lecture 7 banfield Flashcards
what is viral pathogenesis?
entire process by which a virus causes a disease within a host
define virulence
capacity of a virus to cause disease
explain four main determinants of viral pathogenesis.
- virus-target tissue interaction. ( viremia, receptors etc)
- ability to kill target cell (cytotoxic proteins, replication efficiency)
- host response (can the virus evade it)
- immunopathology (disease caused by the host immune response to viral infection
what viral factors influence virulence
- dose of virus
- route of entry (brain virus tested on mice showed virus injection in skin was much less virulent then injection right into the head)
- tissue repsonse
- virus genotype (code for virulence factors)
what is the general flow of virus infection to virus shedding?
(7)
- virus infects you at site 1
- primary replication and innate immune response activated
- dissemination via the blood / lymph / nerve
- now the secondary site of infection occurs
- secondary replication (amplification) and adaptive immune response
- tissue destruction
- shedding
note: 1,2,3 are considered incubation. 4 and 5 are mild symptoms. 6 and 7 are disease
what are the physical barriers of a virus infection?
- skin
- conjuctiva: tears and blinking
- respiratory tract: secretions
- oral cavity: salvia
- GI tract: stomach acid
what are ribonuclease? where are they found in the barriers of infection?
they are enzymes that chew up RNA. They are found on the skin
what are skin langerhans cells?
type of immune cell that identify viruses in the skin
what are peyers patches?
within the intestine. they sample the intestinal lumen for antigens which will be transported to immune cells on the baso-lateral side. It is thought that many viruses enter through these to enter the host.
what is viremia? what is its two forms?
viremia is virus in the bloodstream. It can be present as a free virus or cell associated (much more common)
what kind of transmission facilitate direct viremia after infection?
insect bites like a mosquito and needles
what are the three ways viruses can leave the blood stream to enter a tissue?
- they can replicate in the endothelial cell and transport basolaterally
- hitch a ride with a read blood cell which squeezes through the endothelium
- transcytosis: they can transport through a vesicle
explain the three stages of acute viremia
- passive viremia: infection, it is not replicated by you yet. this is just transmission
- primary viremia: at local site of infection the virus begins to replicate. this primary viremia can leave in blood and infect target tissues
- secondary virus: results when virus has been released from the localized area, infected target tissue, and then re-enters the blood from the new location. This is when it is considered a real infection.
acute viremia is 14 days. why?
this is how long it takes for the immune response to develop a good antibody
explain neurotropic viruses
these viruses don’t need to have a primary and secondary viremia. they can infect neurons and transport through axonal pathways. Some viruses will infect olfactory neurons and travel to the brain.
what is special about a hematogenic infection?
it can cross the blood brian barrier
where do herpesvirus like to infect?
most often sensory neurons where they travel up and establish latency in the ganglia.
t or f, the nose provides access to neurotropic and respiratory infections
true. herpes virus can cause encephalitis by travelling through the nose neurone.
explain the pathogenesis of mouse pox for the first 10 days.
virus introduced to skin. replicates here and by day 2 becomes primary viremia via the lymph system. It then infects the liver and spleen where it replicates and re-enters blood by day 5: now secondary viremia. This then re-infects skin cells (6/7) So far there is no outward appearance of infection. finally by day 9 there is a evident rash that gets worse with time
how is the polio GI infection spread?
fecal to oral route. usually by fecally contaminated water
breifly explain the GI infection of polio virus.
polio is ingested by contaminated water. it enters through peyer patch M cells. polio uses monocytes for replication here. virus travels through lympthnodes to gain access to the blood. it can now cross the BBB. sometimes (rare) it can infect the spinal cord and lead to paralysis. the virus continues it’s spread as it is in feces.
explain rabies virus dissemination
5
- rabies infects muscle where it replicates
- it then infects motor neurons and travels up them to SC
- rabies continues up into the CNS. replication is occurring in neurones which leads to cell death.
- rabbies modulates the behaviour of the animal making it agressive
- it causes salivary glands to produce lots of saliva, then aggressive animal bites you and transmits the virus
explain the most common flow from virus transmission to virus shedding. (via blood not neural)
- virus infects you (multiple entry locations like M cells and skin scratches)
- replication occurs at site of entry
- most often the virus uses a lymph node to access the blood. now a primary viremia
- virus goes to other target tissue commonly the spleen, liver, muscle, or blood vessel
- virus replicates in secondary location and leaves in blood now a secondary viremia.
- virus infects and replicates in new target tissue (skin, lungs, kidney, etc)
- shedding only occurs once symptoms develop (coughing, blistering, etc)
what are the most common ways a virus is spread by humans
- respiratory / saliva (mouth to mouth)
- fecal - oral
- venereal (sex)
t or f, one disease symptom can be caused by multiple types of viruses
true
t or f, hepatitis D can only exist in cells that already have hepatitis B
true
t or f, a certain virus is always connected to a single disease
false, some viruses can cause more than one type of disease
give an example of a virus which causes more than one disease.
human herpes virus 3 (VZV) which can causes chicken pox and then later causes shingles
what is an acute infection?
rapid production of virus followed by rapid clearing of the infection by the host. The virus does not persist inside the host. (flu A, rhinovirus)
t or f, once infected by an acute infection, the adaptive response kicks in
false, there is a threshold of virus growth that must passed
what is the cause of most acute infection symptoms
the hosts robust immune response
what are latent infections
the virus enters a cell and stays there dormant and sometimes can be reactivated by certain environmental reasons.
where do HSV1 and VZV establish latency?
nucleus of neurons
t or f, reactivation from latency causes virus shedding
true
explain the VZV pathway
- virus enters through mouth and infects URT
- primary viremia leads to liver and spleen infection
- secondary viremia leads to skin infection
- VZV also infects T cells and reprograms them to attack go to the skin. this feeds them the virus.
reactivation of latent VZV in ganglia cause rash in skin
explain the VZV infection, chicken pox, and shingles.
- upon infection, infected T cells transfer the virus to epithelial skin cells.
- blisters occur (each blister containing a lot of virus)
- upon enough replication, the virus infects postganglionic neurons where it travels up and establishes latency in those ganglia. since the initial infection (chicken pox) produces a rash all over the body, almost all ganglia will contain the latent virus
- upon reactivation, the virus travels back down the axons from the ganglia. typically a single neural dermatode is infected. this is shingles.
what are the 4 types of virus infection patterns?
- acute
- smoldering persistent: virus never subdues, it is expressed till death (although virus is expressed, symptoms are revealed until later in life)
- latent persistent infections: become latent and reactivate now and then (HSV1)
- slow persistent infections: infection followed by disease. then low levels of virus for long time before a burst of symptoms. death results if not treatment (HIV)
how to smouldering persistent infections differ from slow persistent infections
smoldering –> initial infection produces high levels of virus with no symptoms. you remain like this until late in life when symptoms burst and you die probs
slow –> initial infection produces symptoms and lots of virus, then virus levels drop a lot. After a long time a burst of symptoms occurs again.