chp 11

DNA is a double stranded helical structure.
?It is composed of nucleotides.
?Each nucleotide is a
phosphate, a sugar (deoxyribose), and a nucleotide base.
The components of DNA bind together in a very specific way.
?This permits a ____ and ______ orientation of the nucleotide
correct and precise
Nucleotides join to each other to form a chain.
?The ___________ of a sugar joins to the __________ of another nucleotide.
?This makes the linkage inherently polarized
?And gives structural orientation to the growing chain.
3′ hydroxyl group
5′ hydroxyl group
adenine and guanine
are large double-ring structures
DNA has two types of base
?Purines
thymine and cytosine
have smaller single ring structures.
DNA has two types of base
Pyrimidines –
DNA STRUCTURE:
the strands are ____
one strand is orientented upsidedown relative to the other
antiparallel
DNA is a chemically stable molecule.
Any mismatched pairing is
chemically unstqable
is ususally found in single strand form
contains ribose
RNA
helps maintain the proper shape of ribosomes.
rRNA (ribosomal RNA
contains information derived from DNA (the messenge from the DNA that says this is what you make)
mRNA (messenger RNA)
–carries amino acids to ribosomes
?Transfer RNA
how DNA is copied
incrediably accurate and fast
critical cellular process
DNA replication
occurs when the helix twists around itself
must be relaxed
is a characteristic of helical structures (because of this everything has to loosen up (unwound) b4 you can replicate).
supercoiling
Strands must be uncoiled, unwound, and separated before replication.
?This is accomplished by two enzymes:
topoisomerase and helicase
–unwinds the supercoils
unwinds the supercoils by breaking the DNa so the supercoil relaxes, and then resealing the break
?Topoisomerase
–once the supercoiling has been relaxed this enzyme separates and unwinds the strands
?Helicase
would produce two copies that each contained one of the original strands and one new strand.
cause you are conserving half
semiconservative replication
There are two requirements for replication:
An ample supply of each of the nucleotides adenine, thymine, cytosine, and guanine
A primer: template junction
( a sequence that tells replication to begins/ you have to have a starting point for replication)
A primer: template junction
eacxh single strand of DNA is a
template
a portion of DNA is paired w/ a short piece od RNA called a ________
primer
DNA replication is
unidirectional (preceeds in one direction)
gives the DNA polymerase (adds a lot of nucleotides to a strand of DNA) a place to add the next base
Binding is between the 3’end of one base and the 5’ end of the next base
the primer:template junction
DNA REPLICATION:Direction
Elongation of the bases is from the 3’ end
This is required for
chemical stability
?The binding of a new base uses energy released from
pyrophosphate
DNA replication is performed this enzyme
forms new strands of DNA using the primer: template junction as a guide.
DNA polymerase
aids in accurate replication
takes place @ the primer:template junction active site
proofreading
with proofreading improperly paired bases are removed by an _____ (cuts out a nucleotide)
exonuclease
the double helix is unwound and seperated here
DNA rep occurs here
replication fork
The separated strands at the replication fork are anti-parallel and are identified as:
leading strand and the lagging strand
The leading strand is in the correct orientation for bases added to the 3’ end of the primer: template junction.
?Replication moves towards the
replication fork
is anti-parallel.
?It moves away from the replication fork.
?Bases are only added to the 3’ end of the primer: template junction
is replicated in pieces called Okazaki fragments
the lagging strand
each _____ has its own short RNA primer.
It is created by an RNA polymerase called primase.
okazaki fragment
When the fragment is finished, the enzyme _______ removes the primer.
The gap is filled in by DNA polymerase.
Fragments are linked together by DNA ligase-
RNAase H
(its job is to join together fragments of DNA/ DNA glue/ glue DNA pieces together because of DNA and okaski fragments need to be attached)
DNA ligase
INITIATION AND TERMINATION OF REPLICATION:
Initiation begins at a specific site on the chromosome: the _________
orgin of replication
INITIATION AND TERMINATION OF REPLICATION:
Termination occurs when the entire chromosome has been
copied
INITIATION AND TERMINATION OF REPLICATION:

