Pathogenesis-AuCoin Flashcards
What are 4 possible cellular responses to viral infection?
- no effect
- cytopathology
- hyperplasia-benign, like warts
- cancer-like papilloma virus
What are inclusion bodies?
nuclear or cytoplasmic aggregates or stainable substances, usu viral proteins.
The same disease can be caused by many different viruses. Give examples of this.
Encephalitis & hepatitis viruses have little in common with each other except their end result.
Could have DNA or RNA doesn’t matter.
Give an example where the same virus can cause multiple diseases.
Chickenpox virus.
Causes chickenpox.
Causes shingles.
T/F The disease produced by a virus is mainly determined by the viral morphology-like whether its genome is DNA or RNA.
False. No relationship to morphology. Determined by viral & host factors & is influenced by genetics of each patient
What is the most pathogenic strain of the Ebola virus?
Zaire
What can the super not pathogenic strains of viruses be used for?
live attenuated viruses
What is pathogenesis?
pathogenesis is the study of the origin and development of disease
What is disease pathogenesis?
disease pathogenesis are events during infection that results in disease manifestation in the host
When is a virus considered pathogenic? What makes a strain of a virus particularly virulent?
- *a virus is pathogenic for a host if it can infect and cause signs of disease
- *a strain of virus is more virulent than another strain if it commonly produces a more severe disease
What are the important steps in viral pathogenesis? Note: this is important to consider as it affects the design of effective antivirals.
viral entry into the host primary site of viral replication viral spread cellular injury host immune response viral clearance or persistent infection viral shedding
What is the incubation period?
when you catch the virus until when you first start experiencing symptoms
Why might measles have a longer incubation period than the rhinovirus?
perhaps b/c it has to travel so far to its preferred infectious site. the rhinovirus stays local.
T/F IgA increase is helpful in systemic infections.
False. This is only important for mucosal immunity.
Which shows viremia? Rhinovirus or measles
measles b/c it is a systemic viral infection
rhinovirus remains local
Where are some places where a virus attaches to cells & enters that way?
skin resp tract GI urogenital tract conjunctiva
Where are some places where a virus enters the body via bloodstream?
needles (Hep B, HIV)
transfusions
insect vectors (arboviruses)
What is the most common route of entry for a viral infection?
resp tract
After a virus has entered an organism–what is the most common route of entry next?
blood or lymphatics
**often viruses hop on top of macrophages
T/F When the virus is in the blood-it is ALWAYS associated with a carrier cell.
False. It can be or it can be free.
Can a virus spread neuronally?
Sadly, yes!
Ex: HSV & rabies virus
Once a virus gets to its preferred tissue (_____) it can get back in the blood & replicate in other places.
tropic tissue
**viruses tend to exhibit organ specificities
What mainly determines the pattern of systemic illness produced by a virus?
TROPISM
**determined by VAPs present
What are some of the immune players that help respond to a viral infection?
mononuclear cells
lymphocytes
Induction of _____ is a major part of the viral immune response.
IFNs
If the viral polypeptides on the cell surface of an infected cell are recognized…the virus infected cells may be lysed by _____.
Cytotoxic T lymphocytes
Neutralizing antibodies against what can block the viral infection of cells?
against capsid or glycoproteins
What are interferons?
it is a glycoprotein, more specifically a cytokine
produced by infected cells
protects uninfected cells from viral infection
activate NK & macrophages
infected cells more readily recognized by CTLs
Which MHC do CTLs respond to?
MHCI
What percentage of our body’s antibodies are IgA?
75%!!
What are some of the symptoms of a viral infection that are mediated by the presence of increased IFNs?
aching muscles
fever
When are IFNs produced? Which part of immunity do they belong to?
Innate
produced w/i hours of viral infection
Aside from viral infections, what other types of infections does IFNgamma protect humans from? Also…what is another name for IFNg?
aka Type II Interferon
**also some bacterial & protozoal infection
Note: IFNg is an important activator of macrophages.
Which secrete more IFN–a fibroblast or a dendritic cell?
Dendritic Cell! 1000X as much
Synthesis of IFNs by a cell must be induced before it happens. What are some inducers? Which are the strongest?
DNA viruses bacterial endotoxin Strongest: Single Stranded RNA DSRNA
When does antibody production begin w/ relation to IFN production?
antibody production begins days later, not a part of the innate response
What exactly do IFN molecules do?
