus -corona-like halo formed by their envelopes -transmitted via large droplets (coughing, sneezing, talking, breathing) from the upper respiratory tract -second most common cause of colds *three main viruses: -severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and COVID-19 (SARS-CoV2) -zoonotic disease -distinctive envelopes with glycoprotein spikes that resemble flares from the corona of the sun

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ACE-2 receptor is present

on lung, heart, brain, kidney, gastro-intestinal cells as well as cells of blood vessels and testis

-promotes viral reuptake and fusion at the cellular membrane

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coronavirus virion and life cycle

• coronavirus particles bind to cellular receptors (such as angiotensin-converting enzyme 2 (ACE2)) promote viral uptake and fusion at the cellular or endosomal membrane • following entry, release and uncoating of the incoming genomic RNA takes place • after translation of structural proteins, they translocate into endoplasmic reticulum (ER) membranes and transit through the ER-to-Golgi intermediate compartment (ERGIC) • finally, virions are secreted from the infected cell by exocytosis

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pathogenesis of COVID-19

-blood clotting abnormalities -neurological complications -cardiovascular disease (cytokine storm) -gi complications -renal failure (cytokine storm)

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COVID-19 vaccines

-mRNA vaccines (moderna, pfizer) --two dose vaccines 21-28 days apart -inactivates SARS-CoV-2 vaccine --covaxin (developed in India) --sinovac (developed in China)

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COVID-19 treatment

monoclonal antibody therapy:

-Eli Lily and Co

-Regeneron

-Mabs

Antivirals: -Remdesivir: nucleoside analog and inhibits the RNA-dependent RNA polymerase -Ritonavir (oral) -Molnupiravir increases the frequency of viral RNA mutations and impairs replication

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Retroviridae group

-enveloped, +ssRNA viruses with reverse transcriptase

-genomes contain two identical molecules of positive ssRNA and contain the enzymes reverse transcriptase, protease, and integrase

-transcribe dsDNA from ssRNA using reverse transcriptase

--Human T-lymphotrophic viruses: cancer of lymphocytes

-Lentivirus human immunodeficiency viruses (HIV-1 & 2)

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Acquired Immunodeficiency Syndrome (AIDS)

-certain opportunistic or rare infections that occur in the presence of antibodies against HIV and a CD4 white blood cell count below 200 cells/microliter of blood

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Human Immunodeficiency Syndrome (HIV)

-likely arose from mutation of simian immunodeficiency virus, emerged in human population in Africa in about 1930 -only replicates in humans and destroys the human immune system

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HIV-1

-prevalent in the United States and Europe

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HIV-2

-prevalent in West Africa

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gp120 (HIV)

-primary attachment molecule, responsible for antigenic variability, binds to CD4 receptor molecules on a host cell

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gp41 (HIV)

-promotes fusion of the viral envelope with the target cell, forms syncytium

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Immunosuppressive Retroviruses (Lentivirus) and AIDS

details of synthesis and latency

  1. reverse transcriptase transcribes dsDNA from ssRNA --antigenic variants of HIV result from errors introduced in the genome during transcription

  2. dsDNA provirus enters the nucleus --viral integrase inserts provirus into a human chromosome --integrated DNA passed to progeny cells during replication --provirus can remain dormant for years -macrophages and monocytes are major reservoirs

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Immunosuppressive Retroviruses (Lentivirus) and AIDS (2)

details of release, assembly, and maturation

  1. HIV exits cell at lipid rafts in the cytoplasmic membrane --lipid raft components become the viral envelope

  2. capsomeres form immature capsid outside the cell

  3. viral protease releases proteins that produce a mature virus --protease inhibitors used to treat HIV

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Diseases associated with AIDS

-herpes -kaposi's sarcoma

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