?Replicated chromosomes are separated by ________

topoisomerase.
always read in one direction
The message is translated in a fixed reading frame
There is no overlap or gap in the code
codons
a segment of DNa that codes for a functional product
gene
is the production of the functional product
two features:
it involves specific interactions between DNA and RNA
it is highly regulated
gene expression
?It does not require a primer: template junction.
?RNA does not remain base-paired to DNA.
?It is not as accurate as DNA synthesis (because the RNA polymerase doesn’t have any proofreading).
transcription
three steps to stranscription
initiation elongation and termination
RNA polymerase unwinds strands of DNA and synthesizes the RNA:
It also re-anneals the strands( it puts the strands back together).
elongation
a sequence of DNA signals the end of transcription:
RNA polymerase detaches from DNA
termination
a DNA sequence called the promoter initially binds the RNA polymerase:
This produces a bubble in the DNA.
initiation
The sequence of nucleotides in messenger RNA is transformed into a sequence of amino acids.
It is directly affected by any errors in either DNA or RNA
translation
It is a highly conserved (all cells do it) function seen in all cells.
It requires high levels of energy.
requires all three types of RNA –messenger, transfer, and ribosomal
Translation
indicates the start of an amino acid sequence.
begins with a start codon.
Translation moves from the 5’end to the 3’ end.
ends with a stop codon
An open reading frame (ORF)
mRNA in translation:
mRNA contains a segment that recruits the ribosomal subunits.
Ribosome and mRNA bind here through _______
complementary base pairing
tRNA in translation:
Each tRNA attaches to a specific amino acid at the __________
acceptor arm
It brings amino acids to the ribosome.
It binds to the ribosome at the anti-codon region using complementary base pairing
acceptor arm
The ribosome is a honeycombed structure with tunnels. ?The components of protein synthesis enter these tunnels and move through them. ___ ________ ___________
?mRNA ?tRNA ?Growing polypeptide chain
3 stages of translation
initiation elongation and termination
requires:
Recruitment of the ribosome to the mRNA
placement of a methionine tRNA complex at the P site
Precise positioning of the ribosome over the start codon of mRNA.
initiation in translation
, three things must occur in order for amino acids to be added to methionine.
A tRNA carrying the next amino acid is loaded into the A site.
A peptide bond forms between the amino acids.
Each tRNA moves (out one moves in)–the one at the A site to the P site, the one at the P site to the E site.
elongation:
after initiation
in elongation the ________ moves along the mRNA
ribosome
Translation continues until a stop codon enters the A site.
?Stop codons are recognized by specialized proteins.
?These specialized proteins cause the translation complex to fall apart.
termination
during termination the peptide achain is released from the ribosome and begins to form ___________ and __________ structures
seconday and tertiary
is energetically expensive and highly regulatied:
constituative genes
repressible genes
inducible genes
regulation of gene expression:
protein synthesis
Some genes are on and can be turned off – (can turn off when need to).
repressible genes
Some genes are always turned on – (always on).
constitutive genes
Some genes are off and can be turned on –(can be turned on when needed)
inducible genes
Gene expression is controlled by regulatory proteins:
_______. _____,
activators, repressor
Gene expression is controlled by regulatory proteins:
_______. _____,
activators, repressor
nvolved in positive regulation
DNa binding protein
activators
invovlved in negative regulation
are DNA binding protein
repressors
Regulatory proteins recognize two sites on DNA near the genes they control.
the promoter and the operator
where the RNA polymerase binds. is adjacent to the operator
the promotor
where regulatory proteins bind. adjacent to the promoter
the operator
turns on genes that are off (repressed).
?The best example is the lac operon:
induction
an _____ is a set of genes that is regulated.
?There are many in the chromosome
operon
The lac system has two regulatory proteins
Both proteins bind at the operator site on DNA
the lac repressor and the lac activator- CAP (caraboilte activator protein)
is always produced.
?It binds at the operator site and overlaps part of the promoter site
the lac repressor
The lac repressor binds @ the operator site and overlaps part of the promoter site:
this blocks the RNA polymerase from _______
this prevents transcription of the _______
attaching
lac gene
also binds at the operator site
?It recruits RNA polymerase to the site.
?It then interacts with the polymerase so it binds properly
cap
For the genes of the lac operon to be turned on, the repressor must first be _____
occurs through an allosteric control mechanism
inhibited
it then interacts w/ the polymerase so it binds properly
expression of lac Operon:
allosteric control mechanism
The expression of lac genes is leaky
?A few transcripts are made and there is always a low level of ______
?This allows small amounts of __________ into the cell.
?-galactosidase
lactose
the expression of the lac gene is leaky:
Lactose is converted to ______.
?_______ binds the lac repressor.
allolactose
The expression of lac genes is leaky
?A few transcripts are made and there is always a low level of ?-galactosidase.
?This allows small amounts of lactose into the cell.
?Lactose is converted to allolactose.
?Allolactose binds the lac repressor.
?This changes the shape of the lac repressor and it _________________________________
can no longer bind to the operator site
acts in a similar fashion to allolactose.
?Its activity is based on levels of cyclic AMP (cAMP).
CAP
When cAMP levels rise, cAMP binds to ____
CAP
cAMP binding to CAP:
causes a change to the _______ shape of cap
the cap-cAMP complex binds to the promoter site of the ________
this helps the RNA polymerase to bind to the _______
the lac genes are expressed
3 dimensional
lac operon
promoter site
When cAMP levels fall, ___________
?RNA polymerase does not bind to the promoter site.
?The lac genes are not expressed
no complex is formed.
There are also cellular mechanisms that turn off genes.
?This is very important for the conservation of energy.
has similar mechanisms to feedback inhibition
repression
ex of repression ______ synthesis:

repressor is always produced but cannot bind DNA in its normal form.
?Excess binds the repressor and changes its shape so it can bind DNA and prevent gene expression.
?is a co-repressor of its own synthesis

tryptophan
are changes in the DNA sequence.
?Change in DNA sequence can cause changes in proteins.
so they must be kept to a minimum
mutations
simplest mutation
one base switched for another
point mutation

drastic mutation caused by the insertion or deletion of bases

 

 

¿This is caused by large insertion or deletion of bases
(things that are going to change the reading frame) change how you will read the message and change what it’ll become in the end

frameshift mutations
rates are low
certain sections oof the chromosome have higher rate (hot spots)
spontaneous mutations

can reverse the primary mutation

instead of making a faulty protein you dont make a protein @ all

suppressor mutations
by:
?Hydrolysis
?Deamination
?Chemical mutagens
?Alkylation
?Oxidation
?Base analogs
?Radiation
DNa can be dammaged
cause double-strand breaks in DNA.
gamma radiation and ionizing radiation

causes DNA damage through the formation of thymine dimers.

 

(big gap skipping 2 nucleotides/ reading frame mutations)

ultraviolet radiation
damage to DNA that prevents replication
radiation
look like DNA bases but aren’t.
?They can be mistakenly used in replication.
?This inhibits further replication.
base analogs
what are the 3 principle mechanisms of DNA repair
nucelotide excision, base excision and photoreactivation
?Repair enzymes look for damaged bases.
?The damaged base is removed from the double helix.
?A DNA polymerase fills in the gap.
?A DNA ligase repairs the break in the strand
base excision

 

In all organisms, NER involves the following steps:
Damage recognition
Binding of a multi-protein complex at the damaged site
Double incision of the damaged strand several nucleotides away from the damaged site, on both the 5′ and 3′ sides
Removal of the damage-containing oligonucleotide from between the two nicks
Filling in of the resulting gap by a DNA polymerase
Ligation

nucleotide excision repair

 

repairs thymine dimers.
¿It is accomplished by an enzyme called photolyase.
¿Photolyase binds to the dimer in the dark.
¿Photolyase is activated by light and breaks the thymine-thymine bond.

