Week 1 Flashcards
Organisms that make up the scope of medical microbiology
Viruses, bacteria, fungi and parasites
Different morphologies that are characteristic of bacteria
Spherical- coccus rod- bacilli, spiral- spirochetes
Bacteria may be seen as individual cells in pairs or as chains of connected cells
All bacteria have a diameter of roughly 1 to 2 micrometers
Bacterial cell walls/envelopes
Cell envelope= cytoplasmic membrane and cell wall
Cytoplasmic membrane- no sterols, integral and peripheral membrane proteins
Bacterial cell wall- composed of peptidoglycan n-acetylmuramic acid+ N-acetylglucosamine
Gram positive vs gram negative
Gram positive- thick cell wall, retention of crystal violet, cell wall contains teichoic acids attached to either the cell membrane or the cell wall
Gram negative- thin cell wall, extraction of crystal violet, consists of outer and inner membrane, periplasm contains peptidoglycan layer
Outer leaflet of outer membrane (GRAM -)
LPS: lipid A (embedded in the outer membrane), core polysaccharide, and O antigen to provide serum resistance and antibody recognition
LPS (lipid A)- endotoxin that at low doses causes fever, complement mediated lysis, B cells, macrophages, and acute phase response, at high doses causes septic shock, hypotension, and circulatory collapse
Peptidoglycan
Cross linkages of N-acetylglucosamine, and N-acetylmuramic acid
The third amino acid of some tetrapeptide is crosslinked to the terminal amino acids of other tetrapeptide
Penicillin binding protein- responsible for synthesis of side chains
Vancomycin- binds the side chain preventing crosslinking
Virus
Not cells, metabolically inert
Extracellular form- composed of set of genes protected by a protein containing coat
HIV life cycle
DNA copy of the retroviral genome is made and inserted into the genome of infected cells, proviral DNA is transmitted to all daughter cells, and in some cases is translated. Viral antigens attempt to remove the protein products but offer no response to latent infection
AIDS developement
HIV is actively replicating in lymphoid tissues. CD4 T cells are turning over at an accelerated rate due to immune response during period of clinical latency. AIDS onset is marked by the inability of the immune system to eliminate the virus thus leading to opportunistic infection
Zoonosis
A disease communicable to humans by other animals
Evidence- geographic coincidence, phylogenetic relatedness, prevalence in the natural host, plausible routes of transmission
Ex. HIV, SARS, West Nile Virus
Arbovirus
Insect vector that transmits disease to a single species and feeds off a second host
West Nile Virus and Japenese Encephalitis virus (flavivirus), Eastern equine encephalitis virus (flavivirus)
SARS transmission
coronavirus zoonotic transmission from civets, contagious and sometimes fatal respiratory illness, propagated via superinfectors
Viral replicative strategies
Double stranded DNA virus: Immediate Early Proteins, Early Proteins, Late Proteins
Single strand positive sense RNA viruses: replicated antisense mRNA plus protein cleavage
Single strand negative sense RNA viruses: Virus proteins and sense RNA
Retrovirus: RT to ds DNA transcribed into mRNA, translated and replicated
Types of viral infection
Productive infection- full viral replicative cycle and viral progeny are produced
Abortive infection- viral genes are expressed but infectious progeny do not result, cell dies
Latent infection- viral genome is established inside the cell, some genes may be expressed, cell remains viable
Requirements of productive replicative cycle
Attachment, Penetration, Disassembly/release of genome, Eclipse or Replication, Assembly, Release from cell
Properties of Virus
Virion Size
Virion shape and symmetry (icosahedral, helical, complex)
Numbers and sites of morphological units in the capsid
Presence or absence of a lipid protein envelope
Similarities and differences between enteric and respiratory viruses
Route of entry: mouth/intestinal tract versus respiratory
Trigger mechanism: acid independent versus acid dependent
Primary disease: gasteroenteritis, poliovirus, neuroinvasive versus common cold, respiratory tract infection, encephalitis, mumps, rubella
enteroviruses are naked icosahedral rna’s
Virus entry mechanisms/triggers
Norovirus- naked, cell-surface recptors
Rotavirus- no acidic trigger, relies on proteolysis for trigger, cell surface receptors have not been identified
Poliovirus- CD155 receptor, receptor binding triggers conformational change in capsid shell that forms pore
Virus evasion of innate immune response
Rotavirus- has dsRNA, transcription and processing of +ssRNA occurs while they are extruded through channels of the double layered- particle thus avoiding dsRNA
Poliovirus- dephosphorylation of cab binding protein, stops translation accumulates vesicles and disrupts Golgi, virus maintains translation via IRE’s (cap-inpendent).
