lecture 8 Flashcards
pathogenicity
-refers to ability of virus to cause disease in host
pathogen
virus which causes disease
pathogenesis
manner/mechanism of development of diseases
virulence
- quantitative or relative measure of the degree of pathogenicity of the infecting virus
- not absolute property of virus, depends on many variables
avirulent
not virulent
lethal dose 50 (LD50)
dose of the virus required to cause death in 50% of animals
infectious dose 50 (ID50)
dose of virus that will infect 50% of an experimental group of hosts/animals
with a lower ID50 and LD50 will the virus be more/less virulent?
more
routes of entry of viruses into host
- skin
- mucous membrane
- GI tract
- respiratory tract
defenses of the skin against viruses
- dense outer layer of keratin
- low pH
- presence of fatty acids
- bacterial flora
- dryness
- innate and adaptive immunity (migratory dendritic cells: Langerhans cells)
routes of transcutaneous injection of virus
- bite of arthopods
- bite of infected animal
- contaminated objects
defenses of the GI tract against virus
- mucous membrane of oral cavity & esophagus
- acidity of stomach
- alkalinity of intestine
- layer of mucous covering gut
- lipolytic activity of bile
- proteolytic activity of pancreatic enzymes
- defensins (host defense peptides)
- IgA
- scavenging macrophages
defenses of the respiratory tract against virus
- mucociliary blanket
- alveolar macrophages
- NALT (nasal associated lymphoid tissue)
- BALT (bronchus- associated lymphoid tissue)
- temperature gradient
disseminated infection
-infection spreads beyond primary site of infection
systemic infection
if a number of tissues or organs are infected
apical release of viruses causes…
virus dispersal
basolateral release of virus causes…
spread to underlying tissues (systemic spread)
Directional shedding of viruses from the infected epithelium is critical to what type of viral spread?
-subepithelial spread
viremia
- presence of virus in the blood
- virus may be free in blood or in a cell, such as lymphocytes
primary viremia
initial entry of virus into blood after infection
secondary viremia
virus replicates in major organs and enters the circulation again
active viremia
- viremia following initial virus replication in host
- release of virions from the initial site of replication, such as lymphatics or epithelium of intestine to blood stream
passive viremia
- direct inoculation of virus in host, such as contaminated syringe or bite of arthopods
- no initial replication elsewhere in host before
true/false: mosquito bites are an example of active virema
false, passive viremia
neurotropic virus
- viruses that can infect neural cells
- infection may occur by neural or hematogenous spread
neuroinvasive virus
-viruses that enter the CNS after infection of a peripheral site
neurovirulent virus
-viruses that cause disease of nervous tissue, manifested by neurological symptoms and often death
virus with low neuroinvasiveness, high neurovirulence
- always enters the PNS, rarely enters CNS
- if enters CNS then consequences almost always severe, potentially fatal
virus with neuroinvasivenesss, low neurovirulence
-most infections lead to invasion of CNS, neurological disease is mild
virus with high neuroinvasiveness, high neurovirulence
-readily infects the PNS, spreads to CNS with 100% lethality unless antiviral therapy is administered shortly after infection
retrograde spread of viruses
travel opposite direction of nerve impulse flow, invades axon terminals, then spreads to dendrite or cell body and cross synapse to reach next axon terminal
anterograde spread
travel in direction of nerve impulse flow, virus invades dendrites or cell bodies and then spreads to axon terminals, then cross synaptic contacts to invade dendrite of next neuron
Ways that virus can get into the CNS
- olfactory routes
- through blood-brain-barrier
acute infection
intensive shedding over a short period of time
persistant infection
can be shed at lower titers for months to years
tropism
specificity/affinity of virus for particular host tissue
pantropic viruses
can replicate in more than one host organ/tissue
Virus injury to skin
- vesicles: fluid filled sacs
- ulcers: opening in the skin caused by sloughing of necrotic tissue, extending past the epidermis
- nodule: palpable, solid, elevated mass
- warts: benign skin growths that appear when virus infects top layer of skin
- papule: solid elevations without fluid with sharp borders
- erythema: reddening of skin, from systemic viral infection
virus injury to GI tract
- ingestion
- hematogenouos spread, systemic infection
- causes: destruction of enterocytes due to viral replication, hypersecretion
- GI disease, malabsorption, D+
- pronounced dehydration, acidosis, hemoconcentration
virus damage to respiratory tract
- loss of ciliary activity
- loss of integrity of the lining mucous layer
- multifocal destruction of epithelium
- inflammation
- exudation
- influx of inflammatory cells
- obstruction of air passages
- hypoxia and respiratory distress
- secondary bacterial infection
virus damage to central nervous system
- encephalitis, or encephalomyelitis
- neuronal necrosis
- phagocytosis of neuronss (neurophagia)
- perivascular infiltrations of inflammatory cells (perivascular cuffing)
- progressive demyelination (canine distemper)
- neuronal vacuolation in prion disease
virus damage to endothelium
- hemorrhages- petechiae hemorrhage (pin-point/small spots)
- ecchymoses hemorrhage (larger areas of hemorrhage, ill-defined margins)
disseminated intravascular coagulation (DIC)
- clot forms in small blood vessels throughout the body, organs do not get blood, organ failure
- later stages, raw material for clot exhausted due to over use
- no clot formation in later stages, hemorrhages throughout body
teratogenesis
- abnormal development or arrests in development of the embryo or fetus
- may result in death or malformations during the antenatal period
virus-induced immunopathy
- tissue injury mediated by host immune response to virus infection
- price paid by the host to clear viral infection
- depends on balance between protective and destructive effects of host immune response to viruses
immunopathy
- tissue damage mediated by hypersensitivity reactions
- autoimmune diseases (moon blindness in horse)
- inflammation-mediated tissue damage (fibrosis)
- immunodeficiency disorders
virus injury to organs/tissues (role of T cells)
- cytotoxic cell mediated lysis/killing of infected host cells
- may be release of cytokines from T cells (CD4+ and CD8+) and other cells that cause inflammation and tissue damage that becomes chronic against persistent virus infection
Toll like receptors
-persistent activation of TLRS of innate host cell by viruses cause production of pro-inflammatory cytokines and interferons, as well as signals that recruit and activate cells involved in inflammation
nitric oxide and superoxide
-free radicals that also mediate injury
toxicity from antibody responses
-antibody responses to viruses also may contribute to tissue damage
virus induced immunopathy- immunosupression
- infecious bursal disease: virus replication causes atrophy of bursa and severe deficiency of B lymphocytes resulting in immunosupression
- result: infected birds become susceptible to other pathogens
inapparent infections
- clinical signs and symptoms not evident
- too few cells may be infected
- stimulate host immune response
- possible source of virus spread
acute infection (short term infection)
- short clinical course
- rapid clearance from host immune response
latent infection (persistent infection)
- virus is not demonstrable except when reactivation occurs
- reactivation often stimulated by immunosupression and/or by the action of a cytokine or hormone
chronic infection
-acute infection followed by chronic infection in which the virus is continuously shed from or is present in infected tissue
slow infection (persistent infection)
- prolonged incubation period, lasts months or years
- slow, progressive, lethal disease