Photoreactivation
bacteria shuffling genes occurs by: transposition, transformation, conjugation, and transduction
genetic recombination
genetic recombination that takes place w/in the same cell
transposition
genetic recombination that takes place between cells:
______ __________
_____
transformation, conjugation and transduction
transposition is caused by _______.
?move from one place on the chromosome to another.
?They can move into or out of the chromosome.
?They use cleavage and rejoining mechanisms
transposons
Transposition causes random ___________.
?The results can be beneficial or detrimental.
?Beneficial changes will be selected for and maintained.
?They may be the reason for several human diseases.
rearrangments
involves the shift of genetic material between cells. ?It involves naked DNA.
transformation
 is taken up by a bacterial cell and recombines with genes of that cell
naked DNA
in transformation the ________ must be competent Must be able to take up large molecules such as pieces of DNA. ?Some bacteria are naturally competent, whereas others can become competent after chemical treatment. ?Only a small amount of DNA is actually taken up
recipient cell
involves the transfer of genetic material between cells.
?It is a common event in both Gram-positive and Gram-negative bacteria.
?It uses a bacterial virus (phage) for transfer
transduction
There are two forms of transduction:
generalized- random
specialized- specific
?The original infected cell chromosome is cleaved into pieces.
?Some of this bacterial DNA is incorporated into a newly made phage.
?When these phages infect the next cell, original DNA recombines with host chromosome
There are three phases to generalized transduction.
?Phage DNA incorporates into the host chromosome.
?Phage DNA excises itself from the host chromosome.
Part of the host DNA is taken along.
?Original host DNA is incorporated into the next host chromosome.
During specialized transduction:
?Specialized transduction is used in
biotechnology.
involves the transfer of material between cells.
?requires direct contact between the donor and recipient cells.
?DNA moves from the donor to recipient cell
conjugation
conjugation requires direct contact between the donor and reciepient cells
______ stick together
______ use pili as a conduit for DNA transfer
gram positive cells
gram negative cells
?The sex pilus of the donor cell recognizes specific receptors on the cell wall of recipient cell.
?An enzyme in the donor cell causes the plasmid DNA to unwind.
?One of the two single strands of plasmid DNA stays in the donor cell.
There are several steps in conjugation:
The other moves across the plasmid into the recipient cell.
Both single strands are replicated.
After replication, the donor and the recipient contain identical plasmids
There are several steps in conjugation:
can have several outcomes for the recipient cell:
?The plasmid can remain as a plasmid.
?The plasmid can become incorporated into the recipient cell chromosome.
?When this happens, the recipient cell is then referred to as Hfr.
conjugation
Conjugation:
___________ from Hfrcan be moved into a new recipient.
?This replaces sections of the host chromosome
DNA
mechanisms are involved in making pathogens more dangerous.
?Many genetic
is closely associated with pathogenicity and virulence. ?It transfers virulence genes into bacteria that were previously harmless.
genetic transfer
Genes for antibiotic resistance and toxins are found on
plasmids
?Genes for resistance to disinfectants and environmental pressure are found on
dissimilation plasmids
are defined as obligate intracellular parasites -they cannot live outside a cellular host. have only one goal –a productive infection are specific for a certain cell type
viruses
Viruses can infect:
?Bacteria (called bacteriophages)
?Plant cells
?Animal cells (human cells included in this group).
An intact viral particle
virion
is surrounded by a protein coat called a capsid.
viral nucleic acid
each is made up of capsomeres
capsid
there are 2 types of viuses
DNA and RNA viruses

structure must overcome two basic problems:

 

It must be strong enough to protect the viral nucleic acid. ?It must be able to release the viral nucleic acid for infection

Virion 
have specific nomenclature
viruses

 

It is built from identical protein units called capsomeres.
¿Capsomeres bond together and give the _______ structural symmetry.
¿Viruses possess either helical or icosahedral symmetry

capsid
viruses possesss either ____ or _____ symmetry
helical or icosahedral
There are two shapes of helical viruses:
?Rod –straight and relatively rigid
?Filamentous –flexible, curved, or coiled.
Their shape is derived from 20 triangular faces that make up the capsid
2 types:
simple and complex
ICOSAHEDRAL VIRUSES
Many viruses that infect humans and other animals have this
form when viral glycoproteins and oligosaccharides associate with the plasma membrane of the host cell.
all have a phospholipid bilayer
viral envelopes
Envelopes vary in:
?Size
?Morphology
?Complexity
?Composition

envelope glycoproteins are firmly embedded in the envelope bilayer

 this is facilitated by domains of host membrane proteins called

spanners
envelope glycoproteins can form spikes or other structures on the outside of the virion which can be used to attach to the
 host cell
important in infection
packaged either:
directly in the capsid
enclosed in special proteins
or enclosed in proteins from the host cell
genomic packaging
the host cells fills with virions and bursts.
?The result is cell death.
in a lytic infection
are also known as latent infections.
?The viral genome becomes incorporated into the host cell’s DNA.
?It can remain this way for an extended period.
?The host cell lives
lysogenic infections
For animal viruses, there are six steps in lyticinfection:
?Attachment
?Penetration
?Uncoating
?Biosynthesis
?Maturation
?Release
occurs when a virion binds to specific receptors on a host cell
virion attachment
in virion attachment some viruses require a _______ to attach.
without it theres no infection
coreceptor
interactions occur through random collisions.
?The number of viruses is extremely important.
viral-host cell
WHEN VIRUS MEETS HOST CELL:

produce the maximum number of virions

lytic infections
must be permissive for the infection to succeed.
?It must contain all of the components required to make new virions.
the host cell
at the apical cell surface usually cause acute infection.
at the basolateral cell surface can become systemic
viral infection
Many viruses attach only to specific areas of the host cell membrane _______.
?________ are rich in cholesterol, fatty acids, and other lipids.
?They are more reliable for stable attachment.
?They are also the site of release for many viruses.
lipid rafts
Many different host cell molecules can be used as _____:
?Some viruses use more than one type.
?Some are shared by many viruses.
?can determine host range of virus
viral receptors
is high affinity.
?There are conformational interactions.
virus-receptor binding
Binding takes place between viral capsid and receptor.
non-enveloped viruses
Binding takes place between viral envelope proteins and receptor
enveloped viruses
Once attached, the virus must gain entry to the host cell.
?It must also ______ or _______ the capsid.
uncoat or remove
?Uncoating can occur in three places:
the plasma membrane
in the cytoplasm
@ the nuclear membrane
Use receptor mediated endocytosisto gain entry into the host cell
PENETRATION & UNCOATING: Non-enveloped Viruses
?Virus is enclosed in a vesicle –the early endosome ?Early endosomesfuse with or become late endosomes. ?Late endosomesfuse with the lysosomewhere uncoatingbegins.

receptor mediated endocytosis:

non enveloped viruses

some viruses pore in the host membrane
PENETRATION & UNCOATING: Non-enveloped Viruses
fuses with the host cell membrane
?Fusion is mediated by specialized fusion proteins of the host cell.
?It results in the formation of a fusion pore –a large opening allowing viral entry.
?For some viruses, fusion requires the presence of co-receptor molecules
PENETRATION & UNCOATING: Enveloped Viruses

Viral infection requires ____________ ?Viral genomes, capsids, and other viral proteins are synthesized in specific locations in the host cell.