Viral gene expression strategies
Rotavirus- viral rna have high affinity with ribosome and translation initation factors
Poliovirus- polyprotein with autocatalytic activity, cap-independent translation, inhibts PKR and TATA binding protein
Structural components of virion (HSV)
Core- viral DNA (double stranded linear), tighly packaged
Capsid- 125 nm diameter icosahedron
Tegument- Viral proteins located between capsid surface and envelope, gets injected into cell, subverts normal cellular function
VHS- virion host shutoff
VP16- transcription factor promotes viral gene expression
Envelope- Lipid bilayer composed of membrane proteins and glycoproteins
Latency
Virion latent within neurons (HSV) or B lymphocytes (EBV), exists as an autonomous episome, reactivation occurs post-stress
Acyclovir
Treatment for herpes infection (used more for life-threatening HSV, severe cases of varicella)
Mechanism- Thymidine kinase (viral in origin) phosphorylates acycloguanosine, cellular polymerases phosphorylates twice more, terminates herpes DNA polymerase, only works for nonlatent cells
Primary versus Secondary Hosts
Primary- Species that maintains virus in nature. Typically experiences relatively benign recurrent infections resulting from successful establishment of latency.
Secondary- Virus causes a typically fatal encephalitis
Shingles vs Zoster
Zoster
Mode of transmission- respiratory droplets, person-to person contact, transfer of secretions
Replication of virus in the spleen and liver infecting leukocytes, virus is carried to capillary endothelial cells to epithelium leading to lesions on skin and mucosa
Shingles- seeding of virus in peripheral sensory ganglia (DRG) leads to pain in the dermatome corresponding to the spinal level of the infected ganglia
HPV
Transmission: direct contact with infected tissues or secretions
Proliferation of cells in basal layer of skin and mucosa
Basal layers do not produce viral progeny
As infected cells differentiate and move to surface, malginant transformation occurs as viral progeny is created and released
Viral genome integration is a requirement for malignancy ie. E6 and E7
EBV
Structure: large linear DNA, uses both cell and virus encoded polymerase
Two important genes: LMP1- virus transforming protein, and LMP-2- blocks B cell differentiation
Transmission: saliva, infects oropharynx epithelia
B cells are infected and induced to proliferate, some are latently infected so T cell response is not completely effective
Mechanism of gene disruption- c-myc translocation
Disease caused- Burkitt’s lymphoma, non Hodgkin’s lymphoma, nasopharyngeal carcinoma
HBV cancers
HCV cancers
hepatocellular carcinoma caused by immune response
hepatocellular carcinoma and cirrhosis
Merkel Cell Carcinomas (an agressive skin cancer seen in elderly or immunosuppressed)
80% of MCC tumors express Merkel Cell Virus
Virus- circular episome
Clonal integration of the genome into T antigen leads to a mutagenic event that induces MCC
PKR mechanism
PKR binds viral RNA–> Activates–> Phosphorylates EIF2–> Inhibits translation iniation
This mechanism is inhibited by poliovirus
Common cold
Adenovirus, Picornavirus, Coronavirus, Respiratory syncitial virus (does not produce durable immunity NOT due to antigenic variation)