Bind cell surface receptors on target cells.
Receptor binding-tyrosine phosphorylation & activation of transcription factors in cytoplasm.
Transcription of IFN-inducible genes
What are 2 important IFN-inducible enzymes that are produced?
Protein Kinase R (PKR)
dsRNA dependent protein kinase
RNAseL-interferon-induced ribonuclease
What’s the deal with Protein Kinase R (PKR)?
dsRNA dependent protein kinase
phoshorylates & inactivates cellular initiation factor eIF-2.
prevents both cellular & viral protein synthesis. Basically it degrades proteins nonspecifically
What’s the deal with the RNAseL?
RNAseL interferon induced ribonuclease
it destroys all RNA in the cell nonspecifically when activated
no more mRNA
What are some ways that viruses have developed immune evasion techniques? Give examples.
some viruses infect and damage cells of the immune system. HIV infects T lymphocytes and destroys their ability to function
may encode immunomodulatory proteins that inhibit MHC function (adenoviruses, herpesviruses)
may inhibit cytokine activity (poxvirus, measles virus)
viruses may mutate and change antigenic sites of virion proteins (influenza, HIV
What is an acute viral infection?
acute when a virus first infects a host
usu self limiting-doesn’t require any treatment
this is when you get those nonspecific viral symptoms
What are subclinical infections?
subclinical infections are those that give no overt sign of their presence
What are chronic or persistent infections?
chronic or persistent infections occur when replicating virus can be continuously detected at low levels
What are latent infections?
latent infections are those in which the virus persists in a hidden form, no new virus is produced
here, you don’t have lytic stuff going on
if you are immunocompromised-could be activated
What is stomatitis?
is an inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, gums, tongue, lips, throat, and roof or floor of the mouth.
What is a good example of a latent virus?
herpes!
Herpes Simplex 1-mouth
Simplex 2-genital
**virus can travel neurally via the microtubules of the DRG
What are some things that can cause reactivation of a latent herpes virus?
fever
menstruation
radiation
nerve damage
What are some examples of viruses that enter the skin due to an abrasion?
poxviruses
papillomaviruses
herpes simplex virus
What causes warts? What causes cold sores?
Warts-papilloma virus
Cold Sores-Herpes
Aside from skin abrasion, what are other ways to introduce a virus into the skin?
arboviruses-arthropod vector
blood transfusion or contaminated needles–Hep B & HIV
How do patients get generalized skin rashes?
get them in response to viral infections
develop b/c virus spreads to skin via bloodstream following replication at a different site
Describe the path of the poliovirus.
multiples in GI tract (primary site before it gets systemic)
spreads to the CNS after absorption into the blood, may hop on an immune cell & try to squeeze thru an epithelial tight jcn breakdown.
**if you have the vaccine-IgA antibodies will stop it from being absorbed systemically, while it is still a part of the GI mucosa.
Is poliovirus enveloped or naked capsid? Take into account that it replicates in the GI tract.
Naked Capsid-can withstand pH etc of the GI tract.
What are different ways that viruses can gain access to the CNS?
bloodstream (viral replication in endothelial cells of cerebral vessels)
peripheral nerve fibers (virions can be taken up at sensory nerve endings, herpesviruses travel in axons to the dorsal root ganglia neurons)
What is meningitis?
inflammation of protective membranes covering the brain & spinal cord
What is encephalitis?
acute inflammation of the brain
What are the 4 main functions of glial cells?
- *surrounds neurons & holds them in place
- *supplies nutrients & O2 to neurons
- *insulates one neuron from another
- *destroys pathogens & removes dead neurons
What does the pathologic reaction within the CNS include?
cell necrosis
inflammation
phagocytosis by glial cells
Once again, what is the most common route of viral infection?
resp tract in aerosolized droplet or saliva
What are some of the host defenses that try to keep infection of the resp system from happening?
mucus-produced by goblet cells ciliary action lymphoid cells alveolar macrophages secretory IgA
What are some examples of viruses that don’t remain localized in the lung, but instead spread to other regions of the body?
Chickenpox
Measles
Rubella
How do GI viral infections usu spread?
fecal oral route
thru poorly cooked or contaminated food
**these are usu naked capsid viruses
What is acute gastroenteritis?
is short term disease ranging from mild, watery diarrhea to sever febrile illness (vomiting, diarrhea, and prostration)
What are 2 important viral causes of gastroenteritis?