Newly synthesized viral components are moved to other locations for assembly of viral particles

compartmentalization
Viral infection requires compartmentalization.
Newly synthesized viral components are moved to other locations for assembly of __________
viral compartments
Viral components are moved in vesicles, using host cell ________.
?Specialized host cell proteins are sometimes used.
microtubules
DNA viruses use routine host cell _____ to cross the nuclear membrane.
?The pathways form pores in the nuclear membrane
import pathways
RNA viruses use ____________ to convert RNA to DNA.
?Newly converted viral DNA is put into a pre-integration complex.
?This moves into the host cell nucleus during mitosis when the nuclear membrane is broken down
reverse scriptase
are either DNA or RNA.
?Both can be single or double-stranded.
viral genomes
 use the same mechanisms as the host cell for biosynthesis. ?One strand of viral DNA is transcribed into mRNA. ?It uses either the host cell or viral RNA polymerase
Double-stranded DNA Viruses
is used as a template to make a complementary copy of DNA.
viral strand
Viral strand is used as a template to make a complementary copy of DNA.
?This uses the host cell’s ______.
?The ________ is transcribed into mRNA.
?It is also used to make new copies of the __________
DNA polymerase
complementary copy
viral genome
requires:
?The synthesis of at least one viral protein
?The expression of several viral genes.
BIOSYNTHESIS: Replication of DNA Virus Genomes
has the same configuration as host DNA.
The viral genome
is performed by the host cell machinery
replication of Dna virus genomes
viruses require much less DNA replication.
latent DNA
synthesis is inhibited by the virus. ?All polymerases and proteins concentrate on viral DNA synthesis.
host DNA

form in the host cell –replication compartments ?

They contain both DNA templates and host cell replication machinery.

 ?They are essentially viral factories.

Specialized sites
allows exponential viral replication
Compartmentalization
do not kill host cells. ?The viral genome is inserted into a host chromosome. ?Maximum replication is not required. ?A small number of viral genes are expressed. ?A limited number of viral genomes are replicated
BIOSYNTHESIS:Replication of Latent DNA Viruses

Newly made viral DNA molecule is used as the template for

is performed by the host cell’s RNA polymerase.

transcription
expression begins after DNA synthesis. ?Genes are expressed in a specific order.
transcription: viral gene
Transcription with single-stranded DNA viruses is more complicated. ?The single DNA strands must first be converted to
double strands
?Viral genes are transcribed at very high rates. ?This maximizes the number of
new viruses being produced
Rapid ______ of viral DNA is regulated by host cell proteins. ?______ is coordinated with viral DNA synthesis. ?All host cell _______ and protein synthesis is shut down by the virus.
transcrition
Mechanisms of biosynthesis are more complicated than in DNA viruses. ?Host cells do not possess RNA-dependent polymerases.
 RNA Viruses
They are required to make viral mRNA and replicate genomes. ?Viruses must carry one
RNA-dependent polymerases.
are RNA viruses that contain the enzyme reverse transcriptase. cause latent infections.
retroviruses
converts RNA into DNA. ?Converted viral DNA can be inserted into the host cell _________

reverse transcriptase

 

 chromosome

Involves the movement of newly made viral components to specific sites in the host cell.
maturation
?There are two steps in maturation:
?Intracellular trafficking ?Assembly
Some viral components are synthesized in the cytoplasm, and some in the nucleus. ?They are transported through the cell by host cell microtubules to assembly sites.
 Intracellular Trafficking
depend on: ?The type of genome (DNA or RNA) ?The mechanism of genome replication ?The presence or absence of an envelope
?Assembly sites
in intracellular trafficking many _______ viruses assemble near the host cell membrane ?Others assemble near membrane bound organelles.
enveloped
in intracellular tafficking these viruses assemble in the host cell nucleus
Non-enveloped
in intracellular traffiking travel from the assembly site to the cell membrane in vesicles.
viral proteins
in intracellular trafficking _____ transport depends in whether the virus has an envelope
viral genome transport
in intracellular traficking ___________ genomes move to sites near the membrane
enveloped viruses
in intracellular trafficking ________-genomes move to the host cell nucleus.
?Non-enveloped viruses
All virions must complete a common set of assembly reactions. ?Formation of structural subunits for the capsid ?Assembly of the capsid ?Association of viral genome within the capsid ?Assembly of viral envelope glycoproteins.
 Enveloped viruses:

All virions must complete a common set of assembly reactions: ?Formation of structural subunits for the capsid ?Assembly of the capsid ?Association of the viral genome within the capsid.

 

non enveloped viruses
Capsomeres are assembled 1st. ?Assembly is diff in DNA viruses & RNA viruses. ?The # of capsomeres produced is always more than the # required. ?This maximizes the chances of capsomeres finding each other.
ASSEMBLY: Capsids
can be assisted by host chaperone proteins.
capsid assembly
ASSEMBLY: Viral Genomes This is the most important part of assembly. ?There are two mechanisms:
Concerted assembly and sequential assembly
–the viral genome is inserted into already assembled capsid
?Sequential assembly
–the virion is assembled while the viral genome is being synthesized
?Concerted assembly
New virions can be released from the host cell in two ways:
?Lysis ?Budding
Non-enveloped viruses use _ forr release. ?This causes death of the host cell.
lysis

?Enveloped viruses use _____ for release. ?This allows the host cell to live for a while.

