6.2.3 Pathogenesis Flashcards
What are the stages of viral infection?
routes of entry
viral spread/dissemination in the host
virus replication
shedding
What determines the host range of a virus?
Tropism (it’s all about receptors)
What are the possible entry portals for viruses? (6)
skin
GIT
respiratory system
blood (insect bites, injections etc)
genital
transplacental
What are the innate defences of the skin?
keratinised - effective barrier
must be breached by abrasions or bites
macrophages, neutrophils, dendritic cells, natural killer cells
What are the defences of respiratory tract?
Mucociliary escalator (in URT and bronchii)
Resident commensal bacteria in URT
sneezing and coughing
innate immunological defences
How can viruses enter the resp tract?
aerosolized droplets expelled by an infected individual
spread by coughing or sneezing
contact with saliva from an infected individual
What are the defences of GIT? (5)
low pH in stomach denatures protein and kills most microorganisms
bile and proteolytic enzymes in intestines
high pH in duodenum (rapid change)
commensal bacteria (out complete pathogenic bacteria)
mucous and secretory IgA in the intestinal tract
How can viruses enter via blood?
via haematophagous (blood biting) insects
via blood products and/or sexual contact
How can viruses enter via genital tract?
via infected semen
How can viruses enter transplacentally?
viraemic pregnant animals can transmit virus to foetus in utero
What are two types of infections?
local
spreading (via blood, lymphatics, CNS, immune cells)
Describe local infections
replication in epithelium at initial infection site
cell-to-cell spread, but don’t disseminate to other tissues
usually acute (short incubation period, short duration)
site of shedding = site of entry
Describe systemic infections
primary replication at entry site followed by spread to other distant sites
allows entry and exit routes from host to differ
usually longer incubation period and more severe pathology
greater involvement of adaptive immune responses
What is viraemia?
haematogenous spread
What is primary viraemia?
spread of virus by blood from entry site to other target tissues, e.g. liver, spleen
What is secondary viraemia?
may occur following replication in secondary sites
usually allow higher viral titres and further dissemination to other sites
How does rabies spread?
introduction via bite
primary replication in muscle cells
uses motor neurons to reach CNS
further replication in spinal cord and brain
enters salivary glands for onwards transmission
Where does the virus reach the highest titre?
in organ tissues from which it is shed
How do viruses induce pathology?
Direct effects:
-CPE
-cell stimulation
-cell transformation (tumour formation)
Indirect effects
-immune mediated pathology
What causes CPE?
inhibition of host protein and RNA synthesis (cell can’t repair itself)
lysosomal damage (leakage of enzyme)
cell membrane abnormalities
cell lysis (non-enveloped viruses)
apoptosis
what is a negri body?
Round or oval inclusion bodies that contain ribonuclear viral proteins
only in rabies
What are syncytia?
large, multinuclear ‘giant cells’ caused by virus infected cells
Describe the mechanism of cell stimulation
Poxvirus-infected cells synthesise epidermal growth factor-like protein
stimulates cell cycle of neighbouring cells
makes them ideal infection targets for viral replication (virus can spread to newly dividing cells)
What determines disease?
host, viral and environmental factors