Rotaviruses
Norwalk virus
What is prostration?
complete physical or mental exhaustion
Most viruses do NOT cross the placenta. Except for 2. What are these 2? What can they cause?
Rubella-but there is a vaccine!
Congenital Rubella Syndrome
Cytomegalovirus-NO vaccine!
Congenital HCMV
What is involved in Congenital Rubella Syndrome?
deafness, eye abnormalities, and congenital heart disease
What is involved in Congenital HCMV?
leading infectious cause of deafness, learning disabilities, and mental retardation in children
When a vaccine isn’t available for a virus…what types of drugs do you need to develop? What are examples of this?
need to develop antiviral drugs. even tho you can’t prevent infection-let’s prevent things getting too bad.
Ex: Influenza & rhinoviruses-too many serotypes
HIV-mutates too rapidly!
How do nucleoside analogs show specificity? What do they do?
inhibit viral polymerases by incorporating a terminal nucleoside
**don’t affect host polymerase, though. thus, specificity!
What are the best stages of viral infection to target with antiviral chemotherapy?
attachment of virus to host cells uncoating of the viral genome viral nucleic acid synthesis translation of viral proteins release of progeny virus (prevent egress)
What does a reverse transcriptase inhibitor do?
binds to reverse transcriptase to disrupt enzymes catalytic site
Remember: reverse transcriptase is a polymerase-makes DNA from RNA
What does a protease inhibitor do?
inhibits the viral protease that is required at the late stage of the HIV replicative cycle
Note: RNA viruses make polyproteins-this inhibits the breaking down of them into active viral proteins
What does a fusion inhibitor do?
blocks viral and cellular membrane fusion step involved in entry of HIV into cells
What is the difference b/w a nucleoside & a nucleotide?
a phosphate group
What does the MMR vaccine cover?
measles
mumps
rubella
For mucosal immunity-which antibody do you need a lot of? What is an example of a virus like this?
Need a lot of IgA!
Ex: influenza
For immunity against viruses that have a viremic mode of spread…which antibody do you need a lot of? What are examples of viruses like this?
Need a lot of Serum IgG!
Polio
HepA & B
Varicella
How does cell mediated immunity ever help in infections?
involved against systemic infections
controls the latent stage
includes T cells
ex: shingles comes to flourish when the T cells get tired out & the latent chickenpox virus is reactivated
What’s the deal with killed virus vaccines?
- virus is propagated then inactivated with minimal damage to the viral structural proteins
- generally stimulate development of circulating antibody against viral membrane proteins
- a boost usually needs to be administrated
- cell mediated immunity to killed viruses is generally poor
- have to make sure no live virus in prep!
Why do you usu need a booster when you have a killed virus vaccine?
b/c the antigen is not constantly being reproduced
Why is it that parenteral admin of a killed vaccine may not be ideal to protect against a resp or GI virus?
b/c killed vaccines produce a lot of IgG & IgM
not a lot of IgA–this is what you need for mucosal immunity!
What is cell mediated immunity usu directed at in terms of viruses?
Cell-mediated immunity is directed primarily at microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in removing virus-infected cells, but also participates in defending against fungi, protozoans, cancers, and intracellular bacteria. It also plays a major role in transplant rejection.
What’s the deal with attenuated live virus vaccines?
utilize virus mutants that antigenically overlap with wild-type virus
attenuated viruses can be produced by serial passage in animals or cell cultures
act like the natural infection, they replicate in the host and induce good antibody and cell mediated immunity
induce antibody response and resistance at the portal of entry
Why is it that the polio vaccine from live attenuated virus & from killed virus are both effective?
Killed Virus-get a lot of IgG, but not a lot of IgA. Once the virus multiplies in the GI tract, it will be halted by the time it gets into the blood
Live Attenuated Virus–gives IgA. Stop it right in the GI tract.
What are the pros of live attenuated vaccine as opposed to killed vaccine?
single dose needed no need for adjuvant longer duration of immunity greater protection IgA & IgG made mucosal immunity there cell mediated immunity there no worry about residual live virus in vaccine
What are the cons of live attenuated virus as opposed to killed vaccine?
less stable at room temp
possible reversion to virulence
possible excretion of vaccine virus & transmission to others
could interfere with other viruses in the host
T/F It is more effective to give vaccines separately than in combination with each other.
False. It is equally effective
Trivalent Polio Vaccine
MMR
They work just fine!