 

(picking up that piece of envelope on the way out of the cell).

budding
release: ?In some viral infections, ________ are non-infectious. ?Viral enzymes convert them into an infectious form after release.
completed virions
can spread from cell to cell. ?They can use tight junctions between cells. ?They can also spread through the formation of syncytia.
viruses

allow movement through the body without exposure to the immune system

 

large globs of viruses/ can move through the blood stream to make it to one part of the body to the other

formation of synctica
spread: Some viruses produce _____: ?These are empty capsids or non-infectious virions ?They confuse and distract the host defenses.
decoy virons
spread: Some viruses incorporate host proteins as a type of
camouflage
can be:

Acute (rapid and self limiting)
?Persistent (long term)
?Latent (extreme versions of persistent infections)
?Slow or transforming (complicated types of persistent infections)

Viral infections
produce virions and kill host cells rapidly (cytopathology
Cytopathic viruses
viruses produce virions but do not cause cytopathology
?Noncytopathic
me viruses dont produce virions or cause cytopathology but
still cause infection
periods vary for different viruses.
?Some are as short as days.
?Some are as long as years.
incubation periods
during the incubation period the virus is ______
the host is beginning to ______
replicating
respond
varicella zoster is
chicken pox
rapid production of virions & elimination of infection;
virions can be missed and spread to other tissues
this then causes reinfection
ex: varicella-zoster
acute infections
severe public health problem
associated w/ epidemics
short incubation period
which causes a delay in indentifiable symptoms until the virus has already spread
acute infections
Acute infection epidemics are often seen in
crowded populations.
?Schools
?Military bases
?Nursing homes
hosts that survive acute infections are immune to __________ for life:
some diseases escape this immunity
reinfection
(changes in virion structure)
reinfection occurs because of this
it is due to the specificity of the immune reponse
the new structure isnt recog by the immune system memory
antigenic variation
there are 2 forms of antigenic variation
antigenic drift and antigenic shift
Involves major changes in virion structure
?Is due to the acquisition of new genes
?This is through co-infection or recombination
?Antigenic shift
Involves small changes in virion structure
?Results from mutations
?Occurs after the infection has begun
antigenic drift
Caused when host defenses are either modulated or completely bypassed.
?Virions are produced for months or even years.
PERSISTENT INFECTIONS
There are two variations of persistent infections
chronic and latent infection
the infection lasts for life
latent infection
the infection is eventually cleared
chronic infection
host defense mech against viral infec
They must be given the signal to begin killing infected cells.
Some viruses can kill them first.
cytotoxic T cells
some viruses escape killing by infecting tissues that have reduced immunosurveillance
skin
central nervous system
?No large-scale production of virions
?Reduced or absent immune response
?Persistence of an intact viral genome so infections can reoccur
latent infections
can be reactivated years after entry into host.
latent viruses
are lethal.
?They are usually associated with brain infections.
?Signs may not be seen until years after the primary infection.
?Once signs and symptoms appear, death usually follows very quickly
slow infections
?Sufficient number of viruses present ?Access to susceptible and permissive host cells ?An ineffective host immune response
There are three basic requirements for successful infection
are disseminated within the host and transmitted from one host to another.
viral infections
refers to spread of virus within an infected body.
?There are common sites for viruses to enter into the body.
viral disssemination
what are the three main entry points for viral dissemination
respiratory system, digestive system and the urogenital tract
The most common portal of entry into the human body.
?It is always exposed to large numbers of potential pathogens.
?Viruses easily disseminate from here into other areas of the body
respitory tract
is the second most common portal of entry.
?Many viruses use this portal of entry.
?They must be resistant and resilient to harsh environments in order to survive.
the digetive tract
in the digestive tract some viruses use transcytosis through _______ to enter the body
some viruses stay in the _____ and eventually destroy them
M cells
their destruction causes inflammation of the digestive tract and diarrhea
M cells
The primary point for sexually transmitted viruses to enter the body.
?Some remain in this tract and cause local infections e.g. genital warts.
?Some gain access to underlying tissues and disseminate throughout the body.
urogenital tract
viruses also use this
like when they enter through the eyes
ex: opthalmic herpes infection
portals of entry
Some viruses enter through the skin.
?Usually by _______ transmission from biting insects
?If they remain in the epidermis, a localized, ______ infection occurs.
?If they get into the dermis, a ____ infection can occur
vector
acute
systemic
They can disseminate throughout the entire body.
?Some target neurons.
?Some use neurons to get to their preferred target area.
viral dissemination in the nerous system
Viruses released from the apical surface host cells cause
localized limited infection
?Viruses released from the basement membrane of host cells can
spread systemically
?The bloodstream is the best route for systemic viral infection.
?Referred to as
hematogenous dissemination
refers to virus replicating in the blood
viremia
refers to the spread of the virus from one host to another
viral transmission
there are 2 patterns of viral transmission

human to human and animal to human?

transmission w/ in a single species
transmission between species
Viruses can be transmitted in several ways:
?Via _____ or inanimate objects
?Via poor techniques employed by health care workers: ___________
?________ –the digestive tract
fomites
iatrogenic transmission
Fecal-oral route
Viruses can be transmitted in several ways:
?Respiratory tract Viruria Urogenital tract ?
Contact with ?
the sneeze is the best form of transmission
transmission via urine
sexual transmission
skin
infections are seasonal.
?Respiratory tract infections are higher in winter.
?Digestive tract infections are higher in summer.
most acute viral
in pregnant women can expose the fetus to infection
viremia
some virus transmission from mother to infant can occur through
breast feeding
the capacity of an infectious organsim to cause disease
virulence
viruses can cause significant damage
virulent
(attenuated) viruses cause little or no disease.
nonvirulent
–how much virus is required to paralyze 50% of a subject population.
PD50 (way to measure viral virulence ID50 & LD50 as well)
can be directly affected by:
?Route of entry
?Age and health of host
?The gender of the host
virulence
?Susceptible –can be infected and can also transmit the infection
?Immune –cannot be infected
There are two types of host:
caqn gender play a role in infection?
?Males are more susceptible to viral infection than females.
the most effective way to deal with viral infections.
?It allows for life-long immunity from a particular infection.
?It increases herd immunity
vaccination
what are the 3 groups of vaccines
live attenuated cavvine
inactivated or killed vaccine and subunit vaccine
made of intact virions rendered non-infectious
live attenuated vaccine
composed of killed or dead virons
inactivated or killed vaccine
cposed of immunogenic parts of virions
subunit vaccine
antigen is administered and causes the onset of the immune response
avtive immunization
a preformed antiviral product, such as antibody, is administered
passive immunization
can inactivate genes responsible for suppressing tumor formation.
retroviruses
Some viruses can cause _____ in animals.
?An estimated 20% of human ______ involve viruses
cancer
Viruses associated with human cancers include:
?Epstein-Barr virus
?Hepatitis B and C viruses
?HPV
for many products that modify or block host defense.
?A battle wages between the host immune system and these modifications
viral genomes code
are usually opportunistic infections and have increased with the number of immunocompromised individuals
fungal infections
Parasites can be divided into two groups:
? Protozoans – microscopic, single-celled eukaryotes.
? Helminths – macroscopic, multicellular worms.
Disease causing parasites depend on their ______ for survival
infected host
are intestinal parasites that infect 10% of the world population
entamoeba
parasites infect 16 million people in Latin America each year
trypanosoma
vary in size.
?They contain membrane-bound nuclei and cytoplasm.
paracytic protozoans
the cytoplasm of parasitic protozoans are divided into
inner form- endoplasm
and outer form-ectoplasm
parasitic protozoans can be classified on the basis of their methods of
movement and reproduction
Are facultative anaerobes
?Are heterotrophs
?Have a highly developed reproductive system
most infectious protozoans
some infectious protozoans form ____ as a way of protecting themselves. they can also be a mech of transmission from host to host
cysts
are worms.
?There are two types:
?Free living
?Parasitic
?They are bilaterally symmetrical and of various lengths
helminths
parasitic helminths body is covered by a tough cellular ______
some have suckers, hooks, or plates which are used for _______
cuticle
attachment
?Differentiated organs
?Primitive nervous systems
?Primitive excretory systems
?Highly developed reproductive systems
?They do not have a circulatory system.
All helminths have:
comes in 2 forms: gastrointestinal form and blood and tissue form
nematodes (round worms)
use only one host to complete their life cycle
gastrointestinal form of nematodes
uses multiple hosts to complete their life cycle
blood and tissue form of nematode
what are the three types of helminth that can infect humans
cestodes (tapeworms), trematodes (flukes), nematodes (round worms)
?Have a flat, ribbon-shaped body ?The head contains suckers and frequently has hooks for attachment. ?They generate proglottids– reproductive segments with male and female gonads. ?Have no digestive tract – nutrients are absorbed across their cuticle. ?Some use one host and others two for their life cycle.
cestodes (tapeworms)
Have leaf-shaped bodies ?They have two suckers. ?Oral sucker –takes in nutrients and regurgitates waste ?Distal sucker –used for attachment
trematodes (flukes)
Pathogenesis of protozoan diseases is variable. ?The severity of infection is related to the number of worms. ?A large worm load lead to increased disability of the host
for helminths
can cause: ?Tissue damage ?Allergic or anaphylactic reactions
The host defense reaction
are intracellular parasites. ?They alternate between sexual and asexual reproduction
sporozonans
most important sporozoans diseases that together affect 1/3 of the world’s population
malaria and toxoplasmosis
febrile illness found worldwide transmission by bite of anopheles mosquito mortality mainly seen in children and immunocompromised adults
malaria (plasmodium species)
Male fertilizes female gametocytes ?Resulting zygote forms an oocyst filled with sporozoites ?Oocyst ruptures releasing sporozoites into body ?Sporozoites penetrate salivary glands
(plamodium) Sexual life cycle begins when a mosquito ingests infected blood
Sporozoites are introduced with mosquito saliva. ?Sporozoites move to the liver and produce merozoites. ?Hepatocytes rupture releasing the merozoites. ?Merozoites infect red blood cells (ring stage).
Asexual life cycle begins when a mosquito bites new host.
Within 72 hours, infected red blood cells begin to rupture. ?Merozoites are released. ?Some infect other RBCs. ?Some transform into the gametocyte form. ?Gametocytes are then taken up by the next mosquito
life cycle of the plasmodium
Fever ?Anemia ?Circulatory changes thrombocytopenia
Symptoms of malaria include:
is caused by the destruction of red blood cells. ?It is accompanied by depression of marrow function and an enlarged spleen
anemia in malaria
two factors involved in the treatment of malaria
species of plasmodium and the immunocompetency of the infected individual
are amebas. ?The most primitive form of protozoans that: ?Multiply by simple binary fission ?Move by using pseudopodia. ?Produce a chitin wall for protection
rhizopods
rhizopods produce a chitin wall for protection that is referred to as a
cyst
is an obligate intracellular parasite. ?It is passed from host to host as cysts. ?Uses the fecal-oral route of infection ?Ingestion of a single cyst can cause infection
AMEBIASIS (ENTAMOEBA HISTOLYTICA)
is the third highest parasitic cause of deaths worldwide. ?Only malaria and schistosomiasis are higher. ?is on the rise in the US
amabiasis (entamoeba histolytica)
LIFE CYCLE OF ENTAMOEBA HISTOLYTICA: ?It is found in either the ________ form.
trophozoiter cyst
Initial infection is via the fecal-oral route. ?Systemic ________ occurs only after the colon colonized
PATHOGENESIS OF AMEBIASIS amebiasis
pathogenesis of amebiasis the parasite produces several virulence factors and enzymes which can cause membrane ____ and _______
lesions and cellular death
w/ amebiasis the infection is usually mild and asymptomatic. lesions can open the intestine for _______ and __________
bacterial and viral infection
in amebiasis cysts can pass through the stomach and into the small intestine here they disintegrate and release four
trophozoites
are widespread in nature. ?They use flagella for movement through the host. ?They multiply by binary fission
flagellates
what are the four flagellates that cause disease in humans
?Trichomonas ?Giardia Leishmania ?Trypanosoma
these 2 flagettes are noninvasive, have low morbity rates and theres no intermediate host required
Trichomonas ?Giardia

these 2 flagellates are invasive, have high morbidity rates, are frequently lethal and required an intermediate host

(associated w/ the sandfly)

leishmania and tryanosoma

is a sexually transmitted infection.

It produces vaginitis in females with symptoms:

Pain ?Dysuria ?Discharge

TRICHOMONIASIS (TRICHOMONAS VAGINALIS)
It may cause prostatitis or urethritis in males. ?It can last from weeks to months. ?An estimated 180 million people worldwide are infected each year. ?The peak age of infection is 16 to 35 years old.
TRICHOMONIASIS(TRICHOMONAS VAGINALIS)
does not form cysts. ?It can survive outside the host for 1 to 2 hours. ?In water, semen, or urine, it can survive for up to 24 hours.
trichomonas
Direct contact transmission to genital endothelial cells causes the infection. ?Cells are destroyed and inflammation occurs. ?It is accompanied by petechial hemorrhaging. is noninvasive
pathogenesis of trichomoniasis
TRICHOMONIASIS: ?Infection causes persistent ______. ?Symptoms can last for months. ?Severe cases can cause ________ and ________.

vaginitis

hemorrhaging and tissue errosion

It is caused by the protozoan _______

;

Motile ?Fusiform ?Moves in a spiral fashion

;

The vector is the tsetse fly (Glossina species).

TRYPANOSOMIASIS

;

Trypanosoma.

there are 2 forms of trypanosomiasis the african form which causes ____ and the american form which causes _____

sleeping sickness

;

chaga’s disease

is caused by trypanosomissis and is confined to central Africa. ?There are ten to twenty thousand cases each year. ?The reservoir is humans
sleeping sickness

PATHOGENESIS OF TRYPANOSOMIASIS:

Parasitemia causes localization of parasites in __________ the heart and CNS are particularily vulnerable

SMALL BLOOD VESSELS

PATHOGENESIS OF TRYPANOSOMIASIS

 

Symptoms include:

Hemorrhaging ?Demyelinating panencephalitis ?Headache ?Fever ?Lymph adenopathy ?Skin rash ?Impaired mental status

 TRYPANOSOMIASIS

 ?Symptoms can progress to:

?Eventual diminished alertness. ?Indistinct speech, tremors, and coma. ?Coma can lead to death.
what are the subgroups for nematodes
intestinal nematodes and tissue nematodes
have the following characteristics: ?Fusiformbody shape ?Tough outer cuticle ?Male and female forms ?Thousands of offspring are produced ?Eggs must incubate outside the host to become infective ?There is a larval form
Intestinal nematodes

what type of nematodes are these?

Pinworms

 ?Whipworms 

Large roundworms

 

(eggs must incubate outside the host)

intestinal nematodes

can produce:

 ?Malnutrition

 ?Discomfort

Anemia

Occasionally death

intestinal nematode infection

severity of intestinal nemotodes in directly correlated to worm load.

small worm load ?

large worm load ?

pinworm (enterobius vermicularis)

pathogenesis of enterobiasis:

 

pinworms attach to the mucosa of the _______

females migrate down the ___________ to lay eggs

cecum

 

perianal

once pinworms lay eggs: eggs stick to tissue, bedding towels and fingers eggs can be inhaled or swallowed eggs hatch in the upper intestine larvaw migrate down to the ______
cecum
?Tissue nematodes can induce disease in:
tissue blood and lymph systems
Four major types of ________ use humans as definitive hosts. ?They can live for years in subcutaneous tissues and lymph vessels.
tissue nematodes
?Tissue nematodes discharge live offspring called ________. ?Circulate through the blood or tissue ?Can be ingested by blood sucking insects
microfilariae.

Caused by the parasite Trichinella spiralis:

Lives in the duodenum and jejunum of flesh eating mammals. ?Particularly found in swine and bears

TRICHINOSIS
enters through the host vascular system and is distributed widely. ?Only parasites that penetrate the skeletal muscle survive. ?It can become encapsulated in muscle. ?It can remain viable for 5-10 years.
trichinella

The disease is widespread amongst swine.

 ?Human infection results from eating undercooked meat. ?Over one million people in the US carry either living or dead worms. ?Most infections are asymptomatic

TRICHINOSIS
lesions
in trichinosis ________ are nfound in striated muscle ?Heart muscle ?CNS

PATHOGENESIS OF TRICHINOSIS

 

The area of infection is infiltrated by white blood cells, particularly ___________.

Worms mature in 24-48 hours of eating ______

eosinophiles tainted meat
symptomes of trichinosis include
nausea, andominal pain and diarrhea

PATHOGENESIS OF TRICHINOSIS:

 ?Larval invasion starts _______ later.

Lasts one to ______

Low worm load – __________

 ?Large worm load – ________

one week

 six weeks

asymptomatic

 significant disease and poss death

are commonly called tapeworms. ?The largest of the intestinal parasites ?Lack a vascular and respiratory system ?Lack a gut or body cavity ?Nutrients are absorbed across the cuticle
cestodes

pathogenesis of cestode infec:

 in the _____:

 

 the worms stays in the lumen of the gut

 only minor symptoms are seen

primary host

pathogenesis of cestode infection:

in the ____________:

larval stages of the worm cause serious tissue invasion most patients are asymptomatic

intermediate host
PATHOGENESIS OF CESTODE INFECTION ?Symptoms include
?Gastric disfunction ?Nausea ?Diarrhea ?Weight loss
are known as flukes. ?Have a bilateral symmetry ?Have two deep suckers: ?One in the oral cavity ?One on the ventral side of the worm
trematodes
can live for decades in human tissue and blood vessels. ?They produce progressive damage to vital organs.
trematodes

Eggs are excreted from the human host.

They must reach water in order to hatch.

Hatching releases larvae called miracidia.

Miracadia penetrate snails, the intermediate host

TREMATODES life cycle

LIFE CYCLE OF TREMATODES: Miracadia develop into _______.

_______ are released from the snail.

cercariae

DISEASE CAUSING TREMATODES

 

Three major groups of flukes invade humans:

?Lung flukes –?Liver flukes –?Blood flukes –
?Infections are frequently caused by consuming infected shell fish ?Infections cause eosinophilia and inflammation. ?After infection a capsule forms around the fluke
paragonimiasis: lung flukes
is the study of fungi
mycology

are important for the environment

 are commensal organisms.

 ?They are normally harmless to humans. can be opportunistic pathogens

fungi
are eukaryotes. ?There are two forms: ?Molds –multicellular ?Yeasts –unicellular
fungi

Fungi use __________ metabolism

 

They obtain carbon from decaying organic matter.

heterotrophic
Most fungi are _______ aerobes but some are ___________ anaerobes. ?No fungi are _____
obligate facultative obligate anaerobes.
?Fungi reproduce either sexually or asexually. ?Involves spores -ascospores, zygospores, or basidiospores
sexual reproduction
?Fungi reproduce either sexually or asexually. ?Through conidia ?Involves mitotic division and budding
asexual reproduction

 

Some fungi can grow in mold or yeast form
The_____ form requires environmental conditions similar to in vivo
   proper temperature
   increased nutrients
The ________ form requires:
   ambient temperatures

   minimal nutirents

 yeast

 

 

mold

 

 

form of fungi that requires environmental conditions similar to in vivo. ?Proper temperature ?Increased nutrients
yeast
form of fungi requires: ?Ambient temperatures ?Minimal nutrients
mold
fungi are classified by: ?Ribosomal RNA typing ?The tissue types they parasitize ?The diseases they produce
medically important

are classified into 4 groups:

 

Superficial mycoses ?Mucocutaneous mycoses ?Subcutaneous mycoses ?Deep mycoses

?Fungal diseases 
Fungal infections that do not involve a tissue response: ?Piedra, Tinea nigra, Tinea capitis, favus, and pityriasis 
SUPERFICIAL MYCOSES
–colonization of the hair shaft causing black or white nodules
?Piedra
brown or black superficial skin lesions
Tinea nigra
folliculitis on the scalp and eyebrows
?Tinea capitis
–destruction of the hair follicle.
favus

–dermatitis characterized by redness of the skin and itching:

 ?Caused by hypersensitivity reactions to fungi normally found on skin

Mostly seen in immunocompromised patients

pityriasis
Associated with: ?Skin ?Eyes ?Sinuses ?Oropharynx and external ears ?Vagina
CUTANEOUS AND MUCOCUTANEOUS MYCOSES

(type of cutaneous and mucocutaneous mycoses)

skin lesions characterized by red margins, scales and itching: ?Restricted to the stratum corneum. ?Classified based on location of infection

 ringworm
ringworm on feet or between toes
tineapedis
ringworms between the fingers, in wrinkles on the palms
tineacorporis
ringworms lesions on the hairy skin around the genetalia
tineacruses
ringworms in scalp and eyebrows
tineacapitis
chronic infection of the nail bed ?Commonly seen in toes
?Onychomycosis
type of cutaneous and mucocutaneous mycoses that has extended scaly areas on the hands and feet
Hyperkeratosis
colonization of the mucous membranes ?Caused by the yeast Candida albicans ?Often associated with a loss of immunocompetence
mucocutaneous candidiasis
?There are two clinical types of mucocutaneous candidiasis:
thrush and vulvovaginitis
fungal growth in the oral cavity ?An indicator of immunodeficiency.
thrush

fungal growth in the vaginal canal

?Can be associated with a hormonal imbalance

 

Or can be caused by a superinfection caused by the use of an antibiotics which wipes out normal microflora in the body

vulvovaginitis
Can cause the development of cysts and granulomas. ?Provoke an innate immune response -eosinophilia
localized primary infections of subcutaneous tissue
Usually seen in immunosuppressed patients with: ?AIDS ?Cancer ?Diabetes
deep mycoses
?Can be acquired by: ?Inhalation of fungi or fungal spores ?Use of contaminated medical equipment
deep mycoses
?Deep mycoses can cause a systemic infection – __________ ?Can spread to the skin
disseminated mycoses
very uncommon in immunocompetent individuals are more common in immunodeficient patients
fungal infections
fungi can become invasive. ?They switch from yeast form to mold form. ?The hyphae invade tissues and disseminate
some dimorphic
?Fungi do not produce exotoxins in vivo. ?Primary ________ is due to host inflammatory response.
tissue injury in fungal infections
?Host defense against fungal infection is primarily through:
?Phagocytosis ?Adaptive immune response
cause antibiotic resistance
mutations

classification of viruses

 

1.Type of genetic material
2.Shape of the capsid
3.Number of the capsomere
4.Size of the capsid
5.Presece/absence of an envelope
6.Type of host it infects
7.Type of disease it produce
8.Target cell
9.Immmunological and antigenic properties

 

1.Type of genetic material
2.Shape of the capsid
3.Number of the capsomere
4.Size of the capsid
5.Presece/absence of an envelope
6.Type of host it infects
7.Type of disease it produce
8.Target cell
9.Immmunological and antigenic properties

protein molecule forming capsid
capsomere

protein shell surrounding nucleic acid

protein coat

capsid
nucleic acid plus capsid
nucleocapsid

phospholipid bilayer w/ embedded glycoproteins surrounding the capsid in enveloped virus

 

viral membrane

envelope

complete infectious viral structure: nucleic acid plus capsid for non-enveloped virus; nucleic acid plus capsid plus envelope for enveloped virus

 

viral partical

virion
ribbon like protein that forms spiral around nucleic acid (ex: tobacco)

 

Helical capsid

many sided
polyhedral
triangular faces
icosahedral
 combination of helical and icosahedral
complex capsid

 

The infection cycle was first worked out in bacteriophages (bacterial viruses).
Bacteriaphages generally go thru 5 steps in replication process ending in lysis of the cell

adsorbtion- bac attaches to cell

, penetration- involves injection of virus into cell DNA

synthesis- once in used to make more DNA

maturation- pieces of viruses put together

release- involves lysis or bursting of the cell

Viral infections are _______ within the host and _____ from one host to another

disseminated

 

transmitted

antibiotic resistance, synthesis of pilus, utilization of unusual nutrients, increased virulence, toxin production, antibiotic synthesis
thngs that can be transferred on plasmids

– live on the surface of the host

Ticks, lice

Ectoparasites

live w/in the body of the host

 Some protozoa and worms

endoparasites

must spend part of its lifecycle in or on the host

 Most parasites, plasmodium- protozoa

obligate parasites-

free living soil fungi, but can obtain nutrients from the host

Fungi that cause skin infections

Falcultative parasites-
tapeworms, remain in or on host once they have invaded
Permanent parasites-
biting insects feed on host then leave (mosquito)
Temporary parasites:

invade organisms other than normal host.

Tick invading human rather than dog or wild animals

accidental parasites

parasites that have parasites (mosquitos that have malaria)

Vectors-agents that transmit

Hyperparasitism-

harbors host while it reproduce sexually

Malaria- mosquito

Definative host:

– harbor parasite during a developmental stage

human

Intermediate host
range of different host in which parasite can mature Anopheles mosquitoes (malaria)
host specificity

 

caused by several species of Aspergillus
¿Associated with immunodeficiency
¿Can be invasive and disseminate to the blood and lungs
¿Causes acute pneumonia
¿Mortality is very high.

¿Death can occur in a matter of weeks

aspergillosis

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